Describe vitamin B12 and folic acid with their deficiency states and treatment.

Vitamin B12 — Physiology

Dietary B12 comes almost entirely from animal sources → Released from food protein by gastric acid and pepsin → Bound first to haptocorrin, then transferred to intrinsic factor from gastric parietal cells → The B12–intrinsic factor complex is absorbed in the terminal ileum by the cubilin receptor → Transported in blood on transcobalamin II → Stored in the liver — enough for 3 to 5 years → Required for methionine synthase (methylation and DNA synthesis) and methylmalonyl-CoA mutase (myelin)

Causes of Deficiency

Clinical Features and Treatment

• Haematological — megaloblastic anaemia with macrocytosis, hypersegmented neutrophils, and in severe cases pancytopenia with a hypercellular marrow (ineffective erythropoiesis)
• Neurological — subacute combined degeneration of the posterior and lateral columns, giving paraesthesiae, loss of vibration and joint position sense, ataxia and spasticity; also peripheral neuropathy, optic atrophy, dementia and psychiatric change. Neurological disease may occur without anaemia, which is why a normal haemoglobin does not exclude the diagnosis
• Other — glossitis, angular stomatitis, mild jaundice from ineffective erythropoiesis, and infertility
• Treatment — hydroxocobalamin intramuscularly, loading doses then maintenance every 2 to 3 months; lifelong in pernicious anaemia and after gastrectomy or ileal resection. High-dose oral B12 (1 to 2 mg daily) also works, through passive diffusion independent of intrinsic factor, and is a reasonable alternative for many patients
• Give potassium and iron cover during the initial response, since rapid erythropoiesis can precipitate hypokalaemia and reveal iron deficiency

Folic Acid

• Sources — green leafy vegetables, liver, legumes; destroyed by prolonged cooking. Stores last only 3 to 4 months, so deficiency develops quickly
• Causes of deficiency — poor diet, alcoholism, malabsorption, increased demand (pregnancy, chronic haemolysis, exfoliative skin disease, malignancy), dialysis, and drugs (methotrexate, trimethoprim, phenytoin, sulphasalazine)
• Periconceptional folic acid prevents neural tube defects — 400 micrograms daily for all women planning pregnancy, and 5 mg where the risk is high (previous affected child, antiepileptics, diabetes, obesity). It must be started before conception, since the neural tube closes by day 28, often before pregnancy is recognised
• Folinic acid (leucovorin) is not the same as folic acid — it is already reduced, so it bypasses dihydrofolate reductase and works when that enzyme is blocked; it is the rescue agent after high-dose methotrexate and the antidote in methotrexate toxicity

Applied Aspects

• Never give folic acid alone for an undiagnosed macrocytic anaemia — measure B12 first, or replace B12 alongside; folate alone corrects the blood count while the cord degenerates irreversibly
• Check B12 in long-term metformin users, particularly those with neuropathy, which is otherwise attributed to diabetes and left untreated
• Vegetarian and vegan diets are widespread in India, and B12 deficiency is correspondingly common and frequently unrecognised; supplementation or fortified foods should be advised
• Neurological recovery is incomplete if treatment is delayed, so B12 is started on suspicion after taking the sample, not after the result returns
• Nitrous oxide inactivates B12 and can precipitate acute neurological deterioration in a deficient patient, and is misused recreationally
• Pernicious anaemia carries an increased risk of gastric carcinoma and is associated with other autoimmune disease, particularly thyroid disease, which should be screened for