Makindo Medical Notes

🔑 Neurological signs of B12 deficiency can occur even without anaemia. ⚠️ There is a 1–2% increased risk of thyroid disease or gastric cancer. 🧪 Pernicious anaemia is best confirmed with an anti-intrinsic factor antibody test. Anti-parietal cell antibody is less reliable.

📖 About

• Autoimmune cause of vitamin B12 deficiency → haematological + neurological features.
• Associated with other autoimmune diseases and ↑ risk of gastric carcinoma.

🧬 Aetiology

• Autoimmune destruction of gastric parietal cells → loss of intrinsic factor & HCl.
• Loss of IF → impaired B12 absorption in terminal ileum.
• Occasionally, steroids can reverse the autoimmune gastritis.

⚙️ Physiology

• Normal diet: ~20 μg/day B12 (requirement 1–2 μg/day).
• B12 binds intrinsic factor in stomach → absorbed in terminal ileum.
• Transported via transcobalamin II in portal blood.
• Liver stores last 2–4 years.
• Essential for homocysteine → methionine conversion (DNA synthesis + myelin integrity).

👩‍⚕️ Clinical Features

• Mean age ≈ 60 yrs; more common in fair-skinned, blue-eyed individuals.
• May have pallor, mild splenomegaly.
• Autoimmune associations: vitiligo, Addison’s, thyroid disease.
• Glossitis = “beefy red painful tongue.”

🧠 Neurological Signs

• Optic atrophy, retinal haemorrhages 👁️
• Cognitive decline / dementia 🧑‍🦳
• Peripheral neuropathy → paraesthesia, sensory loss, absent ankle jerks.
• Dorsal column dysfunction → loss of vibration + proprioception.
• Corticospinal tract → brisk reflexes, extensor plantars.
• Untreated → irreversible spinal cord lesions (subacute combined degeneration).

🔎 Investigations

• FBC: Macrocytic anaemia (MCV >110 fL), anisopoikilocytosis, hypersegmented neutrophils, ↓ WCC/platelets.
• Serum B12: Low (normal 160–960 ng/L).
• Folate: Often low; check ferritin too.
• IF antibodies: Highly specific, ~50% sensitive.
• Anti-parietal cell antibodies: supportive but non-specific.
• ↑ Methylmalonic acid & homocysteine = functional deficiency markers.
• Endoscopy: atrophic gastritis, achlorhydria.
• Bone marrow (rarely): megaloblastic erythropoiesis.

🩺 Differentials

• Post-gastrectomy (loss of IF).
• Atrophic gastritis (non-autoimmune).
• Terminal ileal disease (Crohn’s, resection).
• Poor diet (strict veganism).

💊 Management

• Avoid transfusion unless life-threatening (risk of overload).
• B12 replacement: Hydroxocobalamin 1 mg IM twice weekly × 3 weeks → then lifelong 1 mg IM every 3 months.
• Folate 5 mg OD if co-deficient (never give folate alone → can worsen neuro signs).
• Expect:
  • Reticulocytosis day 4–7 📈
  • Temporary fall in Hb before recovery
  • Hypokalaemia risk from rapid erythropoiesis
• Monitor for associated autoimmune disorders & gastric carcinoma risk.

📚 OSCE/Exam Pearls – Always ask about neurological symptoms in macrocytic anaemia. – “Glossitis + peripheral neuropathy + macrocytosis” → think Pernicious Anaemia. – Never give folate alone if B12 deficiency is suspected. – Screen for thyroid & adrenal disease in long-term follow-up.