Most absorbed lead (80% to 85%) is taken up into developing teeth and into bone, where it competes with calcium, binds phosphates, and has a half-life of 20 to 30 years. About 5% to 10% of the absorbed lead remains in the blood, and the remainder is distributed throughout soft tissues. Excess lead is toxic to nervous tissues in adults and children; peripheral neuropathies predominate in adults, whereas central effects are more common in children. The effects of chronic lead exposure in children may be subtle, producing mild dysfunction, or they may be massive and lethal. In young children, sensory, motor, intellectual, and psychologic impairments have been described, including reduced IQ, learning disabilities, retarded psychomotor
Fig. 8.4 Pathologicfeaturesofleadpoisoning.
Adult: Headache, memory loss Child: Encephalopathy, mental deterioration
BLOOD Anemia, red cell basophilic stippling
PERIPHERAL NERVES Adult: Demyelination
BONES Child: Radiodense deposits in epiphyses development, and, in more severe cases, blindness, psychoses, seizures, and coma. Lead-induced peripheral neuropathies in adults generally remit with the elimination of exposure, but both peripheral and CNS abnormalities in children usually are irreversible. Other effects of lead exposure include the following.
Excess lead interferes with the normal remodeling of calcified cartilage and primary bone trabeculae in the epiphyses in children, causing increased bone density detected as radiodense “lead lines” (
Fig. 8.5 ). Lead lines of a different sort also may occur in the gums, where excess lead stimulates hyperpigmentation. Lead inhibits the healing of fractures by increasing chondrogenesis and delaying cartilage mineralization. Excretion of lead occurs by way of the kidneys, and acute exposures may cause damage to proximal tubules.
Lead has a high affinity for sulfhydryl groups and interferes with two enzymes involved in heme synthesis: aminolevulinic acid dehydratase and delta ferrochelatase. Iron incorporation into heme is impaired, leading to anemia. Lead also inhibits sodium-and potassium-dependent ATPases in cell membranes, an effect that may increase the fragility of red cells, causing hemolysis. The diagnosis of lead poisoning requires constant vigilance. It may be suspected on the basis of neurologic changes in children or unexplained anemia with basophilic stippling in red cells in adults and children. Elevated blood lead and red cell free protoporphyrin levels (greater than 50 µg/dL) or, alternatively, zinc-protoporphyrin levels, are required for definitive diagnosis. In milder cases of lead exposure, anemia may be the only obvious abnormality.
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Fig. 8.5 Leadpoisoning.Impairedremodelingofcalcifiedcartilageintheepiphyses(arrows) ofthewristhascausedamarkedincreaseintheirradiodensity,sothattheyareasradiopaqueasthecorticalbone.(Courtesy of Dr. GW Dietz: Department of Radiology, University of Texas Southwestern Medical School, Dallas,Texas.)
MORPHOLOGYThemajoranatomictargetsofleadtoxicityaretheblood,bonemarrow,nervoussystem,GItract,andkidneys(
Fig.8.4