Lead in erythrocytes

Delves, H.T., Clayton, B.E., Carmichael, A., Bubear, M. and Smith, M. (1982) An appraisal of the analytical significance of tooth-lead measurements as possible indices of environmental exposure of children to lead. Ann. Clin. Biochem., 19, 329-337 Delves, H.T., Sherlock, J.C. and Quinn, M.J. (1984) Temporal stability of blood lead concentrations in adults exposed only to environmental lead. Human Toxicol, 3, 279-288 DeSilva, P.E. (1981) Determination of lead in plasma and studies on its relationship to lead in erythrocytes. Br. ]. Ind. Med., 38, 209-217... 

In erythrocytes, the first site in glycolysis for generation of ATP may be bypassed, leading to the formation of 2,3-bisphosphoglycerate, which is important in decreasing the affinity of hemoglobin for Oj. 

The amount of total lead in the blood can be measured to determine if exposure to lead has occurred. This test can tell if you have been recently exposed to lead. Lead can be measured lead in teeth or bones by X-ray techniques, but these methods are not widely available. These tests tell about long-term exposures to lead. Exposure to lead can be evaluated by measuring erythrocyte protoporphyrin (EP) in blood samples. EP is a part of red blood cells known to increase when the amount of lead in the blood is high. However, the EP level is not sensitive enough to identify children with elevated blood lead levels below about 25 micrograms per deciliter ( ig/dL). For this reason, the primary screening method is measurement of blood lead. For more information on tests to measure lead in the body, see Chapters 2 and 6. 

Only a subset of the parameter values in the O Flaherfy model require inputs from the user to simulate blood and tissue lead concentrations. Lead-related parameters for which values can be entered into the model include fractional absorption from the gastrointestinal tract partition coefficients for lead in nonbone tissues and in the surface region of bone maximum capacity and half-saturation concentration for capacity-limited binding in the erythrocyte elimination clearance fractional clearance of lead from plasma into forming bone and the restricted permeability coefficients for lead diffusion within bone, from plasma into bone, and from bone into plasma (O Flaherty 1991a). 

A marked interference with heme synthesis results in a reduction of the hemoglobin concentration in blood. Decreased hemoglobin production, coupled with an increase in erythrocyte destruction, results in a hypochromic, normocytic anemia with associated reticulocytosis. Decreased hemoglobin and anemia have been observed in lead workers and in children with prolonged exposure at higher PbB levels than those noted as threshold levels for inhibition or stimulation of enzyme activities involved in heme synthesis (EPA 1986a). 

The increase in erythrocyte destruction may be due in part to inhibition by lead of pyrimidine-5 -nucleotidase, which results in an accumulation of pyrimidine nucleotides (cytidine and uridine phosphates) in the erythrocyte or reticulocyte. This enzyme inhibition and nucleotide accumulation affect erythrocyte membrane stability and survival by alteration of cellular energetic (Angle et al. 1982 EPA 1986a). Formation of the heme-containing cytochromes is inhibited in animals treated intraperitoneally or orally... 

ALA in plasma was as good a discriminator of lead exposure as ALAD activity in workers at PbB levels between 10 and 40 pg/dL and continued to discriminate up to PbB levels approaching 100 pg/dL (Sakai and Morita 1996). The same group of investigators recently showed that the activity of adenine dinucleotide synthetase (NADS) in erythrocytes is a better predictor of PbB levels >40 pg/dL than ALAD (Morita et al. 1997). The decrease in NADS activity between PbB concentration of 5 and 80 pg/dL was linear with a correlation coefficient of -0.87. 

Alessio L, Bertazzi PA, Monelli O, et al. 1976. Free erythrocyte protoporphyrin as an indicator of the biological effect of lead in adult males II. Comparison between free erythrocyte protoporphyrin and other indicators of effect. Int Arch Occup Environ Health 37 89-105. 

Hammond PB, Bomschein RL, Succop P. 1985. Dose-effect and dose-response relationships of blood lead to erythrocytic protoporphyrin in young children. In Bomschein RL, Rabinowitz MB, eds. The Second International Conference on Prospective Studies of Lead, Cincinnati, OH April, 1984. Environ Res 38 187-196. 

Marcus AH. 1985c. Multicompartment kinetic models for lead III. Lead in blood plasma and erythrocytes. Environ Res 36 473-489. 

Morita Y, Sakai T, Araki S, et al. 1997. Nicotinamide adenine dinucleotide synthetase activity in erythrocytes as a tool for the biological monitoring of lead exposure. Int Arch Occup Environ Health 70(3) 195-198. 

Odone P, Castoldi MR, Guercilena S, et al. 1979. Erythrocyte zinc protoporphyrin as an indicator of the biological effect of lead in adults and children. In International Conference on Management and Control of Heavy Metals in the Environment, London, United Kingdom, September. Edinburgh, UK CEP Consultants, Ltd., 66-69. 

There is a great deal of interest in the determination of lead, particularly micromethods applicable to the analysis blood lead in children. Consequently, reports continue to appear on the atomic absorption determination of lead in blood and urine. Ninety percent of blood lead is found in the erythrocytes and, therefore, whole blood is analyzed rather than serum or plasma. Berman etal. 134) have described a procedure for determining normal lead levels in which only 250 fd of blood are taken. The blood is deproteinized with 1 ml of 10 % trichloroacetic acid and then the lead is extracted with APDC into 1 ml of MIBK, at pH 3.5. 

The fact that zinc is known to be a component of an enzyme carbonic anhydrase leaves no doubt as to its physiological significance. The amount of zinc in erythrocytes seems to parallel the carbonic anhydrase activity.21 The leucocytes which appear to lack carbonic anhydrase contain about 25 times as much zinc (per cell) as do the erythrocytes.20 It seems likely that an investigation of the zinc content of different types of white blood cells coupled with a study of individuals from the standpoint of the different types of white cells present (p. 35) would lead to the discovery of substantial inter-individual differences. The wide spread in the zinc concentrations in three human spleens has already been mentioned (p. 72). A recent study has been made of the intake and excretion of zinc by 13... 

---