RBC Metabolism Notes (Part 5) : Role of Vitamin B12 and Pernicious anemia

COBALAMIN (Vitamin B₁₂)

• Vitamin B₁₂ is required in humans for two essential enzymatic reactions: the synthesis of methionine and the isomerization of methylmalonyl CoA that arises from the fatty acids with odd numbers of carbon atoms (Fig 28.10).

• When the vitamin is deficient, abnormal fatty acids accumulate and become incorporated into cell membranes, including those of the nervous system. 
  
  
  
• This may account for some of the neurological manifestation of vitamin B₁₂ deficiency.
  
  Clinical Indications for Vitamin B12
  
  
  
• In contrast to other water-soluble vitamins, significant amounts (4 to 5 mg) of vitamin B₁₂ are stored in the body.
  
• As a result, it may take several years for the clinical symptoms of vitamin B₁₂ deficiency to develop in individuals who have had a partial or total gastrectomy (who therefore become intrinsic factor-deficient) and can no longer absorb the vitamin.
  

Pernicious Anemia

• Vitamin B₁₂ deficiency is rarely due to an absence of the vitamin in the diet. 
   
• It is much more common to find deficiencies in patients who fail to absorb the vitamin from the intestine, resulting in pernicious anemia. 
   
• The disease is most commonly due to an autoimmune destruction of the gastric parietal cells that are responsible for the synthesis of a glycoprotein called intrinsic factor. 
   
• Normally, vitamin B₁₂ is obtained from the diet binds to the intrinsic factor in the intestine. 
   
• The cobalamin-intrinsic factor complex travels through the gut and eventually binds to specific receptors on the surface of mucosal cells of the ileum. 
   
• The bound cobalamin is transported into the mucosal cell and subsequently into the general circulation, where it is carried by B₁₂-binding proteins (Fig 28.12). 
   
• Lack of intrinsic factor prevents the absorption of vitamin B₁₂, resulting in pernicious anemia. 
   
• Patients with cobalamin deficiency are usually anemic but later in the development of the disease show neuropsychiatric symptoms. 
   
• However, CNS symptoms may occur in the absence of anemia. 
   
• The CNS effects are irreversible and occur by mechanisms that appear to be different from those described for megaloblastic anemia. 
   
• The disease is treated by intramuscular injection of cyanocobalamin. 
   
• Therapy must be continued throughout the lives of patients suffering from pernicious anemia.
   
• [Note: Folic acid administration alone reverses the hematologic abnormality and thus masks the B₁₂ deficiency that can then proceed to severe neurologic dysfunction and pathology; therefore, megaloblastic anemia should not be treated with folic acid alone, but rather with a combination of folate and vitamin B₁₂.]

(Source:  Wintrobe's Textbook of Hematology; Tietz's Textbook of Clinical Chemistry)