system. There is anæmia, but the impoverishment is less in the number
than in the corpuscular richness in hæmoglobin. This fact, first
pointed out by Duncan,[46] has been abundantly confirmed. Thus, for
example, in one case, with a globular richness of 85 per cent., the
hæmoglobin was only 52 per cent., and in another, with 92 per cent. of
red, the hæmoglobin percentage was as low as 64. The numerous
investigations of the past few years[47] have, among other points,
fully established this as perhaps one of the most striking features in
chlorosis. The color-value of the individual corpuscle is very much
reduced. Of 22 observations of Hayem, the average number of red
corpuscles was {895} 3,740,000, and the hæmoglobin reduced to about 50
per cent. In Laache's 13 cases the average percentage of corpuscles was
72, and of hæmoglobin 45. This author has pointed out that in certain
cases with all the clinical symptoms of chlorosis well marked there may
be very slight reduction in the corpuscles or hæmoglobin; and such he
terms pseudo-chlorosis. The red corpuscles in chlorosis vary much in
size. Very large forms--giant red cells--are common, and microcytes are
sometimes to be seen; but there is not the extreme irregularity in size
and outline of the blood in idiopathic anæmia. The presence of a large
number of young, imperfectly-formed corpuscles, especially as regards
the hæmoglobin, is the distinguishing feature of chlorotic blood. Hayem
and Willcocks both regard the average corpuscular diameter to be lower
than normal, though many large forms occur. The color of the red
corpuscles is noticeably pale, and the marked deficiency in hæmoglobin
can be observed in individual corpuscles as well as in the
blood-mixture prepared for counting. Quinquaud found the serum normal
in quality, but the solids were slightly reduced in amount. Hunt[48]
has shown that there are peculiar inter-menstrual oscillations in the
blood in chlorotics. There is usually a fall in numbers just before the
flow, but the individual value remains good; subsequently the number
rises, but the color-value is not maintained (Willcocks). Virchow[49]
pointed out that in many cases of chlorosis there was a defective
development of the circulatory system, either congenital or resulting
in failure of the normal rate of growth; the parts remained infantile.
The heart and arteries were small, the walls of the latter thin, and
the calibre of the aorta narrowed. In some instances there was found a
compensatory hypertrophy of the heart. Defective development of the
uterus and ovaries has also been noted, but these changes on the part
of the circulatory and generative organs are not constant features in
chlorosis.
[Footnote 46: _Sitzungsbericht d. Kais. Akad. d. Wissenschaften zu
Wien_, 1867.]
[Footnote 47: Leichtenstern, _Hæmoglobingehalt des Blutes_, Leipzig,
1878; Hayem, _Recherches sur l'Anatomie, etc. du Sang_, 1878; Malassez,
_Archives de Physiologie_, 1877; Moriez, _La Chlorose_, Paris, 1880;
Laache, _Die Anämie_, Christiania, 1883; Willcocks, _Practitioner_,
1883.]
[Footnote 48: _Lancet_, ii., 1880.]
[Footnote 49: _Ueber die Chlorose_, etc., Berlin, 1872.]
The SYMPTOMS of chlorosis are those of anæmia of moderate grade. As in
idiopathic anæmia, the subcutaneous fat is in full, or even extra,
amount. The complexion is most peculiar, neither the blanched aspect of
hemorrhage nor the muddy pallor of grave anæmia; but there is a curious
yellow-green tinge in marked cases which has given the name to the
disease ([Greek: chlôros]), and also its popular designation, the green
sickness. Breathlessness, palpitation, and tendency to fainting are due
to the anæmia. Digestive troubles are also common, and the appetite is
often depraved. There are venous and cardiac murmurs. The menstrual
functions are almost always deranged, and there may be hysterical and
nervous manifestations. Relapses are not uncommon. The intimate
pathology of the disease is unknown. In its insidious onset, sometimes
causeless, and in certain features of the blood-state, it resembles
pernicious anæmia, but it differs from it in many essential
particulars. The association with menstrual disorders, the hypoplasia
of the circulatory and generative organs in some cases, the favorable
course and response to suitable treatment, as well as the sex and
period of life, are features peculiar to chlorosis. Then, again, the
anæmia is not so intense, and the relation of the hæmoglobin is just
the reverse; in chlorosis the individual corpuscles are deficient in
hæmoglobin, while in idiopathic anæmia the reverse appears to be the
case.
