is rarely a deep white or ashen, as in the pallor of fear or fainting
or the bloodlessness from hemorrhage, but there is a peculiar lemon
tint, a light straw-yellow or grayish-yellow color, which may be
mistaken for a mild icterus. This is one of the most characteristic
features of the disease.
The subcutaneous fat does not waste; on the contrary, the fatty
panniculus may increase, and, as Addison remarked, there may be a
bulkiness of the frame. Actual emaciation is very uncommon.
Slight oedema is present in the feet, particularly toward the close,
and it may extend up the legs, but rarely reaches a high grade.
Occasionally it may appear in the face and hands.
Cutaneous hemorrhages in the form of small petechiæ are liable to
appear on the legs and arms, not often on the trunk.
The sweat secretion is not affected, but in several instances, as in
other chronic affections where death is protracted, a cadaverous odor
has been perceived from the skin or breath.
The blood, as expressed, often with difficulty, from the finger-tip,
has not the rich color of health, but is pale, like a light claret. The
corpuscles usually fill the drop, and we do not see, as in certain
cachectic states, an extreme degree of hydræmia in which the red
corpuscles do not entirely occupy the plasma. It is sometimes difficult
to get a drop of blood from the finger-tip, and to do so the arm should
hang by the side and may be squeezed from the shoulder downward to
press the blood into the hand. The microscopical characters of the
blood are as follows:
(1) The red cells present a great variation in size, and there can
usually be seen _(a)_ large giant forms, the megalocytes measuring 8,
11, or even 15 mm.: these are not often very numerous, and may show
irregular foldings at the edges; _(b)_ medium-sized disks, such as are
usually found in the blood: these always predominate; _(c)_ small round
cells, microcytes, 6, 4, or even 2 mm. in diameter, and of a deep
color. They are rarely absent in typical cases, though varying in
number at different periods. The color of the large and medium-sized
corpuscles may be much less intense than normal.
(2) In addition to the variation in size, the corpuscles show a
remarkable irregularity in form--an irregularity which, so far as my
observation goes, is never met with to the same extent in other
conditions. They may be elongated and rod-like, scarcely recognizable
as blood-disks. Balloon and kidney shapes are common. One end of a
corpuscle may retain its shape, while the other is extended as a
pointed or blunt process. The normal concavity may be lost on one side
and deepened on the other. Many of the large forms are longer than
broad, often quite ovoid, and with sinuous margins. The microcytes are
either globular or present a pit-like depression on one surface. To
this condition of irregularity of the corpuscles in size and form
Quincke has given the name poikilocytosis ([Greek: poikilos], variously
shaped). It possibly depends on an altered state of the serum; I have
failed to produce it with dilution. The corpuscles in the blood of
idiopathic anæmia do not form such well-defined rouleaux as in health.
(3) The colorless corpuscles may be relatively increased, but are
usually diminished to some extent. They present no very special changes
in form or stricture. Larger forms may occasionally occur, but I have
not noted their {902} presence, specially the cases in which the marrow
was found red and lymphoid after death. In two cases the majority of
the corpuscles at several observations were smaller than normal. The
amoeboid movements are active.
(4) In only two instances, in the cases I have examined, were nucleated
red corpuscles present, and these very scanty. They have been noted by
several observers. Ehrlich states[69] that they are present in all
cases.
[Footnote 69: _Berl. klin. Wochenschrift_, 1880.]
(5) Schultze's granule masses, composed of the hæmatoblasts or
blood-plates, are either absent or very scanty. In some cases not a
trace of them could be found, and in others they are less abundant than
in health. In this respect the blood offers a marked contrast to that
of various cachectic states, and also to leukemia, in which the masses
are sometimes very numerous. Leube,[70] however, has recorded a case in
which they were abundant.
[Footnote 70: _Ibid._, 1879.]
(6) The fibrinous network between the corpuscles is thin and
indistinct. The Cercomonas globulus and Cercomonas navicala, described
by Klebs[71] as occurring in pernicious anæmia, are possibly peculiar
to Prague.
[Footnote 71: _Real Encyklopädie_, art. "Flagellata."]
