Erythropoiesis refers to the process by which red blood cells, which carry haemoglobin, are generated. It occurs at a constant rate during normal health, replacing lost red blood cells (which have an average lifespan of 120 days) to maintain a constant red cell mass. It is subject to regulation by a number of factors, allowing it to respond rapidly in times of stress (e.g. major haemorrhage).

 

Erythropoiesis

Erythropoiesis. Erythropoesis starts with a haematopoietic stem cell (see Normal Haematopoiesis), which differentiates into a common myeloid progenitor and then into a megakaryocyte-erythroid progenitor. Further differentiation results in commitment to the erythroid lineage. The proerythroblast is the earliest morphologically identifiable bone marrow red cell precursor, characterised by a large cell with high nuclear:cytoplasmic ratio, prominent nucleoli and blue cytoplasm (presence of RNA). As the erythroid cells mature, they become smaller, have more condensed chromatin, lose their nucleoli, and their cytoplasm changes from blue to pink. Eventually, the nucleus is extruded, resulting in a reticulocyte. Most of the process takes place in the bone marrow over three weeks. The resulting reticulocyte retains some ribosomal RNA to make haemoglobin and after 1-2 days in the bone marrow, it enters the peripheral blood where the RNA is lost after 1-2 days resulting in a mature RBC.

 

 

Factors Affecting Erythropoiesis

Erythropoietin and Iron

Erythropoietin is produced in the kidney and plays a major role in the control of erythropoiesis; iron is a key mineral required for haemoglobin production. A lack of erythropoeitin, which is seen most commonly in renal failure, can result in profound reticulocytopaenia and anaemia. In renal failure, where the erythroid precursors are preserved, exogenous erythropoeitin can correct anemia. Conversely, excessive erythropoietin, which is either a normal response to hypoxia or the result of pathological production (e.g. erythropoietin-secreting tumours), causes erythrocytosis.

 

The control of erythropoiesis

Erythropoietin and the Control of Erythropoiesis. Erythropoietin is produced in the kidney. Hypoxia, which may be caused by anaemia, impaired gas exchange or increased tissue demand for oxygen, increases the production of hypoxia-inducible factor (HIF), which in turn stimulates renal production of erythropoietin. Erythropoietin acts on erythroid precursors, preventing their apoptosis and upregulates their transferrin receptors to stimulate increased RBC production. The resultant increase in circulating RBCs relieves the hypoxia, down-regulating HIF in a negative feedback loop.

 

Other Vitamins, Minerals and Hormones

Factors which influence erythropoiesis

Vitamins and Minerals Influencing Erythropoiesis. Maturation factors such as B12 and folate are key components of DNA synthesis. Deficiency of either results in megaloblastic anaemia, with inefficient DNA replication and selective death of more mature precursors. Androgens and thyroxine also exert a stimulatory effect on erythropoiesis. Copper and pyridoxine are key components of iron incorporation into haem; deficiency of either can result in sideroblastic anaemia.