Leukæmic differs from ordinary blood, and from that of other anæmic or
cachectic states, by the readiness with which the hæmoglobin
crystallizes. Often if a slide is kept and prevented from evaporating
by a rim of paraffin, beautiful plates of hæmoglobin will crystallize.
The pulse is always quickened--80 to 100, and in the final stages
110-130--usually soft and compressible, and not always small in volume.
The heart's action is readily excited. A systolic murmur is not
infrequent at the apex; basic hæmic murmurs are not so often heard as
in anæmia, but a venous hum in the neck is generally present. The
apex-beat of the heart may be pushed up an interspace by the enlarged
spleen. Oedema of the ankles and feet from the feeble circulation is
constantly met with, particularly toward the close, and there may be
general anasarca. Effusion into the pleural cavities is not common.
Hemorrhages are among the most constant features of the disease, and
may occur at any time, early or late, in the course. The tendency to
bleeding is greater in this than in any of the allied affections.
Epistaxis is the most frequent form, and may precede the development of
the disease for months or years. Hæmatemesis may carry off a patient
early (Case II.), or even before the nature of the trouble is suspected
(Case VI.). Hemorrhage from the bowel is common. Hæmoptysis and
hæmaturia are rare. Bleeding from the gums may be present (Cases V. and
VII.). In women there may be profuse menstruation. Petechiæ on the skin
are frequent; occasionally there are large extravasations beneath the
skin or between the muscles. Hemorrhage into the brain may prove
quickly fatal (Case X.), and the extravasations into the retinæ may
impair vision.
The respiratory system offers few special symptoms. The shortness of
breath on exertion is due in great part to the anæmia, and
progressively increases with the advance of the disease. The free
action of the diaphragm is hampered by the enlarged spleen. There may
be cough from bronchitis, and toward the end signs of oedema at the
bases of the lungs. Pneumonia is not uncommon as a final complication.
The temperature in the early stages presents very slight variations,
but when the disease is advanced there is always fever of the remittent
or of the continuous type. There is usually a morning remission, and an
evening exacerbation which reaches 101° or 103°. Periods of pyrexia may
alternate with prolonged intervals of freedom from fever. In some cases
the febrile movement is very slight throughout the entire course.
Genito-urinary System.--The urine is usually normal in amount, pale,
strongly acid, and its specific gravity above the normal. Considerable
variations occur in individual cases. Sediments of lithates are very
common. {914} The urea presents no constant changes; sometimes it is
increased, at others diminished, the quantity depending probably on the
food and the presence or absence of fever. The quantity of uric acid
excreted seems always to be increased, due either to a lessening of the
oxidation processes in consequence of the reduced number of red
corpuscles, or, as Salkowski suggests, it stands in relation to the
existing splenic tumor; but observers have not found the amount
proportionately increased in other forms of splenic enlargement, and
the cause of the constant increase is still doubtful. Hypoxanthine,
lactic, formic, acetic, and hippuric acids have been found, but their
presence is neither constant nor apparently of special import. Albumen
may be present. Sugar is rare. Hæmaturia, as before observed, very
seldom occurs. Cystitis may arise and be troublesome (Case XI.).
A curious symptom in connection with the generative system is priapism,
of which a number of cases have been recorded. Edes[123] narrates the
case of a boy of fifteen in whom obstinate priapism was the first
symptom. Longuet[124] reports a case of six weeks' duration.
Saltzer[125] mentions five cases, in one of which the condition
persisted for seven weeks, and Peabody[126] gives a case in which it
lasted six weeks. It is not definitely settled whether the priapism is
due to thrombosis in the corpora cavernosa or to irritation of the
nervi errigentes.
[Footnote 123: _Boston Med. and Surg. Journ._, 1871.]
[Footnote 124: _Progrès méd._, 1875.]
[Footnote 125: _Berliner klin. Wochenschrift_, 1879.]
[Footnote 126: _New York Med. Journ._, 1880, xxi.]
In women there are the usual menstrual irregularities consequent upon a
grave constitutional disease. Occasionally the flow is excessive; more
commonly it is interrupted altogether.
