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Updated: Dec 16 2021

B12 Deficiency

Images
https://upload.medbullets.com/topic/120229/images/differential for anemia - moises d.jpg
https://upload.medbullets.com/topic/120229/images/hypersegmented_neutrophil_-_by_gabriel_caponetti,md.jpg
  • Snapshot
    • A 52-year-old man presents to his physician for a routine check-up. He reports increasing fatigue and has a smooth, sore tongue. He is a strict vegan and has had bariatric surgery 3 years ago. Physical examination is notable for decreased vibration sensation and proprioception. Laboratory studies demonstrate a macrocytic anemia with reticulocytopenia. Peripheral blood smear demonstrates hypersegmented neutrophils.
  • Introduction
    • Overview
      • vitamin B12 (cobalamin) is a water-soluble vitamin that is involved in the formation of hematopoietic cells and maintainance of myelin integrity
      • vitamin B12 deficiency results in a
        • megaloblastic anemia
        • reversible dementia
        • subacute combined degeneration
  • Etiology
    • Decreased oral intake
      • strict vegan diet
      • breastfeeding in a vitamin B12 deficiency mother
      • decreased animal product intake
    • Decreased absorption
      • gastrointestinal surgeries
        • bariatric surgery
        • grastrectomy
      • illness
        • Crohn disease
        • celiac disease
        • pancreatic insufficiency
        • Diphyllobothrium latum (fish tapeworm)
        • gastric atrophy
      • medications
        • proton pump inhibitors
        • histamine receptor antagonist
        • metformin
      • autoimmune disease
        • pernicious anemia
          • autoantibodies against intrinsic factor or gastric parietal cells
    • Pathophysiology
      • absorption
        • protein-bound vitamin B12 is released from protein by pepsin
          • gastric acid converts pepsinogen to pepsin
        • R-binder binds to vitamin B12 to prevent its degradation by gastric acid
          • R-binder is produced in the salivary glands
        • proteases in the duodenum separate R-binder and vitamin B12, allowing vitamin B12 to bind to intrinsic factor
          • intrinsic factor is produced by gastric parietal cells
            • roux-en-Y gastric bypass creates a small gastric pouch, which contains very few parietal cells
              • reduces acid and intrinsic factor secretion, which impair absorption
          • proteases in the duodenum are produced by the pancreas
        • intrinsic factor bound to vitamin B12 is absorbed in the terminal ileum
      • DNA synthesis
        • vitamin B12 serves as a coenzyme for methionine synthase to produce
          • methionine
            • serves a vital role in methylation reactions
          • tetrahydrofolate
            • serves a vital role in DNA synthesis
      • myelin stabilization
        • methionine is converted to S-adenosylmethionine
          • associated with myelin stabilization
        • vitamin B12 serves as a coenzyme for methylmalonyl-CoA mutase to convert methylmalonyl-CoA (produced from methylmalonic acid) to succinyl-CoA
          • decreased methylmalonic acid is associated with myelin stabilization
      • vitamin B12 deficiency
        • impaired DNA synthesis significantly affects rapidly dividing cells (e.g., hematopoietic precursor cells) and leads to
          • megaloblastic changes, which is cased by slowing of nuclear division
            • due to nuclear-cytoplasmic dyssynchrony
          • ineffective erythropoiesis (intramedullary hemolysis)
            • erythropoietic precursor cells within the bone marrow prematurely die
              • results in a reticulocytopenia
        • impair neuronal function
          • mechanism is not fully clear but hypothesized to be due to decreased methylation of neuronal lipids and proteins (e.g., myelin basic protein)
  • Presentation
    • Symptoms
      • anemia
        • fatigue
        • dyspnea
      • gastrointestinal
        • glossitis
      • neurologic
        • cognitive decline
    • Physical examination
      • subacute combined degeneration
        • lateral corticospinal tracts
          • weakness
          • spasticity
          • hyperreflexia
        • dorsal columns
          • decreased vibration and proprioception sensation
          • gait difficulties
        • spinocerebellar tracts
          • gait difficulties
          • ataxia
          • decreased proprioception sensation
            • impaired proprioception information from the spinal cord to the cerebellum
  • Labs
    • Serum labs
      • macrocytic and megaloblastic anemia
      • decreased serum B12 level
      • reticulocytopenia
      • ↑ serum methylmalonic acid and homocysteine levels
      • anti-intrinsic factor and parietal antibodies
        • seen in pernicious anemia
    • Peripheral blood and marrow smear show
      • hypersegmented neutrophils and megalocytes
  • Differential
    • Folate anemia
      • differentiating factors
        • no neurological manifestations
        • methylmalonic acid levels are not elevated
  • Treatment
    • Medical
      • intramuscular vitamin B12
        • indication
          • first-line for vitamin B12 deficiency
  • Complications
    • Irreversible neurological damage if untreated
  • Prognosis
    • Atrophic gastritis increases risk of gastric cancer
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