HÆMATURIA AND HÆMOGLOBINURIA OR HÆMATINURIA.
BY JAMES TYSON, A.M., M.D.
The above terms are applied, the first to a condition of urine in which, of the constituents of blood, red discs at least are present; the second to that in which, while no corpuscles are found, blood coloring matter is abundant. Each of these conditions has been repeatedly observed as a distinct state at the moment when urine is passed; but it is also to be remembered that a true hæmaturia may, in the course of a few hours, become a hæmatinuria or hæmoglobinuria, by solution or disintegration of the red blood-discs. So far as I know, this subsequent solution and conversion can take place only in an alkaline urine; but as any urine through decomposition may become alkaline, it is evident that any hæmaturia may, in the course of time, become a hæmoglobinuria—a fact sometimes overlooked. I have, for example, known urine to be sent from Southern parts of the United States which, when shipped, contained blood-corpuscles, but which, when received in Philadelphia, contained no blood-discs, only large amounts of blood coloring matter. Especially does this occur in warm weather, when urine decomposes quickly. Such a hæmoglobinuria might be characterized as secondary. Doubtless, too, a more rapid solution is contributed to in some instances by the state of the blood-discs themselves, which are at times disintegrated before or at the moment they leave the blood-vessels, at others are intact, and at others, still, may be just ready to fall to pieces. In the hæmoglobinuria, where the blood-corpuscles have been secondarily dissolved and disintegrated, their remnants may be found in the shape of dark-brown or red granules, which form a sediment of varying bulk.
The immediate cause of this dissolved state of the blood-discs, where not due to the solvent action of an alkaline urine, appears to be the difference in degree of the cachexia which is at the bottom of the renal hemorrhagic tendency.
The term hæmaturia is applied to blood in the urine from whatever part of the urinary passages it may come, whether the bladder, ureters, kidney, or even urethra; whereas the blood in primary hæmoglobinuria always comes directly from the kidney.
In this paper I shall confine myself to the consideration of renal hæmaturia and hæmoglobinuria in the strict sense of the term; nor will I include such renal hæmaturia as constantly occurs in the first stage of acute Bright's disease.
Emphasizing again that all primary hæmoglobinurias are renal, it is important to be able to say of a given hæmaturia whether it is renal or not. Even coarse methods are often sufficient to settle the question. Blood from the kidney, so far as my experience goes, is never discharged in the shape of clots, at least large enough to be recognized as such by the naked eye. More frequently coagula of blood are passed when hemorrhage takes place into the pelvis of the kidney. These coagula generally cause severe pain in their descent, and by this symptom are distinguished from coagula from the lower part of the ureter and bladder.
The smoky hue, which is characteristic of the presence of small quantities of blood in an acid urine, affords presumptive evidence that the blood is renal in its origin, because the conditions which are associated with blood from other parts of the genito-urinary tract are very apt to be associated with an alkaline urine, to which blood imparts a bright-red hue. This is, however, not invariable, as smoke-hued urine may be due to admixture of blood from the bladder and parts of the genito-urinary tract other than the kidney.
The microscope affords valuable assistance in determining the source of blood in the urine. In addition to blood-discs or their molecular débris, tube-casts made up of cemented blood-discs or their débris are very constantly, although not invariably, found in such urine. This evidence is conclusive, and, although sometimes wanting, the invariable absence of clots from blood descended from the kidney, together with the absence of irritation of the bladder, makes it usually quite easy to recognize a renal hæmaturia.
It is scarcely necessary to say that all urine containing blood or hæmoglobin contains albumen, the quantity varying with that of these substances present. Any further deviations from the normal composition of the urine are, in the main, due to admixture of other constituents of blood.
Causes which give rise to Hæmaturia and Hæmoglobinuria.
Hæmaturia is due to a variety of causes, which may be local or general. Local hæmaturia is caused by wounds, blows upon the kidney, or falls in which the kidney receives the force of the blow, as in striking the edge of a fence in falling; from cancer of the kidney, impacted calculus, parasites, embolism, acute Bright's disease; also poisoning from carbolic acid, cantharides, and mustard. General causes of hæmaturia are malaria, purpura, scurvy, blood-dyscrasias due to continued and eruptive fevers, especially typhus fever and smallpox, septicæmia and pyæmia, and cholera. Finally, it must be admitted that there is a hemorrhagic diathesis manifested by hæmaturia and hæmoglobinuria. Primary hæmoglobinuria may be produced by any of the general causes just named, or by the prolonged inhalation of arseniuretted hydrogen and carbonic acid, and the introduction of numerous substances into the blood, as iodine, arsenic, etc.
