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both groups under the title of progressive pernicious anemia in order to
describe the invariable tendency of both. Under Diagnosis (vide infra),
however, will be found differential clinical features.

Pathology. — The subcutaneous fat is rarely diminished, so that
emaciation is exceptional. The skin is pale and of a lemon-yellow
tint, and most of the tissues and organs are anemic, except the
muscles, which are often decidedly red in color. The fat is usu-
ally pale and yellowish, and fatty degeneration is one of the most
striking changes in this aff"ection. The heart is usually large and flabby,
and on section of the ventricular walls there is a marked pallor, as well
as a friability, and a fatty change shown by the yellow tint. Micro-
scopically, the fibers or columns of heart-muscle are seen to be distinctly
fatty. The heart-cavities contain little light-colored blood. Other
organs showing the fatty degeneration (of the epithelium) are the liver,
kidneys, gastric and intestinal walls, and the intima of many of the
smaller blood-vessels (in patches). This general fatty change is prob-
ably due to the deficient oxygenation of the tissues and to the anemic
blood-supply.

Owing to the above degenerative change in the vessel-walls, small
extravasations of blood are found in diff"erent parts. Most frequently
these punctiform hemorrhages are seen in the retina and on the principal
serous membranes. Ecchymoses are also observed occasionally on the
mucous membranes and on the skin. More or less general edema and
dropsical accumulations in the serous cavities are not uncommon. The
spleen and liver are seldom and only slightly enlarged. The lymph-



PROGRESSIVE PERNICIOUS ANEMIA. 465

glands are often somewhat swollen and intensely red in color, owing to
the unusual number of red corpuscles.

In a series of 8 cases, Warthin ^ has found changes in the hemolymph
glands consisting of " dilatation of the blood-sinuses and evidences of
increased hemolysis, as shown by the increased number of phagocytes
containing disintegrating red cells and blood pigment."

A marked and important pathologic feature of pernicious anemia is
the presence of abundant deposits of iron-pigment, especially in the
liver, but also in the spleen, kidneys, pancreas, and other organs. The
fact that the abnormal quantity of iron in the liver is peculiarly distrib-
uted about the periphery and middle zone of the lobules is particularly
noteworthy, and quite characteristic of pernicious anemia. The origin
of this iron is doubtless the enormous destruction of red corpuscles, and
that the pigment in the hepatic lobules is ferruginous may be determined
by a micro-chemic test with ammonium sulphid, granules of black sul-
phid of iron being formed.

Of special interest are the lesions found in the bone-marrow on
account of its hematopoietic function. This is virtually hypertrophied,
and is in many cases deep-red instead of yellow, and more like the
hemoblastic marrow of childhood (H. C. Wood). While formerly held to
be causative, this change is now regarded as being secondary to the severe
anemia. Cellular hyperplasia may be seen microscopically in the
great number of large and small granular medullary cells, and also in
the nucleated red cells.

An atrophied condition of the gastric and duodenal mucosa is noticed
in some cases. The sympathetic ganglion cells may also show changes.
More constant, however, is the sclerosis of the posterior columns and,
to some extent, of the lateral columns of the spinal cord : this is
especially marked, according to Burr, in the cervical swelling. Patveu
examined 9 cases ; in 4 he found hyaline degeneration of the vessels of
the white substance, and in 5 small hemorrhages. These changes are
probably due to a toxic agent.

Ktiology. — There are three etiologic categories into which cases of
pernicious anemia may be grouped : (1) those cases in which no discov-
erable cause for the hemolysis (blood-destruction) is ascertained, either
during life or after death — i. e. the idiopathic variety of Addison ; (2)
those in which an adequate cause is found post-mortem only ; (3) those
that are apparently traceable, ante mortem, to some primary causal con-
dition acting directly or indirectly.

(1) As regards the obscure (genuine) eases of idiopathic anemia, the
essential cause of the symptomatic condition is evidently an actively
increased hemolysis. The blood-generation (hemogenesis) may be nor-
mal in power, or there may be a congenital or acquired underlying
deficiency in hemogenic power. GraAvitz and Stengel believe that the
hemolysis originates in the gastro-intestinal capillaries and depends
upon poisons generated or absorbed from that tract — an auto-intoxica-
tion. Von Jaksch holds that the similarity of pernicious anemia
to Kala-azar suggests a protozoon infection. William Hunter^ concludes

^ Amer. Jour. Med. Sciences, October, 1902.
^ Lancet, January 27, 1900.

30



466 DISEASES OF THE BLOOD AND THE DUCTLESS GLANDS.

that the disease is of infectious (streptoco('cal) nature, dependent primarily
upon caries of the teeth. Goullard and Goodall ' hold that a toxin (not
necessarily its primary seat in the intestines) acts on the bone-marrow and
leads to megaloblastic formation.

