Part 6

24 HOURS' URINE. Quantity (33 oz.) . . . . . . . 1023 c.c. Reaction . . . . . . . . . . . Acid. Specific gravity . . . . . . . 1017. Urea . . . . . . . . . . . . . 15·345 grammes. Uric acid . . . . . . . . . . . ? Bile acids . . . . . . . . . . None. Bile pigment . . . . . . . . . Abundant. Sugar . . . . . . . . . . . . . Increased. {80} Tyrosine, and leucine[25] . . . In small quantity. Solids (total) . . . . 23·426 Organic matter . . . . . . . . 17·698 Inorganic . . . . . . . . . . . 5·728

[Footnote 25: On precipitating the urine with the acetate of lead, filtering, and freeing the clear liquid from the excess of that reagent by means of sulphuretted hydrogen, and again filtering, the liquid, on evaporation, was found to deposit small crystals of tyrosine, and to have floating in it, and on its surface, round balls of leucine.]

Here, is now to be observed, the rapid downward progress of the case. Stomachal digestion, as indicated by the amount of urea, is much impaired. The general health, as indicated by the sugar, is sadly affected, and, to crown all, tyrosine, and leucine, the indicators of atrophy of the liver, have made their appearance. So unfavourable was the result of this analysis considered, that Dr. Prance felt himself bound to fulfil a promise he had made to the family some time previously, of warning them of approaching danger, when we had no longer any hope of the patient's recovery.

Some time afterwards, in the beginning of December, we again saw the patient together, and made a physical examination of the hepatic organ, the result of which only confirmed our suspicions. The liver was decidedly smaller. The epigastric tenderness was increased. The {81} jaundiced tint deeper. Petechial spots had now appeared on the trunk, and arms. The lower extremities were oedematous, and the abdomen two-thirds filled with fluid.

On the 31st December, I received a sample of urine, and a note saying that the patient had slightly rallied. But on examining the urine, it was found to have a neutral reaction--it had previously always been acid--to be of a specific gravity of 1019, and on standing, to deposit a copious sediment of lithates, coloured intensely yellow with the bile pigment. Curiously enough, the bile-acids had reappeared; but only in quantity sufficient to admit of their being detected. In spite of these trifling changes for the better, the ominous one of an increased amount of sugar was still there.

A few days later, and just before his death, the patient had the benefit of another physician's opinion, which, although it differed somewhat from the foregoing, was, nevertheless, equally unfavourable, for he considered it a case of malignant disease.

The gentleman having noticed that his case excited considerable interest, and some difference of opinion among his medical attendants, directed that his body should be examined after death; and as this wish was seconded by his wife, {82} a lady of superior mind and accomplishments, a post-mortem examination was accordingly made, with the following results:--

Firstly,--The pancreatic duct, as had been suspected, was found completely occluded at its outlet, and so distended by the accumulated secretion, that it readily admitted the point of the little finger. (Vide Plate I., _g_.)

Secondly,--The orifice of the common bile-duct was in like manner 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.)

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_.)

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:--