Erythrocytes life-span

B19. Brewer, G. J., Tarlov, A. R., and Kellermeyer, R. W., The hemolytic effect of primaquine. XII. Shortened erythrocyte life span in primaquine sensitive male Negroes in the absence of drug administration. J. Lab. Clin. Med. 58, 217-224 (1961). 

Neonatal samples and individuals with a decreased erythrocyte life spans show high or increased values. 

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. 

Abbrecht, P. H., Erythrocyte Life Span in Mice Acclimatized to Different... 

High levels of administered zinc limits copper uptake in humans and certain animals, and provides protection against toxicosis produced by copper in pigs and sheep. Excessive zinc in humans interferes with copper absorption from the intestine, resulting in copper deficiency, and eventually to cardiovascular diseases hi zinc intakes also decrease iron bioavailability, leading to a reduction of erythrocyte life span by 67%. Copper deficiency induced by excess dietary zinc is associated with lameness in horses, donkeys, and mules. 

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... 

One of the eventual results of lead - induced inhibition of enzymes in the heme synthesis pathway is anemia which can be asymptomatic if mild but associated with a wide array of symptoms including dizziness, fatigue, and tachycardia when more severe. Studies have indicated that lead levels as low as 50 xg/dl can be associated with a definite decreased hemoglobin, although most cases of lead - induced anemia, as well as shortened red-cell survival times, occur at lead levels exceeding 80 xg/dl. Inhibited hemoglobin synthesis is more common in chronic cases whereas shortened erythrocyte life span is more common in acute cases. 

Erythrocyte stability and survival are also affected by lead even in the absence of any genetic disorders predisposing to reduced erythrocyte survival and stability. Shortened erythrocyte life span, associated increase in reticulo-cytosis, and lead-impaired heme and globin synthesis collectively work to produce a lead-associated anemia, largely at the relatively high values of PbB encountered in occupational Pb contact (see, for example, U.S. EPA, 1986, Ch. 12). Genetically induced anemia in individuals also at risk for Pb-induced anemia would, in theory, further aggravate the reliability of the dose portion of dose—toxic response relationships across the spectrum of toxicity. 

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. 

Derelanko, M.J., 1987. Determination of erythrocyte life span in F-344, Wistar, and Sprague-Dawley rats using a modification of the diisopropylfluorophosphate (pHJDFP) method. Fundam. Appl. Toxicol. 9 (2), 271-276. 

Saito, H., Sakai, M., 1977. Determination of mean erythrocyte life span with diisopropylfluorophosphate PP]DFP. Kakulgaku 14 (2), 211-215. (In Japanese). 

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. 

Physiologically, body stores are maintained by extracting approximately 10% of the iron provided in a balanced diet and this corresponds to 1.5 mg each day for males and slightly more for females to compensate for pregnancy and menses. The trace element is derived from food by peptic digestion and after reduction the ferrous form crosses the enterocyte to be released at the serosal pole via the ferroportin-hepcidin mechanism to be transported, by plasma transferrin, to developing red cells in the marrow for haemoglobin synthesis. At the end of their life span effete erythrocytes are removed by the reticuloendothelial system in the spleen, bone marrow and the liver. 

Lead adversely affects a number of systems in the body. The inhibition of the synthesis of hemoglobin by lead has just been noted. This effect, plus a shortening of the life span of erythrocytes, results in anemia, a major manifestation of lead poisoning. 

The life span of the human erythrocyte is — 120 days with about 0.85 percent of the total being broken down each day in the reticuloendothelial (RE) cells of the spleen, liver, and bone marrow. 

The evaluation of micronuclei frequencies in peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) permits an assessment of both recently induced and chronically accumulated bone marrow damage. PCEs have a life span of about 24 hours and are good indicators of acute damage. NCEs have a life span of about 30 days and are good indicators of chronic damage. A... 

In about 90% of all neonates, jaundice occurs after the first 2-5 days of life and rarely exceeds 6 mg/dl serum bilirubin. In premature infants, bilirubin levels can rise to 10-12 mg/dl. The cause is related to a number of factors .) reinforced degradation of haemoglobin as a result of the short erythrocyte survival span of 70-90 days (120 days in adults), (2.) reduction in cellular transport proteins, above all ligandin, (i.) deficiency of uri-dyltransferase and glucuronosyltransferase, and (4.) increasing intestinal absorption of meconium bilirubin. 

A number of these enzymes are expressed in other tissues as well but cause a notable deficiency predominantly in red blood cells because of the life span of the erythrocyte after the loss of protein synthesis. Once an enzyme is degraded or otherwise becomes nonfunctional, it cannot be replaced by new or other compensating proteins because of the lack of nucleus, mitochondria, ribosomes, and other cell organelles in mature red cells. Disorders have been described in the EMP, HMP, Rapoport-Luebering cycle, the glutathione pathway (Figure 21-9), purine-pyrimidine metabolism and methemoglobin reduction. 

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. 

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