1 / 43

Lead

Lead. Sources of Occupational Exposure, Clinical Toxicology, and Control. Lead in the Environment. Lead ( 207 Pb) is a natural element, heavy metal, end product of radionuclide decay Radioactive lead ( 210 Pb, t 1/2 = 22 y) is a convenient way to trace lead

sandra_john
Download Presentation

Lead

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lead Sources of Occupational Exposure, Clinical Toxicology, and Control

  2. Lead in the Environment • Lead (207Pb) is a natural element, heavy metal, end product of radionuclide decay • Radioactive lead (210Pb, t1/2 = 22 y) is a convenient way to trace lead • Lead was insignificant environmentally until about 1800 • Human activity has mobilized lead in the environment

  3. Useful Properties of Lead • Ductility • Low melting point • Density, absorption of radiation, sound and vibration • Chemical properties (e.g. combines with nitrogen) • Resists acid and corrosion

  4. Ancient/Premodern History Lead oxide as a sweetening agent Lead pipes (“plumbing”) Ceramics Smelting and foundries Modern History Gasoline Ceramics Crystal glass Soldering pipes “tin” cans car radiators House paint Historical Sources of Lead Exposure

  5. Contemporary Sources of Lead Exposure • Residue of leaded gasoline • Lead smelting and recycling • Solder (Pb + Sn), welding (minor) • Metalworking • Ammunition and explosives • Exterior paints and remediation • Avocational exposure in crafts • Kohl and certain herbal remedies

  6. Future Sources of Exposure to Lead • Gasoline, in some developing countries • Plastics containing Pb additives (e.g. one type of “thin” Venetian blinds) • Compounding “litharge”, used in making ferrite ceramic magnets • Pb compounds with piezoelectric and thermoelectric properties • Unregulated cosmetics, remedies

  7. Settings for Lead Exposure • Smelting and metalworking • Lead sulfate battery operations • Activities related to firearms and ammunition • Crafts involving glass, ceramics • Hazardous waste disposal • Imported or customized products

  8. Biologically Important Properties of Lead • Readily combines with sulfide, sulfhydryls • Affinity for bone and other calcified tissue • Readily absorbed and mobilized in the body • Cumulative body burden • Narrow margin between population reference levels and toxicity levels • OrganoPb compounds more bioavailable

  9. Lead Exposure in Children • Pica and passive exposure: oral • Pb removed from gasoline • Blood Pb, FEP • CNS more likely to be affected • Needleman controversy

  10. Lead Exposure in Adults • Mostly occupational: inhalation • Maintenance at workplace • Peripheral neuropathy more common • Blood Pb, ZPP • Renal effects more likely

  11. Acute GI effects colic, severe pain severe constipation Acute encephalopathy Acute nephropathy Children Growth retardation Behavioural  Chronic Peripheral, central neuropathy Cardiac toxicity Chronic nephropathy Saturnine gout Reproductive effects Hypertension? Anemia Cardinal Symptoms of Lead Intoxication

  12. Signs of Extreme Lead Toxicity • Acute lead encephalopathy • fatal in 25% • poor prognosis for full neurological recovery • severe clinical impairment in 40% • Severe lead colic • “Burtonian” lines (gingival deposition of Pb sulfide)

  13. Mechanisms of Damage to the Nervous System by Lead Central • Cerebral edema • Necrosis of brain tissue • Glial proliferation around blood vessels Peripheral • Demyelination • Reversible NCV • Irreversible axonal degeneration

  14. Central/Pediatric Lethargy, wakeful Irritability Clumsiness, ataxia Projectile vomiting Visual s Delerium, convulsions, coma IQ performance Peripheral/Adult Lead palsy median n.c. slowing wrist/foot drop demyleinating disease Lead colic Muscle weakness Behavioural, memory  Neurological Manifestations of Lead Toxicity

  15. Anemia and Lead Toxicity • Normochromichypochromic, normocyticmicrocytic • Reduced rbc survival time • Compensatory rbc production • reticulocytosis • Basophilic stippling • variable • represents damaged cell organelles, RNA

