Lead toxicity

Background

• Stable metallic element (no. 82)
• Incredible environmental burden secondary to inclusion in paints, fuels, and industrial uses
• Average blood levels in US have fallen from 12.8 mcg/dL in the late 1970's to 2mcg/dL

MOA

• Interferes with the action of divalent cations and sulfhydryl groups
  • Particularly toxic to Zinc containing enzymes
  • Binds to calcium activated enzymes with 10,000x great affinity that calcium
• Directly toxic to renal tubules

Toxicokinetics

Absorption

• Rapidly and completely absorbed from lungs
• Variable GI absorption
  • Children absorb more than adults (70% vs. 20%)
  • Affected by nutritional status, calcium stores and iron stores

Distribution

• Large Vd
• Distributes to bone, muscles, brain, and blood

Metabolism

• No metabolism as toxin is elemental

Excretion

• Excreted in urine and stool
• Amount excreted varies with age
  • Children retain about 70% while adults only retain about 1%

Sources

• Lead paint
• Occupational
• Soil contamination
• Water
• Food
• Alternative/herbal medications
• Poorly monitored imported products
  • Eg. Toys imported from China which were coated in lead paints

Clinical Features

• Vastly different presentations between children and adults

Adults

Nervous system

• CNS symptoms predominate
• Lethargy, fatigue, Headache, irritability, memory loss, tremor
• Severe symptoms: AMS, coma, Seizures, cerebral edema
• PNS toxicity
  • Causes segmental demyelination
  • Peripheral neuropathy
    • Upper >> Lower extremities
    • Extensors >> Flexors

Nephro

• Highest body levels found in proximal tubules after acute exposure
  • Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase.

Heme

• Basophilic stippling
  • From precipitation of nuclear contents
• Inhibitor of heme synthesis
  • Can lead to either a normochromic or hypochromic anemia

Reproductive

• Can cause placenta
  • Because lead is stored in bones and there is higher bone turnover during pregnancy, women with previous lead toxicity can have lead intoxicated children despite mother being asymptomatic.
• Higher rate of stillbirths and spontaneous abortion
• Decreased sperm counts

Other

• May also have GI upset, vomiting, constiptation, elevated LFTs
• Myalgias

Children

Nervous system

• Encephalopathy appears at lower levels
• Symptoms: Irritability, apathy, fatigue, obtundation
• Severe symptosm: Cerebral edema, Seizures
• Can lead to permanent changes in brain architecture
  • Inhibits enzymes that mediate arborization of synapses and neuronal cellular adhesion molecules
    • Hippcampus thought to be primary sight of action secondary to high zinc levels
• Disturbs blood brain barrier permeability which can be chronic
• Long term sequelae
  • Cognitive disturbances (from slight learning disability to profound mental retardation)
    • Loss of 5 IQ points per 10μg/dL elevation
  • Hyperactivity, aggression and antisocial behaviors
• Peripheral neuropathy similar to adults

Nephro

• Impaired Vitamin D activation

Heme

• Similar to adults

Ortho

• Disturbs bone development
  • Can lead to arrest in growth
• Lead lines on radiographs
  • Generally correlate with levels above 50μg/dL
• Associated with development of dental carries

Work-Up

• Lead level
• U/A
• CBC with smear
• Chem 7 and divalents
• LFTs
• DO NOT LP
  • Cerebral edema may lead to herniation

Diagnosis

• Lead levels

Treatment

• Chelation
  • EDTA
  • BAL

See Also

• Heavy Metals

Source

• Uptodate
• Haddad and Winchester's Clinical Management of Poisoning and Overdose
• http://www.cdc.gov/nceh/lead/
• http://www.nytimes.com/2007/06/19/business/worldbusiness/19toys.html?pagewanted=all&_r=0