Gastrointestinal · Year 2 · from Gastrointestinal
Case 2: Pernicious Anemia (Vitamin B12 Malabsorption)
Patient Presentation
Demographics: 65-year-old female
Chief Complaint: Progressive fatigue, weakness, and numbness in feet for 6 months
History of Present Illness: The patient reports gradually worsening fatigue, shortness of breath on exertion, and generalized weakness. She has noticed tingling and numbness in both feet that has progressed to her ankles. She feels unsteady when walking, especially in the dark. Her tongue occasionally feels sore. She has had mild memory difficulties recently.
Past Medical History: Hashimoto's thyroiditis on levothyroxine, vitiligo
Family History: Mother had thyroid disease and "blood problems"
Physical Examination
- Vital Signs: BP 118/72 mmHg, HR 98 bpm
- General: Pale female appearing older than stated age
- HEENT: Smooth, beefy-red tongue (glossitis); pale conjunctivae
- Neurologic: Decreased vibration and position sense in lower extremities; positive Romberg sign; hyperactive reflexes in knees with absent ankle reflexes
- Skin: Scattered vitiligo patches
Workup and Results
- CBC: Hemoglobin 8.2 g/dL, MCV 118 fL (macrocytic), WBC 3.8 (low), platelets 130
- Peripheral Smear: Macro-ovalocytes, hypersegmented neutrophils (>5 lobes)
- Vitamin B12: 95 pg/mL (severely low, normal >200)
- Methylmalonic Acid: Elevated (confirms B12 deficiency)
- Anti-Intrinsic Factor Antibodies: Positive
- Anti-Parietal Cell Antibodies: Positive
- Gastrin Level: Elevated (hypergastrinemia from achlorhydria)
Peripheral blood smear showing macro-ovalocytes and a hypersegmented neutrophil (>5 nuclear lobes), characteristic findings of megaloblastic anemia due to vitamin B12 deficiency.
Image Source: Wikimedia Commons, CC BY-SA 3.0
Diagnosis
Pernicious Anemia with Subacute Combined Degeneration of the Spinal Cord
Clinical Correlation to Vitamin B12 Absorption Physiology
Vitamin B12 absorption requires a complex pathway. Dietary B12 is released from food proteins by gastric acid and pepsin, then binds R-proteins in the stomach. In the duodenum, pancreatic proteases digest R-proteins, and B12 transfers to intrinsic factor (IF), secreted by gastric parietal cells. The IF-B12 complex travels to the terminal ileum, where specific receptors (cubilin) internalize it. In pernicious anemia, autoimmune destruction of parietal cells eliminates both acid secretion (needed to release B12 from food) and intrinsic factor (essential for ileal absorption). The resulting deficiency affects rapidly dividing cells (causing megaloblastic anemia) and causes demyelination in the spinal cord (subacute combined degeneration affecting posterior and lateral columns).
Treatment
- Intramuscular vitamin B12 injections (1000 mcg daily for 1 week, then weekly for 1 month, then monthly for life)
- Alternative: high-dose oral B12 (1-2 mg daily) - some absorption occurs passively without IF
- Monitor for hypokalemia during treatment (rapid cell production consumes potassium)
- Neurologic deficits may be partially reversible with early treatment
- Surveillance for gastric carcinoid tumors and gastric cancer (increased risk in autoimmune gastritis)