While a rupture of the blood-vessels of the kidney may be supposed to be at the bottom of a certain proportion of cases of hæmaturia, it is by no means a necessary condition of their occurrence, as it is well known that in inflammations there may be extravasations of blood without rupture of the blood-vessels. There is implied, however, in all these conditions an alteration of the vessel-walls which permits such transudation. Indeed, Ponfick1 goes so far as to say that even transudations of hæmoglobin through the blood-vessels of the kidney are impossible without the presence of serious diffuse nephritis. There is every reason to believe, however, that simple alterations of the blood are of themselves sufficient to cause such transudations. Take, for instance, the extravasations in purpura, which are not confined to the vessels of the kidney. It is impossible to conceive inflammatory conditions so general as would have to be presupposed in this disease.
1 "Ueber die Gemeingefährlichkeit der essbaren Morchel," Virchow's Archiv, Bd. lxxxviii. S. 47.
Hæmaturia from Local Causes.
It is unnecessary to consider in detail the local causes of hæmaturia. It is evident how injuries and blows upon the kidney, and impacted calculus may produce hemorrhage. The history of nephritic colic or of gravel in urine, along with blood, would suggest the latter cause. Nor is it necessary to detail the phenomena of hemorrhagic infarction which succeeds embolism and is the direct cause of hemorrhage into the tubules of the kidney. Hæmaturia is by no means a constant symptom in sarcoma and cancer of the kidney. A small amount of blood in the urine is a constant symptom in acute nephritis, where it is due to a rupture of the blood-vessels of the Malpighian tuft. It is accompanied by blood-casts and other symptoms of acute Bright's disease. Carbolic acid, cantharides, oil of mustard, and similar substances produce hæmaturia by causing congestion and inflammation of the kidney.
The parasites which may cause hemorrhage in the substance of the kidney are the Bilharzia hæmatobia, the Filaria sanguinis hominis, the Strongylus gigas, and possibly common intestinal worms which may reach the kidney through fistulous openings. The first is a thread-like worm three or four lines in length, which was discovered by Bilharz, and infests the small vessels of the mucous and submucous tissue of the veins of the intestinal tract, the pelvis of the kidney, ureter, bladder, and more rarely of the kidney itself. It is very frequent in Egypt, where Griesinger found it 117 times in 363 autopsies; also in South Africa (Cape of Good Hope), where it gives rise to an endemic hæmaturia. It has been studied by Bilharz, John Harley, and William Roberts.
The Filaria sanguinis hominis is a long, narrow microscopic worm, not wider than a red blood-disc, and one seventy-fifth of an inch long, which infests the blood. Hemorrhages result from its accumulation in the vessels, causing rupture. The cases which have been studied occurred mostly in India, China, and Australia.
The Strongylus gigas is a large worm, resembling the ordinary lumbricoid, but larger, the male being from ten to twelve inches long and one-fourth of an inch wide, while the female is sometimes more than a yard in length. It infests the kidneys and urinary passages of certain lower animals (the dog, wolf, horse, ox, etc.), but rarely those of man.
Malarial Hæmaturia and Hæmoglobinuria.
SYNONYMS.—Intermittent hæmaturia; Paroxysmal hæmaturia; Malarial yellow fever; Swamp yellow fever; Paroxysmal congestive hepatic hæmaturia (Harley).
Perhaps the most important form of hæmaturia and hæmoglobinuria resulting from general causes is that due to malarial poisoning. I prefer the term malarial to intermittent or paroxysmal, not only because it more precisely indicates the cause of the condition, but also because the condition itself is by no means always intermittent, sometimes continuing without interruption until checked by appropriate treatment; and I have known it to continue uninterruptedly for a year, in spite of all treatment.
The first complete report of an undoubted instance of this affection appears to have been published by Dressler in 1854,2 although incomplete and uncertain cases were reported prior to this date—one as early as 1832 by Elliotson.3 G. Troup Maxwell of Ocala, Florida, writes me, in 1883, that he first observed cases in Florida thirty years ago, and published an article on the disease in the Oglethorpe Medical Journal, Savannah, Ga., July, 1860. George Harley4 early contributed to our accurate knowledge of the subject in 1865, and since then numerous papers and reports of cases have appeared in English and American journals, the southern part of the United States being a fertile scene of the affection, while it is by no means rare in the Middle States.