(2) Apparentli/ causeless cases of a pernicious type of anemia may be
found post-mortem to have been caused by (a) obscure malignant dis-
ease ; (5) parasites, especially the Ancliylostoma duodenalis, and rarely
by the Bothriocephalus. Not infrequently, by a careful study of the
anamnesis of a patient, aided by modern methods of examination, the
cause of pernicious anemia may be detected during life. It is held
that atrophy of ventricular and intestinal glands is an effect rather
than the cause, as formerly believed of the anemia (Grawitz).

(3) Certain exhausting causes, operating directly or indirectly,
may precede this affection, as severe or prolonged hemorrhages or
diarrhea, fevers, mental shock, profound chlorosis, pregnancy, and par-
turition.

Predisposing Causes. — Unfavorable hygienic surroundings and insuf-
ficient nourishment, habitually kept up, may also favor the development
of the disease. Males are more frequently affected than females after
the thirty-fifth year and it occurs mostly during middle life. Griffith
has collected several cases occurring under twelve years of age. The
disease is widely distributed, and it may behave endemically at times,
as in Switzerland and Leipsic. Changes left in the tissues (bones ?)
after syphilis may be the pathologic basis, and osteosarcoma may act
similarly.

Symptoms. — Idiopathic pernicious anemia develops so slowly and
insidiously that it is hardly ever possible to fix upon any precise date as
the commencement of the disease. The transition from health to pro-
gressive pernicious anemia, particularly in persons previously feeble and
pale, is usually too gradual to be demonstrable ; though a rapid and
acute onset is rare, it may occur in pregnant or puerperal women.

Pallor is soon noticed and gradually increases, or when there has
been a previous pallor, this becomes more marked. Shortness of breath
SiTi.^ palpitation of the heart, especially on exertion, are complained of;
the patient is also easily fatigued, and becomes quite languid. Occa-
sional nausea may come on early in those cases in which a previous
gastro-intestinal disturbance has been noted, and headache, vertigo, tin-
nitus aurium, and anorexia ensue and grow progressively worse. Gen-
eral weakness increases, and occasional attacks of faintness and vomit-
ing supervene. Meanwhile, the skin takes on a bloodless, waxy appear-
ance, and soon the characteristic lemon-yellow tint appears. The mucous
membranes are pale and colorless. Prostration in he'd ^r^dLWdMyhecome?,
almost absolute as the feebleness and flabbiness of the tissue increase.
Malleolar edema is sometimes noticeable, and ecchymoses — mucous and
cutaneous — are seen in profound cases of anemia. Although the intellect
is not impaired, except that mental exertion becomes irksome, the tone
and manner of speech are feeble. As the debility becomes severe the
mind wanders, and, to use Addison's words, the patient " falls into a
prostrate and half-torpid state, and at length expires."

^ Jour. Path, and Bad., January, 1905.



PROGRESSIVE PERNICIOUS ANEMIA. 467

Emaciation is rare, the fat being preserved and sometimes increased
in quantity. Pulsation in the large arteries is abnormally visible, and
a diffuse, exaggerated cardiac impulse is felt. The pulse early in the
case may be strong, and generally it is rapid (100—120), soft, and com-
pressible, and as full and quick, often, as the ■water-hammer pulse of
aortic regurgitation. Auscultation reveals the constant and charac-
teristic hemic murmurs, best heard at the base, and the bruit de
diahle in the veins of the neck. There may be visible pulsations in
the latter.

Crastro-intestinal symptoms may be the most prominent signs "where
gastritis polyposa and gastritis atrophica are present. Diarrhea, dyspep-
sia, nausea, and vomiting are then seen throughout the course; otherwise,
constipation, eructations, and simple anorexia are most common.

An ophthalmoscopic examination shows the cause of the anemic
amaurosis, in the profound cases of anemia, to be one or moi'e retinal
hemorrhages. The whites of the eyes become pearly, the conjunctivie
pale. The liver and spleen are rarely palpable. The bones, and espe-
cially the sternum, are sometimes sensitive to pressure.

Respiratory Symptoms. — The breathing is accelerated, and the
anemic dyspnea may become pronounced and stertorous, accompanied
by a sense of thoracic oppression and a "hunger for air." Near the
end pleural and pericardial serous effusions and pulmonary edema may
appear.

The urine is of low specific gravity, and, on account of its pigmenta-
tion with pathologic urobilin, dark in color. The urobilin is detected
both by chemic and spectroscopic examination. In the former the addi-
tion of a few drops of an alcoholic solution of zinc chlorid to the urine
gives a green fluorescence. The presence of indican in the urine
points to albuminous decomposition in the intestines. Albumin and
glucose are absent, but uric acid and urea are both increased in amount,
the former occasionally and the latter usually.

