A 58-year-old Indian woman presents with progressive fatigue and paresthesias in her feet for 6 months. On examination, the structure marked **A** in the diagram is noted — a beefy-red, smooth, atrophic appearance with loss of normal papillae. Laboratory investigations reveal hemoglobin 8.5 g/dL, MCV 128 fL, and serum B12 level of 150 pg/mL. Peripheral blood smear shows hypersegmented neutrophils. Which of the following is the most likely underlying mechanism responsible for the glossitis seen in this patient?

Explanation

## Why Option 1 is right Pernicious anemia, the most common cause of B12 deficiency in adults, results from autoimmune destruction of gastric parietal cells, which produce intrinsic factor (IF). Without IF, dietary B12 cannot be bound and absorbed in the terminal ileum, leading to megaloblastic anemia and the characteristic glossitis (Hunter glossitis) — a beefy-red, smooth, atrophic tongue with loss of papillae due to epithelial atrophy from B12 deficiency. The clinical presentation (age, female, hypersegmented neutrophils, macrocytic anemia, neurologic symptoms) and low B12 level all point to pernicious anemia. This patient would have anti-parietal cell and/or anti-intrinsic factor antibodies confirming the diagnosis. ## Why each distractor is wrong - **Option 2**: While dietary B12 deficiency (vegetarian/vegan diet) can cause glossitis and megaloblastic anemia, it is less common in Indian adults than pernicious anemia and typically develops over many years given hepatic B12 stores of 3–5 years. The acute presentation and laboratory findings are more consistent with autoimmune pernicious anemia. - **Option 3**: Metformin-induced B12 deficiency occurs in ~30% of long-term users but is typically mild and develops insidiously. It does not cause the degree of B12 depletion (150 pg/mL) or the severity of glossitis and neurologic symptoms seen in this case; it is a secondary consideration, not the primary mechanism. - **Option 4**: Atrophic gastritis with hypochlorhydria impairs B12 release from food proteins but does not prevent IF-mediated absorption as severely as parietal cell destruction. This mechanism is less common than pernicious anemia and would not explain the presence of anti-parietal cell antibodies if tested. **High-Yield:** Pernicious anemia (autoimmune parietal cell destruction) is the most common cause of B12 deficiency in adults; glossitis is a cardinal GI sign; neurologic symptoms (subacute combined degeneration) can occur without anemia and require urgent B12 replacement to prevent irreversible damage. [cite: Harrison 21e Ch 95]