Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 3) pptx
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Chapter 101. Hemolytic Anemias and Anemia
Due to Acute Blood Loss
(Part 3)
Figure 101-1
RBC metabolism. The Embden-
Meyerhof pathway (glycolysis) generates
ATP
for energy and membrane maintenance. The generation of NADPH
maintains hemoglobin in a reduced state. The hexose monophosphate shunt
generates NADPH that is used to reduce glutathione, which protects the red cell
against oxidant stress. Regulation of 2,3-b
isphosphoglycerate levels is a critical
determinant of oxygen affinity of hemoglobin. Enzyme deficiency states in order
of prevalence: glucose-6-
phosphate dehydrogenase (G6PD) >>> pyruvate kinase
> glucose-6-phosphate isomerase > rare deficiencies of other
enzymes in the
pathway. The more common enzyme deficiencies are encircled.
Thus, the essential pathophysiologic process common to all HAs is an
increased red cell turnover. The gold standard for proving that the life span of red
cells is reduced (compared to the normal value of about 120 days) is a red cell
survival study, which can be carried out by labeling the red cells with
51
Cr and
measuring residual radioactivity over several days or weeks; however, this classic
test is now available in very few centers and is rarely necessary. If the hemolytic
event is transient, it does not usually cause any long-term consequences. However,
if hemolysis is recurrent or persistent, the increased bilirubin production favors the
formation of gallstones. If a considerable proportion of hemolysis takes place in
the spleen, as is often the case, splenomegaly may become a prominent feature and
hypersplenism may develop, with consequent neutropenia and/or
thrombocytopenia.
The increased red cell turnover also has metabolic consequences. In normal
subjects, the iron from effete red cells is very efficiently recycled by the body;
however, with chronic intravascular hemolysis, the persistent hemoglobinuria will
cause considerable iron loss, needing replacement. With chronic extravascular
hemolysis, the opposite problem, iron overload, is more common, especially if the
patient needs frequent blood transfusions. Chronic iron overload will cause
secondary hemochromatosis; this will cause damage, particularly to the liver,
eventually leading to cirrhosis, and to the heart muscle, eventually causing heart
failure. The increased activity of the bone marrow also entails an increased
requirement for erythropoietic factors, particularly folic acid.
Compensated Hemolysis versus HA
Red cell destruction is a potent stimulus for erythropoiesis, which is
mediated by erythropoietin (EPO) produced by the kidney. This mechanism is so
effective that in many cases the increased output of red cells from the bone
marrow can fully balance an increased destruction of red cells. In such cases we
say that hemolysis is compensated. The pathophysiology of compensated
hemolysis is similar to that just described, except there is no anemia. This notion is
important from the diagnostic point of view, because a patient with a hemolytic
condition, even an inherited one, may present without anemia. It is also important
from the point of view of management because compensated hemolysis may
become "decompensated"—i.e., anemia may suddenly appear—in certain
circumstances—for instance, pregnancy, folate deficiency, renal failure interfering
with adequate EPO production, or an acute infection depressing erythropoiesis.
Another general feature of chronic HA is seen when any intercurrent condition
depresses erythropoiesis. When this happens, in view of the increased rate of red
cell turnover, the effect will be predictably much more marked than in a person
who does not have hemolysis. The most dramatic example is infection by
parvovirus B19, which may cause a rather precipitous fall in hemoglobin, an
occurrence sometimes referred to as aplastic crisis.
Inherited Hemolytic Anemias
There are three essential components in the red cell: (1) hemoglobin, (2) the
membrane-cytoskeleton complex, and (3) the metabolic machinery necessary to
keep (1) and (2) in working order. Here we will discuss diseases of the latter two
components. Diseases caused by abnormalities of hemoglobin are discussed in
Chap. 99.