  16. Haeme Synthesis and Lead Toxicity • Pb inhibits -aminolevulinic acid dehydratase  -ALA in urine • Pb inhibits co-proporphyrinogen decarboxylase  Co-proporphyrinogen in urine • Pb inhibits ferrochelatase  Protoporphyrine IX accumulates in rbcs • FEP, ZPP tests are based on this

  17. Diagnostic Criteria for Lead Toxicity (CDC) • Blood • Blood lead > 80 g/dL • FEP > 190 g/dL • ZPP • Urinary Pb Excretion (24 hour) • Pb > 0.15 mg/L • -ALA > 19 mg/L • Coproporphyrin III > 150 g/L

  18. Other Considerations in the Diagnosis of Lead Toxicity • Blood lead is most generally useful • FEP not useful below about 20 g/dL • Evidence clearly suggests that children should be considered at risk if BPb > 10 g/dL • Early evidence that there may be risk at 5 g/dL • Congenital anomalies have been reported

  19. Toxicokinetics of Lead, I • Ingestion (children), inhalation (adults) • Readily absorbed by inhalation route • Slow absorption by ingestion, with Fe deficiency • OrganoPb compounds (e.g. Et4Pb) much more rapidly absorbed • Cumulative exposure

  20. Toxicokinetics of Lead, II • Carried by red cell, mostly bound to haemaglobin A2 • Rapidly distributed  perfusion • Affinity for bone, which acts as sink (94%) • Bone constitutes reservoir in equilibrium with blood; turnover slow • t = 28 - 36 days in adult

  21. Toxicokinetics of Lead, III • Inorganic Pb is not metabolised • Organic (alkyl) Pb compounds are dealkylated in the liver • Dealkylation involves cytochrome P450 • Some alkyl Pb is dealkylated, stays behind as inorganic Pb, and remobilizes • Children have much less capacity to metabolize than adults

  22. Toxicokinetics of Lead, IV • Excretion of Pb generally reflects body burden, not route of exposure • Ingested Pb not absorbed passes in feces • Enterohepatic circulation, biliary secretion • Excretion by two pathways: • biliary excretion (major with high exposures) • urinary excretion (major)

  23. Genetic Predispositions Inborn errors of haeme metabolism (porphyrias) Hereditary anemias (e.g. the thalassemias) Acquired Characteristics Children < 6 y Pregnant, lactating women Nutritional deficiency, esp. Fe, Ca++, vit D Neurological or renal disease ?Alcohol abuse Susceptibility Factors

  24. Occupational Exposure Levels OSHA PEL 0.05 mg/m3, 8-h TWA NIOSH REL 0.10 mg/m3, 10-h TWA; BEI, Pb compounds covered differ ACGIH TLV 0.05 mg/m3, 8-h TWA

  25. OSHA Pb Standard Actions

  26. Management of Lead ExposureAdults • Prohibit eating, drinking, smoking at work • Housekeeping • Ventilation • Personal protection • Medical removal • Control exposure to OSHA Pb standard • Review other possible sources of contamination

  27. Management of Lead ExposureChildren • Optimize nutrition, avoid fasting • Report through public health dept. • Home Pb abatement • Dust control • water • food containers • home and yard • Rule out passive exposure

  28. Chelation • Not a decision to be taken lightly • Requires close monitoring • Inefficient process, typically reducing body burden only 1 - 2 % • Chelating agents may not significantly reduce tissue levels, esp. in CNS

  29. Chelation with Agents Other than Succimer • Chelation can be dangerous! • May result in Ca++ depletion, hypercalcemia • May result in nephrotoxicity if serum Pb • Agents • CaNa2EDTA 1000-1500 mg/m2/d, iv • BAL 300 - 450 mg/m2/d, 50 - 75 mg/m2 q4h  3 - 5 d, im • D - penicillamine (second-line drug)

