THE PHYSIOLOGICAL PATHOLOGY OF MALARIA 
229 
is often profound, but most of the observa¬ 
tions on man have been purely clinical. 
Brown and Loevenhart (1913) found that 
the injection of alkaline hematin into dogs 
and cats caused dilatation of the splanchnic 
vessels, constriction of the cutaneous ves¬ 
sels and a marked fall in blood pressure. 
The heart rate was slowed and the cardiac 
output diminished. These effects were ap¬ 
parently due mainly to toxic action on the 
vasomotor and cardio-inhibitory centers. 
Dudgeon and Clarke (1917) reported fatty 
degeneration of the heart muscle in fatal 
cases of malaria, similar to that seen in 
diphtheria. They also reported thrombosis 
of vessels in the brain, spleen, kidneys and 
adrenal glands. 
Serious circulatory disturbances in hu¬ 
man malaria occur almost exclusively in 
P. falciparum infections. The two factors 
primarily responsible for these disturb¬ 
ances seem to be the plugging of capillaries 
by parasitized erythrocytes and the liber¬ 
ation of toxic substances from these ery¬ 
throcytes on the completion of schizogony. 
The massive infections often seen in P. 
falciparum infections would appear to be 
sufficient to produce severe toxic symptoms, 
particularly since P. knowlesi infections in 
monkeys produce fatal toxic symptoms 
when the infection becomes massive, even 
though there is no plugging of capillaries. 
These symptoms are partly circulatory and 
are not unlike the toxic effects of hematin 
described above. 
The plugging of capillaries in P. falci¬ 
parum infections is an additional, and 
probably often the principal, cause of the 
alarming symptoms which develop. The 
severe headaches, drowsiness and coma, 
often periodic in occurrence, can be ex¬ 
plained on the basis of obstruction to cere¬ 
bral capillaries. The choleraic and dysen¬ 
teric types of so-called “algid” malaria 
may also be due to obstruction to capillaries 
in the intestinal mucosa. Furthermore, it 
is probable that the mechanical embarrass¬ 
ment of the circulation tends to exaggerate 
the symptoms produced by the toxic sub¬ 
stances liberated from the parasitized 
erythrocytes. 
Liver 
What has been said above concerning 
blood destruction and pigment metabolism 
in malaria indicates the load which is 
placed upon the liver in this disease. It is 
called upon to dispose of bilirubin, hemo¬ 
siderin and possibly hematin. Its storage 
of glycogen is called upon and its relation 
to lipoid metabolism may be affected. The 
secretion of large amounts of thick bile 
rich in bile pigments and the possible effect 
of this secretion on the gastro-intestinal 
tract have given the name of “bilious re¬ 
mittent fever” to one clinical form of P. 
falciparum malaria. The lowering of levu- 
lose and galactose tolerance gives evidence 
of injury to its glycogenetic function, and 
the increase of cholestrin and lecithin in 
the blood at the time of the malarial 
paroxysm suggests its increased activity in 
connection with these lipoids. Histological 
evidence of damage to the parenchymatous 
cells of the liver in fatal cases of malaria 
is not uniform, but both degenerative 
changes and fat infiltration are sometimes 
found. 
Kidneys 
Kidney function is not usually disturbed 
in clinical cases of malaria. Small amounts 
of albumin may be found in the urine, 
usually associated with febrile periods, but 
damage to the water, salt or nitrogen secre¬ 
tory functions of the kidneys are not 
usually demonstrable in acute malaria. 
There is, however, an interesting picture 
which is not infrequently seen in chronic 
malaria, least often in P. vivax, more often 
in P. falciparum and most often in P. 
malariae infections. This is a picture of 
water retention with edema, and with al¬ 
bumin in the urine, often in large amounts. 
Hyaline and granular casts are usually 
present. There is usually little or no reten¬ 
tion of nitrogen. This is the picture which 
is usually given the name lipoid nephrosis. 
Its occurrence in chronic quartan malaria 
has been studied particularly by Goldie 
(1930) in Palestine, and it has also received 
attention in many other parts of the world. 
Usually in P. vivax and P. falciparum in- 
