A 38-year-old woman presents with diarrhoea, weight loss, and megaloblastic anaemia. Endoscopy shows gastric mucosal atrophy with loss of rugae in the body and fundus. Antibodies to intrinsic factor and parietal cells are positive. Serum vitamin B12 is 80 pg/mL. Which is the PRIMARY mechanism of B12 deficiency in this condition?
- A Impaired ileal B12 absorption due to Crohn's disease
- B Anti-intrinsic factor antibodies preventing B12-IF complex formation/absorption ✓
- C Achlorhydria causing failure to release protein-bound B12 from food
- D Bacterial overgrowth competing for dietary B12 in the duodenum
Explanation
Pernicious anaemia is caused by autoimmune gastritis type A affecting the fundus/body, where parietal cells produce both intrinsic factor (IF) and HCl. The primary mechanism of B12 deficiency in pernicious anaemia is the presence of blocking anti-IF antibodies that prevent B12 from binding to IF, thereby preventing the B12-IF complex from binding to ileal cubam receptors. Anti-parietal cell antibodies cause parietal cell destruction and loss of IF production. Achlorhydria contributes by impairing food-bound B12 release but this alone does not cause severe deficiency; loss of IF is the key defect.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.