Transcript blood

Heavy Metal Toxicity
Lead
Mercury
By :Soltani M.D
occupational medicine specialist
Definitions
‘Metals’ originally included only gold, silver, copper, iron,
lead, and tin.
Dense, malleable, lustrous
Conduct heat and electricity, cations
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Many other elements since added to the list with some of
these characteristics
‘Metalloids’ are elements with features intermediate
between metals and non-metals. Example: arsenic
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Periodic Table
‘Heavy metal’
A metal having an atomic weight greater
than sodium, a density greater than 5
g/cm3
 Some notion of toxicity
 Usually includes lead, cadmium and
mercury
 Many others may variably be added to list
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Acute single exposures
urine
Metal levels
blood
time
exposure
Case Presentation
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15-month old boy was treated with ampicillin for
abdominal pain and diarrhea. The problem
continued and the parent gave the child multiple
doses of a Central American “home remedy” called
azarcon. The child developed seizures. PE BP
103/68, P 94, RR 22, Tmax 98 F. Exam: listless,
with poor motor tone. No neck stiffness, the heart,
lungs and abdomen were unremarkable. Sz reoccurred. WBC 9.6 no anemia, Plts Nl, Lytes nl, UA
nl Spinal tap was nl, with elevated opening
pressure, cerebral edema was found on Cat Scan of
the Head.
Case (cont)
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The child was intubated, given lorazepam,
fosphenatoin and phenobarbital without control
of the Sz. An x-ray reveled a radiopaque image
in the GI tract.
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The child expired, despite aggressive supportive
care.
What is azarcon?
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Azarcon
Azarcon is a folk remedy that contains 8596% lead tetroxide
 Other lead containing remedies include
Greta.
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Case (cont.)
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The child was found to have a blood lead
level of 124 ug/dl., and died from lead
encephalopathy.
Lead
Background:
The earliest toxicities
Lead have no function in human body
Soft , Malleable , Blue –gray , High density , Corrosion resistance
Some Sources of Lead Exposure
Battery manufacturing
Chemical industry
Construction workers
Plastics industry
Welders
Jewelers
production
Gasoline additives
Occupational exposure
Pigment manufacturing
Lead miners
Pipe fitters
Pottery workers
Radiator repair
Rubber industry products
Soldering of lead
Solid waste production
Printers
Casting bullets or fishing sinkers
Home remodeling
firing ranges
Target shooting at
Stained glass making
Lead soldering
Auto repair
Glazed pottery making
Some folk remedies
Some "Health Foods"
Substance Use
Moonshine whiskey
Ceramic ware
Toxicology
Absorption
Respiratory (30 to 40 % ): dependent on: particle size
Solubility
respiratory
volume
physiologic interindividual
variation
Gastrointestinal systems: (10 to 15% )
adults < children
Skin:
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Inorganic lead is not absorbed
Organic lead is well absorbed
Lead is carried bound to the RBC
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Increased Absorption: deficient in calcium, iron, phosphorus or Zinc
Distribution :
absorbed in bloodstream (ingestion or inhalation)
highest concentrations: in bone, teeth, liver, lungs,
kidneys, brain and spleen.
Lead half-life: in blood 35 days
in soft tissue 40 days
in bone 20 to 30 years
renal
gastrointestinal
Excretion
nails
excreted quite slowly from the body
sweat
biologic half-life estimated at 10 years
accumulation in the body occurs easily
OSHA Lead Standards for Air and
Blood
PEL: 50 µg per m3
Action level : 30 µg per m3
Medical removal from exposure:
>=60 µg per dL
average of last three levels >=50 µg /dL
Neurological Effects
Gastrointestinal Effects
Heme Synthesis
Renal Effects
Health effects
of lead
Other
Reproductive Effects
Clinical Effects In Adults
Acute Inorganic Lead Toxicity
Excessive exposure in brief period
syndrome.
