Erythrocyte lifespan

Fig. 12.5 Dose-response modeling of the effects of epoetin-a on the hematocrit of a hemodialysis patient. The time to reach a new steady-state hematocrit is determined by the erythrocyte lifespan. Phase A Epoetin-a causes an increase in RBC production rate consequently the hematocrit increases as newly produced erythrocytes do not die at the early stage. Phase B After reaching one RBC lifespan, erythrocytes die at the current production rate (from [58]).

In order to explain the maintenance of purine nucleotide levels and the known turnover of these compounds during the erythrocyte lifespan, it is necessary to invoke the salvage pathway. For the human erythrocyte, only adenine and adenosine can serve as adenine nucleotide precursors. 

The in vivo micronucleus test is used for the detection of damage to chromosomes as well as the mitotic apparatus in bone marrow or peripheral blood cells of rodents. The assay system has been well standardized.14-17 The basic features of the test system are (1) the effect of the test chemical is observed in anucleated polychromatic erythrocytes (PCEs) (2) PCEs have a relatively short lifespan, so that any micronuclei they contain must have been generated as a result of recently induced chromosome damage (3) micronuclei are readily identifiable and their distribution is well defined and (4) the frequency of induced micronuclei in PCEs is dependent on sampling times. 

The existence of some blood cells, such as erythrocytes and platelets, with long lifespans make cell transfusion therapy practical. Cell transfusion therapy cannot be developed for short-lived cells such as neutrophils with turnover rates of less than 8 hours. Fortunately, for neutrophils, colony stimulating factors can be used to recruit the needed number in blood within 24 hours after administration of these factors. 

Ageing erythrocytes are destroyed by the mobile phagocytic macrophages of the reticuloendothelial system, mainly in the spleen. The average lifespan of a red cell is about 120 days. 

Heme oxygenase is the rate-limiting step in the produetion of CO and its activities account for 86% of endogenous CO produetion the remaining 14% is derived from nonheme sourees. The lifespan of red blood cells is approximately 120 days the older the erythrocyte the greater is its CO output. In neonates, red blood cells have a shorter lifespan and relative to erythrocytes of adults, they produce two to three times more CO (Fallstrom, 1968). HO-2 is activated during neuronal stimulation by phosphorylation by the enzyme CK2 (Boehning et al, 2003). 

Blood transfusions Haemolysis is due to the shortened lifespan of transfused erythrocytes. 

One of the biological functions of the carbohydrate chains is to regulate the lifespan of proteins. For example, removal of sialic acid residues from the end of oligosaccharide chains on erythrocytes results in the disappearance of the red blood cells from the circulation. Carbohydrates have also been implicated m cell-cell recognition, and in secretion and targeting of proteins to specific subcellular domains. Recently, defects in protein glycosylation have been linked to several forms of congenital muscular dystrophy that are associated with brain abnormalities. ... 

Folate status may be reliably assessed by direct measurement of serum and erythrocyte or whole blood concentrations, and its metabolic function as coen2yme assessed by metabolite concentrations, such as plasma homocysteine (see Chapters 20 and 26). Serum folate concentrations are considered indicative of recent intake and not of tissue stores, but serial measurements have been used to confirm adequate intake. Whole blood or erythrocyte folate concentrations are more indicative of tissue stores and have been shown to have a moderate correlation with liver folate concentrations taken through a biopsy. Because folate is taken up only by the developing erythrocyte in the bone marrow and not by the mature cell, erythrocyte concentrations reflect folate status over the 120-day lifespan of the ceU. Urine folate excretion is not considered to be a sensitive indicator of folate status. ... 

L. S. Valberg, R. T. Card, E. J. Paulson, and J. Szivek, The metal composition of erythrocytes in different species and its relationship to the lifespan on the cells in the circulation. Comp Biochem Physiol 15(3) 347-359 (1965). 

Heavy lead exposure is associated with reticulocytosis and occurrence of stippled erythrocytes in peripheral blood (US EPA 1986), possible mediated through the effect on P5N. Lead can also shorten the lifespan of circulating erythrocytes, probably by inhibition of the Na, K -ATPase, possibly also affecting the erythrocyte s P5N, and by causing changes in membrane proteins. Anemia may follow of either the nor-mocytic or sideroblastic type. 

APRT (HIO, M15), and since PRibPP concentrations are higher in red cells of Lesch-Nyhan patients, it is logical to assume that the increased substrate is responsible for the increased APRT levels. One puzzling aspect of this work was the observation that the APRT in crude lysates of very young cells seemed more heat labile than that in older cells. This problem was resolved by the later observation that PRibPP levels in young erythrocytes are only one-sixth those in more mature cells (Y2). It is interesting to speculate that these changes are related to ATP concentrations and that the latter is concerned with the fixed lifespan of the erythrocyte. 

This condition causes erythrocytes to form prickle shapes and have a reduced lifespan. Th is causes anaemia, though the oxygen dissociation curve is moved to the right... 

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