Archiv_, Bd. iii.]
[Footnote 21: _Berliner klin. Wochenschrift_, 1877, li.]
[Footnote 22: _Centralblatt f. d. Med. Wissenschaften_, 1879, xvi.]
[Footnote 23: _Revue Mensuelle de Méd. et de Chirurg._, 1877.]
[Footnote 24: _Loc. cit._]
[Footnote 25: _Loc. cit._]
The microcytes which occur in numbers in blood in some cases of
traumatic anæmia have been regarded as young developmental forms, but
there is a great diversity of opinion as to their real nature, and
their connection with productive blood-processes is somewhat doubtful.
Cohnheim suggests[26] that after a profuse hemorrhage the rapid
consumption of red corpuscles may be reduced, in which case we need not
suppose such an active development; but the fact noted by Lyon[27] and
others of the increased reduction after a bleeding is against the view.
In any case, if Quincke is right in assuming that the average life of a
red corpuscle is only three or four weeks, what is the restitution of a
couple of millions of corpuscles per cubic millimeter in comparison
with the monthly renovation of the entire mass?
[Footnote 26: _Loc. cit._]
[Footnote 27: _Loc. cit._]
In the regeneration of the blood the development of the hæmoglobin does
not keep pace with that of the corpuscles, so that they may, even when
normal in amount, have a lowered hæmoglobin percentage, indicated under
the microscope by a paleness in the cells.
2d. There is a large group of cases in which the anæmia is induced by a
long-continued drain on the albuminous material of the blood--pus in a
chronic suppuration, albumen in Bright's disease, prolonged lactation,
etc. Rapidly-growing tumors act in the same way.
3d. The anæmia of inanition, brought about by defective food-supply or
by conditions of the digestive organs which interfere with the proper
reception and preparation of nourishment, as cancer of the gullet,
chronic dyspepsia, etc. The reduction in the blood-mass may be extreme,
but the plasma suffers proportionately more than the corpuscles, which
even in the extreme wasting of cancer of the oesophagus may not be
reduced more than one-half or three-fourths.
4th. Toxic anæmia, induced by the action of certain poisons in the
blood, such as lead, mercury, and arsenic among inorganic substances,
and the virus of syphilis and malaria among organic poisons. They act
by increasing the rate of consumption of the red corpuscles, and the
reduction may be considerable. The gradual impoverishment of the blood
in pyrexia may be in part due to the toxic action of the
fever-producing agent on the blood itself; but in this there is
probably also disturbance of function in the blood-making organs.
The last three groups comprise what are known as secondary anæmias, and
the condition of the blood is characterized by an increase in the water
and diminution in the albuminous elements; the fibrin is often
increased, and the network which separates, as seen under the
microscope, is unusually dense; the white corpuscles are not much
increased; there is rarely microcytosis or poikilocytosis; the
reduction in the number of red corpuscles is not so great; hemorrhages
do not often occur; when fever is present it is due to the disease or
some complication, and is not the pyrexia of anæmia; and, lastly, they
are more or less amenable to the action of iron and other remedies.
II. A consideration of the anæmias induced by disturbance in the
blood-making organs themselves presents difficulties proportionate to
our ignorance of the details of hæmatogenesis. We may regard, as above
stated, the spleen, the general lymphatic tissue, and the marrow as the
sites of production of corpuscles which are passed into the circulation
fully formed. Certain of these organs--the spleen and marrow
particularly--are also concerned with blood-destruction as well as
blood-elaboration; but there is evidence to show[28] that {890} they,
to use an ordinary simile, consume their own smoke, using the waste
products for the purpose of further manufacture. Looking now upon the
hæmatogenetic tissues as a single organ scattered through the body, let
us consider what general disturbances of function it may suffer
comparable to those met with in other structures. We can evidently
suppose the physiological activity to be diminished or increased, and
we should expect to find corresponding to these changes equivalent
alterations in the character of the blood. Unfortunately, our knowledge
of the normal processes as they go on in these tissues is so scanty
that it amounts to a discussion upon the disturbances of a function
itself imperfectly understood.
