like other haemic miu-murs, is ventriculo-systolic in time and is heard at the
root of the neck when the head is turned to the left. It is musical in quality
and resembles â€” as its designation signifies â€” the sound produced by a hum-
ming top; it is caused by the eddy produced by the current of thinned blood
rushing from a large to a smaller vessel. Less frequently a ventriculo-systolic
murmur of soft blowing quality is heard over the pulmonic area and still
more rarely a ventriculo-systolic murmur is audible at the cardiac apex.
This last hruit is due to a relaxation of the mitral ring resulting from weakness
of the heart muscle caused by poor cardiac nutrition. The condition pro-
duced is a true relative insufficiency of the mitral valve. Of course it is quite
possible for two or even all three of these murmurs to co-exist in the same
These murmiu-s, strangely enough, afford a fairly reliable means of estimat-
ing the haemoglobin percentage of the blood. When the first type of murmur
is heard the blood probably contains about 80 percent, of haemoglobin, in
the presence of the second variety of hruit, about 60 percent, and when the
third form is detected, about 40 to 50 percent.
Examination of the blood shows a reduction in the number of the red cells
(the normal being about 5,000,000 per cubic millimeter) and a reduction in the
percentage of haemoglobin rather in excess of that of the number of red corpus-
cles. After haemorrhage the average size of the red cells may be slightly
reduced, their color is noticeably pale and a moderate number of poikilocytes
may be noted. Soon after the haemorrhage nucleated red cells and free
nuclei appear in the blood. The leucocytes are moderately increased in
number, especially the polynuclear neutrophiles while the small mono-
nuclear lymphocytes are relatively diminished. As the condition of the
blood returns to normal the leucocytosis gradually diminishes. The haemo-
globin percentage is somewhat lower than that of the red cells.
In anaemia due to chronic disease, the blood changes are similar to those
described above, but the poikilocytosis may be more extreme; the nucleated
SECONDARY ANEMIA. 489
red cells are generally few and large nucleated corpuscles containing kary-
okinetic figures may be found. There is usually a leucocytosis but in very
persistent chronic conditions the white blood cells may be diminished.
The blood of inanition anaemia is characterized by a relative diminution
of the plasma over that of the red corpuscles.
The diagnosis is usually easily made from the history of the patient and
from the existence of one of the causes. In doubtful instances examination
of the blood will show the characteristic diminution of red cells and haemoglobin
in nearly equal proportion and the cellular changes described above.
Treatment. In anaemia following traumatism usually little is needed in
the way of treatment save rest and plenty of nutritious food. Fresh air
is essential and if the patient is confined to bed he should be placed in a freely
ventilated room to which the sun has sufficient access. The administration
of iron, although often unnecessary, may hasten recovery which frequently
is surprisingly rapid.
The anaemia of chronic disease is more difficult of treatment and is usually
impossible of cure without removal of the primary cause. Here nourishing
food is necessary and one should not hesitate to allow a proper mixed diet
even to the patient afflicted with chronic nephritis. Plenteous food is also
a requirement of the sufferer from inanition and attempts should be made
to render the alimentary tract capable of digesting and assimilating the same,
for little is accomplished in the way of increasing the nutrition of the patient
until this is done. Iron vitellin in half ounce (15.0) doses materially accel-
erates the cure.
Toxic anaemia necessitates the removal of the poisonous substances from
the organism (see the sections upon lead, mercurial and arsenic poisoning
and also those upon syphilis and malaria) and, as in preceding types of the
condition, the administration of plenty of good food and of iron. In sec-
ondary anaemia this substance may be given in any of the various prepara-
tions suggested under the treatment of chlorosis (p. 491), and, as in the latter
disease, arsenic is often a useful adjunct.
In malarial patients who continue to exhibit the symptoms of chronic
malarial poisoning it is necessary to rid the blood of plasmodia before treat-
ment of the anaemia will prove effectual. In such instances the organisms
are often secluded in the spleen where they seem to enjoy a certain immunity
to quinine as ordinarily administered but if the fluid extract of ergot in doses
of I drachm (4.0) twice a day is given, the dosage being increased until the
rate of the heart is slowed and the blood pressure increased, a physiological
squeezing of the spleen follows and the plasmodia are forced into the circu-
lation to become an easy prey to quinine which is best given hypodermatically
in the form of the carbamide, 20 to 30 grains (1.33 to 2.0) in aqueous
49Â° DISEASES OF THE BLOOD.
