Chapter III: Introduction (2)

Thirdly,--There are yet other ways in which gall-stones may give rise to great discomfort, and even imperil life, without inducing jaundice. For example, a calculus may remain in the gall-bladder until it attains a very large size, and then ulcerate its way into the stomach, intestines,[15] peritoneal cavity, or even out of the body through an opening in the abdominal parietes.[16]

[Footnote 15: _Vide_ a case of this kind published by the author in the Pathological Society's "Transactions" for 1857, p. 235.]

[Footnote 16: _Vide_ a case published by Mr. Hinton in the "Brit. Med. Journ." of August 4th, 1860, p. 603, and one by Mr. Sympson in the same Journal of the 7th February, 1863, p. 139.]

In fact, jaundice only appears as a complication of gall-stones when they chance to block up the common duct, and thereby prevent the bile entering the intestinal canal. Hence, also, the reason {45} why jaundice, as a result of gall-stones, is more frequently transient than permanent. If it chances to become permanent, it sooner or later leads to a fatal termination--usually within eighteen months after complete obstruction. Lastly, it may be mentioned that, although gall-stones are liable to form in almost every constitution, yet it is generally considered that they are most frequent in persons of the tubercular, cancerous, and gouty diathesis, either hereditary or acquired.

There are other substances besides gall-stones which, by their accidental presence in the bile-ducts, may give rise to jaundice. Thus, for example, foreign bodies, such as cherry-stones, have found their way from the intestine into the bile-duct, and given rise to jaundice. Intestinal worms have been observed to do the same thing, and recently an interesting case of jaundice, occurring in a girl aged 16, who died after a few weeks' illness, has been reported, which resulted from the presence of hydatids in the ductus hepaticus, and ductus communis choledochus.[17] Hydatids of the liver itself seldom give rise to jaundice, their position being usually such as not to interfere with the biliary function.

[Footnote 17: Dr. Dickinson has reported this case in the Pathological Society's "Transactions," p. 104, vol. xiii. 1862.]

There are still other cases where we find {46} transient jaundice arising from accidental obstruction of the bile-ducts; but in them, instead of the closure of the ducts resulting from plugging from within, it arises from the application of pressure from without. Thus, for example, transient jaundice is met with as the result of closure of the common bile-duct, by pressure exerted upon it by the pregnant uterus, or by impacted fæces in the transverse colon. Certain permanent abdominal tumours may also lead to the same result, but these will with greater propriety be considered under the next head.

PERMANENT JAUNDICE FROM OBSTRUCTION.

In order to give as clear a view as possible of the pathology of permanent jaundice from obstruction, it will be necessary for me to give the history of a case of closure of the outlet of the common bile-duct in consequence of organic disease--such, for example, as cancer of the head of the pancreas. A case of this kind has the further advantage of at the same time furnishing us with a typical example of jaundice arising from the re-absorption of the secreted, but retained bile.

When cancer of the head of the pancreas involves the orifice of the common bile-duct, as the tumour grows, the duct slowly, and gradually becomes impervious to the passage of bile into the {47} intestines, until at length the flow is completely arrested. As this gradual process of occlusion of the outlet goes on, the duct itself becomes more and more distended by the retained bile, till it at length attains an enormous size. The gall-bladder being equally prevented from emptying itself, likewise becomes stretched and dilated, until it may at last become not only palpable to the touch, but even apparent to the eye through the abdominal walls. This was the case in the patient whose liver, and occluded ducts are represented in Plate I.

The distention of the bile-ducts is not limited to those situated external to the liver, but also affects those in the substance of the organ; and to such an extent may this be the case, that, on making a section of a liver that has long had its common duct obstructed, a number of large excavations are observed all over its surface, which excavations are nothing more than the open mouths of the transverse sections of the dilated ducts. Such a state of matters is tolerably well represented in the section of the liver in Plate I. Further, the effect of this obstruction to the exit, and consequent accumulation of the biliary secretion, is not confined to the mere distention of the ducts, but causes various changes to occur in the parenchyma of the liver itself. The first of these is an increase {48} in the size of the organ, arising partly from the accumulation of the bile, and partly from the congestion caused by the pressure exerted on the vessels by the distended ducts. In the second place, gradually as the state of matters here described progresses, the parenchyma of the organ becomes itself affected, partly from the direct pressure exercised upon it, and partly from the derangement of its nutrition, produced by the interruption to the hepatic circulation; so that, after a time, the enlarged liver slowly, and by degrees diminishes, until it at length regains its natural size, thereby rendering, at this period of the disease, the diagnosis of the case extremely difficult. This state of matters is not, however, of long duration; for, in consequence of the continued compression of the blood-vessels and parenchyma, the nutrition of the liver is so disordered, as to lead to a gradual shrinking of the entire substance, or, in other words, to a general atrophy of the organ.

