Action produced by lead B Inhibition I I Postulated inhibition

figure 65-1 Lead interferes with the biosynthesis of heme at several enzymatic steps. Steps that definitely are inhibited by lead are indicated by blue blocks. Steps at which lead is thought to act but where evidence for this is inconclusive are indicated by gray blocks.

with concentrations of >75 mg/dL of whole blood, and lead encephalopathy usually is apparent when lead concentrations exceed 100 mg/dL.

The urinary concentration of lead in normal adults generally is <80 mg/L (0.4 mM). Most patients with lead poisoning show concentrations of lead in urine of 150—300 mg/L (0.7-1.4 mM). However, in persons with chronic lead nephropathy or other forms of renal insufficiency, urinary excretion of lead may be within the normal range, even though blood lead concentrations are significantly elevated.

Because the onset of lead poisoning usually is insidious, it often is desirable to estimate the body burden of lead in individuals who are exposed to an environment that is contaminated with the metal. In the past, the edetate calcium disodium (CaNa-EDTA) provocation test was used to determine whether there is an increased body burden of lead in those for whom exposure occurred much earlier. The provocation test is performed by intravenous administration of a single dose of CaNa2EDTA (50 mg/kg) followed by collection of urine for 8 hours. The test is positive for children when the lead excretion ratio (mg of lead excreted in the urine per mg of CaNa2EDTA administered) is >0.6; it also may be useful for therapeutic chelation in children with blood levels of 25-45 mg/dL. This test is not used in symptomatic patients or in those whose concentration of lead in blood is >45 mg/dL because these patients require the proper therapeutic regimen with chelat-

ing agents (see below). ORGANIC LEAD POISONING

Tetraethyl lead and tetramethyl lead are lipid-soluble compounds that are absorbed readily from the skin, GI tract, and lungs. The toxicity of tetraethyl lead is believed to be due to its metabolic conversion to triethyl lead and inorganic lead. The major symptoms of intoxication with tetraethyl lead are referable to the CNS: insomnia, nightmares, anorexia, nausea and vomiting, diarrhea, headache, muscular weakness, and emotional instability. Subjective CNS symptoms such as

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