Lead toxicity

(Redirected from Lead)

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 mostly due to banning lead in gasoline

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
  • Minimal absorption through intact skin
  • 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
  • After weeks mostly in the bones and teeth
    • In adults 94% of total body lead is in the bones and teeth
  • Some lead can leave the bones and re-enter blood under certain circumstances
    • Pregnancy, periods of breast feeding, fractures, advanced age
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
  • Lead dust
  • Water (old pipes, especially when the water is "soft" or acidic)
  • batteries (especially car), weights, ammunition
  • Food (leafy green vegetables grown in lead-containing soil)
  • Moonshine (made in stills that contain lead-soldered parts)
  • Alternative/herbal medications
  • Poorly monitored imported products
    • Eg. Toys imported from China which were coated in lead paints
    • Eg. plates brought by immigrants from Mexico/South America
  • Old gasoline (phased out of gasoline in the 1980s and banned in 1996)

Clinical Features

Vastly different presentations between children and adults

Adults

Nervous system
Nephro
  • Highest body levels found in proximal tubules after acute exposure
    • Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase.
  • associated with slightly decreased GFRs
Heme
  • Basophilic stippling
    • From precipitation of nuclear contents
  • Inhibitor of heme synthesis
    • Can lead to either a normochromic or hypochromic anemia
Reproductive
  • Can cross 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
  • May cause preterm labor and low birth weights
  • May slow mental development and cause lower intelligence later in childhood
  • Decreased sperm counts
Endocrine
  • changes in T4 and TSH (generally with PbB > 40-60ug/dl)
  • altered levels of testosterone, leutonizing hormone, FSH at PbB > 30-40ug/dl
Other
  • May also have GI upset, vomiting, constipation, elevated LFTs
  • Myalgias
  • associated with increased mortality due to cardiovascular disease
  • associated with increased blood pressure
  • May see thin, blue/black line along gingiva, known as Burton's line (more common in chronic poisoning)

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 intellectual disability)
    • 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
    • Accelerates skeletal maturation which may predispose to osteoporosis later
  • Lead lines on radiographs
    • Generally correlate with levels above 50μg/dL
  • Associated with development of dental caries and periodontal bone loss

Differential Diagnosis

Background

Heavy metal toxicity results from exposure to metals like lead, mercury, arsenic, or cadmium, which interfere with cellular function. Exposure may occur occupationally, environmentally, through ingestion, or from alternative medicines. Chronic toxicity can present insidiously, while acute toxicity may mimic sepsis or encephalopathy. Diagnosis is often delayed due to nonspecific symptoms.

Clinical Features

Symptoms depend on the metal and exposure duration but may include:

Neurologic: Peripheral neuropathy, confusion, tremor, encephalopathy

GI: Abdominal pain, nausea, vomiting, diarrhea, anorexia

Heme: Anemia (especially microcytic or hemolytic), basophilic stippling (lead)

Renal: Tubular dysfunction, proteinuria, Fanconi syndrome

Dermatologic: Mees’ lines (arsenic), hyperpigmentation, hair loss

Others: Fatigue, weight loss, hypertension (cadmium), immunosuppression

Differential Diagnosis

Sepsis or systemic inflammatory response

Drug toxicity or overdose

Metabolic disorders (e.g., porphyria, uremia)

Psychiatric illness (if symptoms are vague or bizarre)

Neurologic diseases (e.g., Guillain-Barré, MS, Parkinson’s)

Vitamin deficiencies (e.g., B12, thiamine)

Evaluation

Workup

History: Occupational exposures, home remedies, hobbies (e.g., jewelry making, battery recycling), diet, water source, imported goods

Labs:

  • CBC, CMP, urinalysis
  • Blood lead level, serum/urine arsenic, mercury, or cadmium (based on suspicion)
  • Urine heavy metal screen (note: spot testing may require creatinine correction)

Imaging: Abdominal X-ray (radiopaque material in GI tract, especially with lead)

EKG: Evaluate for QT prolongation or arrhythmias in severe cases

Diagnosis

Confirmed by elevated blood or urine levels of the specific metal in the context of clinical findings. Hair and nail testing are unreliable for acute toxicity. Interpret results with toxicologist input if possible.

Management

Remove the source of exposure (e.g., occupational control, GI decontamination if recent ingestion)

Supportive care: IV fluids, seizure control, electrolyte repletion

Chelation therapy (in consultation with toxicology or Poison Control):

Lead: EDTA, dimercaprol (BAL), succimer

Mercury/arsenic: Dimercaprol or DMSA

Cadmium: No effective chelation—focus on supportive care

Notify local public health authorities if exposure source is environmental or occupational

Disposition

Admit if symptomatic, unstable, or requiring chelation

Discharge may be appropriate for asymptomatic patients with low-level exposure and outpatient follow-up

Arrange toxicology or environmental medicine follow-up for source control and serial testing

See Also

Evaluation

X-ray demonstrating the characteristic finding of dense metaphyseal lines in lead poisoning.
Lead toxicity resulting from an intra-articular retained bullet.

Work-Up

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

CDC Recommendations for Lead Testing

  • at age 1 and 2 years
  • at ages 3-6 if never tested for lead
  • if they received services from public assistance programs for the poor such as Medicaid or WIC
  • if they live in a building or frequently visit a house built before 1978 that has recently been remodeled
  • if they have a brother/sister or playmate who has had lead poisoning

Diagnosis

  • Based on lead level

Management

  • Environmental Investigations
    • government programs provide intervention for lead levels > 10ug/dl
  • Chelation:
    • Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL[2]
    • Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
  • Penicillamine and Succimer
    • Oral medications
    • Only used in children [3]
    • Succimer has not been studied for Lead levels >60ug/dL
    • Succimer 10mg/kg TID x 5d THEN 10mg/kg BID x 14d
    • Penicillamine: second or third-line agent, requires B6 supplementation, contraindicated in patients allergic to penicillin, not approved during pregnancy, more toxic than Succimer
    • Penicillamine dose: 20-40 mg/kg/day PO divided q8hr
    • Penicillamine reported adverse effects include: rash, fever, anorexia, leukopenia, thrombocytopenia, hemolytic anemia, SJS, nephrotoxicity, proteinuria
  • IM BAL (dimercaprol)
    • First line agent if encephalopathy present
      • Consider giving first before EDTA, regardless of encephalopathy
      • As EDTA, if given first, may chelate lead and cross blood brain barrier
    • Onet of action 30 minutes
    • Increases fetal excretion of lead as chelated lead is excreted primarily in bile after 4-6 hours
    • Also increases urinary excretion of chelated lead
    • Agent of choice in renal failure
    • Dosage of 50-75mg/m^2 every 4 hours, full course is 3-5 days
    • Contraindications: liver failure, G6PD (develop hemolysis), peanut oil allergy, pregnancy
  • 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 or encephalopathy present
    • Increases renal excretion of lead 20-50 times
    • Children: 1-1.5gm/m^2/24hrs given in up to 6 divided daily doses
    • Adults: 1.5gm/24hrs in 2 divided doses
    • Full course of treatment is 5 days, may be repeated if patient still symptomatic or PbB > 50ug/dl

Disposition

See Also

References

  1. ↑ Lead exposure in children: prevention, detection, and management. Pediatrics. Oct 2005;116(4):1036-46.
  2. ↑ Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?. J Occup Health. 2009;51(1):1-12.
  3. ↑ Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.


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