It is thus seen how in _permanent occlusion_ of the common gall-duct the liver may be found _hypertrophied_ in the _first_, of _normal dimensions_ in the _second_, and _atrophied_ in the _third_ and _last stage_ of the disease.

In cases of the kind here described, it is not at all unlikely that the enlargement of the liver in the earlier, as well as its atrophy in the later {49} stages of obstruction, may be mistaken for the cause of the jaundice, instead of the result of the arrest of the flow of bile, and thereby lead to a grave error in treatment. The history of the case, together with a knowledge of the above facts, will, however, tend to facilitate the diagnosis. Thus, it must be ascertained:--

Firstly,--If the jaundice preceded the alteration in size of the organ.

Secondly,--If there is an absence of any history of hepatitis; and,

Thirdly,--If there is no evidence of any pulmonary or cardiac mischief likely to lead to passive congestion of the hepatic tissue.

Even with a knowledge of all these facts, however, it often baffles the skill, and acumen of the ablest physicians to discover the cause of jaundice. Every now and then cases are met with, where the patient tells us that the jaundice has gradually come on without any assignable cause, and where, after the most careful examination of his history, as well as of his physical condition, we fail to detect a clue to the diagnosis. Cases of this kind are far from uncommon, and this is the more to be regretted, seeing that unless we have a clear appreciation of the cause, it is not only difficult, but even dangerous to treat the symptom. The injudicious administration of {50} a remedy here, may hasten the termination we most desire to retard. The truth of this remark will, however, be better appreciated when I come to consider the rationale of the treatment of jaundice. Meanwhile, it may be advisable to point out a method capable of yielding most important information, when all the ordinary means of diagnosis fail. I allude to the chemistry of the excretions. Although the pathological chemistry of the excretions is as yet in its infancy, it has already given the scientific physician a key to the detection of several diseases, and I trust to be able to show, that even in the obscure cases of jaundice above alluded to, it not only gives us a clue to their cause, but presents us with a guide to their treatment.

In jaundice arising from obstruction, the pipe-clay stools are, as in the case of jaundice from suppression, entirely due to the absence of bile from the intestinal canal. The yellowness of the skin is in like manner caused by the accumulation of the bile pigment in the blood, from whence it exudes, and stains the tissues; and, lastly, the saffron-coloured urine results in a similar way from the elimination of the pigment from the blood by the kidneys. Instead, however, of these three conditions arising, as in the case of jaundice from suppression, from the arrest of the biliary functions {51} allowing certain of the constituents of the bile to accumulate in the circulation, they are, in the first place, the result of the re-absorption of the secreted bile from the distended ducts, and gall-bladder. So that while in jaundice from suppression, only those biliary products which exist pre-formed in the blood accumulate in the circulation, in cases of jaundice from obstruction, the biliary products which are manufactured in the liver, equally with those which are pre-formed in the blood, find their way back into the circulation, to be from thence eliminated with the excretions. If then, we could ascertain the presence or absence of these products in the excretions, we should be enabled to distinguish between jaundice resulting from suppression, and jaundice arising from obstruction. Let us now see what the chemistry of the excretions teaches us; and to begin, we shall take the intestinal excretion.

ANALYSIS OF THE INTESTINAL EXCRETION AS AN AID TO THE DIAGNOSIS OF OBSCURE CASES OF JAUNDICE.

The intestinal excretion, in the natural state, consists, firstly,--of those portions of our food which have resisted the action of the digestive juices; secondly,--of the excess of the modified food remaining unabsorbed; and, thirdly,--of the excess, {52} as well as of the effete portions of the digestive secretions themselves. Consequently, if from any cause the digestive secretions do not act properly, the evacuation immediately becomes abnormal, and we can discover by analysis which of the secretions is at fault. Thus, for example, we know that the saliva acts upon the starchy matters of our food, the gastric juice on the albuminous, the pancreatic on the fatty, and that the biliary secretion so modifies the chyme as to allow of its rapid absorption by the lacteal, and portal vessels. If then, from any cause the elaboration, or excretion of any of these digestive juices be interfered with, more of the particular kind or kinds of food on which it acts, passes unchanged through the intestines. Thus, if the salivary secretion be affected, an unusual amount of unmodified starch is found in the stool. If the gastric juice is defective, more albumen than is normal passes away unchanged, and so on with the others.

