THE PHYSIOLOGICAL PATHOLOGY OF 
MALARIA 
By HENRY E. MELENEY 
DEPARTMENT OF PREVENTIVE MEDICINE AND PUBLIC HEALTH, VANDERBILT UNIVERSITY 
SCHOOL OF MEDICINE, NASHVILLE, TENN. 
There is no phase of the study of malaria 
which offers more promise of interest and 
accomplishment to the worker in the clini¬ 
cal and biochemical fields than the physio¬ 
logical changes produced in human sub¬ 
jects and experimental animals by the 
various species of malarial parasites. 
These changes may best be appreciated 
by reviewing briefly the effects produced 
by the asexual cycle of the parasite in the 
human host. When schizogony has been 
completed, the schizont ruptures the ery¬ 
throcyte, liberating hematin, salts, cell 
constituents and possibly toxins into the 
blood plasma. The chill and fever are 
clinical manifestations of this event when 
large numbers of parasites complete schizog¬ 
ony at one time. When large numbers are 
constantly completing schizogony, a con¬ 
tinuous or irregular high fever with other 
severe clinical manifestations occurs. 
The continuous repetition of the asexual 
cycle has further effects on the blood and 
other organs of the body. The number of 
erythrocytes is reduced and an increased 
proportion of young erythrocytes appears 
in the circulation. The proportion of ery¬ 
throcytes to plasma is decreased. The 
plasma proteins, lipoids, carbohydrates and 
salts are thrown out of normal balance. 
The erythropoietic function of the bone 
marrow is stimulated. The secretory and 
excretory activity of the liver and kidneys 
is increased, and the functions of other 
glands, such as the suprarenals, may be 
stimulated or disturbed. In addition, the 
occurrence of chills and fever makes greater 
demands on the carbohydrate and protein 
metabolism, thus depleting the storage of 
these substances in the liver and muscles. 
The phagocytic mechanism of the body is 
stimulated, causing multiplication and in¬ 
creased activity of the reticulo-endothelial 
cells. 
Two other phenomena which produce 
serious physiological disturbances in ma¬ 
laria are the plugging of capillaries by 
erythrocytes parasitized by P. falciparum, 
and the sudden intravascular hemolysis 
known as blackwater fever which severely 
alters the constituents of the blood plasma 
and often places an insuperable strain on 
the excretory functions of the kidneys. 
It is now appropriate to discuss in detail 
the changes which malarial infection pro¬ 
duces in the constituents of the blood and 
in the functions of various organs of the 
body. Although the subject of this sym¬ 
posium is human malaria, certain additions 
to our knowledge have been contributed by 
recent research on monkey malaria, and 
these will be drawn upon to supplement 
observations on human subjects. Space 
permits reference to only a limited number 
of papers in the enormous literature in this 
field. 
Blood Proteins 
Ghosh and Sinton (1935) reviewed the 
observations made previously on the blood 
proteins in human cases of malaria. Most 
of the work had been done on blood serum. 
There was general agreement that the total 
of serum proteins was reduced, both in the 
acute and in the latent stage of the disease. 
This reduction involved principally the 
serum albumin. The serum globulin was 
usually not reduced and was often in¬ 
creased and the proportion of euglobulin 
was always increased. The globulin-albu¬ 
min ratio was always increased though 
usually not above unity. These changes 
were more marked in acute than in 
chronic infections. Radosavljevic and 
Ristic (1926) found that in the blood 
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