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 login to view 1 more bullet Pathophysiology absorption protein-bound vitamin B12 is released from protein by pepsin login to view 1 more bullet R-binder binds to vitamin B12 to prevent its degradation by gastric acid login to view 1 more bullet proteases in the duodenum separate R-binder and vitamin B12, allowing vitamin B12 to bind to intrinsic factor login to view 4 more bullets 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 login to view 4 more bullets myelin stabilization methionine is converted to S-adenosylmethionine login to view 1 more bullet vitamin B12 serves as a coenzyme for methylmalonyl-CoA mutase to convert methylmalonyl-CoA (produced from methylmalonic acid) to succinyl-CoA login to view 1 more bullet vitamin B12 deficiency impaired DNA synthesis significantly affects rapidly dividing cells (e.g., hematopoietic precursor cells) and leads to login to view 5 more bullets impair neuronal function login to view 1 more bullet Presentation Symptoms anemia fatigue dyspnea gastrointestinal glossitis neurologic cognitive decline Physical examination subacute combined degeneration lateral corticospinal tracts login to view 3 more bullets dorsal columns login to view 2 more bullets spinocerebellar tracts login to view 4 more bullets 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 login to view 1 more bullet Complications Irreversible neurological damage if untreated Prognosis Atrophic gastritis increases risk of gastric cancer