Inorganic Lead

PHARMACOLOGY Absorption is by the respiratory and gastrointestinal tracts, whereas skin absorption is negligible. Dietary deficiencies in calcium, iron, copper, and zinc may contribute to increased gastrointestinal absorption in children. Absorption also occurs when retained lead bullets or shot are in contact with body fluids such as synovial fluid. Lead can be transferred placentally to the fetus of a mother with an elevated blood lead level, which can be further exacerbated by increased bone turnover during pregnancy. In the body, lead distributes into the blood, soft tissues, and bone. Greater than 90 percent of the total-body lead is stored in bone, where it easily exchanges with the blood. Excretion of lead occurs slowly; the biologic half-life of lead in bone has been estimated to be 30 years.

PATHOPHYSIOLOGY In the CNS lead injures astrocytes, with secondary damage to the microvasculature and resulting disruption of the blood-brain barrier, 5 cerebral edema, and seizures; decreases cyclic adenosine monophosphate (CAMP) and protein phosphorylation, which contribute to memory and learning deficits; and alters calcium homeostasis, which leads to spontaneous neurotransmitter release. In the peripheral nervous system (PNS), nerves undergo primary segmental demyelination, followed by secondary axonal degeneration, primarily of the motor nerves. In the hematopoietic system, lead interferes with porphyrin metabolism, which may contribute to lead-induced anemia (Fig 1.78-1). The two enzymes chiefly affected are D-aminolevulinic acid dehydratase and ferrochelatase, the latter being the enzyme that catalyzes the transfer of iron from ferritin to protoporphyrin to form hemoglobin. Coexisting iron deficiency may act synergistically with lead toxicity to produce a more profound anemia and, in children, may be more important than lead as the cause of a microcytic anemia. Hemolytic anemia also occurs as a result of inhibition of red blood cell (RBC) pyrimidine 5'-nucleotidase, an enzyme responsible for clearing cellular RNA degradation products. On a blood peripheral smear, these products produce the RBC basophilic stippling sometimes seen in lead-poisoned patients.

FIG. 178-1. Effects of lead on the hematopoietic system. *Enzymes affected by lead. ^Levels elevated in urine. tLevel elevated in RBCs.

In the kidney, acute lead toxicity affects the proximal tubule, producing a Fanconi syndrome with aminoaciduria, glycosuria, phosphaturia, and renal tubular acidosis.

Chronic effects include persistence of a partial Fanconi syndrome for 13 years or longer, 6 interstitial nephritis, and increased uric acid levels due to increased tubular reabsorption of urate. Chronic lead toxicity has been linked with gout, hypertension, and chronic renal failure.

Toxic hepatitis with mildly elevated transaminases, normal bilirubin, and normal alkaline phosphatase can occur. Lead-induced adverse effects on the reproductive system include increased fetal wastage, premature membrane rupture, depressed sperm counts, abnormal/nonmotile sperm, and sterility. Chronic lead toxicity can depress free thyroxine levels without producing clinical hypothyroidism.

CLINICAL FEATURES The common signs and symptoms of acute, chronic, and delayed toxicity are listed in T§ble..JZ8-2, Young children are more susceptible than adults to the effects of lead. Encephalopathy, a major cause of morbidity and mortality, may begin dramatically with seizures and coma or develop indolently over weeks to months with decreased alertness and memory progressing to mania, delirium, and cerebral edema.Z It has developed in infants with blood lead levels of 70 pg/dL or less. Gastrointestinal and hematologic manifestations occur more frequently with acute than with chronic poisoning, and the colicky abdominal pains may be associated with concurrent hemolysis. Patients may complain of a metallic taste and, with long-term exposure, have bluish-gray gingival lead lines. Delayed cognitive development can occur in infants and children whose cord and blood lead (PbB) levels are 10 pg/dL or more. Finally, adult and pediatric patients may be asymptomatic in the face of significantly elevated PbB levels.

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