Some regard the blood circulatory and uterine condition as the
expression of a congenital defect leading to the formation of a
diathesis--and in certain cases this may be so--but some of the most
marked cases I have seen have been in girls of healthy families, who
after a healthy childhood developed chlorosis at puberty, from which,
under suitable treatment, they recovered to become robust and vigorous
women. The almost specific action of iron suggests failure of the
digestion or assimilation of the minute traces of this substance which
are contained in our ordinary foods, and from which {896} the iron of
the corpuscles must be derived. Zander[50] holds that it is largely due
to a defect in the hydrochloric acid of the gastric juice, by which the
iron-holding compounds are dissolved, and claims that in chlorosis the
administration of this remedy after eating fulfils every indication and
enables the iron in the foods to be converted into an absorbable
compound.
[Footnote 50: _Virchow's Archiv_, lxxxiv.]
The condition of the blood-making organs themselves throw no light on
the PATHOLOGY of the disease.
The TREATMENT of chlorosis requires special mention. Iron may be
regarded as a specific when given in sufficient doses. I have found
Blaud's formula, as given in Niemeyer's textbook (ferri sulph. potass.
carb. et tart. aa ounce ss; tragacanth q. s. Make ninety-six pills. Two
or three pills to be taken three times a day), the most satisfactory
method of administering the drug. Under their use I have repeatedly
seen the number of the red corpuscles per cubic millimeter double in a
fortnight; and it is one of the most interesting therapeutic phenomena
to watch with the hæmacytometer the progressive development and
increase of red corpuscles under the influence of fifteen or twenty
grains of iron daily. Other forms may be used--reduced iron, dialyzed,
the lactate, the tinct. of the perchloride--and it does not really make
much difference which form is employed so long as enough is
administered. Dilute hydrochloric acids or the vegetable acids may be
given, and special attention should be devoted to dietetic and hygienic
regulations.
MELANÆMIA
is a condition characterized by an accumulation of granular pigment in
the blood and various organs, particularly the spleen, liver, marrow,
and brain. It is almost invariably associated with prolonged malarial
infection, and the pigment results from the transformation of the
hæmoglobin of the corpuscles, many of which undergo destruction as a
direct consequence of the influence of marsh miasm. Very exceptionally,
however, the dark particles are extraneous, and result from the passage
of carbon-granules into the circulation in cases of intense
anthracosis. Soyka[51] met with a case of this kind in which the coal
particles were distributed throughout the spleen, liver, and kidneys.
In blood the pigment occurs either free in the form of fine granules or
in cloud-like collections of various sizes and shapes, often surrounded
by a hyaline margin, or it occurs enclosed in cells. The free pigment,
not often met with, is either molecular or in the form of irregular
particles which may equal a red corpuscle in size. Aggregations of the
granules are not uncommon, forming various-sized masses which may be
imbedded in a hyaline substance. More commonly the pigment is contained
in cells, ordinary leucocytes or large flattened--endothelial--cells
derived from the spleen or liver. The color varies from yellowish-brown
to a deep black. Except during periods of intense malarial infection
and in the most severe and chronic cases melanæmia is rarely observed.
In most ordinary cases of intermittent one may seek in vain for the
pigment-granules, and I have examined many chronic cases with
well-marked ague-cake with negative results. In other instances the
pigment is found during or after a paroxysm; and this is the period
when an examination of the blood should be made. The greatest care and
cleanliness should be exercised in obtaining the blood-drop; and it
should be remembered that in some of the glass slips used for
microscopic purposes {897} irregular brownish flakes may occur which I
have known to be mistaken for pigment.
[Footnote 51: Quoted by Hindenlang, _Virchow's Archiv_, lxxix.]