It is clear then, that an examination of the stools must afford us important information regarding the presence, or absence of the normal secretions. A simple inspection of the stool will sometimes at once tell us whether or not bile is present. If it be present, the stool varies from a pale yellow, to a dark olive-green hue, according to the kind, and quantity of biliary colouring matter present, and {53} the nature of the food. It must not be forgotten however, that unless care be taken, the colour deducible from highly-coloured food may be mistaken for an excess of bile. This remark is still more applicable to medicines, for mercury, bismuth, iron, and some other mineral remedies, give rise to dark evacuations so closely resembling bilious stools in appearance, that the only way to distinguish them, is by chemical analysis; when, the presence of the mineral, together with the absence of the bile pigment, and the biliary acids (which are always to be found in normal evacuations), will at once reveal the true nature of the case. I have seen a mistake of this kind happen, and that too, where a patient labouring under jaundice from obstruction, was thought to be passing the usual amount of bile in his stools, when in reality not a particle of bile pigment was present. The colour was in this case entirely due to the food, and ferruginous remedies. Blood from the stomach or bowels, is also apt to be mistaken for biliary matter, more especially when acted on by the gastric juice, which has the property of turning red blood brown. With these exceptions, the absence of bile from the stool, is usually very easily ascertained. For if the patient be taking no highly-coloured food, or any of the medicines above indicated, the stools are of a {54} dirty pipe-clay colour. This is not due to the presence of any new or foreign matter, but solely to the absence of bile pigment. In these cases the evacuations, besides being white, are usually of a most offensive odour, for, among other things, bile checks intestinal putrefaction, and the development of offensive gases.

In addition to the colour, and odour of the fæces, in cases of jaundice, another important indication is to be found in the presence of fat. The presence of fat in the stools was at one time looked upon as evidence of pancreatic, at another time of hepatic disease; now, however, experimental physiology has taught us, that it in some measure depends upon both. For while, on the one hand, the pancreatic secretion emulsions the fatty part of our diet, and thereby renders it capable of absorption, recent researches, as has been already pointed out, have established the fact that the biliary secretion also plays an important part in the absorption of the oleaginous constituents of our food. Bidder and Schmidt, as was before said, have shown that a dog, after ligature of the gall-duct, absorbs less than half the average normal quantity of fat; and by experiment it has been found that this arises from the circumstance that bile emulsions only the acid fats, while pancreatic juice transforms the neutral as well as the acid {55} oleaginous matters. The presence of fat in the stools may be due, therefore, partly to hepatic, partly to pancreatic derangement; and I shall immediately point out how we can turn this fact to account in diagnosis, and discover in cases of jaundice from obstruction, whether the seat of the obstruction be at the outlet or in the course of the duct.

EXAMINATION OF THE RENAL SECRETION.

The urine affords us important information in all cases of jaundice. In fact, an examination of it alone would in many cases enable us to discover the presence or absence of this affection.

_Diagnostic Value of the Colour of the Urine._

The urine of jaundice has invariably a peculiar tint, ranging from a saffron-yellow to a dark olive-green, or almost black hue. It must not be forgotten that the colour of normal urine varies with the degree of concentration. Where little is passed, being of a high, where much is passed, of a pale colour; the depth of colour depending on the degree of dilution of the urohæmatine. Again, it must also be remembered that there are many diseases, which change the colour of urine very materially, some only deepening, others actually changing the tint. Foods, and medicines also, {56} alter the colour of the renal secretion. Rhubarb, and santonine give to it a saffron hue, arsenious acid gas a black colour. Bearing in mind these facts, one would hesitate before giving a decided opinion as to the presence or absence of icterus from a mere inspection of the urine. For this reason, it is generally recommended in cases of jaundice to pour a little of the urine on a white plate, and watch the play of colours produced by strong nitric acid. This method, however, is not always satisfactory, for the play of colours depends on the different stages of oxidation through which the pigment passes, and other animal pigments, besides biliverdine, unfortunately act in a somewhat similar manner.

A very simple, and more convenient way of testing the pigment without changing its physical characters, is to separate it in combination with uric acid. This is readily done by simply acidulating the urine with a few drops of hydrochloric acid, and setting it aside for twenty-four hours to crystallize. The white uric acid in crystallizing takes up the colouring matter, and assumes the hue of the pigment present in the urine. I have thus obtained crystals of all the different hues from a bright golden yellow tint through the intervening shades of red, brown, blue, olive, to a dark, almost black colour. This experiment {57} has another advantage, for if we take a measured quantity of urine, and collect, dry, and weigh the uric acid obtained from it, we can readily calculate the total quantity passed in the twenty-four hours, and thereby assist in diagnosing the presence or absence of malignant disease of the liver, as I shall afterwards have occasion to point out.

