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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 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 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 Acute single exposures urine Metal levels blood time exposure Case Presentation 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) 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. The child expired, despite aggressive supportive care. What is azarcon? Azarcon Azarcon is a folk remedy that contains 8596% lead tetroxide Other lead containing remedies include Greta. Case (cont.) 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: Inorganic lead is not absorbed Organic lead is well absorbed Lead is carried bound to the RBC 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 Cadmium What is Cadmium? 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 Cadmium is a by-product of smelters Has been a concern at the Summitville mine site in Colorado Photo of Smelter Exposure Sources - Tobacco 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 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 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? 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 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 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 Skeletal Effects 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 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 Inhalation Chest radiograph Chronic exposure Renal 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 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) Treatment & Management 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 Chronic – Prevent further exposure Mercury Mercury 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 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 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 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 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 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 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?