Life span, normal erythrocyte

ERYTHROCYTES. Erythrocytes are biconcave diskshaped, blood cells (with pits or depressions in the center on both sides), the primary function of which is to transport hemoglobin, the oxygen-carrying protein. The biconcave shape of the erythrocyte provides a large surface volume ratio and thereby facilitates exchange of oxygen. The average diameter of erythrocytes is 7.5 pm, and thickness at the rim is 2.6 pm and in the center about 0.8 pm. The normal concentration of erythrocytes in blood is approximately 3.9-5.5 million cells per pL in women and 4.1-6 million cells per pL in men. The total life span of erythrocytes in blood is 120 days. 

The labeling technique has been used to study the life-span of erythrocytes in patients with anemias and porphyrias (343, 359). In a hemolytic anemia patient most of the labeled stercobilin was found to be excreted some 20 days after feeding of labeled glycine. In sickle cell anemia it was concluded that a random destruction of erythrocytes took place to compensate for this destruction the rate of hemoglobin formation was nearly tripled. In pernicious anemia an abnormal pattern of erythrocyte destruction was also found but the erythrocyte life-span returned to normal after liver therapy. 

Patients with renal insufficiency are often found to be affected by multiple metabolic problems. Anaemia is often present and some of its causes are well identified, but can only partly explain the anaemia of such a severe degree as found in uremia. It is known that a certain degree of decreased erythropoiesis is present. Often occurs blood loss due to bleeding tendency. A third mechanism by which anaemia might develop is hemolysis, in fact the life-span of erythrocytes from uremic patients is shortened, but normal survival is noted when erythrocytes are injected into healthy persons. Erythrocytes from healthy subjects have a shortened survival time when injected into uremic patients. Thus, it seems that extracorpuscular factors account for the development of hemolysis. 

Pyruvate Idnase deficiency (OMIM 266200) is the most common cause of nonspherocytic hemolytic anemia due to defective glycolysis. The allelic frequency is estimated to be around 2%. The consequent lack of sufficient energy, which is required for normal functioning and cellular survival, shortens the life span of the mature PK-deficient erythrocyte. Consequently, PK-deficient patients display a phenotype of nonspherocytic hemolytic anemia albeit with variable clinical severity. The clinical symptoms vary from neonatal death to a well-compensated hemolytic anemia. Patients benefit in general from a splenectomy. Pyruvate kinase deficiency is transmitted as an autosomal recessive disease. To date, more than 130 mutations in PKLR have been reported to be associated with pyruvate kinase deficiency (see Figure 21-10 for overview see reference 221). Most (70%) of these mutations are missense mutations affecting conserved residues in structurally and functionally important domains of PK. Splice site mutations, a deletion. 

The normal human erythrocyte has a life span of about 120 day s, as was first shown by the time course of " N in Shemin s own hemoglobin after he... 

It is of paramount importance to rule out vitamin B12 deficiency when folate deficiency is detected, as symptoms are similar. Laboratory changes associated with folate deficiency are similar to those seen in vitamin Bn deficiency, except vitamin Bn levels are normal. Decreases occur in the serum folate level (<3 ng/mL) within a few days of dietary folate limitations. The RBC folate level (<150 ng/mL) also declines and may be a better indicator of deficiency, as levels remain constant throughout the life span of the erythrocyte. Serum folate levels are sensitive to short-term changes such as dietary restrictions or alcohol intake, which may result in a short-term decline in serum levels with adequate tissue stores. It should be noted that an estimated 60% of patients with pernicious anemia have falsely low RBC folate levels, in all probability due to the requirement of cobal-amin for the normal transfer of methyltetrahydrofolate from plasma to cells. Additionally, if serum or erythrocyte folate levels are borderline, serum homocysteine is usually increased with a folic acid deficiency. If serum MMA levels are also elevated, vitamin B12 deficiency needs to be ruled out. 

ACD is a hypoprolrferative anemia that has traditionally been associated with infectious or inflammatory processes, tissue injury, or conditions associated with the release of proinflammatory cytokines. Alternative names include anemia of inflammation and cytokine-mediated anemia. The pathogenesis of the anemia of chronic disorders is based on three abnormalities shortened erythrocyte survival, impaired marrow response, and disturbance of iron metabolism. Pathologically, the RBCs have a shortened life span, and the bone marrow s capacity to respond to EPO is inadequate to maintain normal Hgb concentration. The cause of this defect is still uncertain, but appears to involve a block in the release of iron from the reticuloendothelial cells of the marrow. Various cytokines, such as interleukin-1, interferon-y, and tumor necrosis factor released during these illnesses may inhibit the production or action of EPO or the production of RBCs. ... 

Glycosylation of the red cell cytoskeleton [e.g., membrane proteins (M25) and in particular spectrin (M13)] leads to decreased deformability and a concomitant decrease in erythrocyte life span. This has been monitored by the centrifugation packing coefficient, filtration, and negative-pressure micropipette techniques with red cell suspensions incubated in vitro with 25 ixiM glucose or from in vivo preparations from normal and diabetic individuals (B13). The relevance of these observations will be discussed in Section 5.5.1. 

Using Cr -labeled cells, a shortened erythrocyte life span was found in newborn premature infants (Kaplan and Hsu, 1961). The susceptibility of their erythrocytes to in vitro hemolysis in hydrogen peroxide suggests a possible relationship to their decreased survival in vivo. Indeed, decreased survival has been observed in the vitamin E-deficient monkey (Marvin et al., 1959) although the normal survival in vitamin E-defident rats suggests a species variability (Goldbloom, 1960). The results in humans are inconclusive. A decreased red cell life span was found in adult volunteers on a tocopherol-deficient diet high in polyunsaturated lipids (Horwitt et al., 1961), but survival was normal in a patient with cystic fibrosis of... 

I. M. London In view of the discussion of GSH in the red cell, I d like to mention some studies which Dr. Dimant and I have been doing. These studies indicate that glycine is rapidly incorporated into GSH of normal maimnalian red cells and avian erythrocytes in vitro. In addition, if one administers labeled glycine to a normal man, the turnover in the GSH of the erythrocytes is rather rapid, with a half-life time of the order of 4 days at a time when the normal life span of the red cell as determined in the same individual is of the order of 120 days. The problem at the present time is that of establishing net synthesis in the erythrocytes this study is now under way. 

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