Vitamin-B12 deficiency Anemia: Overview, Pathogenesis, Causes, Symptoms, Diagnosis, and Treatment

What is Vitamin-B12 Deficiency Anemia?

     Vit-B12 deficiency anemia is a type of megaloblastic anemia, in which, there is a decrease in blood and tissue level Vitamin-B12. Vit-B12 is a complex organometallic compound called Cobalamin. As Vitamin-b12 is very important for RBCs synthesis, that's why deficiency of that vitamin leads to a defect in RBCs, causing anemia of Vit-B12 deficiency.

     The major sources of Vit-B12 are liver, fish, and dairy products. The normal recommended dietary allowance (RDA) of Vit-b12 is 7-30 micrograms/day. But, the daily requirement is just 1-2 micrograms. The human body stores about 2-3 mg of Vit-b12, which will be sufficient for 5-20 years.

Metabolism of Vit-b12

     The saliva contains a protein named Haptocorrin, that moves along with the dietary Vit-b12 towards the stomach, where both bind with each other. Then the complex move towards the duodenum, where both separates due to action of protease enzymes of pancreatic juices.

     The parietal cells of the stomach secrete an intrinsic factor, that reaches the duodenum, and binds with Vit-B12. The IF-Vitamin complex then moves towards the ileum, the receptors of intrinsic factor are present at the mucosal cells of the distal ileum, that receptor is a protein, named Cubulin. As the intrinsic factor-vitamin B12 complex binds, the complex then enters the mucosal cells, where both splits and Vit-b12 transfers to blood by crossing the Basolateral membrane, where it combines with transcobalamin-II and moves towards the liver and other cells of the body.

Biochemical functions of Vit-B12

     Vit-b12 is involved in only two reactions that occur in the body, First is the conversion of homocysteine to methionine, this reaction needs methylcobalamin and methionine synthase. The second reaction is the conversion of methylmalonyl Coenzyme-A to Succinyl Coenzyme-A, which needs Adenosylcobalamin.

     If the Vit-b12 deficiency occurs, it leads to the elevation of methylmalonyl CoA, causes abnormal formation and incorporation of fatty acids into neuronal lipids. This biochemical abnormality predisposes to myelin breakdown and thereby produces neurologic complications of Vit-B12 deficiency.

Pathogenesis of Vit-b12 deficiency anemia

     The pernicious anemia is due to the autoimmune attack on the gastric mucosa, in which antibodies are formed against the cells of the gastric mucosa. The antibodies lead to the atrophy of mucosal parietal cells.

     The antibodies may be Parietal cell antibodies or Intrinsic factor antibodies. The parietal cell antibodies are of two types: Type-1 and Type-2.

• Type-1 antibodies: These antibodies lead to the breakdown of the Vit-b12/intrinsic factor complex. 
• Type-2 antibodies: This type of antibody inhibits the binding of the Vit-b12/intrinsic factor complex with the Ileum. 
• Intrinsic factor antibodies: These antibodies inhibit the secretion of intrinsic factors.

     All of these antibodies are produced by B-cells, but the autoreactive T-cells first produce those B-cells. These antibodies are diagnostically important to detect Vitamin-B12 deficiency Anemia.

     Vitamin B12 deficiency may be due to reasons other than pernicious anemia. As with achlorhydria and pepsin secretion loss, Vit-b12 can not be released readily from the sources. If gastrectomy is done, also due to this, the intrinsic factor will not be available for absorption in the ileum. 

     If the exocrine pancreatic functions are lost, then the Vit-b12 will not be released readily from the complex of R-binder/Vitamin-b12. The removal or damage of intrinsic factor sites may occur due to ileal resection or diffuse ileal disease. An increase in demand for Vit-b12 in pregnancy, malignancy, hyperthyroidism can produce a relative deficiency, even if normal absorption is done.

Causes of Vitamin-B12 deficiency

     Following are the causes of Vitamin-B12 deficiency:

1. Decreased Intake: This will be caused if there is inadequate diet, or the individual is vegetarian. This is also called Nutritional deficiency, and it rarely occurs because Vit-b12 stores present in the body can complete the requirement for almost 5-20 years.
2. Impaired Absorption: This will occur due to intrinsic factor defect either due to pernicious anemia or gastrectomy. The diseases like diffuse intestinal disease(examples may be lymphoma, systemic sclerosis), Ileal resection, Ileitis, fish tapeworm infestation.

These all lead to the deficiency of Vit-b12, which then causes a defect in RBC production, leads to Anemia.

Symptoms of Vit-b12 deficiency

     Following are the signs and symptoms of Vit-b12 deficiency:

1. Anemia
2. Chronic fatigue
3. Depression
4. Shortness of breath
5. Neurologic symptoms include memory loss and mood swings
6. Constipation
7. Difficulty in walking
8. Cardiovascular problems

Diagnosis of Vitamin-B12 deficiency

     The diagnosis of Vit-B12 deficiency is done by the following factors:

• Blood CP is done that shows decreased level of Hemoglobin and decreased or normal levels of WBCs and Platelets.
• Moderate to severe megaloblastic anemia
• Leukopenia with hypersegmented granulocytosis
• Decrease in serum Vit-b12
• An increase in homocysteine and methylmalonic acid, it's a risk factor for atherosclerosis and thrombosis.
• Vit-B12 is confirmed by a striking increase in reticulocytes
• Antibodies that are produced against Intrinsic factors are specific for pernicious anemia

Treatment of Vit-b12 deficiency anemia

     First of all the underlying cause is cured, then other treatments are done. Vitamin-b12 deficiency can be treated by using Parenteral(injections) or high-dose oral Vitamin-b12. Hydroxycobalamin dose of 1000 micrograms (1mg) I.M is given daily for 1 week, then 1mg a week given.