The melanæmia is but the expression of extensive destruction of
corpuscles and accumulation of pigment in the spleen, liver, and
bone-marrow; and these organs in cases of fatal intermittent or
remittent fevers may present important changes. In the spleen, which is
usually enlarged and indurated, the pigment is chiefly in the vicinity
of the arteries and veins, the tissues about which may be absolutely
black, and in both stroma and pulp innumerable cells are found filled
with blood-corpuscles and blood-pigment in all stages of transformation
to melanin. The color of the organ may be of a deep reddish-brown, or
in very chronic states gray or even a dark olive. In the liver the dark
granules are chiefly at the periphery of the lobules, fixed within the
connective-tissue elements and leucocytes, not in the liver-cells
themselves. It may be abundant about the portal branches, staining the
connective tissue of Glisson's sheath, and it is also met with in the
vicinity of the hepatic veins. When much affected the liver may have a
deep bronze tint. As Arnstein has shown,[52] the bone-marrow may
present similar changes and have a grayish-brown color. There may be
deep pigmentation of peritoneum and omentum. The deposition of the
granules in and about the vessels of the cortex cerebri may give a
slate-gray color to the brain, or even a graphite tint in very severe
cases. The capillaries have been found occluded with cells filled with
the pigment-granules. The kidneys--particularly the Malpighian
tufts--the mucous surfaces, and the skin may also be the seat of
pigmentary deposition. These coarse changes in the organs in chronic
malaria were known to the older writers, and in Bright's _Medical
Observations_ a beautiful representation is given of the condition of
the brain. To American physicians, with their extensive experience of
malarial fevers, these changes were well known, and Stewardson of the
Pennsylvania Hospital gave an admirable description of them in
1841;[53] and from the same institution in 1868 came another important
contribution to the subject by Meigs, Pepper, and Rhoads.[54]
Meckel[55] and Virchow[56] gave the first satisfactory explanation of
the discoloration, showing that it was due to pigment, which might also
be free in the blood. Frerichs in his well-known work on the liver gave
an exhaustive account of the coarse and microscopical appearances.
[Footnote 52: _Virchow's Archiv_, lxi.]
[Footnote 53: _Am. Journal Medical Sciences_.]
[Footnote 54: "On the Morphological Changes of the Blood in Malarial
Fever," _Penn. Hospital Reports_, 1868.]
[Footnote 55: _Deutsche Klinik_, 1850.]
[Footnote 56: _Virchow's Archiv_, Bd. i.]
There is still some difference of opinion as to the mode of origin of
the pigment. Most writers hold that it results from the destruction of
the red corpuscles in the spleen and liver, and from these situations
the pigment gets into the blood; but more recently Arnstein[57] and
Kelsch[58] have urged the view that the melanæmia is the primary
process, the destruction of corpuscles going on in the blood itself,
and the particles and coloring material taken up by the leucocytes are
transformed into melanin, and then the cells collect in the spleen,
liver, and bone-marrow, producing the condition of melanosis. It is
probable that the older view is the true one, and we may regard the
process as an exaggeration or intensification, under the stimulus of
the malarial poison, of the normal process of blood-destruction which
goes on in the spleen and bone-marrow, and under some circumstances in
the liver and lymph-glands. We can often trace in the cells of these
organs the stages of transformation from red corpuscles to
melanin-granules, just as can be done in the tissues in the
neighborhood of an extravasation, where also the process is chiefly
intracellular (Langhans). On the other hand, in those very states in
which the red corpuscles are destroyed in the blood and the hæmoglobin
set free, we do {898} not find melanæmia. It happens occasionally in
fevers that we meet with colorless cells in the blood containing red
blood-corpuscles, which in time would be transformed into pigment, but,
so far as we know, such a condition has not been observed in the blood
in malaria. The connection between the fever paroxysm and the
appearance of the pigment in the blood depends, most likely, on changes
in the volume of the organs under the influence of the fever, whereby
cells containing the pigment are dislodged and get into the
circulation. This explains, too, their rapid appearance in some cases
with the onset of a paroxysm. No doubt, as Virchow originally taught
and as well shown in Gussenbauer's[59] observations, the pigment may
result from the diffusion of the coloring matter and gradual
precipitation of it in the granular form within the protoplasm of
colorless cells; but of the occurrence of such a process in the
circulating blood in malaria we have no satisfactory evidence, and we
incline to the belief that the melanosis of the organs is the primary
condition, while the melanæmia is secondary and inconstant.
[Footnote 57: _Loc. cit._, and _ibid._, lxxi.]
[Footnote 58: _Archiv de Physiologie_, 1875.]
[Footnote 59: _Virchow's Archiv_, lxiii.]
Occasionally, in cases of extensive melano-sarcoma, pigment-granules
may be found in the blood in large numbers, and even appear in the
urine and be deposited in the organs and skin. In a few instances also
free pigment has been observed in the blood in Addison's disease.
PROGRESSIVE PERNICIOUS ANÆMIA.
DEFINITION.--Extreme and progressive anæmia developing without evident
or apparently adequate cause.
SYNONYMS.--Idiopathic anæmia (Addison); Essential anæmia (Lebert);
Anæmatosis (Pepper).
HISTORY.--During the first two or three decades of this century cases
of severe and fatal anæmia were noted by Andral and others, but the
credit of having given the first accurate series of cases belongs to
Walter Channing of Harvard, who in the _New England Quarterly Journal
of Medicine_ for 1842 published a paper entitled "Notes on Anhæmia,
particularly in connection with the Puerperal State and with Functional
Disease of the Uterus, with Cases."[60] Any one who reads this
communication will be convinced that Channing's description,
particularly of the seven cases occurring in the puerperal state, is
that of the disease to which Gusserow and Biermer have more recently
directed attention.