2 "Ein Fall von intermittirender Albuminurie und Chromaturie," Virchow's Archiv, Bd. vi. S. 264, 1854.
3 "Clinical Lecture on Diseases of the Heart, with Ague (and Hæmaturia)," London Lancet, 1832, p. 500.
4 "Intermittent Hæmaturia," Medico-Chirurg. Trans. London, 1865.
Two degrees of the disease are met with—a milder form, in which other symptoms as well as the hæmaturia are less pronounced, and of which instances occur in the Middle States as well as the South and West of the United States. Of this kind seem to be the cases studied by Harley and other English physicians. In addition to this, there is a second, more malignant, form, attended by great prostration, vomiting, and yellowness of the skin, along with copious discharges of bloody urine. Instances of the latter are numerous in the Southern States of this country, where they have recently been studied with much care; also in the East and West Indies and in tropical countries generally. In neither degree of the disease is it necessary that the red corpuscles of the blood should be present. They may be represented by their coloring matters alone, when the condition is called a hæmoglobinuria or a hæmaturia.
The Milder Form.—The subjects, in my experience of eight cases, have been, with one exception, men, and I believe the experience of others included more men than women. They are generally able to recall a history of exposure to malaria, and often of distinct attacks of malarial fever, intermittent or remittent. The hæmaturia appears suddenly, and when paroxysmal may occur daily or on alternate days or a couple of times a week, or even at longer intervals. When the attacks occur at longer intervals, say of ten days or two weeks, if the disease is left alone the interval is apt to gradually diminish until the passage of bloody urine becomes daily. The urine in the morning may be perfectly clear, and at two o'clock is evidently bloody. It continues so through one or two acts of micturition, and then becomes clear again; or it may be bloody on rising and clear up by noon. Sometimes the bloody urine is preceded or accompanied by a sense of weariness and chilly feeling, or sometimes simply by cold hands and feet or by cold knees, or by pallor and blueness of the face, or by accelerated pulse, or by no other symptoms whatever. There is sometimes a sense of fulness in the region of the kidney and sacrum. The attacks are often induced by exposure to cold.
Harley states that in one of the two cases which he reported there was a slight jaundice, and in the second a "sallowness which appeared to be due to a disturbance of the hepatic functions," but in none of the cases which I have met was this symptom present. In the more malignant form occurring in the tropics and the Southern States of America, jaundice is a constant symptom.
While a majority of cases of malarial hæmaturia are intermittent, many are continuous, and of my eight cases only three were distinctly intermittent. One of these cases I published in a clinical lecture in the Philadelphia Medical Times as far back as September 1, 1871.
Negroes are not exempt from this milder form of the disease, as they seem to be from the more malignant form of the South. While writing this paper I was consulted by a negro thirty-one years old who had a true malarial hæmoglobinuria, which yielded promptly to the treatment by quinine. But this was the only negro out of seven cases.
The duration of the disease is very various, and if neglected may be indefinite. Stephen Mackenzie5 reports a case which lasted twenty-three years.
5 "On Paroxysmal Hæmoglobinuria," London Lancet, vol. i., 1884, p. 156.
PHYSICAL AND CHEMICAL CHARACTERS OF THE URINE.—The urine is usually acid in reaction when passed, sometimes neutral, rarely alkaline, and ranges in specific gravity from 1010 to 1028. It is always albuminous, and always tinged by blood coloring matters, the depth of color varying from the trifling degree known as smoke-hued to a dark-red or claret color. Sometimes it is even darker, and is often compared to porter, though this degree of coloration is more characteristic of the malignant form. The urine deposits a dark, reddish-brown sediment, generally copious, but varies in quantity with the degree of coloration of the urine. This sediment is made up chiefly of red blood-discs or the granular débris resulting from their disintegration.
Casts of the uriniferous tubules are also often present. They are usually made up of aggregated red blood-discs or the granular matter referred to; but they may also be hyaline or hyaline with a moderate amount of granular matter attached. Granular urates also at times contribute to the sediment and also adhere to the casts. Renal and vesical epithelium may occur. Crystals of oxalate of lime and of uric acid are sometimes present, while blood-crystals have been found by Gull6 and Grainger Stewart, and a hæmatin crystal once by Strong.7
6 Guy's Hosp. Reports, 1866, p. 381.
7 British Med. Journ., 1878, vol. ii. p. 103.
That red blood-discs are at times exceedingly scarce, and even totally absent at the very moment when urine is passed, is a well-recognized fact; while that the coloring matter present is still that of the blood, even though no corpuscles are present, is easy of demonstration by the production of Teichmann's hæmin crystals,8 by spectrum analysis, or by the guaiacum test.