PRIMARY OR ESSENTIAL ANiEMIAS.
Synonyms. Chlorsemia; Chloranaemia.
Definition. An anaemia characterized by a relative diminution of the
haemoglobin in the blood and most frequently observed in girls and young
.etiology. While the direct causation of chlorosis is unknown there are
certain well-recognized facts to be stated concerning the incidence of the disease.
It occurs almost exclusively in the female sex, some clinicians definitely
stating that they have never observed an instance in the male; it is most fre-
quent between the ages of 13 and 17 although it may appear both earlier and
later than these limits. Climatic influence is not a factor in its causation
but it seems to be more common in blondes than in brunettes.
Predisposing factors are insufficient food, lack of fresh air, unhygienic
surroundings, over-work, menstrual disorders, excessive emotion, especially
of sexual character, and such hereditary influences as tuberculous disease.
The wearing of too tightly laced corsets has been held responsible and the
affection may be associated with developmental defects of the circulatory
and generative systems. It has been suggested that chlorosis is the result
of constipation and intestinal putrefaction, toxic substances being absorbed
from the alimentary tract which interfere with the development of the red
Pathology. Aside from the blood changes the affection has no character-
istic pathology; the developmental defects sometimes observed in the hearty
blood-vessels and genitalia are probably adventitious.
Symptoms. The skin is of a peculiar and characteristic yellowish-green hue
which has given rise to the name of the disease; pigmented spots over the
joints and other parts may be observed and in mild instances there may be
a slight redness of the cheeks, particularly after exercise. The patient com-
plains of weakness, dyspnoea on exertion and a tendency to faint; vertigo,
cardiac palpitation and irregularity may be present. Functional cardiac
murmurs such as those described on p. 488 may be audible; the pulse is
soft and full and there may be pulsation of the veins of the neck and of other
superficial veins. Venous thrombosis may occiu*. The face is often swollen
and the ankles may become oedematous; the extremities are frequently cold.
The patient is often despondent and easily irritated. Neuralgic headaches
and menstrual disturbances, which are usually rather a manifestation of the
affection than a factor in its causation, are common. A febrile movement
of slight degree may be noted.
The patient's appetite is often depraved and she craves acid foods or even
various indigestible substances such as chalk. Gastric hyperacidity is
common and constipation very frequent. The association of chlorosis,
especiaUy in subjects who are prone to wear tight corsets, with gastroptosis,
enteroptosis and nephroptosis has been observed in numerous instances.
The patient as a rule is well-nourished.
The Blood. The characteristic changes in this fluid are of the utmost
importance in the diagnosis of the affection. The red cells are only moder-
ately diminished in number-3,500,000 to 4,500,00Â° P^r cubic miUimeter-
while the diminution of the percentage of hemoglobin is proportionately
much greater-40 to 50 percent.-consequently the hemoglobm index (the
relative proportion between the hemoglobin percentage and the number of
red corpuscles) is low. This feature, while not absolutely constant, is typical
of chlorosis and is observed in no other variety of anemia. With the dim-
inution of the hemoglobin the iron content of the blood is dimimshed the
alkalinity of the fluid is increased and its color becomes noticeably hghter.
Microscopically the red cells are of Hghter color than normal and may be
somewhat changed in shape. Poikilocytosis is usually present and m extreme
instances of the disease may be marked. Large red blood cells (megalocytes)
may be observed in small number but the average size of the red corpuscles
is likely to be below normal. Some nucleated red cells may be noted. The
number of white cells, as a rule, is close to the normal or very shghtly increased
The diagnosis, when proper methods are employed, is usually easy and
may be made upon the characteristic appearance of the patient. Important
points are the greenish-yellow tinge of the skin and the bluish-white color
of the sclerotics. Tuberculosis may be ruled out by physical exammation
of the lungs, and cardiac disease by auscultation of the heart, while urinary
examination will differentiate the disease from renal affections. Blood
examination will clinch the diagnosis and enable the physician to rule out
other forms of anemia.
The prognosis is favorable under proper treatment although months may
be necessary before a complete recovery is established.
