Megaloblastic anaemia
Why does deficiency of vitamin B12 or folate lead to megaloblastic anaemia?
Key characteristics of these essential vitamins are summarised in Table 13.1.
Table 13.1
| Characteristic | Vitamin B12 | Folate |
| Average dietary intake/day (µg) | 20 | 2501 |
| Minimum adequate intake/day (µg) | 1–2 | 1501 |
| Major food sources | Animal produce only | Liver, vegetables |
| Normal body stores | Sufficient for several years | Sufficient for a few months |
| Mode of absorption | Combined with transport protein (IF) secreted by gastric parietal cells – then absorbed through ileum via special receptors | Dietary folate converted to methyl THF and absorbed in duodenum and jejunum |
Both folate and vitamin B12 are necessary for the synthesis of DNA (Fig 13.1). Folate is needed in its tetrahydrofolate form (FH4) as a cofactor in DNA synthesis. Deficiency of B12 leads to impaired conversion of homocysteine to methionine causing folate to be ‘trapped’ in the methyl form. The resultant deficiency in methylene FH4 deprives the cell of the coenzyme necessary for DNA formation.
Fig 13.1 The cause of megaloblastic anaemia.
Both vitamin B12 and folate (FH4) are necessary for normal synthesis of DNA (see text).
All dividing cells in the body suffer from the impaired DNA synthesis of B12 and folate deficiency. However, the actively proliferating cells of the bone marrow are particularly affected. As RNA synthesis progresses unhindered in the cytoplasm, the erythroid cells develop nuclear–cytoplasmic imbalance with abundant basophilic cytoplasm and enlarged nuclei. The chromatin pattern in the nucleus is characteristically abnormal; one author has described it as resembling ‘fine scroll work’, another as ‘sliced salami’ (Fig 13.2). The slowed synthesis of DNA leads to prolonged cell cycling and the cells being discharged into the blood without the normal quota of divisions. Red cells are enlarged and egg-shaped and the neutrophils hypersegmented due to retention of surplus nuclear material (Fig 13.3).
