Editing Red blood cell (section)

==Life cycle==
Human red blood cells are produced through a process named [[erythropoiesis]], developing from committed [[stem cell]]s to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term [[infant]]).<ref>{{cite journal | vauthors = Harrison KL | title = Fetal erythrocyte lifespan | journal = Australian Paediatric Journal | volume = 15 | issue = 2 | pages = 96–97 | date = June 1979 | pmid = 485998 | doi = 10.1111/j.1440-1754.1979.tb01197.x | s2cid = 5370064 }}</ref> At the end of their lifespan, they are removed from circulation. In many chronic diseases, the lifespan of the red blood cells is reduced.

===Creation===

[[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 [[reticulocyte]]s; these constitute about 1% of circulating red blood cells.

===Functional lifetime===

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.<ref>{{cite journal | vauthors = Higgins JM | title = Red blood cell population dynamics | journal = Clinics in Laboratory Medicine | volume = 35 | issue = 1 | pages = 43–57 | date = March 2015 | pmid = 25676371 | pmc = 4717490 | doi = 10.1016/j.cll.2014.10.002 }}</ref>

===Senescence===

The aging red blood cell undergoes changes in its [[plasma membrane]], making it susceptible to selective recognition by [[macrophage]]s and subsequent [[phagocytosis]] in the [[mononuclear phagocyte system]] ([[spleen]], [[liver]] and [[lymph node]]s), thus removing old and defective cells and continually purging the blood. This process is termed [[eryptosis]], red blood cell programmed death.<ref name=Lang2012>{{cite journal | vauthors = Lang F, Lang E, Föller M | title = Physiology and pathophysiology of eryptosis | journal = Transfusion Medicine and Hemotherapy | volume = 39 | issue = 5 | pages = 308–314 | date = October 2012 | pmid = 23801921 | pmc = 3678267 | doi = 10.1159/000342534 }}</ref> 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, and energy depletion, as well as by a wide variety of endogenous mediators and [[xenobiotic]]s. Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK. [[Enzyme inhibitor|Inhibitor]]s of eryptosis include [[erythropoietin]], [[nitric oxide]], [[catecholamine]]s and high concentrations of [[urea]].

Much of the resulting breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into iron (Fe<sup>3+</sup>) 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 [[Hemolysis|hemolyze]]. Hemolyzed hemoglobin is bound to a protein in plasma called [[haptoglobin]], which is not excreted by the kidney.<ref>{{cite journal | vauthors = Föller M, Huber SM, Lang F | title = Erythrocyte programmed cell death | journal = IUBMB Life | volume = 60 | issue = 10 | pages = 661–668 | date = October 2008 | pmid = 18720418 | doi = 10.1002/iub.106 | s2cid = 41603762 | doi-access = free }}</ref>