Treatment. In the treatment of chlorosis iron is essential. Of the prepara-
tions of this substance there are two main groups, the inorganic and the massed,
this term being appHed to irons in inorganic combination, which are not dis-
sociated by the gastric juice. The great objection to all the inorgamc irons
is that upon contact with the hydrochloric acid of the gastric juice they are
converted into iron chloride. Even hemoglobin and all other blood irons
undergo this change, and while the action of iron chloride in chlorosis is bene-
ficial it has certain disadvantages. This salt, when taken into the mouth,
exercises an injurious action upon the teeth; it is irritant to the stomach;
it causes constipation. These disadvantages we may overcome by giving
iron in the same form in which it occurs in the food and consequently a massed
492 DISEASES OF THE BLOOD.
iron must be employed. In the present state of our knowledge of the chem-
istry and therapeutics of iron the necessary qualifications which an accept-
able iron compound should possess are:
a. It must be in definite chemical organic combination.
h. It must be able to resist the action of the free hydrochloric acid of the
gastric juice without becoming decomposed with the formation of iron chloride
which has been demonstrated to coagulate the gastric mucosa, cause localized
necrosis and produce inflammatory' exudation.
1:. It must not interfere with digestion.
d. It must not be irritating nor astringent.
e. It must show definite results in (i) an increase of the number of red
blood cells and (2) in the amount of contained hsemoglobin.
At first sight haemoglobin, when administered by mouth, would seem to be a
proper organic iron for exhibition in ansemia and allied conditions; as a matter
of fact, however, Cloetta as early as 1896 showed that it is not absorbed as such
but is destroyed as soon as it enters the stomach. With this, the theory of
the advantage of blood, or products made from blood, for oral administra-
tion, falls. The crucial test for the actual massed iron preparation is that
of MacCallum. Briefly, a small quantity of ^ to i percent, solution of haema-
toxylin is added to the suspected iron compound. If the iron is inorganic,
a characteristic blue-black color is produced; if the iron is organic or massed
no color reaction results. That many so-called organic iron compounds are
practically only combinations of iron salts with albuminoids is readily demon-
strated by the addition to them of a few drops of silver nitrate solution, which
will cause a precipitation of these albuminoids.
The solution of iron vitellin, marketed as ovof errin, is a definite true organic
iron compound in that it complies with aU the requirements given above and
is applicable in all instances where a massed iron is desired. Its usual dosage
is J an ounce (15.0) 3 times daily before meals, and is the most satisfactory
form of administering this important element.
In instances where the susceptibility of the stomach does not preclude their
administration, increasing doses of the astringent salts, especially iron sulphate
and chloride may be given to advantage. Large quantities of these salts are
often well borne, but it must be remembered that considerable amounts of
the sulphate have been known to cause intestinal obstruction. WTien they
produce untoward eft'ects they should be replaced by other preparations,
preferably the most astringent ones which the stomach wiU tolerate. The
astringent iron compounds lose, to some extent, their st}'ptic taste when com-
bined with glycerin, which also has the effect of reducing some of the ferric
to a ferrous salt. To restore the haemoglobin and red blood cells small doses
of reduced iron â€” i to 2 grains (0.065 to 0.13) â€” of the carbonate or of some
one of the combinations with vegetable acids are usually the most serviceable.
As the scale preparations rarely disagree they may be used for patients with
weak digestions and in smaU doses can usually be continued for indefinite
periods. Oftentimes in chlorosis better results are obtained from iron with
str}'chnine or arsenic than from iron alone, the syrup of iron, quinine and
strychnine phosphate, the elixir of iron, strychnine and quinine of the National
Formulary and the piU of the three phosphates which contains i grain (0.065)
of quinine, -j-j of a grain (0.002) of strychnine, ij minims (o.io) of concen-
trated phosphoric acid and licorice powder to 5 grains (0.33) being useful
preparations. Iron arsenate ^ to yV of ^ grain (0.008 to 0.006) is an excel-
lent remedy in chlorosis. Iron may also be given hypodermaticaUy when
gastric disorders preclude its exhibition by the mouth. The following for-
mula may be employed: Iron and ammonium citrate, 75 grains (5.0), sodium
arsenate | of a grain (0.048), sterilized water to 12^ drachms (50.0), 15 to 30
minims (i.o to 2.0) daily to be injected into the muscles of the shoulder or
buttock. Usually the use of iron must be persisted in for a period of several
months and it may be necessary to continue the treatment, the doses being
diminished, for even longer periods. Recurrences of the chlorosis, which
are not uncommon, necessitate a renewal of treatment. With regard to
manganese in anaemic conditions it may be definitely stated that as a regen-
erator of the haemoglobin and red cells it is absolutely inert.
