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ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition

ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition. David S. Wilkinson, MD, PhD. Environmental Pathology Magnitude of the Problem in US. 600,000 cancer cases/year related to chemical carcinogens (est) 400,000 deaths related to smoking Reported Chemical Exposures

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ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition

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  1. ENVIRONMENTALPATHOLOGYChemical and Physical AgentsNutrition David S. Wilkinson, MD, PhD

  2. Environmental PathologyMagnitude of the Problem in US • 600,000 cancer cases/year related to chemical carcinogens (est) • 400,000 deaths related to smoking • Reported Chemical Exposures • 2.4 million reported chemical exp/yr (2005) • 80% accidental • Children <6 yo account for 50% • 1261 fatalities, 50% suicides

  3. US Government Agencies Regulate Environmental Hazards • Environmental Protection Agency • Food and Drug Administration • Occupational Safety and Health Administration • Consumer Products Safety Commission

  4. Sources of Exposure • Environmental • Man-made • Intentional (Hg, Minimata, Japan) • Accidental • methyl isocyanate, Bhopal, India • radiation, Chernobyl • Natural (H2S/CO/CO2, Cameroon) • Occupational (mining, dye, chemical) • Iatrogenic (drugs) • Self-administered (substance abuse, suicide)

  5. Mechanisms of Toxicity • Corrosive, tissue destruction (acids, alkali) • desiccation • protein destruction • denaturation • hydrolysis • fat saponification • Inhibition of enzyme activity cyanide: cytochrome oxidase

  6. Cyanide Poisoning

  7. Mechanisms of Toxicity • Alternate metabolic pathways • ethanol: NAD/NADH • Disturbances of homeostasis • steroids: immune system • aspirin: acidosis • Mutagenesis • Carcinogenesis

  8. Clinical Findings • Symptoms-patient complaints • Signs-what you observe • Clinicopathologic correlation • related to mechanism and tissue localization • Acute vs chronic-the signs and symptoms may differ

  9. Lung Injury Related to Air Pollution • Acute and chronic inflammation • direct cell injury • Emphysema-enhanced proteolysis • Asthma-allergic or irritant effect • Hypersensitivity pneumonitis • immunologic injury related to organic dusts • Pneumoconiosis-cytokines • Neoplasia • mutagenic/promoting effects

  10. Main Constituents of Smog • SO2 respiratory irritant (acid rain) • NO2*, NO respiratory irritant (xs O2) • CO carboxyhemoglobin ( O2) • O3* respiratory irritant • Pb binds sulfhydryl groups *Oxidant pollutants Mostly produced by combustion of fossil fuels

  11. Inhalation Toxins Related toMining and Similar Occupations Pneumoconiosis, characterized by cytokine-mediated, progressive fibrotic scarring • coal dust (anthracosis) • silica (silicosis) • asbestos (asbestosis), Ca/Mg silicate • pleural plaques, mesothelioma, bronchogenic ca • beryllium (berylliosis) Macrophages produce cytokines Size matters-0.5 to 5μ

  12. Normal Lung

  13. Pulmonary Fibrosis

  14. Inhalation Toxins Related to Farming • Organic dusts (hypersensitivity pneumonitis) • moldy hay (Farmer’s Lung) • bird droppings (bird breeders lung) • Pesticides • organophosphate (acetycholine esterase inhibitors) • organochlorine (DDT, chlordane) • Herbicides (paraquat, diquat, dioxin) • Fertilizer (ammonia)

  15. Tobacco Smoking • 400,000 deaths/yr (21% of all deaths in US) • 50 Million smokers in US • Smoke composition • carcinogens (polycyclic HC, b-naphthylamine, nitrosamines) • Irritants and toxins • ammonia, formaldehyde, oxides of nitrogen • CO • Nicotine

  16. Relative Disease RisksAssociated with Smoking Male Female Lung Ca death 22 12 Mouth Ca 27 6 Larynx Ca 10 18 Esophogus Ca 8 10 CAD >35 yo 3 2 Cerebro VD >35 yo 4 5 COPD 10 10 Ill health effects of smoking partially reversible

  17. Heavy Metal Toxic Agents • Mercury (HgCl2 , ATN; org Hg, CNS function) • Lead ( inhibits heme synthesis, CNS function, kidneys, GI) • 2-11% of children in US exceed 10 μg/dL • Arsenic • Iron

  18. Lead Lines

  19. Basophilic Stippling

  20. Normal Kidney

  21. Acute Tubular Necrosis

  22. Organic Alcohols • Ethanol • 1/3 of Americans characterized as heavy drinkers • CNS depressant • legally intoxicated >100 mg/dL • Nearly 50% of fatal MVA • Methanol (toxic metabolites inhibit hexokinase, may cause blindness) • Ethylene glycol (antifreeze, ATN)

  23. Fatty Change in Liver

  24. Normal Liver

  25. Fatty Change in Liver

  26. Alcoholic Hepatitis Mallory Body

  27. Alcoholic Cirrhosis

  28. Alcoholic Cirrhosis Bands of Fibrosis Regenerating Nodules

  29. Adverse Drug Events Adverse Drug Reactions + Therapeutic Misadventures

  30. Adverse Drug Events • 3-6% of all medical admissions • 160,000 deaths/yr Shapiro et al. JAMA 1971; 216: 467-472. • Most common adverse event in hosp pts Leape et al. NEJM 1991;324: 377-384. • 6.5 ADE/100 admissions, 1% fatal Bates et al. JAMA 1995; 274: 29-34.

  31. Major Patterns of ADRs • Blood dyscrasias (Chloramphenicol) • dose related or idiosyncratic • pan or line specific • Skin eruptions (Penicillin) • Hepatic reactions • fatty change (Tetracycline) • cholestasis (Chlorpromazine) • hepatitis (INH) • massive hepatic necrosis (Halothane)

  32. Major Patterns of ADRs • Renal reactions • predictable (aminoglycosides) • hypersensitivity (sulfa) • Lung reactions • congestion • edema • hemorrhage • interstitial fibrosis

  33. Major Patterns of ADRs • Cardiac reactions • arrhythmias • cardiomyopathy • CNS reactions • respiratory depression • Systemic reactions • anaphylaxis • vasculitis • hormonal effects (HRT, OC)

  34. Syndromes Related to Drugs of Abuse • Pulmonary complications (edema, septic emboli, absess, opportunistic infections) • Granulomas (adulterants) • Infectious complications • Kidney disease Often related to diluents, cutting agents, and needle sharing

  35. Physical Injuries • Mechanical force • abrasion • laceration • incision • contusion • Gunshot wounds • entry wound • exit wound

  36. Contusion/22 hours

  37. Laceration with Marginal Abrasion

  38. Incision

  39. Stab Wound

  40. GSW/Contact

  41. GSW/Close Range/Stippling

  42. GSW/Distant and Contact

  43. Radiation Injury • Direct (target) effect-radiation acts directly on target molecules, such as DNA • Indirect effect-free radical intermediary • Cell death, mutations, developmental abnormalities • Tissues have differential radiosensitivity • Oxygen effect • Whole body radiation

  44. Radiation Injury

  45. Lymphocytes Thrombocytes Granulocytes GI lining Endothelial cells Neural tissue Sensitivity Cell Division Most Sensitive Fastest Least Sensitive Slowest Radiation Sensitivity of Biological Tissue

  46. Vitamin Deficiency

  47. Vitamin Deficiency

  48. Vitamin Deficiency

  49. Vitamin Deficiency

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