Megaloblastic Anemia

Megaloblastic anemia is a term used to describe a group of blood disorder which is characterized by a defect in DNA synthesis and by a change in the size of the RBC.

The red blood cells are very large.  When DNA synthesis in the hematopoietic system is disrupted or slows down, there will be an abnormal synthesis of megaloblasts. However, the primary reason for the disrupted synthesis is a depletion of thymidine triphosphate, which is due to a deficiency in vitamin B12 and folic acid.

Therefore, two types of megaloblastic anemias are:

  1. Vitamin B12 (cobalamin) deficiency and
  2. Folic acid deficiency

Vitamin B12 (Cobalamin) Deficiency

Vitamin B12 also called cobalamin is essential to our bodies. It is found in meats, eggs, and dairy products. For it to be absorbed in our bodies it requires an intrinsic factor which is synthesized in the parietal cells of the stomach.

The average American diet contains about 5-7ug of cobalamin per day and our bodies stores about 2-5mg. If today we should stop taking in B12, it would take 3-4years for the stored amount in our bodies to be depleted.

How is Vitamin B12 absorbed?

The absorption of B12 from our diet as stated before requires an intrinsic factor (IF) which is secreted by the parietal cells of the stomach. When we eat say for instance eggs, cobalamin is bound to the protein in the egg.  In order for the cobalamin to be released from the protein, peptic digestion at low pH in the stomach is required.  The released cobalamin then binds to R proteins in saliva. This will form a B12-R-protien complex. In the duodenum, the B12-R-protien complex is broken down by pancreatic proteases. 

B12 then binds to the intrinsic factor which is produced in the stomach and forms a B12-IF complex. The B12-IF factor then moves to the ileum, where it binds to IF cobalamin receptors on ileal cells.  In the enterocyte, vitamin B12 is released and binds to transcobalamin II (TCII), a plasma transport protein.  Vitamin B12 is then absorbed in the circulation where it is stored in the liver and bone marrow. The IF factor is destroyed.

What are the causes of Vitamin B12 deficiency?

Vitamin B12 deficiency can be a result of a defect in any of the steps in metabolism mentioned above. Some possible causes are:

  1. Decrease intake (vegetarianism, poor diet)
  2. Absence of TCII
  3. Malabsorption (lack of gastric acid, lack of IF)- Pernicious Anemia
  4. Not having enough ileal receptors for the B12-IF complex
  5. Parasites (Tapeworm)

What are the signs and symptoms of Vitamin B12 deficiency?

  1. Beefy, red smooth tongue
  2. Pallor
  3. Weakness
  4. Lightheadedness
  5. Neurological disturbances (tingling of extremities, numbness and mental disturbances).

How is vitamin B12 deficiency diagnosed?

  1. Complete Blood Count (CBC)
  2. Check the level of  B12 in blood
  3. Schilling test– this test is used to determined the site of metabolic defect that has led to B12 deficiency.

Treatment of B12 Deficiency

  1. The cause of the B12 deficiency should be treated first.
  2. A shot of vitamin B12 once a month.
  3. Oral replacement of B12


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