[Footnote 28: Quincke, quoted above.]
With diminished functional activity in an organ we commonly meet with
reduction in volume, the one depending on the other: now, the only
instance in the blood-making organs in which a decrease in size and
diminished functional activity go together is in the senile atrophy in
which the spleen becomes small, the marrow more fatty, and the
lymph-glands sclerotic, and in consequence the blood also is reduced in
amount; but this is only a part of the general failure of nutrition in
old age. Pathologically, there is no such well-recognized condition of
uniform atrophy of spleen, lymph-gland, and bone-marrow, with a
corresponding general reduction in the elements of the blood. Certain
cases of idiopathic anæmia come close to it, in which these parts are
wasted, but there are other differences which make the two conditions
scarcely comparable. In fact, as we shall see, diminished activity in
blood-making is usually associated with an increase in what we call
hæmatogenetic tissues. Of increased functional activity in these parts
we know very little, apart from the changes met with in cases of
traumatic anæmia, in which the hyperplasia of the spleen and
bone-marrow may be regarded as intimately connected with the rapid
development of red corpuscles.
One fact is evident: that a progressive increase in the cytogenic
tissues, local or general, is associated with disturbance in the
process of blood-formation, and sooner or later induces anæmia. Thus,
progressive enlargement of the spleen or of the lymph-glands or marked
hyperplasia of the marrow, either singly or combined, is invariably
accompanied with alteration in the characters of the blood. Even in
those rare instances in which the lymphoid elements of the tonsils and
fauces or of the gastro-intestinal canal are chiefly involved the same
change may take place.
The nature of the process in the organs is of a hyperplastic character.
In the spleen the pulp at first increases and the Malpighian bodies
enlarge, but ultimately there is such a development of the fibrous
reticulum that the consistence is greatly augmented and the organ
becomes indurated. Histologically, there is very little distinction to
be made between forms of chronic enlargement of this organ. In the
lymph-glands there is increase in the cells; the tissue becomes more
succulent, and is in a state of hyperplasia which may terminate in a
great development of the fibrous elements, with induration. So also
with the bone-marrow: in the short and flat bones, where in the adult a
reddish or slightly fatty tissue exists, the fat disappears entirely,
and the long bones, normally filled with yellow marrow, become occupied
with a red-gray or greenish-gray cytogenous tissue not unlike
spleen-pulp, and in many instances more consistent than the red marrow
of early life.
A reduction in the number of red corpuscles is the chief and most
constant change in the blood; anæmia seems to be the invariable result,
whether the spleen, marrow, or lymph-glands are affected singly or
together, and is the central feature in the entire group of cases. This
diminution in the red cells may or may not be accompanied by an
increase in the white corpuscles, which in some cases may be so
striking as to be regarded as the special blood-change, and is, as a
rule, permanent, though it may be a variable or even a transitory
state.
{891} The general and histological differences between forms of
hypertrophy of these blood-making organs are exceedingly slight, and in
their clinical features they present a large number of symptoms in
common; indeed, we may say that all the important symptoms are present,
whether the spleen is affected alone or with the lymph-glands and
bone-marrow, or whether these parts are independently involved, and
whether there is simple reduction in the red or with it an increase in
the white corpuscles. Such common features are--the progressive anæmia
with its group of circulatory symptoms; the irregular febrile reaction,
essential fever of anæmia; the absence of marked emaciation; the
tendency to effusions of serum; the progressive debility; the
occurrence of hemorrhages; gastric and intestinal disturbances; and
resistance to treatment.
The affections characterized pathologically and clinically by so many
similar features are known and recognized as distinct diseases under
the names leukæmia, Hodgkin's disease or pseudo-leukæmia, splenic
anæmia, and idiopathic anæmia (some cases); and we shall now consider
these a little more closely.
