Definition:
Megaloblastic anemia is a type of macrocytic anemia characterized by impaired DNA synthesis, leading to delayed nuclear maturation and cell division. As a result, erythroblasts in the bone marrow appear large and immature (megaloblasts), while cytoplasmic maturation proceeds normally.
Etiology:
A. Folic Acid Deficiency or Abnormal Folate Metabolism
- Low dietary intake: Seen in the elderly, individuals with poor diets, or in starvation.
- Increased demand: Pregnancy and lactation increase folate requirements.
- Malabsorption: Conditions affecting the small intestine (e.g., celiac disease, tropical sprue).
B. Vitamin B12 Deficiency or Abnormal Vitamin B12 Metabolism
- Low dietary intake: Rare, but may occur in strict vegans.
- Abnormal utilization: Nitrous oxide inactivates vitamin B12.
- Impaired absorption:
- Stomach-level issues:
- Pernicious anemia: Autoimmune atrophic gastritis with destruction of parietal cells → ↓ intrinsic factor.
- Gastrectomy: Removes intrinsic factor-producing cells.
- Intestinal-level issues:
- Small bowel disease (e.g., Crohn’s)
- Bacterial overgrowth
- Diphyllobothrium latum (fish tapeworm)
Pathogenesis:
- Defective DNA synthesis (due to deficient thymidine production) results in nuclear-cytoplasmic asynchrony.
- This causes ineffective erythropoiesis with destruction of abnormal precursors in the marrow (intramedullary hemolysis), leading to anemia, pancytopenia, and elevated bilirubin levels.