Megaloblastic anaemias: B12 and folate
- Lesion
Without vitamin B12 or folate, cells cannot copy DNA. Precursors grow large and die, the blood shows big oval cells, and B12 lack also harms nerves.
What it is
Megaloblastic anaemias result from impaired DNA synthesis, most often from deficiency of vitamin B12 or folate. Nuclear maturation lags behind cytoplasmic maturation, so precursors are large (megaloblasts), many die in the marrow (ineffective haematopoiesis) and the blood shows macro-ovalocytes and hypersegmented neutrophils with pancytopenia. B12 deficiency also causes demyelination of the spinal cord. Pernicious anaemia, the commonest cause of severe B12 deficiency, is an autoimmune atrophic gastritis that destroys parietal cells and intrinsic factor.
Structure
- Marrow: hypercellular, large erythroid precursors with fine open chromatin despite haemoglobinized cytoplasm; giant metamyelocytes and bands.
- Blood: macro-ovalocytes, anisopoikilocytosis, hypersegmented neutrophils, sometimes pancytopenia.
- Stomach in pernicious anaemia: thin fundic mucosa, loss of parietal cells, lymphocytes and plasma cells, intestinal metaplasia.
- Tongue: smooth, red, atrophic glossitis; spinal cord: demyelination of posterior and lateral tracts.
Step by step
- B12 from animal food is released by gastric acid, binds haptocorrin, then intrinsic factor in the duodenum, and is absorbed in the terminal ileum via cubilin.
- Loss of intrinsic factor (pernicious anaemia), gastrectomy, ileal disease, fish tapeworm or a strict vegan diet causes B12 deficiency.
- Without B12, folate is trapped as methyl-tetrahydrofolate; thymidylate synthesis fails.
- Folate deficiency (poor diet, alcohol, pregnancy, haemolysis, malabsorption, methotrexate, phenytoin) blocks the same step directly.
- DNA replication stalls: cells grow but cannot divide, and most die in the marrow.
- In B12 deficiency, methylmalonyl-CoA builds up and myelin is damaged.
B12 vs folate deficiency
| Feature | Vitamin B12 deficiency | Folate deficiency |
|---|---|---|
| Causes and time to deficiency | Pernicious anaemia, gastrectomy, ileal disease, vegan diet, some drugs; stores last years | Poor diet, alcohol use disorder, pregnancy, haemolysis, malabsorption, methotrexate; stores last months |
| Metabolites and nerves | Methylmalonic acid and homocysteine high; subacute combined degeneration | Homocysteine high, methylmalonic acid normal; no neurologic damage |
Clinical notes
- Pallor with mild jaundice (from ineffective erythropoiesis), sore tongue, paraesthesia, ataxia, loss of vibration sense, dementia.
- Giving folate alone to a B12-deficient patient corrects the blood but lets the neurologic damage progress.
- Folate fortification and supplementation before conception reduce neural tube defects.
In the lab
- Serum B12 and folate, methylmalonic acid and homocysteine, antibodies to intrinsic factor and parietal cells.
Test yourself
Think of the answer, then tap the question to see it.
Which metabolite separates B12 from folate deficiency?
Methylmalonic acid, raised only in B12 deficiency (homocysteine rises in both).
Why is the marrow hypercellular while the blood shows pancytopenia?
Precursors accumulate but many die in the marrow because DNA synthesis fails (ineffective haematopoiesis).
Which gastric lesion causes pernicious anaemia?
Autoimmune atrophic gastritis of the body and fundus, with loss of parietal cells and intrinsic factor.
Elsewhere in DurgiPedia
- One-carbon metabolism (folate, B12 and SAM)
- Cobalamin (vitamin B12)
- Folate (vitamin B9)
- Absorption of iron, calcium and vitamin B12
- Thymidylate synthase
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Pernicious anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Vitamin B12 deficiency anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Folate-deficiency anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.