Fever of a moderate degree is commonly, though not invariably,
present, the evening temperature sometimes reaching 102° F. (38.8° C).
Previous to death the temperature may be subnormal.

Nervous Syin-ptoms. — Paresthesia, spastic paralysis of the limbs, and
a loss of control of the sphincters indicate the paralytic tendency of
those cases in which sclerosis of the cord occurs. Tabetic symptoms
are sometimes marked.

Blood-examination. — The blood is usually pale, though sometimes dark
and watery, and the oligocythemia is distinctive of pernicious anemia.
The number of red corpuscles may be reduced to less tJian 200,000 per
c.mm., and is seldom more than 1,000,000. The percentage of hemo-
globin may be approximately proportionate to the number of red corpus-
cles in the earlier stages, but as the disease progresses the index rises, so
that the individual corpuscles are rich in hemoglobin. In other words,
although there is a reduction in the total amount of hemoglobin, it is
usually not so great as the reduction in the number of erythrocytes ;
therefore, the color index is nearly always relatively higher than that of
the red globules (see Fig. 36), a condition in marked contrast with
chlorosis. Macrocytes (which cause the relatively higher percentage of



468 DISEASES OF THE BLOOD AND THE DUCTLESS GLANDS.

hemoglobin), microcytes, poikilocytes, and polycliromatophilia are con-
stantly present, and the former abundant. The presence of nucleated
red corpuscles is also a striking characteristic of pernicious anemia. When
normal in size they are knoAvn as normoblasts ; when very large, as
megalohlasts. In the former, according to Ehrlich, the eccentrically
placed nuclei stain deeply: in the latter the large nuclei stain faintly.
The former are typical of those nucleated red globules found in the
hematopoietic organ of adults ; the latter, of those found in the blood-
development of embryonic life. The gigantoblasts are numerous in this
disease. There are other and various forms of degeneration of the red



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■PiG 36.— Blood-chart of a case of progressive pernicious anemia. Black, red corpuscles ; red,

hemoglobin.

cells, but these are of minor import. There is usually a relative increase
in the small lymphocytes at the expense of the polynuclear cells ; and,
according to Cabot, there was always a marked leucopenia in a series of
110 cases. ^ Myelocytes are almost constantly present, though usually in
low percentage. The average is about 2 per cent. The blood-plates are
generally fewer than normal. The relative proportion of the proteids in
the blood-plasma is altered (Adami). and the hitter is markedly decreased.
Cabot^ found that a blood examination made for the first time during the
period of remission may resemble that in chlorosis, and in 9 of 14 cases
ring-like bodies were seen in the red cells.

Diagnosis and Differential Diagnosis. — The clinical charac-
teristics of the affection, particularly their steady progression with remis-
sions, are quite as important as microscopic study of the blood. The
essential blood feature of the disease is a high color index. The possi-
bility of hidden carcinoma, gastric atrophy, the anchylostoma or other
parasite, and incipient tuberculosis should be borne in mind also. Intes-
tinal parasites are recognized from the microscopical examination of the
feces after a brisk purge when the eggs of the parasites or the parasites
themselves may be found. Atrophic gastritis may be discriminated by
examining the viscus and gastric juice by modern methods. The fol-
lowing table will permit the elimination of obscure gastric carcinoma as
a rule :



1 Cabot Medical News, May 5, 1900.



Amer. Jour. Med. Sciences, Aug., 1900.



PROGRESSIVE PERNICIOUS ANEMIA. 469

Progressive Pernicious Anemia. Obscure Gastric Carcinoma.

The blood shows characteristic changes, Blood shows characteristics of secondary
and the red corpuscle count falls to or anemia, and the count does not fall to

below 1,000,000 per c.mm. _ 1,000,000, as a rule.

Leukopenia and relative lymphocytosis There may be leukocytosis or a relative

common. increase in the polynuclear ceils.

Found earlier in life. Occurs after middle life.

Gastric symptoms not so prominent. Gastric symptoms more suggestive.

Lemon-tinted skin common. Skin of a pale, muddy color, or only

slightly jaundiced (saffron-yellow).
Adipose tissue fairly well preserved. Progressive emaciation.

No glandular enlargements palpable. Supraclavicular or inguinal glands may

be palpable.
No physical signs over stomach. There may be an area of increased re-

sistance over the stomach.
Examination of gastric contents after Examination of gastric contents shows
test-meal usually negative. deficiency or absence of free hydro-

chloric acid and presence of lactic acid.
Some improvement may be brought about Condition becomes steadily worse until
— even cure, though very rarely. death ends the case.