The urine of jaundice is generally described as being of a saffron colour; but if I may be allowed to form an opinion from my own observations, which are tolerably numerous, I should say that it, in colour, much more frequently resembles old ale than anything else with which I am acquainted. On standing, the colour changes very considerably, in consequence of the pigment becoming slowly oxidized by its exposure to the air. When there is a very great excess of bile pigment present in the blood, the kidneys have some difficulty in eliminating it. Occasionally even, it chokes up the renal capillaries, and thereby complicates the jaundice by inducing secondary disease in the kidney. In such cases the external surface of the kidney, after the removal of the capsule, looks as if it had been sprinkled over with ink. The black specks vary in size from the minutest visible point to that of a pin-head. The accompanying chromo-lithograph (Plate II.) represents a kidney in this condition. {58} It will also be observed that it is studded over with a number of small abscesses; but whether these resulted from the blocking-up of the capillaries just alluded to or not, it is impossible to say. In the case in question no albumen was detected in the urine during life, and it was only on careful analysis, after the post-mortem had revealed the above state of matters, that a small quantity was discovered; and even then, had not the experiment been carefully performed, the presence of albumen might have been overlooked.

_Diagnostic Value of the presence of the Bile-Acids in the Urine._

All acquainted with the recent literature of jaundice know how hard a battle is being fought between two sets of observers in Germany, regarding the presence of bile-acids in urine. One class, with Frerichs and Städler at their head, believe that the biliary acids are decomposed in the blood, and are consequently never to be detected in the urine. The other class, headed by Kühne, state as positively that they have detected these substances in the urine. Indeed, Kühne states that by adopting Hoppe's method,[18] he never fails to {59} detect the presence of the biliary acids in the urine of patients labouring under icterus, as well as in the urine of dogs with the bile-duct ligatured. When first studying this question, I was very much perplexed by these contradictory statements, for neither the judgment, nor the power of observation of either of the authorities could for a moment be called in question; and on experimenting for myself, so unsatisfactory were the results obtained, that I almost threw the question aside in despair. On one occasion, however, I at length met with such unmistakeable evidence of the presence of bile-acids in the urine, that I could no longer doubt the fact of their existence, and was forced to search for an explanation of the previous contradictory results. Fortunately, it was not very long before a solution to the difficulty was obtained, and, what was of still greater importance, led to the observation that the contradictory results arose from a circumstance which might be turned to account, as a means of differential diagnosis. The discovery was, that in certain cases of jaundice not a trace of the biliary acids is to be detected in the urine, although the {60} bile pigment is present in abundance; while in certain other cases both biliary acids, and bile pigment occur in notable quantity. What, then, is the cause of this difference? Simply this. In jaundice from suppression the liver does not secrete bile; consequently no bile-acids being formed, none can enter the circulation, and they are therefore not to be detected in the urine. In jaundice from obstruction, on the other hand, bile is secreted, and absorbed into the blood; and the bile-acids not being all transformed in the circulation, as Frerichs supposed, are eliminated by the kidneys, and appear in the urine, where they can be detected by Hoppe's method, or even, with proper precautions, by simply adding sulphuric acid and sugar. Here, however, some skill and experience are requisite, in order not to confound the colour produced by the action of the reagents on other substances with the fine purple produced by the biliary acids. As the majority of cases of jaundice result from suppression of the hepatic function, and as many of the cases of obstruction ultimately merge into the former, it is easily understood how the existence of the biliary acids in the urine has been so frequently denied. I have myself seen, in a case of obstruction of the common duct, the biliary acids slowly and gradually diminished in the urine, until they at length almost entirely {61} disappeared as the case approached a fatal termination. Here the disappearance of the biliary acids went on step for step with the impairment of the secreting powers of the liver, in consequence of the pressure exercised on its parenchyma by the retained bile.

[Footnote 18: Professor Hoppe tests for bile-acids in the following manner:--The urine is boiled with an excess of milk of lime for about half an hour, and filtered to free it from the precipitate thus formed. The filtrate is evaporated to dryness, decomposed with hydrochloric acid, washed with water, and then extracted with alcohol. The alcoholic extract contains the bile-acids, which are recognised by Pettenkofer's test.]

The readiest mode by which the biliary acids may be detected is the following: To a couple of drachms of the suspected urine add a small fragment of loaf-sugar, and afterwards pour slowly into the test-tube about a drachm of strong sulphuric acid. This should be done so as not to mix the two liquids. If biliary acids be present, there will be observed at the line of contact of the acid, and urine--after standing for a few minutes--a deep purple hue.[19] This result may be taken as a sure indication that the jaundice is due to obstructed bile-ducts. On the other hand, the absence of this phenomenon, and the occurrence of merely a _brown_ instead of a _purple_ tint, although, in the earlier stages of jaundice, equally indicative of suppression, is of course, for the reasons already given, no indication of the cause of the suppression. That must be gleaned from other circumstances.

