THE REGULATION OF ERYTHROPOIESIS

Erythropoiesis  is the process which produces red blood cells (erythrocytes). It is stimulated by decreased oxygen in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells.

In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow.

In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver.

 After seven months, erythropoiesis occurs in the bone marrow. Increased level of physical activity can cause an increase in erythropoiesis.

However, in humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is termed extramedullary erythropoiesis.

The bone marrow of essentially all the bones produces red blood cells until a person is around five years old. The tibia and femur cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.

the negative feedback regulation of aerythropoiesis

REGULATION OF IRON METABOLISM

IRON METABOLISM 

• Lumen side of small intestine 
• iron is reduced from its ferric form(Fe3+) to ferrous form(Fe2+) by ferric reductase. 
• Ferrous iron is then transported in enterocytes by DMT1(divalent metal transporter).

• Membrane 
• Iron can be stored within the enterocytes as ferritin.
• It can also be transferred across the basolateral membrane to the plasma by transport protein Ferroportin1 and MTP1.
• Requires oxidation of Ferrous to Ferric by Hephaestin.

• Blood Circulation
• Transferrin transport iron in the blood.

WHAT IS HEPCIDIN?

Hepcidin is a poy pepetide hormone secreted by the liver – major regulator of iron homeostasis. Hepcidin acts on enterocytes of small intestine and the macrophages where iron is stored to cause ferroportin channels to be removed from plasma membrane and destroyed. Hepcidin thereby promotes cellular storage of iron and lowers plasma iron concentration – this completes a negative feedback loop in which the liver’s production of hepcidin is decreased by iron deficiency and most anemias, and increased by excessive iron intake.

 It also binds to ferroportin and form hepcidin-ferroportin complex, which is degraded in the lysosomes and iron is locked inside the cells(mainly enterocytes,hepatocytes and macrophages). So, hepcidin lowers iron absorption in the intestine, lowers iron releasing from hepatocytes and macrophages. serum iron is decreased.