Erythrocyte protoporphyrin elevation

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

Erythrocyte protoporphyrin (EF) elevation in males Erythrocyte protoporphyrin (EP) elevation in females ALA-D inhibition... 

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. 

PbB concentrations reflect the absorbed dose of lead. However, the interpretation of PbB data depends on a knowledge of the past history of exposure to lead. This is because in the body, bone constitutes the major lead sink and this results in lead having a long body half-life. Thus, in the absence of intense exposure to lead for a considerable period up to its body half-life, the PbB concentrations reflect recent lead exposures. However, if intermittent exposure to lead is occurring in several distinct environments, the PbB concentration reflects both recent and past exposures to lead. Thus, biological effects for populations with the same PbB concentrations may not be the same since different exposure times scales may be involved. This is the reason why free erythrocyte protoporphyrin (FEP) and erythrocyte zinc protoporphyrin (ZPP) have been used as additional biological markers since their elevation is more related to chronic lead exposure than acute lead exposure (see Section 2.7). 

If the patient presents with acute burning pain, the examination of choice is erythrocytic protoporphyrins. If the free protoporphyrin is significantly elevated (more than 6 pmol/1), the diagnosis of erythropoietic protoporphyria is established. Plasma porphyrins are used in patients on chronic hemodialysis who suffer from skin blisters to differentiate between PCT and pseudoporphyria the latter does not show increased plasma porphyrins. 

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... 

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). 

In chronic lead poisoning (2 mg lead per day) a lead colic results (due to competition between Pb++ and Ca++) and a polyneuritis. Lead-poisoned workers have S-AL and PBG in their urine and blood (390). Basophilic aggregations are seen in over 2% of the red blood cells. The erythrocyte protoporphyrin is elevated. Iron cannot get into the immature erythrocytes or cannot be used and obin mthesis is also decreased. The kidneys are also afiiected resulting in an amino aciduria. Bone marrow hyperplasia... 

Monkeys were exposed to lead from day 1 of life onward, at doses equivalent to 0, 50, 100 or 500 lg/kg per day. For all treated groups, blood lead (PbB) levels peaked by 100 days of age and decreased to a steady level after withdrawal from infant formula at 200 days of age (Willes et al, 1980) (Table 1). The highest dose of lead resulted in both peak and steady-state blood levels considered to be deleterious to children by criteria of the United States Environmental Protection Agency (1984) and Centers for Disease Control (1985). Both agencies regard a blood concentration for an individual child of 25 /ig/dl without elevation of erythrocyte protoporphyrin (EP) concentration to be safe. This presumably allows an adequate margin of safety... 

Zinc protoporphyrin IX is a normal metabolite that is formed in trace amounts during haem biosynthesis. However, in iron deficiency or in impaired iron utilization, zinc becomes an alternative substrate for ferrochelatase and elevated levels of zinc protoporphyrin IX, which has a known low affinity for oxygen, are formed. This zinc-for-iron substitution is one of the first biochemical responses to iron depletion, and erythrocyte zinc protoporphyrin is therefore a very sensitive index of bone-marrow iron status (Labbe et ah, 1999). In addition, zinc protoporphyrin may regulate haem catabolism by acting as a competitive inhibitor of haem oxygenase, the key enzyme of the haem degradation pathway. However, it has been reported... 

Chromatographic determination of protoporphyrins in erythrocytes has the same indications as the spectrophotometric one. In addition, the method enables the differentiation between zinc-protoporphyrin and (metal-)free protoporphyrin. The first is elevated in iron deficiency and lead intoxication, the second in erythropoietic protoporphyria. 

Along with blood lead and urine, effects on the heme system can be used as indicators of exposure to lead. Elevations of zinc protoporphyrin (ZPP) or free erythrocyte protoporph)Tin (FEP) can indicate past lead exposures while blood lead will indicate a recent exposure. As shown in Table 22.2, OSFIA requires action when blood lead is 40 pg/100 g of whole blood and removal from lead exposure when the blood lead reaches or exceeds 60 tg/100 g of whole blood or if the average of three consecutive blood lead levels are over 50 pg/lOO g of whole blood. 

Elevated erythrocyte zinc protoporphyrin indicates iron-deficient erythropoiesis. Protoporphyrin concentrations may also be elevated by inflammation and lead exposure. 

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