[Footnote 19: The immediate formation of a reddish coloured line is due to the acid setting free urohæmatine, the normal colouring matter of the urine.]

It is seen that I have taken no notice of {62} Frerichs' theory regarding the bile-acids being changed into bile pigment. I have done so advisedly, feeling as I do, that when that observer investigates the subject more fully, he will himself abandon such an untenable doctrine, founded as it is, on an erroneous view regarding the nature of bile pigment. The colour induced by sulphuric acid on the acids of the bile, is as different in its chemical nature from animal pigment, as any two substances can possibly be. Indeed, they have no bond of connection whatever, except the mere tint. All animal pigments, whether they be green, like bile-colouring matter, or red, like hæmatine, spring from the same source, and contain iron. Besides this, the mere fact of an increase of animal pigment being found in the urine after the bile-acids have been injected into the circulation, to which Frerichs attaches such importance, in reality proves nothing more, as Kühne pointed out, than that an increased destruction of blood corpuscles has taken place. I have found the urine of dogs loaded with dark colouring matter after injecting chloroform, and other stimulants into their portal veins, in order to establish artificial diabetes; and, assuredly, in these cases the presence or absence of bile-acids in the blood had nothing to do with the result.

{63} _Diagnostic Value of the presence of Tyrosine, and Leucine in Urine._

There are two other abnormal products occasionally met with in the urine of jaundice, namely, tyrosine, and leucine. These substances, although for many years known to chemists, attracted comparatively little attention until Frerichs discovered their diagnostic value in hepatic disease.

In that peculiar form of complaint, described as acute or yellow atrophy of the liver, the {64} urine is said invariably to contain tyrosine, and leucine. The presence of these substances may therefore assist us in diagnosing the case. When tyrosine, and leucine are present in quantity, they are very readily detected, all that is required being slowly to evaporate an ounce of urine, to the consistency of syrup, put it aside during a few hours to crystallize, and then examine it with the microscope. The tyrosine is recognised by being in fine stellate groups of needle-like crystals, as represented in fig. 4, or spiculated balls not unlike a rolled-up hedgehog, with the bristles sticking out in all directions.

{65} Tyrosine may be obtained in a pure state by adding to four ounces of urine a solution of acetate of lead, till a precipitate ceases to form, filtering, and freeing the liquid from the excess of lead by a current of sulphuretted hydrogen, again filtering, and evaporating the clear solution. The tyrosine is now colourless, and crystallizes with the microscopic characters above alluded to, but still better marked. Tyrosine may be further recognised by putting a few crystals on a platinum spatula, adding a drop or two of nitric acid, and evaporating to dryness. If present, the yellow residue thus obtained assumes a pumpkin hue on the addition of potash, and leaves on incineration a dark greasy stain. Frerichs recommends another test, namely, the following:--Put the suspected substance into a watch-glass, along with some sulphuric acid, and after they have been in contact about half an hour, dilute the mixture with water. Next boil, and then neutralize with carbonate of lime. Filter, and to the clean filtrate add a few drops of perchloride of iron, devoid of free acid. The formation of a dark violet blue colour indicates the presence of tyrosine.

Leucine is known by its flat, circular, oily-looking discs, without any crystalline structure. At the first glance, a globule of leucine might be mistaken for oil, not only on account of its {66} microscopical characters, but also on account of its being lighter than water. The globules of leucine are distinguished from those of oil by their being soluble in water, and boiling alcohol, and insoluble in ether. Besides this, the discs are occasionally opaque and laminated like the granules of potato starch. They are then not at all unlike microscopic crystals of the carbonate of lime; but the carbonate of lime crystals sink in water.

Both tyrosine, and leucine are usually deeply impregnated with the colouring matter of the urine.

Since Frerichs' views were first published I have found tyrosine, and leucine in the urine of cases of chronic, as well as of acute atrophy of the liver. Their presence may therefore aid in diagnosing the latter as well as the former condition of the hepatic organ.

{67} I have little doubt that future research will discover other conditions of the liver, besides those just mentioned, in which tyrosine, and leucine, may appear in the urine; for, as will be subsequently pointed out at page 96, I have been successful in producing them artificially in the urine of animals in which there was no evidence either of acute or chronic atrophy of the liver having taken place. In the cases cited, indeed, it will be seen that the jaundice was the result of suppression, consequent upon congestion of the liver, produced by blood poisoning.

