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
{105} 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 {106} the blood-vessels. There is implied, however,
in all these conditions an alteration of the vessel-walls which permits
such transudation. Indeed, Ponfick[1] 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.
[Footnote 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.
{107} 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 Harley[4] 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.
[Footnote 2: "Ein Fall von intermittirender Albuminurie und
Chromaturie," _Virchow's Archiv_, Bd. vi. S. 264, 1854.]
[Footnote 3: "Clinical Lecture on Diseases of the Heart, with Ague (and
Hæmaturia)," _London Lancet_, 1832, p. 500.]
[Footnote 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 {108} 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 Mackenzie[5] reports a case which lasted
twenty-three years.
[Footnote 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
Gull[6] and Grainger Stewart, and a hæmatin crystal once by Strong.[7]
[Footnote 6: _Guy's Hosp. Reports_, 1866, p. 381.]
[Footnote 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, {109} 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.
[Footnote 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. Ponfick[9] goes
so far as to say that the exudation of hæmoglobulin is not possible
without the concurrence of marked diffuse nephritis. Recently
Lebedeff[10] 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 Litten[11] and
Lassar.[12]
[Footnote 9: "Ueber die Gemeingefährlichkeit der essbaren Morchel,"
_Virchow's Archiv_, Bd. lxxxviii. S. 476, 1882.]
[Footnote 10: "Zur Kenntniss der feineren Veränderungen der Nieren bei
der Hämoglobinausscheidung," _Virchow's Archiv_, Bd. xci. S. 267, Feb.,
1883.]
[Footnote 11: "Verhandl. des Vereins für innere Medicin," _Deut. Med.
Wochenschr._, No. 52, Dec. 29, 1883.]
[Footnote 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
{110} 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 {111} 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.