Trace Element and Micronutrient Unit
Scotland's specialised laboratory for trace elements and vitamins in health and disease
Metabolism of Lead
In adults some 5-10% of orally ingested lead is absorbed from the gastrointestinal tract. In children absorption is higher and values of up to 30-50% have been quoted. Lead inhaled as dust and accumulated on the lung surfaces is variably absorbed depending upon the particle size and the lead compounds involved. As much as 50% of the lead contained in automobile exhaust fumes reaches the blood stream. Absorbed lead is transported on the surface of the red cell and less than 5% is bound to plasma proteins. Lead is taken up by most tissues but, after equilibration is complete, more than 95% is deposited in skeletal bone as a lead phosphate complex. Lead is poorly excreted from the body and continued exposure causes tissue accumulation. The most important route of excretion is in urine, but normally this is less than 0.5 µmol/l. On a group basis the increased excretion of lead in urine of exposed workers is a useful index, but individual variations are large.
The promotion of a lead diuresis by administration of chelating agents (penicillamine, EDTA) is a standard therapeutic measure in severe cases of symptomatic lead poisoning. Then sequential measurements of urinary lead output are useful
Lead ions can complex with ligands such as -SH, and -COOH and the imidazole groups of proteins. This means that Pb2+ affects numerous enzyme pathways. Resultant general depression of energy metabolism and of protein and nucleic acid synthesis causes a reduction in cell division and effects on growth. Practical use is made of the inhibitory effects of lead on various stages of haem biosynthesis. A decrease in the activity of red cell d -aminolaevulinic acid dehydratase (ALA-D) is seen even at low levels of lead exposure. Inhibition of ferrochelatase is detected by a build-up on the red cell of protoporphyin, and increases in plasma and tissue iron. Red cell protoporphyrin is in the form of a highly fluorescent Zn-protoporphyrin (ZPP) which can be measured readily with a filter fluorimeter. Inhibition of ALA-D is almost complete when blood lead concentrations reach 1.5-2.0 µmol/l at which point there is a detectable increase in red cell ZPP. The increased urinary excretion of porphyrin metabolites, coproporphyrin II and d -aminolaevulinic acid are useful on a group basis but have been superseded by the more sensitive and convenient blood porphyrin measurements.
The continued inhibition by lead of haem biosynthesis and a reduction in protein synthesis causes anaemia, but this is now recognised as a late effect of lead poisoning. Lead poisoning can also be recognised through basophilic stippling of the red cells.
Sources of Lead Exposure