8 Place a drop of the sediment upon a glass slide and allow it to dry. Mix thoroughly with a few particles of common salt and cover with a thin glass cover, under which allow two or three drops of glacial acetic acid to pass. Carefully warm the slide for a few seconds over a spirit-lamp, and when most of the acetic acid is evaporated, examine by the microscope. Hæmin crystals will be seen to crystallize out as the mixture cools.
In the matter of the presence or absence of blood-discs, it is to be remembered that these may be present at the moment the urine is passed, but disappear by subsequent solution if the urine happens to be alkaline or becomes so secondarily. It is an interesting fact, too, that colorless blood-corpuscles are often present intact, even when red discs are absent. While I have frequently examined urine sent me from the South in which the coloring matter of the blood and no corpuscles were present, only one of the cases coming under my own observations furnished urine of this character. The proportion of urea varies, and bears no evident relation to the condition itself.
PATHOLOGY AND MORBID ANATOMY.—The pathology of malarial hæmaturia consists, as yet, chiefly of theoretical deductions. We can only conclude that the malarial poison acts upon the blood and blood-vessels, impairing the integrity of both. This goes so far occasionally as to produce an actual destruction of blood-discs, and always so alters the capillaries that they permit the transudation of blood-elements ordinarily retained.
The morbid anatomy is scarcely more precisely defined. Ponfick9 goes so far as to say that the exudation of hæmoglobulin is not possible without the concurrence of marked diffuse nephritis. Recently Lebedeff10 has sought to investigate the more minute alterations of the kidney in hæmoglobin exudation, but without very definite results. These, however, on the whole, seem to confirm Ponfick's view as to the presence of an inflammatory process, as also do those of Litten11 and Lassar.12
9 "Ueber die Gemeingefährlichkeit der essbaren Morchel," Virchow's Archiv, Bd. lxxxviii. S. 476, 1882.
10 "Zur Kenntniss der feineren Veränderungen der Nieren bei der Hämoglobinausscheidung," Virchow's Archiv, Bd. xci. S. 267, Feb., 1883.
11 "Verhandl. des Vereins für innere Medicin," Deut. Med. Wochenschr., No. 52, Dec. 29, 1883.
12 Ibid., No. 1, Jan. 3, 1884.
DIAGNOSIS.—The diagnosis of this condition is not usually difficult. We have first to determine whether the hemorrhagic discharge is from the kidney rather than the bladder or ureters. The former is the case when tube-casts are found. But tube-casts are not always present even when the hemorrhage is from the kidneys. The absence of clots and of vesical irritation, and of pain in the course of the ureters, is characteristic of blood from the kidneys. Finally, all hæmoglobinurias are renal.
It being certain that the blood comes from the kidney, we have to distinguish it from that due to cancer, to calculus-irritation, and to cachexias, as purpura and scurvy; or to grave forms of infectious disease, septicæmia, pyæmia, etc.; or, finally, to poisonous substances introduced into the blood, such as arsenic, iodine, arseniuretted hydrogen, carbonic acid and carbonic oxide gas, and even certain species of edible fungi.
The diagnosis is greatly aided if it is found we have to do with a hæmoglobinuria rather than a hæmaturia. For although the former condition is produced by toxic and septic agencies of another kind, the attending symptoms, when it is thus produced, are so characteristic that it is not likely that error can be made.
To aid in distinguishing it from cancer we have the history of malarial exposure, and often that of other forms of malarial disease; and, notwithstanding the seeming drain upon the system, none of the cases I have ever seen present the profound anæmia of cancer. The bloody discharge in cancer of the kidney is always a true hæmaturia; there are always blood-discs in the urine. There is often pain in the region of the kidney in cancer, but never in malarial hæmaturia.
In calculous disease there is almost always pain before or during the hæmaturic attack, and characteristic crystalline sediments often appear in the urine.
The disease, being comparatively rare in this latitude, is sometimes overlooked on this account. Of the 8 cases which I have noted during sixteen years, 5 originated in Pennsylvania, 1 in New Jersey, 1 in Delaware, and 1 in North Carolina.