From chlorosis the affection may be differentiated easily by the blood-
examination. The relative increase in hemoglobin, the presence of gi-
gantoblasts and many macrocytes, and the severe oligocythemia are
pathognomonic of pernicious anemia, and are in marked contrast to the
oligochromemia, and slight, if any, reduction in the number of red
globules of chlorosis. Again, the progressive pernicious character of
the former and the tendency to hemorrhage should be remembered, as
well as the contrasting factors of age and sex in the two affections.
Talley^ states that anemia secondary to portal cirrhosis without hem-
orrhage occasionally resembles progressive pernicious anemia. Tabes
dorsalis msiy be simulated, but the blood examination will show character-
istic indications of pernicious anemia.

Prognosis. — The disease, as a rule, terminates fatally, though not
so frequently now as at one time, for obvious reasons. The course of
pernicious anemia is usually slow and gradual, and may be interrupted
by improvement or apparent recovery. Recurrences, however, invari-
ably occur. Idiopathic anemia is therefore almost hopeless, although a
few apparently substantial recoveries have been reported. The dura-
tion of the disease is seldom more than a year, and may not be more
than two or three months. The nucleated red corpuscles usually become
much more numerous shortly before death (Billings). Death may be
caused either by syncope, cerebral hemorrhage, or by slow asthenia.

Treatment. — Hygienic measures must be regarded as of signal im-
portance, and rest in bed, together with light nutritious food given at
short regular intervals, is indicated first of all. Salt-water baths and
gentle and systematic massage are useful adjuvants. Fresh, open air is
advisable when it can be taken.

The value of arsenic in this disease is, I think, analogous to that of
iron in chlorosis. The best action of the drug will be obtained by the
administration of gradually ascending doses of Fowler's solution. Begin-
ning with four or five drops of the former, three times daily during the
first week, and thereafter adding one drop to the dose every day or two
up to the point of tolerance, as much as twenty or thirty drops, well diluted,
^ Jour, of the Amer. Med. Assoc, October 3, 1908.



470 DISEASES OF THE BLOOD AND THE DUCTLESS GLANDS.

may be taken (see Fig. 37). Evidences of gastro-intestinal irritation should
be watched for, and the arsenic discontinued temporarily should they appear.
Sometimes it is advisable to use the remedy hypoderraically, Arsenous
acid is given in pill form, commencing with gJ^- or ^V g^'- (0.0021-0.0032).
The introduction by Fraser of Edinburgh of bone-marrow in the
treatment of pernicious anemia has been followed by various results ;
some cases have been reported in Great Britain and in the United States
in which it has seemed to do good, while in others it was found to be
useless. While the glycerin extract is the preparation generally used,
it is not so reliable as the raw red bone-marrow, or that freshly prepared
each day by mixing with it an equal quantity of glycerin ; an ounce or
two may be administered daily. Hunter suggests the use of anti-strep-
tocccus serum coupled with the antiseptic care of the mouth and



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Fig. 37."



-Chart of a case of progressive pernicious anemia, showing the improvement following
the administration of arsenic. Black, red corpuscles ; red, hemoglobin.



gastro-intestinal antisepsis. Iron is unnecessary, as there are enormous
quantities of it in the liver (Gulland).

Near the end of the disease the danger often greatly increases, owing
to the marked reduction in the quantity of the blood {oUgemia). This
may be combated by the injection of warm water or a week saline solu-
tion into the colon, and also into the subcutaneous tissue. Both the
former procedure and gastric lavage are of value in ameliorating the
gastro-intestinal disturbance from fermentation. Intestinal antiseptics
(salol and beta-naphtol) should be given by the mouth.

Anthelmintics must be used in those cases of pernicious anemia in which
intestinal parasites are associated. Morgenroth and Reicher^ have shown
experimental anemias in animals are benefited by administration of choles-
terin, which they have employed in the treatment of pernicious anemia with
encouraging results. A 3 per cent, solution of cholesterin in oil is pre-
pared and 100 grams of this administered daily. Dilute hydrochloric acid
and bitter tonics are serviceable in cases in which digestion is impaired.

Recurrences will yield to the same treatment, if they yield at all.

Aplastic Anemia. — Senator^ has called attention to a form of pernicious
anemia to which he gave the term aplastic. A variety of pathologic changes
have been found. Blumer classifies these into three groups : (1) Cases in
which the lesions are those of progressive pernicious anemia; (2) those cases

1 Berlin. Klin. Woch., Oct 12, 1908. '^Zeit.f. klin. Med., vol. liv., Nos. 1 and 2.



THE SECONDARY ANEMIAS. 471

in which the bone-marrow shows primary aplasia ; and (3) cases in which
there is a hyperplasia of the mononuclear elements of the bone-marrow.

The symptoms a,nd pht/sical signs are those of pernicious anemia, but the



Online LibraryJames M. (James Meschter) AndersA text-book of the practice of medicine → online text (page 63 of 178)