where does the breakdown of red blood cells occur
Red blood cell 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.[47] 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.
Hemoglobin When red cells reach the end of their life due to aging or defects, they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within the circulation. Free hemoglobin is then cleared from the circulation via the hemoglobin transporter CD163, which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the iron gets recycled. This process also produces one molecule of carbon monoxide for every molecule of heme degraded.[71] Heme degradation is one of the few natural sources of carbon monoxide in the human body, and is responsible for the normal blood levels of carbon monoxide even in people breathing pure air. The other major final product of heme degradation is bilirubin. Increased levels of this chemical are detected in the blood if red cells are being destroyed more rapidly than usual. Improperly degraded hemoglobin protein or hemoglobin that has been released from the blood cells too rapidly can clog small blood vessels, especially the delicate blood filtering vessels of the kidneys, causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or ferritin in tissues and transported in plasma by beta globulins as transferrins. When the porphyrin ring is broken up, the fragments are normally secreted as a yellow pigment called bilirubin, which is secreted into the intestines as bile. Intestines metabolise bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolised into amino acids that are then released into circulation.