TREATMENT.—The treatment is distinctly that of malarial disease, and I have seldom seen more brilliant and satisfactory results than have followed the use of quinine in a case accurately determined, although such success is not invariable; and I have known the disease to resist for a long time the most thorough and judicious use of anti-malarial remedies. Usually, however, I take hold of a case of this kind with considerable confidence. When there are distinct remissions my practice has been to administer 16 to 20 grains of sulphate of quinia in the usual manner of anticipation of the paroxysm in intermittent fever—from 3 to 5 grains every hour until the required amount is taken; the whole amount may be taken in two doses, or even in one dose. Where there is no distinct remission I more usually direct 3 to 5 grains every three hours, until the hemorrhage ceases or decided cinchonism is produced.
The advantage well known to accrue in malarial disease from the combination of mercurials with quinine applies to hemorrhagic malaria as well, although I usually reserve the mercurial until I have ascertained whether the simple quinine treatment answers the purpose. If the usual method fails, I give 8 or 10 grains of calomel in the evening, followed by a saline in the morning, before reinstituting the quinine treatment. In the case of the colored man alluded to who had malarial hæmoglobinuria 36 grains of quinine failed to break the attack; but the same quantity, given after 10 grains of calomel had acted, succeeded.
Where these means failed I have not found the other methods of treatment commonly resorted to in obstinate malarial disease to be any more efficient. I allude to the treatment by arsenic or by iron and arsenic. Indeed, in the only two cases in which, after failure with the quinine treatment, iron and arsenic were used at my suggestion, they failed absolutely. In the one case, under the care of James L. Tyson, this treatment was carried out most faithfully. After four weeks' treatment with quinine without effect, Fowler's solution was given, at first in 5-drop doses three times daily, subsequently increased to 10 and 15, along with 20- and 30-drop doses of tincture of the chloride of iron, until oedema of the eyelids occurred, when the arsenic was discontinued, but the iron continued. In two or three days the arsenic was recommenced in 3- and 4-drop doses for three or four weeks longer without effect. Fluid extract of ergot in 20-drop doses was then substituted for the iron, alternating with the arsenic for two weeks longer, when some slight favorable change was apparent, but it was temporary. Repeatedly throughout the treatment the patient complained of weariness and backache, cold feet and knees, headache and acceleration of pulse, and a feeling of utter wretchedness; and then again he would feel quite comfortable for a day or two, but with little or no change in the urine, except occasionally in the morning, when it would sometimes be quite light-hued, but after breakfast would again assume its bloody character. A sojourn at the seaside for two weeks was without effect.
It will appear from the above that ergot, which has been found useful in some forms of hæmaturia, is of little service here, as is attested by two other cases in which I tried it faithfully. At the same time, it is a remedy which should be tried in case of failure with others.
The usual astringents, mineral and vegetable, of known efficacy in the treatment of hemorrhagic conditions, should be used alone or in conjunction with the specific anti-malarial treatment after the latter has been found of itself insufficient. To this class of remedies belong the mineral acids, persulphate of iron, acetate of lead, alum, gallic acid, catechu, kino, the astringent natural mineral waters, etc.
Rest is certainly an important adjuvant in the treatment of this form of malarial disease. I have known a recurrence to take place after a long drive.
It is claimed for many natural mineral waters that hemorrhage from the kidneys is one of the affections cured by their use. Chalybeate and alum springs might be expected to be of advantage by the local action of these astringents in their transit through the kidneys, and they frequently are. The following case illustrates their efficiency: The patient was a lawyer who consulted me in June, 1881, at the suggestion of W. W. Covington of North Carolina. He had frequently had chills, and a congestive chill in 1873. Three months before I saw him he began to pass bloody urine. He had no other symptoms, except a soreness and weakness in the neighborhood of the sacrum, extending into the outer part of the left thigh. The urine passed for me at the time of his visit was dark reddish-brown in color, acid in reaction, had a specific gravity of 1028, highly albuminous, and deposited a sediment of almost tarry consistence, which was made up almost entirely of blood-corpuscles. There were no tube-casts. He had been a dyspeptic since seventeen years of age, and medicines disagreed with him; but he was treated faithfully with quinine, iron, arsenic, ergot, benzoate of lime, all without the slightest effect. At the end of about a year from the time he consulted me he heard of the Jackson Spring, located in Moore county, North Carolina, fifteen miles distant from Manly Station on the Raleigh and Augusta Railroad. He went there, and remained one week. He stated that for the first two or three days the water acted decidedly on his kidneys, and he voided a number of clots of blood. On the third day all traces of blood disappeared, and it recurred but once since, on a very cold day in November last, but again disappeared after a day or two in the house. Unfortunately, no precise analysis of this water seems to have been made, but from what my friend writes it evidently contains iron and sulphur, and magnesia is also said to be present. It is promptly diuretic. Since this occurred I have used the water of alum springs in other instances with advantage.13