The importance of proper treatment for the accompanying constipation
cannot be over-rated. The daily administration of a mild saline purge is
often indicated and in obstinate instances the condition should be treated
as ad\'ised in the section upon the treatment of constipation.
Gastric disorders such as h}^ochlorhydria, etc., should receive appropriate
treatment. The administration of dilute hydrochloric acid in 10 drop (0.66)
doses in a glass of water to be taken with meals is advised in conditions of low
gastric acidity, the acid being useful in dissolving the iron as weU as in cor-
recting the secretory abnormality.
The theory has been advanced by Bunge that intestinal fermentation bv
producing sulphides interferes with the proper absorption of the iron of the
food and, in order to prevent this decomposing process, it is suggested that in'
connection with other treatment, it is well to render the intestinal contents as
nearly aseptic as possible by giving such intestinal antiseptics as bismuth naph-
tholate â€” 5 grains (0.33) â€” 3 times a day or sodium glycocholate J grain (0.032),
with a little menthol to prevent distressing eructations, at similar intervals.
The absence of intestinal decomposition is shovni by testing the urine for
indican and the disappearance of the sulphides from the stools by giving
bismuth subnitrate which, in the presence of these substances, causes the
faeces to assume a black color.
In connection with the drug treatment of anaemia the diet and general
hygiene of the patient should also be considered. Rest in bed is important,
494 DISEASES OF THE BLOOD.
particularly in severe instances, and plenty of good easily digestible food should
be allowed. The foods which contain iron, such as fish, spinach, apples, oats,
beef, lentils, strawberries, beans, potatoes, eggs, wheat, rye, veal, milk, rice,
etc., should be eaten in abundance and the red wines, and natural chalybeate
waters such as those of La Bourbole, Levico, Flitwick, and the Columbian
Spring, Saratoga, may prove useful. As the haemoglobin becomes increased
the patient may be allowed to sit up for a little time each day until finally
she remains up all day. During this period massage may be employed to
a&vantage as well as mild hydrotherapeutic measures, tepid sponging, douching
and the like. For a considerable period after being out of bed the patient
should not be allowed to tire herself but as strength returns she may be per-
mitted to indulge in the milder forms of exercise. Sea voyages and a change
of climate, particularly a sojourn at the sea side, will materially benefit the
patient's condition during convalescence.
Progressive Pernicious Anaemia.
Definition. A chronic anaemia characterized by a marked diminution of
the red blood cells and a relatively high haemoglobin content.
jEtiology. The disease is rather rare in the United States. It appears
to affect males rather more commonly than women and usually appears after
the incidence of middle age but has been observed in young adults and in
Its actual causation has not been definitely determined; in some instances
it appears during pregnancy but may occur after delivery and during lacta-
tion as well. The anaemia caused by certain intestinal parasites, particularly
the bothriocephalus latus and the anchylostomum duodenale is often of the pro-
gressively pernicious type, and as other causes, severe and protracted digestive
disorders and gastric atrophy may be mentioned. StiU another type of the
disease occurs idiopathically without previous haemorrhage, renal, tubercu-
lous, diarrhoeal, malignant or other disease and attributable to no discoverable
cause. The condition of the blood which obtains in pernicious anemia has
been considered as resulting from haemolysis with an accumulation of iron
in the liver and an abnormal increase of the urobilin of the urine. The
destruction of the blood cells is believed by the adherents of the theory of
increased haemolysis to be due to the absorption of toxic substances generated
as a result of improper performance of the digestive function. Other theorists
hold that small internal capillary haemorrhages are in great measures re-
sponsible for the disease, while still others consider that it is due to a faulty
haemogenesis which turns out red cells of poor powers of resistance.