Acute lead poisoning
Classic clinical findings :
Abdominal colic
Constipation
Fatigue
CNS dysfunction
Acute encephalopathy
Coma
Convulsions
In milder exposures :
headaches
personality changes
Chronic Inorganic Lead Toxicity
Symptoms: Arthralgias
Headache
Weakness
Depression
Loss of libido
Impotence
Vague gastrointestinal difficulties
Late effects :
Chronic renal failure
Hypertension
Gout
Chronic encephalopathy
Range of Lead-induced Health
Effects in Adults and Children
Blood lead
levels
Adults
Children
10 g/dL
Hypertension may occur
•Crosses placenta
•Impairment IQ, growth
•Partial inhibition of heme
synthesis
20 g/dL
Inhibition of heme synthesis
Increased erythrocyte
protoporphyrin
Beginning impairment of nerve
conduction velocity
30 g/dL
•Systolic hypertension
•Impaired hearing()
Impaired vitamin D metabolism
40 g/dL
•Infertility in males
•Renal effects
•Neuropathy
•Fatigue, headache, abd pain
Hemoglobin synthesis inhibition
50 g/dL
Anemia, GI sx, headache,
tremor
Colicky abd pain, neuropathy
100 g/dL
Lethargy, seizures,
encephalopathy
Encephalopathy, anemia,
nephropathy, seizures
Childhood Lead Poisoning
Childhood lead poisoning is now defined 
as a blood lead level of 10 g/dl
Medical Examination of Lead-Exposed Workers
Medical and occupational history
Attention to lead exposure history (occupational
and nooccupational)
Personal and workplace hygiene
History of(GI, hematologic, renal, reproductive and
neurologic) disorders
Blood pressure measurement
Physical examination
Attention to neurologic and hematologic abnormalities
pulmonary evaluated
Blood testing
Blood lead level
Zinc protoporphyrin or free erythrocyte protoporphyrin level
Hemoglobin, hematocrit and peripheral smear
U/A with microscopic examination
Supplementary laboratory tests as deemed clinically indicated
What Lead Levels are Considered Elevated in Adults?
B.L>80 μg/dL, serious, permanent health damage.
50 - 80 μg/dL, serious health damage.
30 - 50 μg/dL, health damage, even if no symptoms.
20-30 μg/dL, regular exposure. some evidence of potential
physiologic problems.
1-20 μg/dL, lead is building up in the body.
Primary Prevention of Lead Poisoning
Engineering controls
Personal protective equipment
Work practices
Housekeeping activities to remove lead dust
Personal hygiene practices
Periodic inspection
Secondary prevention
All health care providers should be aware of (OSHA) Lead Standard.
If lead exposure is suspected, the patient's medical evaluation should include:
An occupational and environmental history.
Laboratory testing for blood lead and ZPP levels
If elevated
Ph/E includes:
1)lab testing : Hb,Hct, RBC indices, PBS, BUN,Cr,U/A ,pregnancy or male fertility
BLL>25 μg/dL shows :substantial exposure to lead
increasing health effects
Tertiary prevention
Possible treatment :
Removal
Drug
Drug
DMSA:30 mg/kg/d for 5 day
20mg/kg/d for 20 day
 EDTA:25 mg/kg/d for 5 day
 BAL:25mg/kg/d for 6 dose deep IM
 D-penicillanin: BLL>45
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Cadmium
What is Cadmium?
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A metal most often encountered in earth’s crust combined with
chlorine (cadmium chloride), oxygen (cadmium oxide), or sulfur
(cadmium sulfide)
Exists as small particles in air, result of smelting, soldering or other
high temp. industrial processes
By-product of smelting of zinc, lead, copper ores
Used mainly in metal plating, producing
pigments, batteries, plastics and as a
neutron absorbent in nuclear reactors
Cadmium is used in batteries
Cadmium and Smelters/Mine
Sites
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Cadmium is a by-product of smelters
Has been a concern at the Summitville
mine site in Colorado
Photo of Smelter
Exposure Sources - Tobacco
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Tobacco smoke (a one pack a day smoker
absorbs roughly 5 to 10 times the amount
absorbed from the average daily diet)
Tobacco smoke is an
important source of
cadmium exposure
Exposure Sources – By Mouth
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Foods (only a small amount is absorbed)
Itai Itai disease (cadmium contamination + diet low in
calcium & vitamin D)
Cadmium a component of chuifong tokwan, sold illegally
as a miracle herb
Low levels are found in grains, cereals, leafy vegetables, and other basic
foodstuffs
Biologic Fate
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Cadmium has no known beneficial function in
the human body
Is transported in the blood bound to
metallothionein
Greatest concentrations found in kidneys & liver
Urinary excretion is slow
Biologic half-life may be up to 30 yrs.
Why Is Cadmium a Health Hazard?