13 See the report of a case treated successfully by Rockbridge alum-water by Radcliffe, Med. News, Jan. 12, 1884.
The following are some of the chalybeate and alum springs the waters of which may be expected to be of service in hæmaturia: Orchard Acid Springs, New York; Rockbridge Alum Springs, Pulaski Alum Springs, Bath Alum Springs, Stribling Springs, and Bedford Alum Springs, all in Virginia. In all of these waters iron and alum are both present, accompanied, in many instances, by free sulphuric acid, by which their efficiency is increased. In one of my cases the hemorrhage disappeared temporarily under the use of the water from the Bedford Springs, Penna., but again returned. These waters contain a little iron, but no alum. Subsequently, the same patient was promptly relieved by quinine, which had not been previously tried.
But the cases most promptly relieved by the alum waters are the non-malarial cases depending, upon hemorrhagic diathesis without other local disease. A remarkable instance of this kind was related to me by letter by J. Macpherson Scott of Hagerstown, Md. After enormous doses of quinine had been used under the supposition that it was malarial, it was promptly and totally cured.
Malignant Malarial Hæmaturia.
The second more serious form of this disease, as it occurs in the tropics and the southern part of the United States, is characterized by such increased intensity of all the symptoms that it may be well called malignant. Singularly, however, the disease has seemed to be much more prevalent during the last fifteen years. My attention was first called to it in September, 1868, when I received specimens of urine and the history of some cases from R. D. Webb of Livingston, Ala., who wrote also that it was not known in that part of his State prior to 1863 or 1864.
In this, as in the milder form, there is a distinct but more invariable history of malarial exposure, and the attack often begins as an ordinary case of chills and fever, there being often one or two paroxysms before the hæmaturia appears. At other times the hemorrhage ushers in the disease suddenly. The urine is often black and almost tarry in consistence, and passed in unusually large quantities—it is said as much as a pint every fifteen or twenty minutes until a couple of quarts have been passed, or one or two gallons in the course of twelve hours. But after twenty-four hours the quantity diminishes. Epistaxis sometimes occurs, but is not often profuse. Distressing nausea, and vomiting of bilious and even black matter, like that of black vomit, also occur. Intense jaundice rapidly supervenes—said to come on sometimes in the course of an hour, often in from two to six hours. The tongue is brown and dry. The bowels are at times constipated, and at others loose. Although the patient may be feverish at first, with a temperature of 104° to 106°, and the skin dry, the pulse rapidly becomes small and feeble until it is scarcely perceptible. Drowsiness and coma sometimes intervene, and at others the mind is clear until the moment of death, which frequently supervenes within twenty-four or sixty hours; or the symptoms may subside, to be repeated again the next day if not prevented by treatment. If recovery takes place, which it sometimes does, and lately more frequently, convalescence is slow and tedious, the patient remaining for weeks in an enfeebled and anæmic state.
In this form, especially, of the disease it often happens that the coloring matter and the débris of blood-discs only are found in the urine, very few and often no entire ones being discernible: in other words, we have a true hæmoglobinuria or hæmatinuria. The urine is of course albuminous. A specimen recently received from North Carolina and analyzed by Wormley contained no corpuscles, but revealed the spectroscopic band characteristic of hæmoglobin. It contained 2½ per cent. of urea. The specific gravity of the urine ranges between 1010 and 1020, being lower when it is copious.
As to the jaundice, it is evidently a hæmatogenetic, and not a hepatogenetic, form with which we have to deal. It is due, not to the retention of bile, but to the disintegration of blood-corpuscles and the solution of their coloring matter, which diffuses through the tissues and stains them yellow or yellowish-green. This form too, apparently, is more frequent in males, and negroes appear to be exempt. This is not the case with the milder form, for it will be remembered that one of my patients was a negro.
Autopsies reveal the same intense yellow coloration of internal organs—lungs, liver, spleen, stomach, kidneys—anæmia rather than congestion, while the blood is dark-hued and is indisposed to coagulate. The spleen is often enlarged.
The TREATMENT for the breaking of the paroxysm is pre-eminently quinine or quinine with mercurials, and although this does not always succeed, there seems to be no other remedy. The quinine may be given hypodermically. The nausea has been controlled by morphia and lime-water, by carbolic acid, and by creasote. In addition, restorative measures are necessary, including the free use of stimulants. Turpentine has been used in large doses (fluidrachm j), it is said with advantage, in Alabama.