The reduction in the number of the red corpuscles is the special
feature of the disease, the diminution reaching far below that met with
after the most severe hemorrhage. Instead of a corpuscular richness of
5,000,000 per cubic millimeter, the number may be reduced to
one-quarter, or even one-tenth. In the more extreme anæmia from
hemorrhage, in cancer or in phthisis, the reduction rarely reaches as
low as 1,500,000, while this figure is common in pernicious anæmia, and
in advanced cases may sink below 1,000,000, or even to 500,000. This
latter figure is exceptional. In only 2 cases have I counted the number
so low as this. In a case of Quincke's the red were reduced to 143,000
per c.m., and, strange to say, the man recovered. Great variations may
occur from month to month in the course of the disease. An increase in
the number is not always associated with an improvement in the
patient's condition.
The hæmoglobin is also greatly reduced, but not in proportion to the
reduction in the red corpuscles. The relative coloration of the
corpuscles is increased, and this seems as marked a feature in
pernicious anæmia as the relative reduction is in chlorosis.[72] Owing
to the fact that the hæmoglobin value of individual corpuscles is
increased, the anæmia is never quite so intense as the number of
corpuscles would appear to indicate.
[Footnote 72: Laache, _Die Anämie_, Christiania, 1883; _Deutsche
Medicin Wochenschrift_, 1884, No. 43.]
The circulatory system presents many symptoms of importance. When the
patient is recumbent and at rest, the heart's action is quiet, but on
exertion or excitement the action becomes rapid, and there are
palpitation, fluttering, and sometimes painful sensations in the
cardiac region. Stairs are particularly trying to these patients. There
may be slight enlargement of the heart, indicated by an increased area
of visible pulsation, and an impulse in the third or fourth left
intercostal space, near the sternum, is frequently seen. The hæmic or
functional murmurs are usually present, variable in intensity and site,
most often heard at the base and in both aortic and pulmonary areas,
but also at the apex. Indeed, their variability is often puzzling;
sometimes it would seem that there might be a murmur at each orifice,
at another limited only to one; and for the bruit to be present at one
examination and absent at the next is not uncommon. In several of
Eichorst's cases there was a variable diastolic murmur at apex or base.
The larger arteries pulsate visibly--so much so that at times it
suggests the water-hammer pulsation of aortic insufficiency. The
carotid pulsation may be most evident, and still more so in the
abdominal aorta, the throbbing of which may be very distressing to the
patient. A systolic arterial murmur may be heard in all the arteries.
The pulse is soft, compressible, usually {903} rapid (80 to 100 or
over), depending a good deal on the position and state of excitement.
One is sometimes surprised in these cases to find a full and at the
same time very soft pulse. It may be dicrotic.
The venous hum is well marked, and is rarely absent except after
prolonged rest in bed, when both cardiac and venous murmurs may
disappear, to return at once on making the patient stand up. Channing,
in the paper already referred to, speaks of the thin, scanty state of
the blood, and yet notes the prominent appearance of the veins beneath
the skin, particularly about the hands and wrists.
Hemorrhages occur very frequently. Epistaxis is most common, and may
have preceded for years the onset of the grave anæmia. It may recur
repeatedly and be a source of constant drain, or ultimately be the
cause of death. From other mucous surfaces bleeding is not so common. I
have seen one case in which there were for months repeated small
hemorrhages from the bowels, and bleeding from the gums has been
observed in several cases. The petechiæ on the skin have already been
referred to. Retinal hemorrhages, as first noticed by Biermer, are very
common. They are numerous and small, scattered around the disk. They
are not peculiar to any special form, but are liable to occur in severe
anæmia from any cause.
Respiratory symptoms are not prominent: a short cough may be present,
but the only special feature is the shortness of breath, which is often
early and troublesome, and depends on the condition of the blood, not
of the lungs. There may be a very distressing and persistent sense of
insufficient aëration (Pepper). Toward the close hydrothorax may
develop.
The gastro-intestinal system is in the majority of cases more or less
deranged. Dyspepsia may precede for years the anæmia, and may persist
throughout the illness. There is loss of appetite, amounting sometimes
to a positive repulsion toward all forms of nutriment. Nausea and
vomiting are rarely absent throughout the illness, and there are some
cases in which the gastric symptoms are so marked as to suggest a
primary stomach lesion as the atrophy to which Fenwick[73] has called
attention, or even arouse a suspicion of cancer.
