Megaloblasts result from the impaired synthesis of
A. DNAB. RNA
C. Glutathione
D. β-globin chains
The
answer is a. Deficiency of either vitamin B12 or folate results in megaloblastic
anemia. Deficiency impairs DNA syn-thesis and delays mitotic division, which in
turn causes the nuclei to be enlarged. The synthesis of RNA and cytoplasmic
elements is not affected, however, so there is nuclear-cytoplasmic asynchrony.
These cellular changes affect all rapidly proliferating cells in the body, but
in the bone marrow they result in enlarged erythroid precursors, which are
referred to as megaloblasts. These abnormal cells produce abnormally enlarged
red cells, which are called macroovalocytes. These megaloblasts also undergo autohemolysis
within the bone marrow, resulting in ineffective erythropoiesis. Granulocyte
precursors are also enlarged and are called giant metamyelocytes. These
abnormal cells produce enlarged hypersegmented neutrophils. The megakaryocytes
are large and have nuclear abnormalities, but, although the platelet count is
decreased, the platelets are not enlarged. Abnormalities of glutathione
production are seen in patients with glucose-6-phosphate dehydrogenase
deficiency, while decreased synthesis of β-globin chains is seen in patients
with β thalassemia. Abnormalities of decay-accelerating factor are seen in
patients with paroxysmal nocturnal hemoglobinuria.
