Outline the factors which regulate red blood production.

Outline:

·        Need for regulation

·        Factors stimulating and inhibiting erythropoiesis

·        Role of erythropoietin

Essay:

            The total mass of red blood cells in the circulatory system is regulated within narrow limits to ensure that an adequate number of red cells is always available to provide sufficient tissue oxygenation and that the cells do not become so concentrated that they impede blood flow. The formation of red blood cells (erythropoiesis) is subject to a feedback control. Any condition that causes the quantity of oxygen transport to the tissues to decrease will increase the rate of red blood cell production. Factors that decreases oxygenation are low blood volume (due to hemorrhage), anemia, low hemoglobin levels, poor circulatory flow, and pulmonary disease. It is inhibited by a rise in the circulating red cell level to supernormal values.

            The rate of erythropoiesis is mainly regulated by a circulating hormone, erythropoietin. Erythropoietin is a glycoprotein that contains 165 amino acid residues and 4 oligosaccharide chains that are necessary for its activity in vivo. In adults, about 85% of the erythropoietin comes from the kidneys and 15% from the liver. Both these organs contain the mRNA for erythropoietin. The usual stimulus for erythropoietin secretion is hypoxia, but secretion of the hormone can also be stimulated by cobalt salts and androgens. Secretion of hormone is also facilitated by the alkalosis that develops at high altitudes. Erythropoietin increases red blood cell production by stimulating the production of proerythroblasts from hemopoietic stem cells and shortens the time taken for these cells to pass through the different erythroblastic stages. The mechanism by which it produces its intracellular effects is unsettled, but it is probably a tyrosine kinase. However, it appears that when erythropoietin levels are low, erythroid stem cells show DNA cleavage followed by programmed cell death (apoptosis). In erythroid stem cells, erythropoietin reduces the DNA cleavage and causes the cells to survive.

            The principal site of inactivation of erythropoietin is the liver, and the hormone has a half-life in the circulation of about 5 hours. However, the increase in circulating red cells that it triggers take 2-3days to appear, since red cell maturation is a relatively slow process.