Briefly describe the role of iron and vitamin B₁₂ in erythropoiesis. How is erythropoiesis affected by their deficiencies?

Outline:

·        Source of nutrient

·        Role in erythropoiesis

·        Causes of deficiencies

·        Clinical consequence of deficiencies

Essay:

            A regular supply of minerals and  vitamins is required for normal erythropoiesis. Out of these, iron and vitamin B₁₂ (cobalamin) are more important since they are one of the most common dietary deficiencies.

            Normal diet provides about 12-15 mg/day of iron out of which only 10% is absorbed. Liver and red meat are rich sources of iron. Iron is an important component of hemoglobin, the oxygen carrier in erythrocytes. Synthesis of hemoglobin begins in the proerythroblasts and continues into the reticulocyte stage. First succinyl CoA binds with glycine to form a pyrrole molecule. In turn, four pyrroles combine to form protoporphyrin IX< which then combines with iron to form heme molecule. Finally, each heme molecule combines with a globin chain to form a hemoglobin chain, four of which aggregate to form the whole hemoglobin molecule. Oxygen binds loosely with one of the coordination bonds of the iron atom. This is an extremely loose bond that allows hemoglobin to combine with oxygen in the lungs and then release this oxygen readily in the tissue capillaries where the gaseous tension of oxygen is much lower than in the lungs.

            Iron deficiency leads to a microcytic, hypochromic anemia, indicating a prolonged period of negative iron balance and anemia severe enough to stimulate the production of poorly hemoglobinized cells. Causes of iron deficiency are blood loss, menstrual blood loss, inadequate diet, blood donation, pregnancy and malabsorption. The symptoms and signs of severe iron deficiency largely reflect the severity of the patient’s anemia and include fatigue, pallor, and a decreased exercise capacity. When iron deficiency is severe and prolonged, the patient may complain of mouth soreness, difficulty swallowing, and a softening and curling of the nails called spooning.

            Because of the continuing need to replenish red blood cells, the cells of the bone marrow are among the most rapidly growing and reproducing cells of the entire body. Especially important for final maturation of the red blood cells are the two vitamins cobalamin, and folic acid. Both of these are essential for the synthesis of DNA because each in a different way is required for the formation of thymidine triphosphate, one of the essential building blocks of DNA. Therefore, lack of cobalamin causes diminished DNA and, consequently, failure of nuclear maturation and division. A common cause of maturation failure is failure to absorb cobalamin from the gastrointestinal tract. This often occurs in pernicious anemia, in which intrinsic factor secretion ceases owing to atrophy of the gastric mucosa. The parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor, which combines with cobalamin of the food and binds to a receptor in the mucosa of the terminal ileum, facilitating its absorption. Lack of this factor will result in cobalamin deficiency, leading to slow reproduction of the erythroblasts in the bone marrow. As a result, these grow too large, with odd shapes, and are called megaloblasts. Because the erythroblasts cannot proliferate rapidly enough to form normal numbers of red blood cells, the cells that are formed are mostly oversized, of bizarre shapes, and have fragile membranes. These cells rupture easily, leaving the person in need of an adequate number of red cells.