Blood-glandular System.--Slow increase in the volume of the spleen,
causing a sense of weight in the left hypochondrium, is an early
symptom in many cases. Patients do not usually come under observation
until the enlargement is established and the organ can be felt below
the costal border. Pain and tenderness over the organ are very common,
though sometimes it is painless throughout. Palpation often elicits a
creaking fremitus due to the rubbing together of the adhesions. The
gradual enlargement causes an evident increase of girth in the lower
thoracic and upper abdominal zones, and marked prominence of the left
hypochondrium. The tumor extends to the right and downward, and may
occupy a large portion of the abdomen, extending even to the pelvis.
When there is no ascites the edge can be easily felt with the anterior
notch or notches. The pressure of a large spleen causes distress after
a full meal, and by its mechanical effect may even compress the bowels
and produce fatal obstruction.[127] The effect upon the heart and
respiration has already been noticed. The adhesions may interfere with
the depression of the organ during a deep inspiration. The size varies
in an inexplicable way, considering the indurated fibroid nature of the
enlargement. It may be perceptibly larger after a meal.[128] A
hemorrhage or free diarrhoea may reduce the size very much, as in
Morrill's case.[129] A murmur may occasionally be heard, and an
enlarged spleen has been known to pulsate.[130]
[Footnote 127: Collins, _Brit. Med. Journ._, 1882, i.]
[Footnote 128: Johnson, _Lancet_, 1870, Jan.]
[Footnote 129: _Bost. Med. Journ._, 1877.]
[Footnote 130: Gerhardt, _Zeitschrift f. klin. Medicin_, Berlin, Bd.
iv.]
Lymphatic Glands.--In the great majority of cases the lymph-glands are
but slightly if at all involved. Even when they are affected it is rare
to see such large bunches as in Hodgkin's disease. When they are
growing there may be pain and tenderness, and if large they may be a
source of inconvenience, but severe pressure symptoms are not often
witnessed. Enlargement of the glands in the superficial groups is
readily detected, but the deep-seated collections in the mesentery and
retro-peritoneum can rarely be palpated unless of considerable size.
Mediastinal lymph-tumors in leukæmia are exceptional. In none of the
cases I have seen were the lymph-glands {915} greatly enlarged. It is
stated that in children the lymphatic variety is more common than in
adults.
There may be tenderness over the bones, and in rare instances swelling,
but unless the tenderness is marked and accompanied by some local
expansion or softening, we cannot determine positively the existence of
the myelogenous variety. The sternum, ribs, and flat bones are most
often affected, and there may be great irregularity and deformities, as
in a case I saw with Riess of Berlin. It is well to bear in mind that
in perhaps the majority of persons there is a tender spot upon the
sternum which may cause marked wincing when touched firmly. No reliance
should be placed upon tenderness without swelling or softening. Such
tenderness may exist, and post-mortem the marrow be found normal;[131]
and, on the other hand, there may be extensive changes in the
bone-marrow without any tenderness (Litten).
[Footnote 131: _Deutsches Archiv f. klin. Med._, xxvi.]
MORBID ANATOMY.--There may be extreme wasting. Dropsy of the feet is
common, and ascites may be present.
A noteworthy feature is the full amount of blood in the heart and
blood-vessels, usually in the form of large coagula. In one case (XI.)
the weight of clots alone in the heart-chambers, not including what
came from the veins, was 620 grammes. The portal, cerebral, pulmonary,
and subcutaneous vessels were also greatly distended with clots. The
portal vein just above the union of the branches measured eleven
centimeters in circumference.
