Heavy Metal Toxicity

1. Heavy Metal Toxicity M.D By :Soltani occupational medicine specialist Lead Mercury

2. 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

3. Periodic Table

4. ‘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

5. Acute single exposures urine blood Metal levels time exposure

6. 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 re-occurred. 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.

7. 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?

8. Azarcon • Azarcon is a folk remedy that contains 85-96% lead tetroxide • Other lead containing remedies include Greta.

9. Case (cont.) • The child was found to have a blood lead level of 124 ug/dl., and died from lead encephalopathy.

10. Lead

11. Background: The earliest toxicities Lead have no function in human body Soft , Malleable , Blue –gray , High density , Corrosion resistance

12. Battery manufacturing Chemical industry Construction workers Welders Plastics industry Jewelers Gasoline additives production Lead miners Pigment manufacturing Pipe fitters Pottery workers Radiator repair Rubber industry products Soldering of lead Solid waste production Printers Occupational exposure Some Sources of Lead Exposure

13. Hobbies Casting bullets or fishing sinkers Home remodelingTarget shooting at firing ranges Stained glass making Lead soldering Auto repair Glazed pottery making

14. Substance Use • Moonshine whiskey Ceramic ware Some folk remedies Some "Health Foods"

15. 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

16. IncreasedAbsorption: 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 blood35 days in soft tissue 40 days in bone 20 to 30 years

17. Excretion nails sweat excreted quite slowly from the body biologic half-life estimated at 10 years renal gastrointestinal accumulation in the body occurs easily

18. OSHA Lead Standards for Air and Blood 30µg per m3 PEL:50 µg per m3 Action level : Medical removal from exposure: >=60 µg per dLaverage of last three levels >=50 µg /dL

19. Gastrointestinal Effects Health effects of lead Heme Synthesis Other Renal Effects Reproductive Effects Neurological Effects

20. Clinical Effects In Adults Acute Inorganic Lead Toxicity Excessive exposure in brief period Acute lead poisoning syndrome. Classic clinical findings : Abdominal colic Constipation Fatigue CNS dysfunction Acute encephalopathy Coma Convulsions In milder exposures : headaches personality changes

21. Chronic Inorganic Lead ToxicitySymptoms: Arthralgias Headache Weakness Depression Loss of libido Impotence Vague gastrointestinal difficulties Late effects: Chronic renal failure Hypertension Gout Chronic encephalopathy

22. Range of Lead-induced Health Effects in Adults and Children

23. Childhood Lead Poisoning Childhood lead poisoning is now defined as a blood lead level of 10 g/dl

24. MedicalExamination 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

25. 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

26. 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.

27. Primary Prevention of Lead Poisoning Engineering controls Personal protective equipment Work practicesHousekeeping activities to remove lead dust Personal hygiene practices Periodic inspection

28. 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

29. Tertiary prevention Possible treatment: Removal Drug

30. 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

32. Cadmium

33. What is Cadmium? Cadmium is used in batteries 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

34. Cadmium and Smelters/Mine Sites Photo of Smelter Cadmium is a by-product of smelters Has been a concern at the Summitville mine site in Colorado

35. Exposure Sources - Tobacco Tobacco smoke is an important source of cadmium exposure Tobacco smoke (a one pack a day smoker absorbs roughly 5 to 10 times the amount absorbed from the average daily diet)

36. Exposure Sources – By Mouth Low levels are found in grains, cereals, leafy vegetables, and other basic foodstuffs 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

37. 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.

38. 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

39. 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

40. 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

41. 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

42. Signs and Symptoms - Acute Children who eat dirt (pica behavior) are at risk Food poisoning (ingestion) Bronchitis (inhalation) Interstitial pneumonitis (inhalation) Pulmonary edema (inhalation) A condition that mimics metal fume fever

43. 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

44. Direct Biologic Indicators No quantitative relationship between hair cadmium levels and body burden 24 hour urine cadmium – reflects exposure over time an total body burden Blood cadmium Cadmium in hair – not reliable

45. Indirect Biologic Indicators Urinary ß2-microglobulin – evaluate urine levels > 300 g/g creatinine Urinary RBP Urinary metallothionein (MT)

46. 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

47. Mercury

48. 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.

49. 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

50. 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.