It may be added that since these observations were made I have found in the artificially concentrated urine of a case of jaundice from obstruction consequent upon impacted gall-stone, a few balls closely resembling leucine in shape, and size, but differing from it in being excessively dark in colour. No tyrosine crystals were observed, and unfortunately there was not sufficient of the leucine-like substance present in the urine to admit of its being chemically tested. I have thought it my duty to record this fact for the benefit of other observers, as there can be little doubt that we are gradually verging towards some important discovery in a diagnostic point of view.

{68} _Melanine in the Urine._

Four years ago (1858), Dr. Eiselt of Prague called attention to the fact that in cases of melanotic cancer of the liver, melanine appears in the renal secretion.[20] When the urine is passed it is usually quite clear; but after standing it becomes of a dark colour, even as dark as porter, without, however, losing its transparency. This deepening of the colour is no doubt due to the oxidation of the melanotic pigment, as the employment of an oxidizing agent, such as nitric or chromic acid, causes the same change to occur instantly.

[Footnote 20: Dr. Eiselt states that he also found melanine in the urine in a case of melanotic cancer of the eyeball.]

In addition to the cases related by Dr. Eiselt, I am able to add one of considerable importance, as it not only offers a striking illustration of the correctness of his views, but has the double advantage of being an unbiassed record of facts, in consequence of its having been observed, and recorded long before Dr. Eiselt's views were published, and therefore at a time when the author had no idea of its significance. The case occurred about thirteen years ago, in the wards of the Royal Infirmary of Edinburgh. The history of the case I extract from my private note-book. It is briefly as {69} follows:--In the month of May a sailor was admitted into the clinical wards of the Royal Infirmary with symptoms of jaundice from enlarged liver. He stated that he had been a great deal abroad, in hot climates, and admitted that he had been a hard drinker. On admission his skin was of a dusky yellow colour, and had been so since the month of February. The liver was considerably enlarged, and he complained of sudden violent pains in the neighbourhood of the umbilicus. The pain was usually most severe during the night. The urine was of a dark colour, and on the addition of nitric acid, became nearly quite black. It contained no albumen. The patient died ten days after admission. On post-mortem examination, the hepatic duct was found blocked up with malignant deposit, and the liver of a dark green colour. There was also a considerable amount of malignant deposit in the mesentery. This patient, as frequently happens in such cases, became delirious before death.

In jaundice arising from melanotic cancer of the liver, the recognition of the presence of melanine in the urine would be an important aid to the diagnosis. Care must be taken not to confound the dark olive-green urine occasionally met with in other forms of jaundice, with the melanotic urine just described, or both {70} patient and doctor may become unnecessarily alarmed.[21]

[Footnote 21: While I was Resident Physician in the Royal Infirmary of Edinburgh, in 1850, a woman, aged 28, was admitted with a universal and bright jaundice of three weeks' standing. Her urine was high coloured, and of a specific gravity of 1022. It contained a small quantity of albumen, and became perfectly black on being boiled with nitric acid. In this case there was no reason to suspect malignant disease of the liver; the colour of the urine was, therefore, most probably due to the bile pigment being more than usually oxidized. After a six weeks' stay in the hospital, I dismissed the patient as cured.]

_Urea, Uric Acid, and Sugar._

The presence, and quantity of certain other substances met with in the urine of jaundice, although not peculiar to that condition, nevertheless afford us important information, not only as to its cause, but also as to its probable mode of termination.

Firstly, a correct knowledge of the quantity of urea, and of uric acid passed in the twenty-four hours is of great value; and, secondly, the presence, or absence of sugar is a fact which ought never to be lost sight of. The value of this statement, as well as of several of the preceding, will, I think, be better appreciated by giving a short account of a case of obscure disease (where a correct diagnosis, and prognosis could not have been arrived at without the application of the chemical knowledge referred to), than by any mere abstract {71} treatment of the question. I shall, therefore, at once proceed to relate the brief history of the case.