The blood is usually clotted in the heart and vessels, and the
aggregation of the colorless corpuscles densely infiltrating the
fibrinous clots and the serum gives a pus-like appearance, so that it
has not infrequently happened, as in Virchow's memorable case, that the
observer on opening the right auricle believed for the moment that he
had cut into an abscess. The leukæmic clots often have a peculiar
greenish color, and resemble somewhat the fat of the turtle. Similar
coagula may fill the veins of the brain and abdominal viscera. The
tendency of the white corpuscles to aggregate together, and the
subsidence of the red to the lower part of the heart-chambers and
vessels, may give an appearance of more intense leukæmia than actually
exists. The reaction of the blood is usually acid. The chemical
constitution has been carefully studied, but with no very satisfactory
results. Hypoxanthine, lactic acid, leucin, tyrosin, a mucin-like body,
and a gelatinous substance have been described, but none of them may be
regarded as characteristic of the disease. The octahedral crystals are
thought by some to be tyrosin,[132] but Schreiner[133] says they
consist of the phosphate of an organic base, the composition of which
is not yet settled.
[Footnote 132: Huber, _Archiv der Heilkunde_, Bd. xviii.]
[Footnote 133: _Liebig's Annalen_, cxciv.]
The specific gravity of the blood is lowered, 1036 to 1049. The water
is increased. The fibrin in many observations has also been found
increased; 4.8 per 1000 was the average of ten observations by Bennett.
The albumen and the salts have not often been estimated. The former is
stated to be diminished. The fatty bodies have been found in excess of
the normal quantities.
The heart is often pushed up by the large spleen; the pericardium, more
rarely the endocardium, may present ecchymoses, and the fluid may be in
excess. In a few instances leukæmic growths have been met with. The
chambers are usually distended, the walls soft, and a moderate grade of
fatty change is very common. No special alteration has been met with in
the blood-vessels. I have seen extensive fatty degeneration of the
intima and small arteries.
In the great majority of cases the spleen is increased in size, but the
shape is retained. It is usually of a deep violet-red color, and strong
adhesions may unite it to the abdominal wall, diaphragm, or stomach.
The capsule {916} may be greatly thickened, forming a firm
fibro-cartilaginous investment. The vessels are enlarged, particularly
the veins at the hilus. The weight may vary from two to eighteen
pounds. The largest on record is given by Langley Browne[134]--18½
pounds. Six or seven pounds is an average weight. The length may vary
from seven to twenty inches, and the breadth eight to twelve. The organ
is in a condition of chronic hyperplasia--hard, firm, cuts with
resistance, and displays a uniform reddish-brown surface on which the
trabeculæ are more or less prominent. There may be hemorrhages or
infarcts, and it is not uncommon to see regions of yellow or
rusty-brown staining, indicating where an extravasation had occurred.
As a rule, no trace of the Malpighian bodies can be seen.
Grayish-white, circumscribed lymphoid tumors may occur throughout the
organ, contrasting strongly with the reddish-brown matrix. The process
of gradual enlargement is a simple hyperplasia. In the early stage, not
often seen, there is swelling of the pulp, increase in the
cell-elements, without the firmness and induration of the
fully-developed leukæmic organ. Rupture may occur at this period from
the intense hyperæmia. The Malpighian bodies are enlarged and prominent
by their grayish-white color. A gradual and progressive induration
results from the increase in the adenoid network and the fibrous
trabeculæ. A section shows the enormous development of the fibrous
elements. The cells may be scanty, only two or three in meshes, or,
indeed, the reticulum may be so close that only a single cell is
enclosed. As a rule, the hyperplasia extends over the whole organ, and
the Malpighian bodies become involved and lose their distinctness. In
only one of the cases which I have examined were they at all prominent.
Leukæmic new growths in the spleen are rare.
[Footnote 134: _Lancet_, 1877, ii.]
Uncomplicated cases of the lymphatic form are very uncommon: usually
they enlarge with the spleen, and in the majority of instances the
hypertrophy is not extensive, scarcely ever reaching the high grade
seen in Hodgkin's disease. The groups of cervical, axillary,
mesenteric, and inguinal are most frequently affected; the bronchial
and mediastinal but rarely. The bunches of glands are not usually
larger than walnuts, moderately soft, isolated, movable; large matted
groups do not often occur. They may vary a good deal in size during the
course of the disease, often diminishing notably before death. In
chronic cases they may become very indurated. The leukæmic
lymphadenitis is a simple hyperplasia, and the soft glands may look, on
section, of a normal gray color or may have a deep gray-red appearance.