[Footnote 73: _Lancet_, 1877, ii.]
Diarrhoea is also a frequent symptom, and in some cases hastens the
fatal result. There may be melæna, and in Müller's monograph a case is
given in which leucin and tyrosin were found in the stools.
The urine is pale, acid, and of low specific gravity. Occasionally it
becomes darker in color. The urea may be diminished, but it has been
found increased in some cases by Quincke, Eichorst, and Laache. The
uric acid is more commonly increased, and the phosphoric acid. The
percentage of iron has been found larger than normal. Albumen is rarely
found. Peptones, leucin, and tyrosin may be present (Laache). Blood
does not often occur.
Fever is not a constant symptom; some cases run their course without
any elevation, but there is usually slight febrile reaction of an
irregular, remittent type, an evening elevation of two or three
degrees, and a morning remission to the normal standard. There may be a
week or ten days of fever, and then a long spell without any. Toward
the close there is commonly an elevation, occasionally depression, of
temperature, as in one case reported by Müller in which it sank to
24.8° C.
COURSE.--In the majority of cases the disease runs a steadily downward
course, well indicated by the terms progressive and pernicious. In
almost every case periods of temporary improvement occur. Recovery is
possible, and Pye-Smith[74] gives a summary of 20 undoubted cases which
got well. The lactation and parturition cases stand a better chance of
recovery than others. {904} The average course of the affection is from
six to twelve months; there are rapid cases in which a fatal
termination may be reached in a few months, and there are others which
drag on for two, or even three, years, periods of improvement
alternating with relapses. Death is usually by asthenia. It may be
hastened by hemorrhage from the nose or bowels or by persistent
vomiting or diarrhoea.
[Footnote 74: _Guy's Hospital Reports_, 1883.]
MORBID ANATOMY.--The body is not often emaciated; usually, indeed, the
panniculus adiposus is well developed. The peculiar lemon tint of the
skin is present in the majority of cases, and there may be petechiæ.
The voluntary muscles may appear normal, but are often of an intense
flesh color, more like horse muscle. In six cases the words "rich red
color" and "remarkably deep red color" occur in my notes. In other
instances they are pale. When the cavities are opened the general
pallor of all the organs is most striking. The serous surfaces are
smooth and glistening, and occasionally present ecchymoses. The amount
of fluid may be increased. The mucous membranes are pale; minute
hemorrhages are not uncommon.
The heart is in many cases large and flabby, in others normal, and in a
few undersized. The pericardial fluid may be in excess, and the
subpericardial fat is often increased. The flaccid relaxed state of the
walls is very noticeable, and on opening the chambers the amount of
blood is always very slight. In one case I could only obtain two
drachms from the right heart, and between three and four from the left.
There may be small clots entangled with the chordæ tendineæ of the
valves. The muscle-substance is pale, of a faded-leaf, light-yellow
color, and beneath the endocardium, particularly of the left side and
of the papillæ, there are flaky spots (tabby mottling) of fatty
degeneration. The peculiarities of general fatty degeneration of the
heart are nowhere better seen than in these cases. The valves and
orifices are usually normal. The intima of the aorta may show fatty
changes. The smaller arteries and veins contain most of the blood.
The lungs are crepitant, pale, with a slight bloody oedema at the
bases. The fluid expressed has often a yellowish tinge. Exudation into
the pleural cavities is common. The air-passages do not offer any
special changes.
The liver is of normal size, pale and generally fatty, not invariably;
in none of Eichorst's cases was this a marked feature. Quincke and
others have found the amount of iron increased.
The mucous membrane of the gastro-intestinal tract is pale, covered
with a thin mucus, and may present ecchymoses. Post-mortem solution of
the gastric mucosa is common, and I have seen oedema of it. Fatty
degeneration of the cells of the peptic tubules is common, and they may
be in an atrophic state, as well described by Fenwick.[75] Ecchymoses
of the small and large bowel are common; ulceration is rare. In a few
instances the lymphatic elements of the mucosa have been found swollen.
