Vitamin B12 deficiency historical perspective

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Common Causes

Decrease intake 

• Strict vegan diet more than 3 years .
• Breast fed infants of pure vegan may also develop deficiency .
• Malnutrition most likely happen in elderly patients.

Malabsorption

• 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

Increased requirement

• pregnancy

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.

Laboratory Finding

• 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 .