[Footnote 60: My attention was accidentally called to Channing's
observations in the Periscope of Hall's _British-American Journal_ for
1845. Since then Musser, in the _Med. News_, Oct. 7, 1882, has given a
valuable abstract of the paper.]
In Addison's monograph on the suprarenal capsules (1855) there is a
brief but clear account of the disease, which he speaks of as follows:
"For a long period I had from time to time met with a very remarkable
form of general anæmia occurring without any discoverable cause
whatever--cases in which there had been no previous loss of blood, no
exhausting diarrhoea, no chlorosis, no purpura, no renal, splenic,
miasmatic, glandular, strumous, or malignant disease. Accordingly, in
speaking of this form of anæmia in clinical lectures, I, perhaps with
little propriety, applied to it the term idiopathic, to distinguish it
from cases in which there existed more or less evidence of some of the
usual causes or concomitants of the anæmic state." As early as 1843
this acute observer had spoken in his clinics of this condition.[61]
[Footnote 61: McKenzie, S., _Lancet_, 1879, ii.]
{899} The physicians at Guy's appear to have been well acquainted with
the disease, and in 1857 Wilks described cases under the heading
"Idiopathic Fatty Degeneration." To the labors of Zurich professors we
are indebted for much of our knowledge. That versatile clinicist
Lebert, then at Zurich, published in 1853 cases of puerperal chlorosis,
and we owe to him the excellent designation of essential as applied to
these cases of anæmia (1858). It was in 1871-72 that the communications
of Gusserow[62] and Biermer[63] aroused a very general interest in the
disease. Gusserow's cases, like some of Channing's, were in connection
with pregnancy. Biermer, thinking he was dealing with a previously
unknown affection, gave it the name of progressive pernicious anæmia.
In the past ten years the literature of this form of anæmia has
enormously increased. In Germany, in addition to the articles in the
encyclopædias (Ziemssen's, Eulenberg's) and innumerable contributions
and dissertations, two important monographs have appeared by Müller
(Zurich, 1877) and Eichorst (Leipzig, 1878). In France, Hayem, Lepine,
and others have published important observations. In England, the Guy's
Hospital physicians, Taylor and Pye-Smith, in the _Hospital Reports_
(1878-83) have fully established Addison's claim to having given a
clear account of the disease. Important contributions have been made by
Stephen Mackenzie, Coupland, Bramwell, Bradbury, and others. In this
country Pepper in 1875 brought the disease to the notice of the
profession and suggested the name anæmatosis. Howard (R. P.) of
Montreal at the Centennial Medical Congress (1876) gave a full account
of the affection, the existence of which he had long recognized and
taught. Musser[64] has reviewed the American literature, and has given
a tabular synopsis of 39 cases which have been recorded in this
country.
[Footnote 62: _Archiv f. Gynäkologie_, ii.]
[Footnote 63: _Correspondenzblatt für Schweizerische Artze_, 1872.]
[Footnote 64: _Proceedings of Philadelphia County Med. Society_, 1885.]
ETIOLOGY.--The disease is widely distributed, and there are no special
geographical influences. In Germany and certain of the Swiss
cantons--Zurich particularly--the cases seem to occur more frequently
than in England or America. In this country it can scarcely be called
one of the rare diseases, although up to January, 1885, Musser[65]
could collect only 39 cases. During ten years in Canada I saw 16 cases,
most of them with colleagues at Montreal.
[Footnote 65: _Loc. cit._]
That bad hygienic conditions have much to do with the induction of the
disease is shown by the records of Zurich and Berne, where the cases
have been very numerous among the lower classes, who are hard worked,
ill fed, and poorly housed. Possibly here other unknown causes may be
at work, as the conditions which prevail in the Zurich canton are not
unknown in other countries. In Ireland, where the peasants have poor
food and wretched houses, the disease does not appear to be common. In
the Montreal cases the subjects were chiefly of the upper or of the
higher mechanic classes.
The age most subject to the disease is the adult period; cases are rare
under twenty and over fifty. In Pye-Smith's table of 103 selected cases
there were only 6 under fifteen years of age; 4 between fifteen and
twenty; 29 between the twenty-first and thirtieth years; 26 cases
between the thirty-first and fortieth years; 21 between the forty-first
and fiftieth years; 13 between the fifty-first and sixtieth; and only 4
above sixty. The youngest case I have seen was in a girl of twenty, and
oldest in a woman over sixty. The youngest case on record was at the
fifth year.[66]
[Footnote 66: Quoted in _Am. Journ. Med. Sci._, Jan., 1885.]
