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 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
- CNS symptoms predominate
- Lethargy, fatigue, headache, irritability, memory loss, tremor
- Severe symptoms: altered mental status, 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.
- 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
- Impaired vitamin D activation
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
- Aluminum toxicity
- Antimony toxicity
- Arsenic toxicity
- Barium toxicity
- Bismuth toxicity
- Cadmium toxicity
- Chromium toxicity
- Cobalt toxicity
- Copper toxicity
- Gold toxicity
- Iron toxicity
- Lead toxicity
- Lithium toxicity
- Manganese toxicity
- Mercury toxicity
- Nickel toxicity
- Phosphorus toxicity
- Platinum toxicity
- Selenium toxicity
- Silver toxicity
- Thallium toxicity
- Tin toxicity
- Zinc toxicity
Evaluation

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
- First line agent if encephalopathy present
- 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
- ↑ Lead exposure in children: prevention, detection, and management. Pediatrics. Oct 2005;116(4):1036-46.
- ↑ 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.
- ↑ Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.
- 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