Hemorrhages may occur, and twice I have seen the enlarged glands deeply
hyperæmic. Histologically, the appearance is very like a normal gland,
only the lymph-spaces are more closely packed. In the harder glands the
fibrous reticulum is much increased, the capsule thickened, and the
section more grayish in color. Caseation or suppuration rarely occurs,
and invasion of contiguous parts is most exceptional.
The tonsils and the lymph-follicles of the tongue, pharynx, and mouth
have been found much enlarged.
The bone-marrow is usually the seat of important changes, which in some
cases appear early and persist as very prominent features of the
disease. The most constant alteration is a uniform substitution of a
grayish-red or gray-green puriform-looking tissue for the normal red
and fatty marrow of the long and short bones. The entire medulla may
resemble the consistent matter which forms the core of an abscess, and
the term pyoid applied to this condition by German authors well
expresses the general characters. More rarely the marrow has a
reddish-brown hue. The difference depends largely on the number of
colorless corpuscles, which in the pyoid form are enormously increased,
and there are but few red cells. Ponfick has met with dark-red, dense
hemorrhagic infarctions in leukæmic marrow. The condition of the {917}
bones is variable; usually, the compact and cancellated tissues appear
normal, but the hard shell may be much thinned and expanded, the
cancellæ widened, and the whole substance rendered spongy. In marked
cases there may be localized swellings which are tender, and even
yield, on firm pressure. The sternum and ribs are most frequently
affected in this way. There are instances in which the bone-marrow has
not been involved, and in one case there was osteo-sclerosis.[135]
Histologically, the chief change is hyperplasia of the colorless
marrow-cells, which in the pyoid variety compose the chief part of the
tissue. They vary much in size and appearance. Three forms can usually
be recognized: large granular cells with distinct nuclei; medium-sized
cells, like colorless blood-corpuscles; and smaller forms, like
lymph-cells, with large nuclei and a narrow zone of investing
protoplasm. The red corpuscles and microcytes are in variable numbers.
In one case the latter were very abundant. Nucleated red corpuscles are
very constant elements. Corpuscles containing red blood-corpuscles are
not so numerous as in ordinary red marrow, nor, as a rule, are the
myeloplaques abundant. Charcot's crystals are always to be found--if
not at first, when the marrow is quite fresh, certainly later, when
decomposition has begun.
[Footnote 135: Heuck, _Virchow's Archiv_, lxxviii.]
The thymus is rarely affected, and even in children is not often
swollen. A few cases of enlargement have been recorded.
The thyroid is even less frequently involved.
In one case the suprarenal capsules were large and swollen,[136] and in
addition to the leukæmia there was bronzed skin. Hemorrhage, caseous
degeneration, and in one instance rupture,[137] have been noted.
[Footnote 136: Barclay, _Lancet_, 1863, i.]
[Footnote 137: Fleischer and Penzoldt, _loc. cit._]
In the digestive system the stomach rarely presents any changes other
than catarrhal. Even when death has occurred from hæmatemesis the
mucous membrane may be pale, without erosion, hemorrhage, or ulceration
(Cases II. and VI.). In a few instances lymphatic growths have been
described. In many cases the intestines have been the seat of leukæmic
tumors which have originated in the solitary and agminated glands of
Peyer. Occasionally the lymphoid infiltration is diffuse in the mucosa
and not confined to the follicles. Ulceration may occur in the patches,
and in a few cases the bowel lesions have been so pronounced that the
term intestinal leukæmia seemed justifiable.[138] The cæcum and colon
may also present these new growths, and in a few cases dysenteric
processes have been observed (Case II.). The peritoneum has been found
covered with small lymphoid growths. In Willcocks' case of lymphatic
leukæmia[139] there were growths on the surface of the stomach and
gastro-splenic omentum. Blood may be found in the cavity from rupture
of the spleen. Ascitic fluid is common. Fibroid thickening, induration,
and adhesions are very often met with, particularly in the neighborhood
of the spleen.
