Lead toxicity: Difference between revisions

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===Children===
===Children===
=====Nervous system=====
=====Nervous system=====
*Encephalopathy appears at lower levels
*'''Encephalopathy''' appears at lower levels
*Symptoms: Irritability, apathy, fatigue, obtundation
*Symptoms: Irritability, apathy, fatigue, obtundation
*Severe symptoms: Cerebral edema, [[seizures]]
*Severe symptoms: Cerebral edema, [[Seizures]]
*Can lead to permanent changes in brain architecture
*Can lead to permanent changes in brain architecture
**Inhibits enzymes that mediate arborization of synapses and neuronal cellular adhesion molecules
**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
**Hippcampus thought to be primary sight of action secondary to high zinc levels
*Disturbs blood brain barrier permeability which can be chronic
*Disturbs blood brain barrier permeability which can be chronic
*Long term sequelae  
*'''Long term sequelae'''
**Cognitive disturbances (from slight learning disability to profound mental retardation)
**Cognitive disturbances (from slight learning disability to profound mental retardation)
***Loss of 5 IQ points per 10μg/dL elevation  
**Loss of 5 IQ points per 10μg/dL elevation  
**Hyperactivity, aggression and antisocial behaviors
**Hyperactivity, aggression and antisocial behaviors
*Peripheral neuropathy similar to adults
*'''Peripheral neuropathy''' similar in adults and children<ref>Lead exposure in children: prevention, detection, and management. Pediatrics. Oct 2005;116(4):1036-46.</ref>
 
=====Nephro=====
=====Nephro=====
*Impaired [[Vitamin D]] activation
*Impaired [[Vitamin D]] activation

Revision as of 16:48, 16 December 2014

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 symptoms: 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 in adults and children[1]
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

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:
    • Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL
    • Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
  • Penicillamine and Succimer
    • Oral medications
    • Only used in children
    • Succimer has not been studied for Lead levels >60ug/dL
    • Penicillamine: second-line agent, requires B6 supplementation
  • IV/IM EDTA (edetate calcium disodium)
    • do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
    • Must have given BAL for at least 4h if Lead >100ug/dL
  • IM BAL (dimercaprol)
    • First line agent if encephalopathy present
    • excreted in bile, can use in renal failure

See Also

Source

  1. ↑ Lead exposure in children: prevention, detection, and management. Pediatrics. Oct 2005;116(4):1036-46.
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