Vitamin B12 deficiency historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Vitamin B 12 deficiency may be caused by:

Decrease intrinsic factor due autoimmune destruction of parietal cell
Decrease Gastric acid production due to proton pump inhibitor and histamine 2 receptor antagonists
Gastric by pass surgery because intrinsic factor is produce by parietal cell of stomach
Tapeworm (Diphyllobothrium latum ) ingested from contaminated fish , tapeworm saps nutrients
Crohn's disease

Pathophysiology

Dietary Vitamin B12 binds to salivary R factor then the complex arrives at small intestine
In duodenum Vitamin B12 is detach from R- factor by pancreatic proteases
Now free B12 binds to intrinsic factor which is secreted by gastric parietal cell
The intrinsic factor - B12 complex is absorbed in the ileum
Absorbed vitamin B12 is use in metabolic pathways which is important for neurologic and hematologic function if vitamin B12 is deficit regardless of the cause many impairments may occur
Vitamin B12 is a cofactor for the enzyme methionine synthase which convert homocysteine to methionine as a result methyl- THF is converted to THF which is use in synthesis of pyrimidine base of DNA.
In B 12 deficiency homocystein accumulate which cause megaloblastic anemia and hypersegmented neutrophils.
Vitamin B 12 is a cofactor for enzyme methylmalonyl-COA mutase , which converts methylmalonic-COA to succinyl-COA. In B 12 deficiency methylmalonic acid (MMA ) will accumulate. MMA and elevated level of homocysteine cause damage of myelin as a result subacute combined degeneration of spinal cord ( SCDSC ) occur . This affects dorsal columns, lateral corticospinal tracts and spinocerebellar tract as result loss of proprioception , ataxia , peripheral neuropathy and dementia.

Initial lab tests is a complete blood count (CBC) with a peripheral smear and serum B12 and folate levels.
In some cases needed to check methylmalonic acid (MMA ) and serum homocysteine levels.
With above elevated finding macrocytic anemia and peripheral blood smear show hypersegmented neutrophils .