Lead toxicity: Difference between revisions
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*Stable metallic element (no. 82) | *Stable metallic element (no. 82) | ||
*Incredible environmental burden secondary to inclusion in paints, fuels, and industrial uses | *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 | *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=== | ===MOA=== | ||
*Interferes with the action of divalent cations and sulfhydryl groups | *Interferes with the action of divalent cations and sulfhydryl groups | ||
Line 12: | Line 12: | ||
=====Absorption===== | =====Absorption===== | ||
*Rapidly and completely absorbed from lungs | *Rapidly and completely absorbed from lungs | ||
*Minimal absorption through intact skin | |||
*Variable GI absorption | *Variable GI absorption | ||
**Children absorb more than adults (70% vs. 20%) | **Children absorb more than adults (70% vs. 20%) | ||
**Affected by nutritional status, calcium stores and iron stores | **Affected by nutritional status, calcium stores and iron stores | ||
=====Distribution===== | =====Distribution===== | ||
*Large Vd | *Large Vd | ||
*Distributes to bone, muscles, brain, and blood | *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===== | =====Metabolism===== | ||
*No metabolism as toxin is elemental | *No metabolism as toxin is elemental | ||
Line 25: | Line 32: | ||
**Children retain about 70% while adults only retain about 1% | **Children retain about 70% while adults only retain about 1% | ||
=== | ===References=== | ||
*Lead paint | *Lead paint | ||
*Occupational | *Occupational | ||
*Soil contamination | *Soil contamination | ||
*Water | *Lead dust | ||
*Food | *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 | *Alternative/herbal medications | ||
*Poorly monitored imported products | *Poorly monitored imported products | ||
**Eg. Toys imported from China which were coated in lead paints | **Eg. Toys imported from China which were coated in lead paints | ||
**Eg. plates brought by immigrants from Mexico/South America | |||
*Phased out of gasoline in the 1980s and banned in 1996 | |||
==Clinical Features== | ==Clinical Features== | ||
''Vastly different presentations between children and adults'' | |||
===Adults=== | ===Adults=== | ||
=====Nervous system===== | =====Nervous system===== | ||
*CNS symptoms predominate | *CNS symptoms predominate | ||
*Lethargy, fatigue, [[ | *[[Lethargy]], fatigue, [[headache]], irritability, memory loss, [[tremor]] | ||
*Severe symptoms: [[ | *Severe symptoms: [[altered mental status]], [[coma]], [[seizures]], cerebral edema | ||
*PNS toxicity | *PNS toxicity | ||
**Causes segmental demyelination | **Causes segmental demyelination | ||
Line 47: | Line 60: | ||
***Upper >> Lower extremities | ***Upper >> Lower extremities | ||
***Extensors >> Flexors | ***Extensors >> Flexors | ||
=====Nephro===== | =====Nephro===== | ||
*Highest body levels found in proximal tubules after acute exposure | *Highest body levels found in proximal tubules after acute exposure | ||
**Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase. | **Results in [[proteinuria]], particularly β 2-microglobulin and N-acetylglucosidase. | ||
*associated with slightly decreased GFRs | |||
=====Heme===== | =====Heme===== | ||
*Basophilic stippling | *Basophilic stippling | ||
Line 56: | Line 72: | ||
**Can lead to either a normochromic or hypochromic [[anemia]] | **Can lead to either a normochromic or hypochromic [[anemia]] | ||
=====Reproductive===== | =====Reproductive===== | ||
*Can | *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. | **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 | *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 | *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===== | =====Other===== | ||
*May also have GI upset, vomiting, | *May also have GI upset, [[vomiting]], [[constipation]], elevated [[LFTs]] | ||
* | *[[Myalgia]]s | ||
*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=== | ===Children=== | ||
=====Nervous system===== | =====Nervous system===== | ||
*Encephalopathy appears at lower levels | *'''[[Encephalopathy]]''' appears at lower levels | ||
*Symptoms: Irritability, apathy, fatigue, obtundation | *Symptoms: Irritability, apathy, fatigue, [[altered mental status (peds)|obtundation]] | ||
*Severe symptoms: Cerebral edema, [[ | *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 | |||
*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 | **Cognitive disturbances (from slight learning disability to profound intellectual disability) | ||
**Loss of 5 IQ points per 10μg/dL elevation | |||
**Hyperactivity, aggression and antisocial behaviors | **Hyperactivity, aggression and antisocial behaviors | ||
*Peripheral neuropathy similar | *'''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 | ||
Line 84: | Line 111: | ||
=====Ortho===== | =====Ortho===== | ||
*Disturbs bone development | *Disturbs bone development | ||
** | **Accelerates skeletal maturation which may predispose to osteoporosis later | ||
*Lead lines on radiographs | *Lead lines on radiographs | ||
**Generally correlate with levels above 50μg/dL | **Generally correlate with levels above 50μg/dL | ||
*Associated with development of dental | *Associated with development of [[dental caries]] and periodontal bone loss | ||
==Work-Up== | ==Differential Diagnosis== | ||
{{Heavy metals list}} | |||
==Evaluation== | |||
===Work-Up=== | |||
*Lead level | *Lead level | ||
* | *[[UA]] | ||
*CBC with smear | *CBC with smear | ||
*Chem 7 and divalents | *Chem 7 and divalents | ||
*LFTs | *[[LFTs]] | ||
*'''''DO NOT LP''''' | *'''''DO NOT [[LP]]''''' | ||
**Cerebral edema may lead to herniation | **Cerebral edema may lead to herniation | ||
==Diagnosis== | ====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== | ||
*Chelation | *Environmental Investigations | ||
**EDTA | **government programs provide intervention for lead levels > 10ug/dl | ||
**BAL | *Chelation: | ||
**Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL<ref>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.</ref> | |||
**Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL | |||
*[[Penicillamine]] and [[Succimer]] | |||
**Oral medications | |||
**Only used in children <ref>Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.</ref> | |||
**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 ([[dimercapro]]l) | |||
**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 | |||
==See Also== | ==See Also== | ||
*[[Heavy Metals]] | *[[Heavy Metals]] | ||
== | ==References== | ||
<references/> | |||
*Haddad and Winchester's Clinical Management of Poisoning and Overdose | *Haddad and Winchester's Clinical Management of Poisoning and Overdose | ||
*http://www.cdc.gov/nceh/lead/ | *http://www.cdc.gov/nceh/lead/ | ||
*http://www.nytimes.com/2007/06/19/business/worldbusiness/19toys.html?pagewanted=all&_r=0 | *http://www.nytimes.com/2007/06/19/business/worldbusiness/19toys.html?pagewanted=all&_r=0 | ||
[[Category: | <references/> | ||
[[Category:Toxicology]] |
Revision as of 17:44, 16 October 2019
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%
References
- 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
- 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
Heavy metal toxicity
- 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
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