Extensive atrophy of the mucosa has been found associated with
degeneration of the nerve-elements, but these changes, as shown by the
observations of Nothnagel[76] and Schleimpflug,[77] are not uncommon in
many other conditions.[78]
[Footnote 75: _Loc. cit._]
[Footnote 76: _Beiträge zur Phy. u. Path. des Darms_, Berlin, 1884.]
[Footnote 77: _Zeitsch. f. klin. Med._, ix., 1885.]
[Footnote 78: Sasaki, _Virchow's Archiv_, 96.]
The blood vascular organs have naturally received special attention.
The spleen offers, as a rule, no important changes; the size is
variable, rarely enlarged, occasionally reduced in size, but for the
most part normal. The smallest I have seen was in one of Howard's
cases, in which the organ weighed only one ounce and five drachms. In
the 51 autopsies noted in Howard's paper the spleen was stated to be
normal in 36 and enlarged in 13. Ten ounces is the heaviest I have
seen. The spleen-tissue is moderately firm, of a light brown-red color.
I have never noticed either the extreme softening of an acute splenic
swelling or the hardness of chronic induration. {905} The histological
characters present nothing special. Cells containing red corpuscles
occur, but not in such numbers as in cases of acute splenic swelling
from fever. I have seen the nucleated red corpuscles in several
instances.
The lymph-glands are, as a rule, normal in size and appearance. In
three instances I found them decidedly smaller than normal, and in two
they had a rich deep-red color, and on section looked more like
spleen-tissue than lymph-gland. Weigert has noted the same
appearance.[79] In one of the cases there were nucleated red corpuscles
in the glands, as has been observed by Rindfleisch in a case of
rickets,[80] and more recently in tuberculosis.[81]
[Footnote 79: _Virchow's Archiv_, Bd. lxxix.]
[Footnote 80: _Archiv f. Mikros. anatomie_, Bd. xxiii.]
[Footnote 81: _Med. News_, xiv. No. 23.]
The fatty tissue of the long bones is in many instances replaced by a
red marrow resembling that of the short bones of the adult and the
entire osseous system of the infant. This was first noticed by Pepper
in 1875,[82] and has since been frequently observed. The color is
usually of a reddish-purple when fresh, becoming a bright red on
exposure. Sometimes there is a grayish-red appearance. It may not be
universally distributed in the long bones, and the change would appear
to proceed from the trunk toward the periphery--a direction the reverse
to that in which the red marrow of the child becomes fatty. In many
cases the marrow has been found normal; in others, the change known as
gelatinoid has been observed. In five Montreal cases I found the marrow
of the long bones lymphoid, in one gelatinoid, and in two the long
bones could not be examined. It must be borne in mind that the short
and flat bones of the adult contain a red lymphoid marrow mixed with a
variable amount of fat, in which nucleated red corpuscles can always be
found.
[Footnote 82: _American Journal of Medical Sciences_, lxx.]
The brain and cord present an intensely anæmic appearance; the
membranes are relaxed and oedematous, and petechiæ may exist. The
convolutions are often wasted, and the amount of cerebro-spinal fluid
increased. No important changes have been found in the substance.
The ganglia of the sympathetic system have been examined by Queckett in
one of Addison's cases and found fatty. Wilks and others have found
them normal. Brigidi[83] has described an increase in the interstitial
tissue and pigmentation of the cells. In two instances I found nothing
abnormal. Sasaki[84] has described marked degenerative changes in
Auerbach's and Meissner's plexuses in two cases of pernicious anæmia.
[Footnote 83: _London Med. Record_, 1878.]
[Footnote 84: _Loc. cit._]
The kidneys are usually pale and without special change beyond the
fatty degeneration. Quincke has found the amount of iron increased. The
suprarenals have in several instances been found very small. The sexual
organs show no constant changes.
PATHOLOGY.--Under the general subject of Anæmia the pathology has been
discussed at sufficient length. After excluding pregnancy, parturition,
lactation, and inanition cases, as partaking more of the characters of
secondary anæmia, we can recognize three groups of cases: First, those
in which the bone-marrow has been found extensively affected--cases of
anæmia medullaris; second, cases in which a primary atrophic change in
the mucous membrane of the stomach appears to have been the
starting-point of the trouble; and, third, cases in which after death
no special changes have been found sufficient to explain the anæmia. To
the latter the term idiopathic is applicable, and possibly they may be
instances of hæmophthisis due to increased destruction of the
corpuscles from causes unknown at present.