First, of the hyperplasias of the cytogenic tissues associated with
simple anæmia. The various groups, spleen, lymph-glands, and marrow,
may be involved singly or together; usually one is first affected, and
the others, if at all, subsequently. Progressive enlargement of the
spleen induces sooner or later anæmia, the anæmia splenica of
Griesinger. These cases are by no means rare: certain of them represent
the final stage of a malarial intoxication, but there are others in
which the enlargement seems causeless. There may also be hyperplasia of
the bone-marrow, less often of the lymph-glands. The anæmia may be
profound, and the clinical picture is that mentioned above. Two cases
of it under my care died of hæmatemesis. The diagnosis of this
affection from splenic leukæmia rests solely on the microscopical
examination of the blood. It is also classed as the splenic form of
Hodgkin's disease or pseudo-leukæmia.
Primary enlargement of the lymph-glands with anæmia constitutes
Hodgkin's disease or pseudo-leukæmia, in which there may be general
hyperplasia of the lymphatic elements throughout the body, with nodular
growths of adenoid tissue in other organs. The spleen and marrow are
not often affected. Here, too, the diagnosis from lymphatic leukæmia
rests with the microscope.
Is there a form of anæmia dependent upon hyperplasia of the
bone-marrow--an anæmia medullaris? In 1875, Pepper and Tyson[29] found
affection of the marrow in idiopathic anæmia, and Pepper suggested that
this might be the starting-point of the disease, which could thus be
regarded as a medullary form of pseudo-leukæmia. Cohnheim in 1876[30]
described the same condition, and I had an opportunity of examining
several cases.[31] Granting that the marrow is a tissue which shares in
the blood-making functions, it seemed reasonable to suppose that a
general hyperplasia of its elements might disturb the processes of
hæmatosis and produce anæmia, just as in hyperplasia of the spleen and
lymph-glands. Two facts soon came to light which seem opposed to this
explanation of the pathology of idiopathic anæmia. A hyperplasia of the
marrow was found in cases of chronic disease with wasting, and cases of
idiopathic anæmia were described in which the marrow was normal. The
numerous observations of the past five or six years have not brought us
nearer to a solution of the problem. The observations of Neumann,[32]
and those of Litten and Orth,[33] on the changes in the marrow in
chronic diseases have been abundantly confirmed, and a red lymphoid
marrow may be met with in various cachectic states. This, too, I have
frequently seen, {892} yet it is in my experience rare to find such
marked, rich hyperplasia of the marrow, such an entire absence of fat,
as in some cases of idiopathic anæmia. In 9 autopsies in typical cases
at Montreal, not parturition cases, the marrow of the long bones was
lymphoid and red in 6; in 1 it was not examined; in 1, which I did not
see, the marrow was stated to be normal; and in 1, an old woman over
sixty years of age, the marrow of the short bones was rich in lymphoid
cells and nucleated red corpuscles, and the long bones contained a
grayish gelatinoid--atrophic--marrow. It does not appear possible with
our present knowledge to arrive at a satisfactory conclusion on this
question. Some regard the marrow-change as the consequence, others as
the cause, of the anæmia. Both Cohnheim[34] and Pye-Smith[35] regard
those cases of idiopathic anæmia in which the marrow-changes are
pronounced as cases of anæmia medullaris.
[Footnote 29: _American Journal Med. Sciences_, 1875, ii.]
[Footnote 30: _Virchow's Archiv_, Bd. lxviii.]
[Footnote 31: _Centralblatt f. d. Med. Wissenschaften_, 1877, Nos. 15
and 28; 1878, No. 26.]
[Footnote 32: _Berl. klin. Wochenschrift_, 1877, xlvii.]
[Footnote 33: _Ibid._, 1877, li.]
[Footnote 34: _Loc. cit._, Bd. i. S. 467.]
[Footnote 35: _Loc cit._]
Next of the parallel series of hyperplasias of the blood-forming organs
with anæmia, plus an increase of the colorless corpuscles--leukæmia.
Here, too, we have the three forms--splenic, lymphatic, and medullary.
