Lead toxicity

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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
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

Diagnosis

  • Lead levels

Work-Up

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

Treatment

  • Chelation
    • EDTA
    • BAL

Source