  30. Chelation with Succimer • Dimercaptosuccinic acid • Oral administration • Minimal side effects in decade of experience • Displaced D-penicillamine as oral agent since 1991 • If adverse reactions to succimer, EDTA, D-penicillamine is the alternative

  31. Paediatric Chelation Therapy - Encephalopathy - 1 • A medical emergency! • BAL and CaNa2•EDTA at 1500 mg/m2/d, iv • Stat BAL + continuous EDTA infusion • EDTA alone may cause deterioration • Generally continued 5 days • D/C BAL at 3 days, continuing EDTA if prompt response and BPb  <50 g/dl

  32. Paediatric Chelation Therapy - Encephalopathy - 2 • Fluid management critical • risk of cerebral edema, SIADH • monitor I/O, spec grav, electrolytes • NPO for first several days • Adequate fluid replacements • 1 ml/kcal/d energy requirements (100/kg first 10 kg, then 50 for next 10, thereafter 20) • Urine output: 0.5 ml/kcal/d or 350 - 500 ml/m2/d

  33. Paediatric Chelation Therapy - Encephalopathy - 3 • Seizure control by benzodiazepines • Suspect cerebral edema • avoid LP • mannitol, glycerol hyperosmotic therapy • modest hyperventilation • steroids • more aggressive management not evaluated

  34. Paediatric Chelation TherapyBPb > 70 g/dl • If milder symptoms and/or blood Pb > 70 g/dl, chelation on regimen similar to encephalopathy • 3 days of BAL + 5 days EDTA • PICU for first few days • Repeated courses only if required: • Second course should follow >2 d • Third course by 10 - 14 d, to equilibrate

  35. Paediatric Chelation TherapyBPb 45 - 69 g/dl • If asymptomatic, treatment with succimer is preferred • Succimer initiated with 30 mg/kg/d or 1050 mg/m2/d in three divided doses  5 d • Succimer maintained at 20 mg/kg/d or 70 mg/m2/d in two divided doses  14 d • Consider hospitalization if home abatement is not possible

  36. Paediatric Chelation TherapyBPb 20 - 44 g/dl • CDC and AAP recommend environmental interventions but not chelation • These guidelines considered conservative • Reasonable to consider chelation if: • Pb levels do not decline • symptoms, even if subtle • elevated FEP after Fe supplementation • Age < 2 y

  37. Paediatric Chelation TherapyBPb 10 - 19 g/dl • Excessive exposure to Pb • Currently not considered as indication for chelation • Home Pb abatement and control of exposure is recommended

  38. Indications for Paediatric Therapy May Change • Safety of succimer may change recommendations • NIEHS is sponsoring a clinical trial: Treatment of Lead-Exposed Children (TLC) • multicentre • randomized, double-blind • succimer v. placebo • outcomes include developmental indices

  39. Adult Chelation Therapy - 1 • Indicated for symptomatic Pb toxicity • Generally less effective • Never a substitute for control of exposure • Unethical to give chelation for prophylaxis • Indications for chelation depend on symptoms and BPb (g/dl), not BPb alone

  40. Adult Chelation Therapy - 2

  41. Adult Chelation Therapy - 3 • Encephalopathy: • BAL 450 mg/m2/d, 75 mg im q4h  5 d • EDTA 1500 mg/m2/d, iv  5 d • Start EDTA 4 hours after stat BAL • Symptomatic, BPb > 70 • BAL 300 - 450 mg/m2/d, 50 - 75 mg im q4h  3 - 5 d • EDTA 1000 - 1500, otherwise as above

  42. Adult Chelation Therapy - 4 • Mild Symptoms treated with Succimer • Succimer 700 - 1050 mg/m2/d • Give 350 mg/m2 (or 10 mg/kg)  5 d, then bid  14 d • The availability of a safe chelating agent does not mean that prophylaxis is acceptable.

  43. Every Case of Lead Toxicity is a Failure of Society • Lead toxicity is entirely preventable • This problem should not exist in 2000 • A worker exposed to lead represents an insult in the present • A child exposed to lead represents an assault on the future

More Related