Erythrocyte protoporphyrin levels

Many imported cosmetic agents contain lead. Not infrequently children will ingest these agents accidentally and may develop lead poisoning. It is, therefore, appropriate to measure the whole blood lead and erythrocyte protoporphyrin levels. 

Dose-Response Curve for Erythrocyte Protoporphyrin (EP) as a Function of Blood Level in Subpopulations... 

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. 

Mahaffey KR, Annest JL. 1986. Association of erythrocyte protoporphyrin with blood lead level and iron status in the Second National Health and Nutrition Examination Survey, 1976-1980. Environ Res 41 327-338. 

Toriumi H, Kawai M. 1981. Free erythrocyte protoporphyrin (FEP) in a general population, workers exposed to low-level lead, and organic-solvent workers. Environ Res 25 310-316. 

An example of an indirect marker of xenobiotic-in-duced renal disease is the elevated level of red cell content of either delta amino-levulinic acid dehydrase or free erythrocyte protoporphyrin in patients with lead nephrotoxicity [3,4]. Direct examples of biomarkers of... 

Biochemical evidence of lead poi.son-ing is by the finding of raised protoporphyrin levels in the erythrocytes due to the inhibition of a number of the synthetic enzymes of the haem pathway by lead (Fig. 2). A clinical sign is the appearance of a blue line on the gums. 

Several other classes of proteins have also been implicated as possible targets for lead, including other proteins in the heme biosynthetic pathway, leadbinding proteins in the kidney and brain, and heat shock proteins (342, 500-502). Lead is known to affect several steps in the heme biosynthetic pathway other than that catalyzed by ALAD Other profound effects include stimulation of 5-aminolevulinic acid synthase (ALAS) and decreased levels of iron incorporation into protoporphyrin by ferrochelatase (see Section VI.E.2 and Fig. 34) (10, 503-505). However, not all of these effects are due to direct interactions between lead and enzymes in the heme biosynthetic pathway. For instance, the widespread assertion that lead inhibits ferrochelatase is not supported by studies on the isolated enzyme (506, 507). Furthermore, increased levels of both erythrocyte protoporphyrin IX (EP) and zinc protoporphyrin (ZPP) are observed at high BLLs, suggesting that ferrochelatase is stiU competent to insert zinc into EP and that the increased levels of EP and ZPP associated with lead poisoning are most likely caused by lead interfering with iron uptake or transport (see Sections VI.C.4 and VI.E) (10, 506, 507). 

Erythrocytic protoporphyrin Weeks to months Level increases due to lead s inhibition of hematopoiesis integrates exposure over several months sensitivity poor for sustained mild-to-moderate elevations of blood lead (25 0 pgdL ) increased levels also seen in iron deficiency... 

B. Elevations in free erythrocyte protoporphyrin (FEP) or zinc protoporphyrin (ZPP) (> 35 mcg/dL) reflect lead-induced inhibition of heme synthesis. Because only actively forming and not mature erythrocytes are affected, elevations will typically lag lead exposure by a few weeks. A high blood lead in the presence of a normal FEP or ZPP therefore suggests very recent exposure. Protoporphyrin elevation is not specific for lead, and may also occur with iron deficiency. Protoporphyrin levels are not sensitive for low-level exposure (blood lead < 30 mcg/dL). 

The other indirect measures which can be used to monitor lead exposure are changes in the levels of a range of enzymes and metabolites involved in the synthesis and operation of haem. Thus, increases in the levels of free erythrocyte protoporphyrin (FEP) or of zinc protoporphyrin (ZPP) in blood can be associated with increased levels of lead in blood, as can decreased levels of activity of the enzyme delta-aminolaevulinic acid ddiydratase (ALAD). Similarly increases in the levels of urinary coproporphyrin (CP) and urinary aminolaevulinic acid (ALAU) also reflect increased lead exposure. These measures are not, however, always reliable since they can be affected by other factors, for exattqrle ZPP may be increased by iron deficiency. Measurements of these parameters tend, therefore, to be us only in conjunction with, and to provide supplementary data to, blood lead measurements. 

Geometric mean maximum safe level for entire population of children erythrocyte protoporphyrin elevation. 

Another way to measure lead in the body is via ZINC (or erythrocyte) protoporphyrin (ZPP or EP). This medical marker is not affected by the rebound effect as is the blood lead level. ZPP is an index of the level of lead or iron deficiency or both, as is EP, discussed in Chapter 4 on diagnosing lead poisoning. This index can be useful in indicating... 

Another enzyme, ferrochelatase, is also inhibited at low blood lead levels. Inhibition of ferrochelatase leads to increased free erythrocyte protoporphyrin (FEP) in the blood which can then bind to zinc to yield zinc protoporphyrin. At a blood lead level of 50 [ig/dl or greater, nearly 100 percent of the population will have an increase in FEP. There is also an exponential relationship between blood lead levels greater than 40 [ig/dl and the associated ZPP level, which has led to the development of the ZPP screening test for lead exposure. 

Lead interference with the insertion of iron into protoporphyrin results in an accumulation of protoporphyrin in erythrocytes (red blood cells). It appears that free erythrocyte protoporphyrin (FEP) begins to increase at a PbB of 17-20 Mg (100 ml) in children and women, and at slightly higher levels of 20-25 Mg (100 ml)" in adult males [6], although these thresholds are ill-defined and are still open to question. This accumulation of FEP has been taken by the... 

Of particular interest will be the iron and calcium data. However, other nutrients must also be carefully considered. Unfortunately, data on the zinc content of food is as yet unavailable and will have to wait for later analysis. Regression analysis between serum ferritin levels and blood lead concentrations will be performed as well as a comparison with other hematological determinations such as free erythrocyte protoporphyrins, hemoglobin, hematocrit, and serum iron, which are all indicators of iron status. 

Immature red blood cells contain free PROTO. The level of PROTO in the circulating erythrocytes is affected by a number of factors. In iron deficiency, or in anemia following hemorrhage, a high erythrocyte protoporphyrin (EP) is found of 20Q-400 itg per 100 cc. of erythrocytes as contrasted to normal values of 20-40 fig. EP is found to be high also in anemias of infectious nephritis and leukemia. It is low in pyridoxine and folic acid deficiencies (see 5-AL formation) (ISO). In acute lead poisoning of rabbits the EP is 500 fig. In phenylhydrazine poisoning the EP is 300 fig and COPRO is increased also (131). 

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