Page 50 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

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Hemolytic Anemias
Erythrocytes can only attain their normal life- fonamides) increase oxidative stress and thus
span when their flexibility, their ability to aggravate the situation; 3) a defect of hexoki-
withstand osmotic and mechanical stress, nase results in a deficiency of both ATP and
their reductive potential, and their energy sup- GSH (→ A2,3).
ply are normal (→ p. 30). Defects in these prop- ! Sickle cell anemia and thalassemias (→ p. 36)
erties lead to a shorter life-span (in some cases also have a hemolytic component (→ A4).
to just a few days [corpuscular hemolytic ane- ! In (acquired) paroxysmal nocturnal hemo-
mia]). There are, however, many other causes globinuria (PNH) some of the erythrocytes (de-
that shorten the life-span of normal erythro- rived from somatically mutated stem cells)
cytes (extracorpuscular hemolytic anemia). A have increased complement sensitivity. It is
common feature of these anemias is an in- based on a defect of certain membrane pro-
creased concentration of erythropoietin, which teins that are involved in regulating the com-
provides compensatory stimulation of eryth- plement system (especially the decay acceler-
ropoiesis (→ p. 33, A and B3). ating factor [DAF]; → A5). Complement activa-
Causes of corpuscular hemolytic anemia tion then leads to perforation of the erythro-
(→ A) are usually genetic defects: cyte membrane. It is not clear why this usually
! One of the membrane diseases is hereditary occurs during sleep.
spherocytosis (spherocyte anemia). It is caused Examples of the causes of extracorpuscular
Blood by a functional abnormality (defective anky- hemolytic anemia are:
rin) or deficiency of spectrin, which, as an im-
! Mechanical causes, such as damage to the
3 portant constituent of the cytoskeleton, is es- erythrocytes by collision with artificial heart
sential for its stability (→ A1). The volume of valves or vascular prostheses, especially if car-
spherocytes is normal, but the defect in the cy- diac output (CO) is raised;
toskeleton results in erythrocytes being spher- ! Immunological causes, for example, in ABO
ical, instead of having a normal flexible discoid blood group transfusion mismatches, or Rh in-
shape. The osmotic resistance of these cells is compatibility between mother and fetus;
reduced, i.e., they hemolyse when the hypoto- ! Toxins, for example, certain snake poisons.
nicity of the external medium is still low. As In most hemolytic anemias the erythrocytes
they are prematurely segregated in the spleen, will, as would occur normally, be phagocytized
splenectomy is therefore therapeutically effec- and “digested” in bone marrow, the spleen and
tive. liver (extravascular hemolysis), and Fe is reused
! Enzyme defects disturb the glucose metabo- (→ p. 38). A small amount of Hb released intra-
lism of erythrocytes (→ A2): 1) if pyruvate ki- vascularly is bound to haptoglobin (→ p. 38).
+
+
nase is affected, ATP to Na -K -ATPase supply In massive acute intravascular hemolysis
is stopped, the cells swell up so that they be- (→ B) haptoglobin is, however, overloaded and
come vulnerable and hemolyse early; 2) defec- free Hb is filtered in the kidneys. This results
tive glucose-6-phosphate dehydrogenase (gluc- not only in hemoglobinuria, but can also
6-PDH; → A3) slows the pentose phosphate cy- through tubular occlusion lead to acute renal
cle, so that oxidized glutathione (GSSG), failure (→ p.108). Chronic hemoglobinuria ad-
formed under oxidative stress, can no longer ditionally causes Fe deficiency anemia, cardiac
be adequately regenerated to the reduced form output rises and the resulting mechanical he-
(GSH). As a result, free SH groups of enzymes molysis creates a vicious circle (→ B). Finally,
and membrane proteins as well as phospholip- the erythrocytic fragments produced in intra-
ids are no longer sufficiently protected against vascular hemolysis may cause thrombi and
oxidation, leading to premature hemolysis. emboli, which can result in ischemia in the
Eating horsebeans (vicia faba major, causing fa- brain, cardiac muscle, kidneys, and other or-
vism) or certain drugs (e.g., primaquin or sul- gans.
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