Sex.--If we exclude all cases in women directly connected with the
puerperal state, primary idiopathic anæmia is more frequent in men than
in women. Of the 16 Montreal cases, 4 were dependent upon parturition,
and of the remainder, 9 were in men and only 3 in women. But most of
the {900} collected figures include the parturition cases, and the
women are in excess; thus, of 93 cases from the Swiss clinics at Zurich
and Berne, 67 were females. Eichorst's figures are 65 women and 30 men.
Of 110 cases collected by Coupland, 56 were men and 54 women. In
Pye-Smith's careful tabulation of 103 selected cases, 48 were men and
59 women.
As observed by Channing, Lebert, and Gusserow, pregnancy and
parturition are important factors in the production of a grave form of
anæmia. In the majority of cases the symptoms develop post-partum,
often, but not necessarily, in consequence of loss of blood during
delivery. Obstinate vomiting during pregnancy and prolonged lactation
may bring about the same condition. Of 29 cases of this sort in
Eichorst's table, in 19 the symptoms developed during pregnancy and in
10 after delivery.
Gastric and intestinal disturbance, dyspepsia, vomiting, and diarrhoea
have occurred in a number of cases prior to the development of the
anæmia.
In some instances loss of blood, chronic discharges, ulcers, or other
sources of drain have been present.
In not a few cases there has been mental worry, grief, or fright. This
has been specially noted by Wilks and Howard, and more recently by
Curtin.[67] It does not seem probable that malaria has any predisposing
influence.
[Footnote 67: "Nervous Shock as a Cause of Pernicious Anæmia," _Med.
Times_, Philada., April 4, 1885.]
It is by no means always the ailing or delicate who are attacked; many
of the cases have occurred in men previously strong and robust.
After excluding all these factors, which prevail in a considerable
proportion, there still remain cases without, as Addison says, any
discoverable cause whatever--cases to which in our present knowledge we
may apply the term idiopathic. These may be primary, and the others, in
which some one or other of the above-mentioned causes appears to have
prevailed, secondary anæmias, the latter to be distinguished from a
host of other sequential anæmias only by the fact of a progressive and
pernicious course.
Of 91 observations collected by Eichorst, in 24 cases the disease
appeared to have come on spontaneously, and 67 as the result of various
causes: pregnancy and parturition, 29; digestive troubles, 24; loss of
blood, etc., 7; bad hygienic conditions, 7.
SYMPTOMS.--The classical description of Addison must ever be quoted in
this connection: "It makes its approach in so slow and insidious a
manner that the patient can hardly fix a date to the earliest feeling
of that languor which is shortly to become so extreme. The countenance
gets pale, the whites of the eyes become pearly, the general frame
flabby rather than wasted, the pulse perhaps large, but remarkably soft
and compressible, and occasionally with a slight jerk, especially under
the slightest excitement. There is an increasing indisposition to
exertion, with an uncomfortable feeling of faintness or breathlessness
in attempting it; the heart is readily made to palpitate; the whole
surface of the body presents a blanched, smooth, and waxy appearance;
the lips, gums, and tongue seem bloodless; the flabbiness of the solids
increases; the appetite fails; extreme languor and faintness supervene;
breathlessness and palpitations are produced by the most trifling
exertion or emotion; some slight oedema is probably perceived about the
ankles; the debility becomes extreme--the patient can no longer rise
from his bed; the mind occasionally wanders; he falls into a prostrate
and half-torpid state, and at length expires: nevertheless, to the very
last, and after a sickness of several months' duration, the bulkiness
of the general frame and the amount of obesity often present a most
striking contrast to the failure and exhaustion observable in every
other respect."[68]
[Footnote 68: Monograph on _Disease of Suprarenal Capsules_, p. 3.]
The mode of onset is variable: in many cases there are etiological
{901} conditions, such as pregnancy, loss of blood, etc., which for
weeks or months precede, and perhaps determine, the development of the
anæmia. There may have been mental worry or shock, and after a
prolonged period of ill-health the anæmic symptoms become marked.
Failure of strength, lassitude and disinclination for exertion, with
shortness of breath and palpitation and an increasing pallor,
accompanied by headache, giddiness, and dyspepsia, are the symptoms for
which the patient seeks advice.