The splenic leukæmia is the most common, and in its general features is
identical with splenic anæmia, the excess of white corpuscles being the
only distinguishing feature. It is almost invariably associated with
changes in the marrow.
The lymphatic leukæmia may arise in connection with hyperplasia of the
lymph-glands or of the adenoid elements in the alimentary
tract--tonsils and Peyer's glands. It is much less common than
lymphatic anæmia or Hodgkin's disease, and there are not many
uncomplicated cases on record. Apparently, a very limited bunch of
glands--cervical--may induce the change in the blood.[36] Medullary
changes are almost invariably associated with a great increase of
colorless corpuscles in the blood, and a myelogenous form of leukæmia
is now, owing chiefly to the investigations of Neumann, well
established. Indeed, he would regard the change in this tissue as the
primary and important, and those in the lymph-glands and spleen as
secondary.
[Footnote 36: Gowers, _Reynolds's System of Medicine_, art.
"Leucocythæmia."]
The hyperplasia, either lymphadenoid in character or pyoid, may result
in the expansion and softening of the bones, with the production of
irregular tumor-like masses.
We have, then, the following group of anæmias induced by a primary
disturbance of function in the blood-making organs:
PRIMARY OR | Leucocytic | Splenic, |
CYTOGENIC | | Lymphatic, | Leukæmia.
ANÆMIA. | | Medullary, |
|
| Non-leucocytic | Splenic, Anæmia splenica.
| Lymphatic, Hodgkin's disease.
| Medullary, Idiopathic anæmia
(certain cases).
There remain for consideration the relation of the tissue-change to the
anæmia and the nature of the leucocytosis; but until the chief facts in
the development of the corpuscles are thoroughly known we cannot expect
a satisfactory solution of these problems.
The anæmia may be explained on the view of diminished production
(anæmatosis) or increased consumption of the red corpuscles
(hæmophthisis). We know nothing of the intimate processes connected
with lessened production, but as anæmia so constantly accompanies the
hyperplasia, we assume they are intimately connected with each other,
and the diminution in the number of corpuscles in some way the result
of disturbed functional activity in the blood-making organs. An
increased consumption of corpuscles in anæmia is {893} indicated by the
presence in large numbers of cells containing red blood-corpuscles in
the spleen and marrow, and occasionally in the lymph-glands; by the
increased amount of iron which has been found in the liver; and in some
cases by the deep color of the muscles and an intensification of the
color of the urine. Either a failing production with normal rate of
consumption, or a normal output with heightened destruction, would
produce anæmia. Possibly, in some instances, both factors may prevail.
Quincke's interesting observations[37] may enable us to determine the
cases in which one or other has been dominant. Where there is great
destruction we shall expect to find the granules of iron albuminate in
the spleen, bone marrow, and liver-cells, possibly in the cells of the
cortex of the kidneys, and the iron reaction should be present.
[Footnote 37: _Loc. cit._]
The relation of the hyperplasia of the cytogenic tissues to the
increase in the colorless corpuscles is even more obscure. A prime
difficulty is the circumstance that apparently identical tissue-changes
may be associated with either a leucocytic or non-leucocytic anæmia.