A gentleman, aged fifty, who had been a remarkably healthy man, observed, within eighteen months of his death, that his skin gradually assumed a more and more jaundiced tint without any assignable cause. The stools were clay-coloured, the urine loaded with bile pigment. Soon afterwards, the patient began to lose flesh. The liver became enlarged, and somewhat tender to the touch; the gall-bladder being at the same time so distended that it could be seen, as well as felt, projecting from under the false ribs. As the case resisted the usual remedies, the patient was recommended to try change of air. During his absence from town, he suddenly passed a large quantity of yellow matter by stool (supposed to be bile), and immediately afterwards the fulness in the abdomen disappeared. On the patient's return to town, the gall-bladder could no longer be seen or felt, and it was naturally supposed that it had emptied itself on the occasion referred to. As, notwithstanding this, the jaundice continued, and the health and strength gradually declined, Dr. Prance, under whose care the patient was, sought the assistance of a physician of distinguished reputation in these affections. At this period, {72} however, the entire absence of physical signs beyond the clay-coloured stools, and those directly referrable to the jaundice, rendered it impossible for any decided opinion to be arrived at. The liver had now resumed its natural size, and the only thing detectable was slight tenderness on pressure, with a doubtful fulness in the pancreatic region. These signs, associated as they were with gradually increasing emaciation and debility, led to the suspicion of malignant disease, either in the course of the bile-ducts, or at the head of the pancreas. About this time it was discovered that the patient occasionally passed a considerable amount of a fatty-looking matter by stool--not mixed with the motion, but separate, though upon it. After the passage of this matter, there in general appeared to be a slight improvement in the patient's condition. The substance in question, on cooling, solidified into a firm pale-brown matter, resembling Windsor soap, and not at all unlike some of the biliary products. This led to the idea that it might be composed of the fatty acids of the bile. On one occasion a portion of it was forwarded to me for analysis, and on subjecting it to chemical examination it proved to be, strangely modified fish-oil, the oleine of which had entirely disappeared. In fact, it was nothing but the sparingly soluble fatty acids of cod-liver oil, which had {73} been transformed in the stomach, and from which all the liquid principles had been absorbed. This was considered an important discovery, as it not only negatived the idea of the bile still reaching the intestines, but also proved that the _pancreas_, as well as the _liver_, was affected. Having thus learned that the pancreatic juice, as well as the bile, failed to reach the intestines, an effort was made to counteract the pernicious effect on the system caused by the absence of the former secretion, by giving 1½ grains of pancreatine in the form of pill three times a day. During the period that the patient was taking this medicine, the quantity of fat passed by stool was supposed to diminish. No decided improvement in the patient's condition took place, however, and on the 2nd of November the gentleman was brought to me by his medical attendant. At this time the patient was much in the state already described,[22] and after a careful physical examination, I failed to elicit any new fact of importance. The hepatic dulness was perfectly natural; there was no tenderness to speak of, no history of gall-stones, and {74} no evidence of any tumour beyond the doubtful fulness in the pancreatic region. The digestive, and other functions of the body, except those already mentioned, seemed unimpaired, and yet the patient's strength daily declined. As physical as well as symptomatical diagnosis proved inadequate to unravel the mystery of this obscure case, and as chemical means had already, in as far as it had been tried, been of advantage, it was resolved to subject the excretions to a rigid chemical examination. The patient was accordingly desired to collect all the urine he passed during twenty-four hours, and while I analysed it, Dr. Prance examined the stools, in order to ascertain their composition--especially as regarded the amount of fatty and albuminous matters contained in them. The urine yielded on analysis the following result:--

24 HOURS' URINE.
Quantity (55 oz.) . . . . . . . . . . . . . . . . . . 1705 c.c.
Reaction . . . . . . . . . . . . . . . . . . . . . . Acid.
Specific gravity . . . . . . . . . . . . . . . . . . 1018.
Colour . . . . . . . . . . . . . . . . . . . . . . Greenish yellow.
Urea . . . . . . . . . . . . . . . . . . . . . . . . 27·28 grammes.
Uric acid (crystals large, and of a dark-green colour) 0·511 "
Bile acids[23] . . . . . . . . . . . . . . . . . . . Abundant. {75}
Bile pigment[24] . . . . . . . . . . . . . . . . . . Abundant.
Albumen . . . . . . . . . . . . . . . . . . . . . . . None.
Sugar . . . . . . . . . . . . . . . . . . . . . . . . None.

[Footnote 22: I noted his state to be as follows:--Skin of a black jaundiced tint (dark green). Eyes deeply stained. Lips anæmic. Considerable emaciation and debility. Extreme languor. Appetite good. Tongue, and pulse not remarkable. Slight pain on pressure over the gall-bladder. Indistinct fulness in pancreatic region, and to the left of middle line.]

[Footnote 23: On the addition of sulphuric acid, and white sugar to the urine, a very marked, and beautiful purple hue was obtained.]

[Footnote 24: Nitric acid at first turned the urine green, but on the application of heat it became red, and after prolonged boiling, of a pale straw colour. Hydrochloric acid changed the colour of the urine immediately to a deep olive-green tint.]

The facts here elicited were interpreted as follows:--

1st,--The quantity of urea which might be said to be normal, was considered a favourable sign, as it indicated that the stomachal digestion was unimpaired.

