<P> Erythropoiesis is the process by which new red blood cells are produced; it lasts about 7 days . Through this process red blood cells are continuously produced in the red bone marrow of large bones . (In the embryo, the liver is the main site of red blood cell production .) The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney . Just before and after leaving the bone marrow, the developing cells are known as reticulocytes; these constitute about 1% of circulating red blood cells . </P> <P> The functional lifetime of a red blood cell is about 100--120 days, during which time the red blood cells are continually moved by the blood flow push (in arteries), pull (in veins) and a combination of the two as they squeeze through microvessels such as capillaries . They are also recycled in the bone marrow . </P> <P> The aging red blood cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophages and subsequent phagocytosis in the mononuclear phagocyte system (spleen, liver and lymph nodes), thus removing old and defective cells and continually purging the blood . This process is termed eryptosis, red blood cell programmed cell death . This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count . Eryptosis is increased in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle cell anemia, beta - thalassemia, glucose - 6 - phosphate dehydrogenase deficiency, phosphate depletion, iron deficiency and Wilson's disease . Eryptosis can be elicited by osmotic shock, oxidative stress, energy depletion as well as a wide variety of endogenous mediators and xenobiotics . Excessive eryptosis is observed in red blood cells lacking the cGMP - dependent protein kinase type I or the AMP - activated protein kinase AMPK . Inhibitors of eryptosis include erythropoietin, nitric oxide, catecholamines and high concentrations of urea . </P> <P> Much of the resulting breakdown products are recirculated in the body . The heme constituent of hemoglobin are broken down into iron (Fe) and biliverdin . The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin . The iron is released into the plasma to be recirculated by a carrier protein called transferrin . Almost all red blood cells are removed in this manner from the circulation before they are old enough to hemolyze . Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin, which is not excreted by the kidney . </P>

Where does the breakdown of red blood cells occur