The splenic hyperplasia of leukæmia and of anæmia splenica are
histologically identical. The excess of white corpuscles may be due
either to over-production or to failure in their transformation into
red. That they develop in the hyperplastic spleen, marrow, and
lymph-glands is not to be doubted, and it seems reasonable to attribute
the excess to the hyperplasia. Their variable size, as spleen or
lymph-glands are chiefly affected, was early observed by Virchow, and
when the marrow is involved there may be many large leucocytes similar
to the larger marrow-cells. Virchow's original explanation, that the
excess of colorless cells was due to a failure in their transformation
into red corpuscles, rests upon the presumption that such a
transformation is the normal process--a view not fully established. If
this is the case, we should expect to find some relation between the
increase of the white and the decrease in the red, but this is not
always constant; as a general rule, with a diminution of the white
there is an increase in the red, but the red and the white cells may
increase or diminish in numbers simultaneously, or, again, the
leucocytes may be greatly reduced while the red corpuscles remain about
stationary. Griesinger,[38] Biesiadecki,[39] and others regard the
increase in leucocytes as a primary blood-change. Several recent French
writers support this view, as Renant,[40] who believes that the unequal
size of the leucocytes indicates their division in the blood, and
Variot.[41] One of the most interesting features in connection with an
increase in the colorless cells is that it may be only transitory, and
a case which clinically and pathologically may present the features of
idiopathic anæmia to-day may to-morrow present the characters of
leukæmia; a case of splenic anæmia may become one of splenic leukæmia,
or vice versâ. Thus, in Litten's oft-quoted case--about which there can
be no doubt[42]--of acute anæmia of three weeks' duration, an enormous
increase of colorless corpuscles took place, and finally a ratio of one
white to four red was reached. Quite as interesting is the case of
Fleischer and Penzoldt,[43] in which for eight months the patient
presented the ordinary symptoms of anæmia lymphatica or Hodgkin's
disease, and then, before death, the blood became intensely leukæmic,
the ratio 1:9. Still more so as the case of Goodhart's,[44] in which,
with an enlarged spleen and lymphoid growths in liver and kidneys,
there were variations in the number of corpuscles every few days--at
one time great excess of white, at another no increase whatever. Again,
a case may early come under observation as one of leukæmia, with a
ratio of 1:20 or 1:30, and in the course of a few months, with
persistence or even aggravation of {894} the general symptoms, the
normal ratio of white to red may be reached. This was the history in
one of the Montreal cases.[45]
[Footnote 38: _Virch. Archiv_, Bd. v.]
[Footnote 39: _Wien. Med. Jahrbuch._, 1876.]
[Footnote 40: _Archives de Physiologie_, 1881.]
[Footnote 41: _Thèse de Paris_, 1882.]
[Footnote 42: _Berl. klin. Wochenschrift_, 1877.]
[Footnote 43: _Deutsches Archiv f. klin. Medicin_, Bd. xxvi.]
[Footnote 44: _Clin. Society's Transactions_, London, 1877.]
[Footnote 45: Howard, _Montreal General Hospital Reports_, vol. i. p.
39.]
It seems questionable whether such a variable feature as increase in
the colorless corpuscles should be permitted to separate diseases which
have all essential characters in common. We shall probably, however,
continue for a long time to speak of these conditions as separate and
distinct, but it is evident that as time goes on, and our knowledge of
the diseases and of blood-development increases, the identity of many
of them will be acknowledged, and we shall find that here, as so often
the case in natural history, the multiplication of species has been the
result of imperfect information, and that as points of resemblance in
essential characters and development are studied minor differences
disappear.
With reference to the general tissue-changes in anæmia there are two
points of interest: The metabolism of the proteids is increased, as
shown by the increased excretion of urea, and owing to defective
exudation the decomposition of the fats is lessened; hence the
retention of fat, or even increase, in anæmic persons. The influence of
repeated small bleedings in hastening the fattening of cattle has been
known since the time of Aristotle, and horse-dealers still affirm that
there is nothing like bloodletting to put an animal into good
condition.
CHLOROSIS
is a special form of anæmia distinguished by certain etiological and
anatomical peculiarities. In the first place, it is a disease of the
female sex; cases in the male are of extreme rarity. In the majority of
instances it is associated with disturbed menstrual function or with
the evolution of the reproductive organs at the period of puberty.
Occasionally it occurs in pregnant women and in children. It is a
common disease among the ill-fed, overworked young girls in large towns
who are confined all day in close, badly-lighted rooms or who have to
do much stair-climbing. Girls of the better classes are by no means
exempt; indeed, some writers speak of it as specially prone to affect
the higher ranks of life. Lack of proper exercise, good food, and fresh
air, the mental stimulation of unhealthy literature, and masturbation,
are important factors. Emotional and nervous symptoms may be
prominent--so much so that the disease is regarded by some as a
neurosis.