Pathology. The usual hue of the skin is suggestive of that of the lemon,
the fat is light yellow and the voluntary muscles are distinctly, even abnormally
PROGRESSIVE PERNICIOUS ANEMIA. 495
red. The heart muscle is yellowish from its infiltration of fat. The stomach
may be normal but in certain instances an atrophy of the gastric tubules
has been observed. Enlargement and fatty degeneration of the liver are
common and in the liver cells of the outer and middle zones of the lobules
iron is deposited which may be distributed in such a manner as to outline
the bile capillaries. This deposition of iron in the hepatic cells has been
considered characteristic of pernicious anaemia. The spleen may contain
iron in excess and may be smaller than normal but these changes are not
constant. The kidneys also may show an increased quantity of iron. The
bone-marrow is dark red, its lymphoid cells are increased in number and
it contains many nucleated red blood cells especially megalo- or giganto-
blasts. Eosinophiles and neutrophiles are also present.
Associated changes in the nervous system, such as alterations in the cells
of the posterior columns of the cord and softening of the upper portion of the
lumbar cord, have been described.
Symptoms. The onset of the disease is gradual and may be preceded by
symptoms of digestive disorder. The patient notices an increasing weakness
finally becoming extreme even to prostration; accompanying the physical
debility there is usually progressive distaste for mental exertion. The main-
tenance of body weight is remarkable and characteristic, emaciation being a
rare manifestation. The skin assumes the typical lemon-yellow tinge which
in extreme degrees simulates that of jaundice. The yellow color is usually
preceded by pallor and may be absent in certain instances. A pigmentation
resembling that of Addison's disease is often observed, usually occurring as
a result of the administration of arsenic. Patches of leucoderma may be
noted. The sclerotics are usually pearly white. The mucous membranes
are markedly pale.
Digestive symptoms are frequent; anorexia, nausea and vomiting and
obstinate diarrhoea are the most common of these.
A moderate febrile movement of irregular type it not rare. The urine is,
as a rule, of low specific gravity and either light or of very dark color due to
the presence of an increased amount of urobilin.
Circulatory symptoms are very noticeable. The pulse is large, full and
may suggest the pulse of aortic insufficiency. The pulsation in the capil-
laries is often visible and visible pulsation of the arteries and even of the veins
may occur, murmurs of functional type (see p. 488) are frequent. Haemor-
rhages into the skin, mucous membranes or retinae may take place. A tend-
ency to fainting or to dyspnoea on exertion is often observed.
Nervous symptoms such as numbness of the extremities, pain and the
symptoms of sclerotic change in the postero-lateral columns of the cord may
The blood changes are frequently very characteristic. In color the blood
496 DISEASES OF THE BLOOD.
may be quite pale, dark or normal. In consistency it is thin, the specific
gravity is reduced in extreme instances and coagulation is retarded. As a
rule there is great reduction in the number of red corpuscles, the average
being not far from 1,000,000 per cubic millimeter. Fresh specimens reveal
a marked poikiloc}'tosis and the absence of any great degree of rouleau for-
mation. The average diameter of the red cells is increased, the reverse of
the condition present in chlorosis and secondary anaemia. Large red cells
(macroc}1;es) are often abundant even early in the disease. Gigantoblasts
(â– ^ery large nucleated red corpuscles) may be present late in the disease,
these are the most abundant of the three tjpes of nucleated red cells which may
be observed, the others being normoblasts and microblasts, the latter being
usually few. The normoblasts are, as a rule, fewer than the megaloblasts,
while in, secondary anaemia the opposite is the case. Red blood cells with
the faint remains of nuclei are not uncommon and kar}^okinetic figures may
be seen in the megaloblasts.
The hemoglobin is not diminished in proportion to the reduction in the ,1
number of red ceUs, the hsemoglobin index being high in consequence. This I
appears to be due to the fact that the megalocytes contain a relatively greater
amount of haemoglobin than does a corresponding number of normal sized
corpuscles; this is a characteristic of pernicious anaemia.
The leucoc}1:es are usually diminished, 4000 to the cubic millimeter being
a fair average. There is a relative increase in the lymphoc}i;es and a decrease
in the number of pol}Tiuclear neutrophils.
The diagnosis in severe instances is easily made upon blood examination;
in milder instances the separation of the disease from other anaemias is more