ENVIRONMENTAL PATHOLOGYChemical and Physical Agents NutritionDavid 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 2.4 million reported chemical exp/yr (2005) 80% accidental Children 35 yo Cerebro VD >35 yo COPD

Male 22 27 10 8 3 4 10

Female 12 6 18 10 2 5 10

Ill health effects of smoking partially reversible

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 g/dL

Arsenic Iron

Lead Lines

Basophilic Stippling

Normal Kidney

Acute Tubular Necrosis

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)

Fatty Change in Liver

Normal Liver

Fatty Change in Liver

Alcoholic Hepatitis

Mallory Body

Alcoholic Cirrhosis

Alcoholic Cirrhosis

Bands of Fibrosis Regenerating Nodules

Adverse Drug EventsAdverse Drug Reactions + Therapeutic Misadventures

Adverse Drug Events 3-6% of all medical admissions 160,000 deaths/yrShapiro et al. JAMA 1971; 216: 467-472.

Most common adverse event in hosp ptsLeape et al. NEJM 1991;324: 377-384.

6.5 ADE/100 admissions, 1% fatalBates et al. JAMA 1995; 274: 29-34.

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)

Major Patterns of ADRs Renal reactions predictable (aminoglycosides) hypersensitivity (sulfa)

Lung reactions congestion edema hemorrhage interstitial fibrosis

Major Patterns of ADRs Cardiac reactions arrhythmias cardiomyopathy

CNS reactions respiratory depression

Systemic reactions anaphylaxis vasculitis hormonal effects (HRT, OC)

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

Physical Injuries Mechanical force abrasion laceration incision contusion

Gunshot wounds entry wound exit wound

Contusion/22 hours

Laceration with Marginal Abrasion

Incision

Stab Wound

GSW/Contact

GSW/Close Range/Stippling

GSW/Distant and Contact

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

Radiation Injury

Radiation Sensitivity of Biological Tissue Lymphocytes Thrombocytes Granulocytes GI lining Endothelial cells Neural tissue

Sensitivity Most Sensitive

Cell Division Fastest

Least Sensitive

Slowest

Vitamin DeficiencyVitamin Function A Vision Immune system Epithelium Deficiency State Diet, malabsorption Night blindness, xerophthalmia, keratomalacia, immune deficiency Blood calcium Diet, malabsorption, and phosphate inadequate sun, liver and renal disease Rickets, osteomalacia

D

Vitamin DeficiencyVitamin Function Deficiency State E Antioxidant Diet, malabsorption tocopherols Free radical Neuromuscular scavenger deficits K Clotting Malabsorption, loss factors of gut flora, II, VII, IX, Coumadin therapy X bleeding

Vitamin DeficiencyVitamin Thiamine (B1) TPP Function Deficiency State Diet, EtOH Polyneuropathy, cardiomyopathy, Wernicke-Korsakoff Diet, EtOH Cheilosis, glossitis, dermatitis (atrophy) Diet, EtOH Pellagra, dermitis, diarrhaea, dementia Enzyme cofactor, nerve conduction Riboflavine Enzyme co(B2) factor FMN, FAD Niacin Enzyme coNAD, factor NADP

Vitamin DeficiencyVitamin Function Deficiency State Pyridoxine Enzyme co- Drugs (INH), EtOH (B6) factor Similar to riboflavin and niacin deficiency C HydroxylDiet, EtOH ation of Scurvey, weak proteins connective tissue Antioxidant Bleeding, fractures, gingival swelling, peridontal disease, poor wound healing