Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
is the most common enzyme deficiency known to cause hemolysis.
G-6-PD reduces NADP (nicotinamide-adenine-dinucleotide phosphate)
to NADPH. NADPH reduces oxidized glutathione (GSSH) to its
reduced form GSH. GSH prevents oxidation of RBC membranes
More than 200 million people, mainly Mediterranean, West
African, Mid-East, and Southeast Asian populations, are estimated
to be G-6-PD deficient.
The deficiency is sex-linked (M>F), but with varying degrees
of deficiency - mild in blacks and severe in Mediterranean
populations. Blacks often have an episodic variant in which
oxidant compounds such as antimalarials, sulfonamides, or
infections cause hemolysis. In Mediterranean populations G-6-PD
deficiency may result in a chronic hemolysis. Women heterozygotes
(half the normal amount of RBC) G6PD show increased resistance
to P falciparum.
During times of oxidant stress the PBS usually shows spherocytes,
schistocytes, and "bite" cells and "blister" cells where denatured
hemoglobin (Heinz bodies) were removed in the spleen.
G6PD enzyme assays reveal relatively high levels in reticulocytes
and young erythrocytes, declining in older RBCs. In hemolysis
it is the older cells which destroyed. Because of this hemolysis
is usually self-limited.
Pyruvate kinase deficiency an autosomal recessive disorder
causing polychromasia, anisocytosis, poikilocytosis with burr
cells and acanthocytes, and NRBCs.
Reduced ATP formation causes RBC membrane rigidity, resulting
in hemolysis. Symptoms are usually mild as increased 2,3-DPG
causes a right shift of the 02-dissociation curve.
Persons homozygote for PK deficiency show severe anemia and
are usually discovered in childhood. Splenomegaly, cholelithiasis
and jaundice are frequent.
Methemoglobin is hemoglobin that has been oxidized from
the ferrous (Fe++) to the ferric (Fe+++) state, thus unable
to bind oxygen. The NADH- methemoglobin reductase enzyme reduces
methemoglobin to hemoglobin. Methemoglobinemia results from
either inadequate enzyme activity or too much methemoglobin
Hereditary autosomal recessive deficiency of NADH-methemoglobin
reductase presents with cyanosis because methemoglobin cannot
carry oxygen. The cyanosis is usually mild, but if severe
can be treated with IV methylene blue, activating NADH- methemoglobin
Methemoglobin production may exceed the capacity
of the normal NADH-
methemoglobin reductase pathway. This can be acquired due
to drug or toxic oxidation of hemoglobin (analine dyes, anesthetics-benzocaine;
prilocaine, naphthalene, nitrates, nitrites, nitroglycerin,
paraquat, phenazopyridine, sulfamethoxazole, trimethadione,
Certain single amino acid substitutions within a hemoglobin
globin chain can cause the iron to stabilize in the ferric
Related is the carboxyhemoglobin that results from carbon
monoxide binding to hemoglobin. Hemoglobin binds CO more tightly
than oxygen by a factor of 200. The tissues are deprived of
Co poisoning produces massive amounts of
carboxyhemoglobin causing a cherry pink discoloration
of the brain.
If in an inherited M hemoglobin the amino acid substitution
was in the ß-globin chain would you expect cyanosis:
A. To cause fetal death
B. At birth
C. At 6 months
D. As an adult only
E. Not to occur
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