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Essay on Erythropoietin

Section B examples:

1. Write an essay on erythropoiesis.

Answer points: description or summary of the stages of RBC formation in bone marrow; possible consequences of the appearance of immature forms in the blood.
Describe regulation by EPO. Outline of what EPO is, its induction by hypoxia, EPO receptors and responses generated. Clinical uses for EPO (recombinant EPO), doping.

Erythropoietin (EPO) is a highly glycosylated hormone produced predominantly in the kidneys; 90 % of its production occurs here. EPO stimulates the quick production of red blood cells (RBC). EPO has a mass of 38kDa and is produced on demand as it is not stored anywhere in the body. Production of EPO is depended on the oxygen levels in the body. Production of EPO is initiated by low oxygen levels because of which it is said to be hypoxia dependent. This EPO and hypoxia link is proven by an altitude-oxygen partial pressure graph. As the altitude increases, the partial pressure of oxygen in the air decreases. This causes an increase in EPO production to raise the RBC levels in the blood.
RBC formation happens through a process known as erythropoiesis in the bone marrow, more precisely the red bone marrow. On a daily basis this process produces around x1012 number of RBC. Over time the red marrow turns into a yellow marrow. Yellow marrow has a significantly lower rate of erythropoiesis occurring within it, therefore RBC production reduced in the later stages of life.
Haemopoietic stem cells are the stem cells from which erythrocytes originate from. Main sites of RBC production are in the bone marrow of the vertebrae, pelvis, sternum and the proximal ends of the humeri and femur. These are have a local network of capillaries embedded within them to quickly allow the newly produced RBC to be transported into the blood circulation of the body.
The RBC are produced in the spaces of the spongy bones. RBC cells are biconcave disc cells that don’t contain a nucleus, DNA or RNA. However the precursor cells of RBC contain a nucleus. The stages of erythropoiesis is as follows:
Stem cell Early BFUE Late BFUE CFUE Pro-normoblast normoblast late normoblast reticulocyte erythrocyte
BFU is a blast forming unit whereas CFU is a colony forming unit. A pro-normoblast is a large cell with a purple DNA contained in a nucleus and a blue cytoplasm, this divides into an early normoblast which is basophilic. An early normoblast divides into an intermediate normoblast which is a polychromatic cell. This further divides into a late normoblast which is eosinophilic. Each division causes the cells to shrink in size and the nucleus of the late normoblast is expelled whilst forming a reticulocyte. A reticulocyte has pink staining due to the presence of RNA in the cytoplasm. Reticulocytes stay in the bone marrow for 1-2 days before maturing into erythrocytes and it can be used before autologous blood transfusion.
EPO can be abused for non-medical related reasons such as using it as a performance enhancing drug by athletes. EPO doping increases the athletes’ haematocrit which means that the VO2 max (time to exhaustion) increases. This increase can prove to be significant in sports.

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