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lead poisoning

Monday 23 March 2009

More than 4 million tons of lead are produced each year for use in batteries, alloys, exterior red lead paint, and ammunition. Workers employed in these industries as well as in mining, smelting, spray painting, recycling, and radiator repair are exposed to lead. In some countries, tetraethyl lead is still used as a gasoline additive, thus polluting the air.

Inhalation is the most important route of occupational exposure. Environmental sources of lead are urban air due to use of leaded gasoline, soil contaminated with exterior lead paint, the water supply due to lead plumbing, and house dust in homes with interior lead paint. Consumers may be exposed to lead-glazed ceramics, lead solder in food and soft drink cans, and illegally produced alcoholic beverages (moonshine). Lead ingested in this manner is absorbed through the gastrointestinal tract.

Intestinal absorption of lead is enhanced by calcium, iron, or zinc deficiency; compared with adults, the absorption is greater in children and infants and hence they are particularly vulnerable to lead toxicity. Absorbed lead is mainly (80% to 85%) taken up by bone and developing teeth in children; the blood accumulates 5% to 10%, and the remainder is distributed throughout the soft tissues. Lead clears rapidly from blood, but that deposited in bones has a half-life of 30 years. Thus, the presence of lead in blood indicates recent exposure, and it does not allow the determination of total body burden.

Lead has no known physiologically relevant role in the body. The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme’s ability to catalyze its normal reaction(s).

Lead is removed from the body extremely slowly (mainly through urine, normally at a rate of 0.5 µmol/L), causing accumulation in the tissues. 95% of the absorbed lead is deposited as a lead phosphate complex in the bones.

lead toxicity

Most lead poisoning symptoms are thought to occur by interfering with an essential enzyme delta-aminolevulinic acid dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the cofactor found in hemoglobin.

Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form heme. Genetic mutations of ALAD cause the disease porphyria, a disease which was highlighted in the movie The Madness of King George.

Lead poisoning is sometimes mistaken for porphyria but the distinction is that lead poisoning usually causes anemia while true porphyria does not.

The toxicity of lead is related to its multiple biochemical effects:

- High affinity for sulfhydryl groups. The most important enzymes inhibited by lead due to this mechanism are involved in heme biosynthesis: δ-aminolevulinic acid dehydratase and ferroketolase. These enzymes catalyze the incorporation of iron into the heme molecule, and hence patients develop hypochromic anemia.

- Competition with calcium ions. As a divalent cation, lead competes with calcium and is stored in bone. It also interferes with nerve transmission and brain development.

- Inhibition of membrane-associated enzymes. Lead inhibits 5’-nucleotidase activity and sodium-potassium ion pumps, leading to decreased survival of red blood cells (hemolysis), renal damage, and hypertension.

- Impaired production of 1,25-dihydroxyvitamin D, the active metabolite of vitamin D.

Lead contributes to multiple chronic health effects. Injury to the central and peripheral nervous systems causes headache, dizziness, memory deficits, and decreased nerve conduction velocity. Blood changes occur early and are characteristic.

Because lead interferes with heme biosynthesis, it causes a microcytic hypochromic anemia; punctate basophilic stippling of erythrocytes is characteristic. There is also an element of hemolysis because lead inhibits membrane-associated red cell enzymes. Because lead inhibits incorporation of iron into heme, the iron is displaced, and zinc protoporphyrin is formed. Thus, an elevated blood level of zinc protoporphyrin or its product, free erythrocyte protoporphyrin, is an important indicator of lead poisoning.

Gastrointestinal symptoms include colic and anorexia. The kidneys are a major route of excretion of lead. Acutely, there is damage to the proximal tubules, with intranuclear lead inclusions and clinical evidence of renal tubule dysfunction. Chronically, lead can cause diffuse interstitial fibrosis, gout, and renal failure.

Even in the absence of overt clinical symptoms of kidney damage, lead causes hypertension. Lead can cause infertility in men due to testicular injury; failure of implantation of the fertilized ovum can occur in women.

Infants and children are especially vulnerable to lead toxicity. It is estimated by the CDC that in the year 2000 approximately 454,000 children in the United States had blood lead levels greater than 10 μg/dL.

Even below this level there is an inverse correlation between blood lead concentration and IQ scores. Very slightly elevated blood levels (∼3 μg/dL) in young females have also been reported to delay puberty.

Thus, lead toxicity continues to be a matter of concern. Lead may be mobilized from the maternal skeleton during pregnancy and readily crosses the placental barrier. Hence lead exposure can begin in utero. Similar to neurotoxicity caused by methylmercury, the developing nervous system of the fetus and infants is extremely susceptible to lead toxicity.