DIAGNOSIS.--A case in which anæmia comes on without obvious cause and
without enlargement of the spleen, and progressively increases in spite
of remedies, diet, change of air, etc., may be regarded as one of an
idiopathic or essential character. If the case goes on to a fatal
termination, the designation of pernicious is appropriate. I would
place some reliance on the {906} microscopical examination of the
blood, and would consider the presence of microcytes with great
irregularity in the ordinary red corpuscles strong confirmatory
evidence. The absence of wasting, the peculiar lemon tint of the skin,
the occurrence of epistaxis and retinal hemorrhages, would render a
diagnosis certain.
In that class of cases so well described by Fenwick,[85] Nothnagel,[86]
and Nolen,[87] in which there has been an interstitial inflammation of
the gastric mucosa and atrophy of the glands, the question has not yet
been decided how far this condition is to be considered causal, and how
far a part of the general disturbance of nutrition. The clinical
picture may be identical with that of idiopathic anæmia, and in some of
the cases the gastric symptoms have been so marked that the relation of
the atrophy and the anæmia has evidently been that of cause and effect.
And yet in these cases there does not appear to be the pronounced
emaciation of inanition anæmia. In other instances the diarrhoea and
chronic intestinal trouble may, with or without gastric participation,
bring about a similar condition.
[Footnote 85: _Loc. cit._]
[Footnote 86: _Deutsches Archiv f. klin. Med._, xxiv.]
[Footnote 87: _Centralblatt f. d. Med. Wissenschaft._, xx.]
Profound anæmia may arise during or after pregnancy, and a considerable
proportion of the cases on record have been in this connection.
From ordinary cases of Hodgkin's disease, anæmia lymphatica, there
could be no difficulty in making a diagnosis if the superficial glands
were enlarged. In splenic anæmia, if the enlargement was not great,
there might for a time be uncertainty, which the progressive increase
of the organ would remove. Neither in anæmia splenica nor lymphatica
are we so likely to meet with the microcytes or irregular corpuscles.
Chlorosis occurs chiefly in young girls, and is amenable to treatment.
From the various cachexias--malarial, syphilitic, metallic--the history
will commonly afford grounds for a diagnosis, and in these states, as
in latent cancer, the wasting is apt to be more pronounced than in
essential anæmia. Cases of gastric cancer are occasionally met with
which simulate closely pernicious anæmia, and the diagnosis may be
doubtful for months.[88]
[Footnote 88: Richard Neale, _Practitioner_, 1883.]
The enteritis and hemorrhages caused by the presence of Anchylostoma
duodenale in the intestines may produce an aggravated form of anæmia
resembling closely the form under consideration. It prevails among the
workers in mines and tunnels, hence the name miner's anæmia or
anchylostomiasis. The diarrhoea and the detection of the ova or worms
in the discharges would afford grounds for a diagnosis.[89]
[Footnote 89: _Trans. of the International Med. Congress_, London,
1881, vol. i. 437.]
The PROGNOSIS is unfavorable, particularly in those cases which have
arisen without any cause or previous ill-health. In the cases arising
from defective food, etc.--inanition anæmias--pregnancy, or lactation,
the outlook is less grave. Of the 64 Zurich cases in Müller's
monograph, 7 recovered, and of Quincke's 31 cases, 11 recovered.
Pye-Smith gives a table of 20 recorded cases of recovery.[90] Great
improvement may occur, or even recovery for a period of several years,
after which the disease may recur and prove fatal. This was the history
in a case under the care of Wilkins at the General Hospital, Montreal.
[Footnote 90: _Loc. cit._]
TREATMENT.--The designation pernicious applied by Biermer indicates the
hopeless character of the disease in perhaps a majority of the cases;
of late the records happily show a considerable percentage of
recoveries. Thus, Pye-Smith has collected 20 cases in which
convalescence was established after severe and profound anæmia,
belonging undoubtedly to the class here considered. The intractable
nature of a case and the resistance to ordinary treatment are points
which may first suggest to the practitioner the fact that he is dealing
with a something more than simple anæmia.