Lead disrupts the normal physiological effects of calcium, causing inappropriate release of neurotransmitters, and interferes with excitatory neurotransmission by glutamate, especially the N-methyl-D-aspartate (NMDA) receptor, which is blocked selectively by lead. Disruption of NDMA-medi-ated long-term potentiation is believed to be responsible for the cognitive manifestations of lead toxicity, especially in children. At higher blood levels, lead disrupts the function of endothelial cells in the blood-brain barrier, causing subsequent hemorrhagic encephalopathy, seizures, and coma (see Chapter 9 for biological monitoring) (13,14).
Mental status examination may detect changes in more severe cases of lead toxicity, while detailed neuropsychological testing is often needed to diagnose the less obvious cases. In both children and adults, impaired fine-motor coordination or subtle visual-spatial impairment may be seen, while chronic distal motor neuropathy with decreased reflexes and weakness of extensor muscles and relatively spared sensory function is more common in adults (15).
In addition to common environmental sources of lead (paint and leaded gasoline), identification of some of the sources of lead may present a challenge, since cosmetics ("surma" or kohl in the Middle East), folk remedies (often applied to the umbilical stumps of infants), and even alternative medical remedies may contain lead. A puzzling use of lead acetate is as an aphrodisiac, which has been reported historically and in some areas of Latin America (15).
Blood lead levels higher than 10 |g/dL are considered toxic, but no level of lead, no matter how minute, is considered safe. A complete blood count (CBC) with peripheral smear may demonstrate basophilic stippling of the red blood cells (RBCs), a finding also observed in arsenic toxicity, sideroblastic anemia, thalassemia, and normocytic or microcytic anemia (11,12,15).
Cerebral edema and microhemorrhages may be seen on magnetic resonance imaging (MRI) in patients presenting with encephalopathy. Patchy calcifications, although not specific, are seen on MRIs of patients with chronic lead exposure. In adults, neurophysiological testing may be helpful if symptoms of lead-induced neuropathy are seen (15).
The key to treating lead toxicity is removal of the offending agent and reducing the total body load. Chelation agents [calcium disodium ethylenedi-aminetetraacetic acid (CaNa2 EDTA), dimercaprol, 2,3-dimercaptosuccinic acid (DMSA)] are used to reduce the body stores of lead. Treatment for acutely ill patients includes whole-bowel irrigation with polyethylene glycol electrolyte solution if radiographic evidence of lead toxicity is present (15).
A water-soluble, oral chelating agent, DMSA (succimer, Chemet®), is appropriate for use with blood lead levels ranging from 40 to 70 |g/dL. It is contraindicated in children with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or those allergic to sulfa drugs. D-penicillamine (Cuprimine) is a second-line oral chelating agent, although it is not approved by the U.S. Food and Drug Administration (FDA) for use in lead poisoning (15).
Calcium disodium ethylenediaminetetraacetic acid (CaNa2 EDTA) is a parenteral chelating agent that is administered intravenously to patients with blood lead levels in the range of 40 to 70 | g/dL who do not respond to suc-cimer or cannot take it. In addition, it is used immediately before oral succimer in patients with blood lead levels higher than 70 |g/dL (15).
Dimercaprol [British antilewisite (BAL)] is another parenteral chelating agent recommended by some authors as an agent of first choice. With high blood lead levels (> 100 |g/dL), it is used in conjunction with CaNa2 EDTA (16).
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