Megaloblastic anemias – etiology, pathogenesis, and clinical manifestations.
Megaloblastic anemias are a group of macrocytic anemias characterized by the presence of megaloblasts in the bone marrow and large, abnormal RBCs in peripheral blood, due to impaired DNA synthesis.
Etiology
- 1 Vitamin B12 (cobalamin) deficiency
- Nutritional deficiency:
- Strict vegan diet (B12 is only in animal products).
- Malabsorption:
- Pernicious anemia (autoimmune destruction of parietal cells → intrinsic factor deficiency).
- Gastrectomy (loss of intrinsic factor source).
- Ileal resection, Crohn's disease (affects terminal ileum where B12 is absorbed).
- Competition:
- Fish tapeworm (Diphyllobothrium latum) infection.
- Bacterial overgrowth.
- 2 Folate (vitamin B9) deficiency
- Nutritional deficiency:
- Poor diet (elderly, alcoholics).
- Increased requirement:
- Pregnancy, hemolytic anemias.
- Malabsorption:
- Celiac disease.
Drugs:
- Methotrexate, phenytoin, sulfa drugs.
Pathogenesis
- Deficiency of B12 or folate → impaired thymidine synthesis → defective DNA replication.
- Nuclear-cytoplasmic asynchrony:
Cytoplasmic maturation normal (RNA synthesis preserved).
Nuclear maturation delayed → large immature nuclei in developing cells.
- 3 Bone marrow:
Ineffective erythropoiesis → megaloblasts → intramedullary hemolysis.
- 4 Peripheral blood:
Macrocytic (MCV >100 fL), oval-shaped RBCs (macro-ovalocytes).
Hypersegmented neutrophils (>5 lobes).
- 5 In B12 deficiency only:
Abnormal myelin synthesis → demyelination of posterior and lateral columns of spinal cord.
Clinical manifestations
General anemia symptoms
Fatigue, weakness.
Dyspnea on exertion.
Pallor.
Gastrointestinal
Glossitis (smooth, beefy-red tongue).
Anorexia, weight loss.
Neurological symptoms (specific to B12 deficiency)
Paresthesias (tingling, numbness in hands and feet).
Gait disturbances (ataxia).
Loss of position and vibration sense.
Cognitive changes (memory loss, irritability).
Other
Mild jaundice (due to intramedullary hemolysis → increased bilirubin).
Summary table