A 72-year-old Indian man with a history of subtotal gastrectomy 8 years ago for peptic ulcer disease presents with progressive weakness and cognitive decline over 6 months. His wife reports he has become forgetful and unsteady while walking. On examination, he has glossitis, loss of vibration sense in both lower limbs, and a positive Lhermitte sign. Laboratory investigations show hemoglobin 6.8 g/dL, MCV 132 fL, WBC 2.8 × 10⁹/L, and platelet count 95 × 10⁹/L. Peripheral blood smear shows hypersegmented neutrophils, macro-ovalocytes, and occasional nucleated RBCs. Serum B12 is 65 pg/mL and serum folate is 8.2 ng/mL (normal: >5.4). What is the primary mechanism of anemia in this patient?

Explanation

## Mechanism: Post-Gastrectomy Vitamin B12 Deficiency ### Clinical Context **Key Point:** Subtotal gastrectomy removes the fundus and body of the stomach, where **parietal cells secrete intrinsic factor (IF)**. Without IF, dietary B12 cannot be absorbed in the terminal ileum, leading to B12 deficiency 5–10 years post-operatively. ### Pathophysiology of B12 Absorption ```mermaid flowchart TD A["Dietary B12 (cobalamin)"]:::outcome --> B["Stomach: Parietal cells secrete Intrinsic Factor"]:::action B --> C["B12-IF complex formed"]:::outcome C --> D["Terminal ileum: Receptor-mediated absorption"]:::action D --> E["B12 enters portal circulation"]:::outcome E --> F["Transcobalamin II transport to tissues"]:::action F --> G["Mitochondrial & cytoplasmic metabolism"]:::outcome H["Gastrectomy"]:::urgent -.->|"Removes parietal cells"| B H -.->|"Loss of IF production"| C ``` **Clinical Pearl:** Gastrectomy causes B12 deficiency through **loss of intrinsic factor**, NOT dietary insufficiency. Patients can eat normally but cannot absorb B12. ### Laboratory Interpretation | Parameter | Finding | Interpretation | |-----------|---------|----------------| | Hemoglobin | 6.8 g/dL | Severe anemia | | MCV | 132 fL | Macrocytic (>100 fL) | | WBC | 2.8 × 10⁹/L | Mild leukopenia (megaloblastosis affects all cell lines) | | Platelets | 95 × 10⁹/L | Mild thrombocytopenia | | Hypersegmented neutrophils | Present | Nuclear maturation lag | | Macro-ovalocytes | Present | Cytoplasmic-nuclear asynchrony | | Nucleated RBCs | Present | Severe ineffective erythropoiesis | | Serum B12 | 65 pg/mL | **Severely deficient** (<200 pg/mL) | | Serum folate | 8.2 ng/mL | **Normal** (>5.4 ng/mL) | **High-Yield:** The **normal serum folate** rules out primary folate deficiency. The **low B12** with history of gastrectomy is diagnostic. ### Neurological Manifestations: Subacute Combined Degeneration 1. **Dorsal column involvement** → loss of vibration and proprioception (positive Lhermitte sign) 2. **Lateral corticospinal tract demyelination** → weakness, ataxia, hyperreflexia 3. **Cerebral white matter changes** → cognitive decline, memory loss, dementia **Mnemonic: SCD (Subacute Combined Degeneration) — "3 D's":** - **D**orsal columns (vibration, proprioception loss) - **D**escending corticospinal tracts (weakness, spasticity) - **D**ementia (cognitive decline, personality changes) ### Why Post-Gastrectomy B12 Deficiency? **Mechanism:** 1. Subtotal gastrectomy removes fundus/body → **loss of parietal cells** 2. Parietal cells produce **intrinsic factor (IF)** and gastric acid 3. Without IF, dietary B12 cannot bind and be absorbed in terminal ileum 4. B12 stores (liver: 2–5 years) deplete over 5–10 years 5. Megaloblastic anemia and neurologic disease emerge **Timing:** B12 deficiency typically manifests 5–10 years post-gastrectomy (after hepatic B12 stores are exhausted).