2nd,--The quantity of uric acid being below the average, was likewise regarded as favourable, tending as it did to negative the idea of cancerous disease of the liver; the uric acid being in such cases usually increased.

3rdly, and lastly, the presence of the biliary acids, as well as the bile pigment, in the urine, showed that bile was still being secreted, but re-absorbed, and this led at once to the diagnosis that the case was one of jaundice from obstruction.

Here, then, was an important step gained. The next point was, if possible, to ascertain the cause of the obstruction. Taking into account the absence of any tumour, and any history of gall-stones, together with the fact of the sudden disappearance of the enlarged gall-bladder, my {76} first idea was that it might be a case of hydatids blocking up the common gall-duct, and that on one occasion, some large cyst had ruptured, and discharged itself through the intestines. On talking the case over with Dr. Prance, however, that idea was abandoned, and we were forced to content ourselves with the simple fact that the case was one of jaundice from obstruction of the common bile-duct, complicated with occlusion of the pancreatic duct, which fact had been previously ascertained by the discovery of the fatty acids in the fæces. About this time the patient took three grains of benzoic acid, in the form of pill thrice a day, and it was thought, with the advantage of slightly diminishing the jaundiced state of the skin. But no permanent benefit was obtained, and after a time this remedial agent had to be discontinued, in consequence of its having induced slight dyspepsia. In the letter I received informing me of this fact, it was also noted that there was much less both of the oily matter, and albumen in the stools. There was, at the same time, a considerable deposit of urates in the urine. The specific gravity continued to be about 1018. The quantity in twenty-four hours about forty ounces. On the 29th of November, the patient was again brought to me, and we made a careful examination of the size, shape, and exact position of the {77} hepatic organ. The measurements were found to be 5 inches at the extreme right, 4 inches at a line drawn perpendicularly to the nipple, and 2¾ inches midway between nipple and sternum. Beyond the centre of the sternum the liver did not reach. As regards the size of the liver then, there was still nothing very remarkable.

On this occasion it was observed, that the patient's memory was not so good as formerly, and that there was a certain amount of mental as well as bodily languor. His hearing was likewise sluggish, the words having occasionally to be repeated before they made an impression on the cerebral organ. This, no doubt, arose from the poisonous effects of the bile circulating in his blood.

It may be here mentioned, that in cases of jaundice from suppression we seldom or never meet with those extreme symptoms of cerebral disturbance which are so common in cases of jaundice from obstruction. I believe the reason of this difference in the two forms of jaundice arises from the circumstance that the really poisonous parts of the bile are the biliary acids, and that they, like urea, are powerful narcotic poisons. The results of the experiments on artificial jaundice (page 95) led me to this conclusion.

As neither the symptoms nor physical signs threw any additional light on this interesting case, {78} it was determined once more to bring chemistry and the microscope to bear upon it, with the view of, if possible, extending the information these methods of investigation had already yielded. Accordingly, a specimen of the urine was again obtained for analysis, and it yielded the following results:--

24 HOURS' URINE.
Quantity, (43 oz.) . . . . 1333 c.c.
Specific gravity . . . . . 1016.
Reaction . . . . . . . . . Acid.
Urea . . . . . . . . . . . 23·994 grammes.
Uric acid . . . . . . . . 0·266 "
Bile pigment . . . . . . . Abundant.
Bile acids . . . . . . . . Small quantity.
Sugar . . . . . . . . . . A little.
Solids (total) . . 41·989
Organic matter . . . . . . 31·992
Inorganic . . . . . . . . 9·997

A marked change is here seen to have occurred in the constitution of the renal secretion. First--the quantity of urea has notably diminished (from 27·28 to 23·99 grammes, or in other words, from 423·84 to 370 grains.) The amount of uric acid has also fallen (from 0·511 to 0·266 grammes, or in other words, from 8 to 4 grains); while at the same time the biliary acids have considerably decreased. These changes are also seen to be accompanied by another, which I at once regarded {79} as a most unfavourable sign,--namely, the appearance of sugar in the urine. Although the quantity of sugar was as yet small, and it was associated with a diminution in the bile acids, it nevertheless made me look forward with gloomy forebodings, for as far as my experience goes, when the urine becomes saccharine in the course of a chronic, and exhausting disease, it has generally been the forerunner of a fatal termination. This case, I am sorry to say, proved no exception to the rule. There was, indeed, but one consolatory fact in the analysis, and that was the diminution of the uric acid, which, as I before remarked, tended to negative the idea of malignant disease of the liver, and this was a great source of satisfaction to the patient.

Eight days later, 12th November, a qualitative, and quantative analysis of the urine was again made, with the following result:--

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.