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Affects lungs & kidneys
2o effects on skeletal system
Binds to sulfhydryl groups, displacing other metals from
metalloenzymes, disrupting those enzymes
Competes with calcium for binding sites on regulatory
proteins
Lipid peroxidation has been demonstrated
Respiratory Effects
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Acute inhalation may mimic metal fume fever
Fever, chills & decreases in FVC and FEV1
Initial symptoms: flu-like symptoms
 Later: chest pain, cough, dyspnea
 Bronchospasm and hemoptysis may occur
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Chronic inhalation MAY result in impairment of
pulmonary function with reduction in ventilatory capacity
Renal Effects
May cause tubular and glomerular
damage with resultant proteinuria
 May follow chronic inhalation or ingestion
 Latency period of ~10 yrs
 Nephropathy is progressive & irreversible
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Skeletal Effects
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Bone lesions occur late in severe chronic
poisoning
 Pseudofractures
 Other
effects of osteomalacia and
osteoporosis
 Appear to be secondary to increased urinary
calcium and phosphorus losses
Signs and Symptoms - Acute
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Food poisoning (ingestion)
Bronchitis (inhalation)
Interstitial pneumonitis (inhalation)
Pulmonary edema (inhalation)
A condition that mimics metal fume fever
Children who eat dirt
(pica behavior) are at risk
Evaluation
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Inhalation
 Chest
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radiograph
Chronic exposure
 Renal
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tests
Serum electrolytes, BUN, serum and urinary
creatinine, serum creatinine, cadmium in blood &
urine, urinary protein
 Other
tests – CBC & LFTs
Direct Biologic Indicators
24 hour urine cadmium – reflects
exposure over time an total body
burden
 Blood cadmium
 Cadmium in hair – not reliable
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No quantitative relationship between
hair cadmium levels and body burden
Indirect Biologic Indicators
Urinary ß2-microglobulin – evaluate urine
levels > 300 g/g creatinine
 Urinary RBP
 Urinary metallothionein (MT)
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Treatment & Management
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Acute Exposure
 No
proven treatment
 Supportive treatment includes fluid
replacement, oxygen, mechanical
ventilation. With ingestion, gastric
decontamination by emesis or gastric
lavage soon after exposure.
Activated charcoal not proven
effective
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Chronic – Prevent further exposure
Mercury
Mercury
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Occurs in three forms (elemental,
inorganic salts, and organic compounds)
Contamination results from mining,
smelting, and industrial discharges.
Mercury in water can be converted by
bacteria to organic mercury (more toxic) in
fish.
Can also be found in thermometers,
dental amalgams, fluorescent light bulbs,
disc batteries, electrical switches, folk
remedies, chemistry sets and vaccines.
Mercury - Exposure
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Elemental
 liquid at room temperature that volatizes readily
 rapid distribution in body by vapor, poor in GI tract
Inorganic
 poorly absorbed in GI tract, but can be caustic
 dermal exposure has resulted in toxicity
Organic
 lipid soluble and well absorbed via GI, lungs and skin
 can cross placenta and into breast milk
Elemental Mercury
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At high concentrations, vapor inhalation
produces acute necrotizing bronchitis,
pneumonitis, and death.
Long term exposure affects CNS.
 Early: insomnia, forgetfulness, anorexia,
mild tremor
 Late: progressive tremor and erethism (red
palms, emotional lability, and memory
impairment)
 Salivation, excessive sweating, renal toxicity
(proteinuria, or nephrotic syndrome)
Dental amalgams do not pose a health risk.
Inorganic Mercury
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Gastrointestinal ulceration or perforation
and hemorrhage are rapidly produced,
followed by circulatory collapse.
Breakdown of mucosal barriers leads to
increased absorption and distribution to
kidneys (proximal tubular necrosis and
anuria).
Acrodynia (Pink disease) usually from
dermal exposure
 maculopapular rash, swollen and
painful extremities, peripheral
neuropathy, hypertension, and renal
tubular dysfunction.
Organic Mercury
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Toxicity occurs with long term exposure and
effects the CNS.
 Signs progress from paresthesias to ataxia,
followed by generalized weakness, visual and
hearing impairment, tremor and muscle
spasticity, and then coma and death.
Teratogen with large chronic exposure
 Asymptomatic mothers with severely affected
infants
 Infants appeared normal at birth, but
psychomotor retardation, blindness, deafness,
and seizures developed over time.
Diagnosis and Treatment
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Dx made by history and physical and
lab analysis. Inorganic mercury can be
measured in 24 hour urine collection;
organic mercury is measured in whole
blood.
The most important and effective
treatment is to identify the source and
end the exposure
Chelating agents (DMSA) may enhance
inorganic mercury elimination.
Dimercaprol may increase mercury
concentration in the brain.
Mercury - Prevention
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Many mercury compounds are no longer sold in
the United States.
Elemental mercury spills:
 Roll onto a sheet of paper and place in
airtight container
 Use of a vacuum cleaner should be avoided
because it causes mercury to vaporize
(unless it is a Hg Vac)
 Consultation with environmental cleaning
company is advised with large spills.
State advisories on public limit or avoid
consumption of certain fish from specific bodies
of water.
Questions?