• A 72-year-old man of European ancestry presents for a routine check-up with increased fatigue, a smooth shiney tongue and yellowing of his skin.  The man is a strict vegan and refuses to eat anything that casts a shadow.  On physical exam you note markedly decreased vibration sensation and proprioception.  A peripheral smear is ordered demonstrating large RBC's as well neutrophils with nuclei that have 7 lobes.

  • A megaloblastic anemia resulting from decreased DNA synthesis with normal RNA/protein synthesis
  • Pernicious anemia is the most common cause of vitamin B12 deficiency
    • antibody to gastric parietal cell leads to ineffective secretion of intrinsic factor (IF) 
    • leads to vitamin B12 deficiency due to decreased uptake in terminal ileum
    • accompanied by achlorhydia and atrophic gastritis
      • atrophic gastritis increases risk of gastric cancer
      • must monitor periodically with fecal occult blood testing
    • found mainly in mature persons of Northern European or African descent
    • neuro findings caused by demyelination
  • Other causes include
    • malabsorption secondary to total or partial gastric resection 
      • loss of IF producing cells
    • resection of terminal ileum
    • drugs
      • azathioprine
      • zidovudine
    • intestinal infections
      • Diphyllobothrium latum
  • Symptoms of megaloblastic anemia WITH neurological symptoms
    • neurological findings
      • numbness and parasthesias of the extremities (worse in legs)
      • hyporeflexias
      • decreased vibratory sensation
      • ataxia
      • demetia
    • gastrointestinal findings
      • glossitis
  • Best initial test: CBC and peripheral smear
  • Most accurate test: B12 levels
    • Serum B12 levels can be misleading at times
  • Confirmatory tests
    •  serum methylmalonic acid
    • ↑ homocysteine levels
    • anti-intrinsic factor and parietal antibodies
    • Schilling's test not relevant clinically (but on Step exams)
  • Peripheral blood and marrow smear show
    • hypersegmented neutrophils and megalocytes
      • B12 and folate needed in DNA synthesis
      • defect results in large immature nuclei in all nucleated cells
    • pancytopenia
      • most of these abnormal cells are destroyed
  • Get TSH to rule out hypothyroidism
  • Macrocytic anemia
    • alcoholism
    • folate deficiency
    • vitamin B12 deficiency
    • hypothyroidism
    • liver dysfunction
    • drugs (methotrexate, phenytoin, trimethoprim, and zidovudine)
  • Treat with
    • monthly vitamin B12 injections
      • high dose oral treatment proven to be equivalent in patients that can absorb B12

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