ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition David S. Wilkinson, MD, PhD
Oct 26, 2014
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