[Footnote 138: Behier, _loc. cit._]
[Footnote 139: _Loc. cit._]
The liver is very commonly enlarged, pale, smooth, and retains the
normal shape. It may be greatly increased in size, as in case of
Walshe's, where it weighed 13½ pounds. The substance is usually firm,
of a grayish-brown color, or even marbled. Two chief changes have been
met with--a diffuse leukæmic infiltration and numerous small leukæmic
tumors. The infiltration may be very slight, and not noticeable with
the naked eye, or it may be in the form of irregular scattered areas of
a yellowish-white appearance, not distinctly isolated, but merging into
the hepatic tissue. When moderate, a section shows the columns of
liver-cells to be separated by wide spaces occupied by leucocytes,
which are partly within and partly outside of the capillaries. The
accumulation of these elements produces atrophy of the liver-cells, and
their aggregation and increase in certain regions produce the
grayish-white areas, in the midst of which traces of liver-tissue may
be found. {918} The defined leukæmic growths are small, not often
attaining a large size, and may resemble tubercles. They are usually
situated in the interlobular tissue, and consist of lymphoid cells in a
well-defined reticulum, and they possibly have a different origin from
the diffuse infiltrations.
Fatty degeneration of the liver-cells is a very common change.
The respiratory system is not often the seat of important lesions.
Lymphoid growths have been found in the mucous membrane of the trachea
and bronchi, and occasionally in the lungs, in which situation they may
closely resemble tubercles, but differ from them in not tending to
caseate or soften. Oedema of the bases of the lung is almost always
found. Many patients are carried off by a low pneumonia. The greenish
leukæmic clots projecting from the cut ends of the vessels may give a
very curious appearance to the section of the lung. The pleural
surfaces may be the seat of lymphoid growths.
The kidneys are usually pale, often enlarged, and show signs of
parenchymatous swelling. The capillaries, like those of the liver, may
be distended with leucocytes, and leukæmic tumors may occur, generally
situated in the cortex and ranging in size from a pea to a cherry. In
none of the cases I have examined were there any special changes in
these organs beyond slight enlargement and filling of the capillaries
with leucocytes.
The generative organs are usually normal. No changes have been found to
account for the persistent priapism met with in certain cases.
The meninges of the brain, the veins, and sinuses, are often filled
with grayish clots. Occasionally meningitis has been found, with
exudation of lymph. The small vessels of the brain may be plugged with
leucocytes, forming thrombi, from which softening results. Cerebral
hemorrhage may prove rapidly fatal. In Case X. of the Montreal series
the patient died suddenly, and without any premonition, with a huge
apoplexy of the ventricles and posterior part of the hemispheres.
Leukæmic growths in the skin have been described.
The leukæmic tumors demand further consideration. They are not common.
In 10 of the 11 Montreal cases careful post-mortem examinations were
made, and in not one were there definite new growths. In Case I. there
was diffuse leukæmic infiltration of the liver, the histological
characters of which were carefully studied. In the 157 cases collected
by Gowers[140] there were only 13 instances of leukæmic nodules in the
liver, and 10 in the kidneys. They are still more uncommon in the
lungs. In the spleen--unlike this organ in Hodgkin's disease--they are
very rarely seen. The nodules consist of leucocytes in a meshwork of
delicate reticular tissue. Their mode of origin has been much
discussed. There can be no doubt, I think, that they are new growths of
lymphoid tissue of local origin. Possibly they start from accumulations
of colorless corpuscles which pass out of the capillaries. In the
infiltration of the liver one sees diffuse collections which resemble
new growths, but which have evidently resulted from the aggregation in
and outside of the capillaries of enormous numbers of leucocytes, which
cause the atrophy of the cells of the organ. Doubtless, they multiply
in loco by a process of fission, and these aggregations may themselves
be foci for the origin and development of colorless cells which pass
into the blood-current and augment the number.[141] Quite recently
Bizzozero has studied the development of these leukæmic new growths,
and has shown clearly that the cells which compose them are in process
of active fission.
[Footnote 140: _Loc. cit._]
[Footnote 141: "On the Histology of Leucocythæmia," _Canada Medical and
Surgical Journal_, 1876.]