A patient undergoes total gastrectomy for gastric cancer. Three months later, she develops macrocytic anemia and peripheral neuropathy. Which of the following BEST explains the sequence of physiological events leading to this deficiency?

• A Loss of gastric acid impairs iron absorption, causing iron-deficiency anemia with peripheral neuropathy from pyridoxine depletion
• B Loss of gastric parietal cells eliminates intrinsic factor (IF) secretion; without IF, dietary cobalamin (B12) cannot be absorbed in the terminal ileum by the IF-cubilin receptor complex → B12 deficiency → megaloblastic anemia and subacute combined degeneration ✓
• C Without gastric pepsin, protein digestion is impaired; amino acid absorption failure reduces folate-binding protein synthesis → folate deficiency anemia
• D Loss of gastrin eliminates the trophic effect on duodenal enterocytes, reducing B12-transport proteins secreted by the small intestine

Explanation

Intrinsic factor (IF) is a 60 kDa glycoprotein secreted exclusively by gastric parietal cells. IF binds cobalamin (vitamin B12) in the duodenum, forming an IF-B12 complex that is recognized by cubilin receptors on terminal ileal enterocytes, enabling transcytotic absorption. Total gastrectomy abolishes IF production entirely. Since hepatic B12 stores last 3–5 years, neurological and hematological manifestations appear months to years post-surgery. B12 deficiency impairs DNA synthesis (megaloblastic anemia) and disrupts myelin synthesis through impaired methylmalonyl-CoA conversion, causing subacute combined degeneration of the spinal cord (dorsal and lateral columns). Monthly parenteral B12 is required lifelong after total gastrectomy. Options B, C, and D describe mechanisms that do not specifically cause B12-deficiency anemia with neuropathy.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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