What is the pathophysiology of macrocytosis?

Updated: Dec 16, 2018
  • Author: Vincent E Herrin, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The most common cause of macrocytic anemia is megaloblastic anemia, which is the result of impaired DNA synthesis. Although DNA synthesis is impaired, RNA synthesis is unaffected, leading to a buildup of cytoplasmic components in a slowly dividing cell. This results in a larger-than-normal cell. The nuclear chromatin of these cells also has an altered appearance. [6]

Vitamin B-12 and folate coenzymes are required for thymidylate and purine synthesis; thus, their deficiency results in retarded DNA synthesis. In vitamin B-12 deficiency and folic acid deficiency, the defect in DNA synthesis affects other rapidly dividing cells as well, which may be manifested as glossitis, skin changes, and flattening of intestinal villi.

DNA synthesis may also be delayed when certain chemotherapeutic agents are used, including folate antagonists, purine antagonists, pyrimidine antagonists, and even folate antagonist antimicrobials.


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