ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition David S. Wilkinson, MD, PhD.
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Transcript of ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition David S. Wilkinson, MD, PhD.
![Page 1: ENVIRONMENTAL PATHOLOGY Chemical and Physical Agents Nutrition David S. Wilkinson, MD, PhD.](https://reader035.fdocuments.net/reader035/viewer/2022081519/56649dd25503460f94ac96b4/html5/thumbnails/1.jpg)
ENVIRONMENTALPATHOLOGY
Chemical and Physical AgentsNutrition
David S. Wilkinson, MD, PhD
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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
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US Government Agencies Regulate Environmental Hazards• Environmental Protection Agency
• Food and Drug Administration
• Occupational Safety and Health Administration
• Consumer Products Safety Commission
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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)
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Mechanisms of Toxicity
• Corrosive, tissue destruction (acids, alkali)– desiccation– protein destruction
• denaturation• hydrolysis
– fat saponification• Inhibition of enzyme activity
cyanide: cytochrome oxidase
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Cyanide Poisoning
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Mechanisms of Toxicity
• Alternate metabolic pathways– ethanol: NAD/NADH
• Disturbances of homeostasis– steroids: immune system– aspirin: acidosis
• Mutagenesis
• Carcinogenesis
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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
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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
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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
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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
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Normal Lung
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Pulmonary Fibrosis
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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)
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Tobacco Smoking
• 400,000 deaths/yr (21% of all deaths in US)• 50 Million smokers in US• Smoke composition
– carcinogens (polycyclic HC, -naphthylamine, nitrosamines)
• Irritants and toxins– ammonia, formaldehyde, oxides of nitrogen
• CO• Nicotine
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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 10Ill health effects of smoking partially reversible
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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
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Lead Lines
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Basophilic Stippling
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Normal Kidney
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Acute Tubular Necrosis
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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)
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Fatty Change in Liver
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Normal Liver
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Fatty Change in Liver
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Alcoholic Hepatitis
Mallory Mallory BodyBody
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Alcoholic Cirrhosis
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Alcoholic Cirrhosis
RegeneratingNodules
Bands of Fibrosis
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Adverse Drug Events
Adverse Drug Reactions
+
Therapeutic Misadventures
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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.
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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)
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Major Patterns of ADRs
• Renal reactions– predictable (aminoglycosides)– hypersensitivity (sulfa)
• Lung reactions– congestion– edema– hemorrhage– interstitial fibrosis
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Major Patterns of ADRs• Cardiac reactions
– arrhythmias– cardiomyopathy
• CNS reactions– respiratory depression
• Systemic reactions– anaphylaxis– vasculitis– hormonal effects (HRT, OC)
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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
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Physical Injuries
• Mechanical force– abrasion– laceration– incision– contusion
• Gunshot wounds– entry wound– exit wound
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Contusion/22 hours
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Laceration with Marginal Abrasion
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Incision
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Stab Wound
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GSW/Contact
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GSW/Close Range/Stippling
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GSW/Distant and Contact
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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
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Radiation Injury
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Radiation Sensitivity of Biological Tissue
• Lymphocytes• Thrombocytes• Granulocytes• GI lining• Endothelial cells• Neural tissue
Sensitivity Cell Division
Most Sensitive Fastest
Least SensitiveSlowest
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Vitamin DeficiencyVitamin Function Deficiency State
A VisionImmunesystemEpithelium
Diet, malabsorptionNight blindness,xerophthalmia,keratomalacia,immune deficiency
D Blood calciumand phosphate
Diet, malabsorption,inadequate sun, liverand renal diseaseRickets,osteomalacia
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Vitamin Function Deficiency State
Etocopherols
AntioxidantFree radicalscavenger
Diet, malabsorptionNeuromusculardeficits
K ClottingfactorsII, VII, IX,X
Malabsorption, lossof gut flora,Coumadin therapybleeding
Vitamin Deficiency
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Vitamin DeficiencyVitamin Function Deficiency State
Thiamine(B1)TPP
Enzyme co-factor,nerveconduction
Diet, EtOHPolyneuropathy,cardiomyopathy,Wernicke-Korsakoff
Riboflavine(B2)FMN, FAD
Enzyme co-factor
Diet, EtOHCheilosis, glossitis,dermatitis (atrophy)
NiacinNAD,NADP
Enzyme co-factor
Diet, EtOHPellagra, dermitis,diarrhaea, dementia
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Vitamin Deficiency
Vitamin Function Deficiency State
Pyridoxine(B6)
Enzyme co-factor
Drugs (INH), EtOHSimilar to riboflavinand niacin deficiency
C Hydroxyl-ation ofproteinsAntioxidant
Diet, EtOHScurvey, weakconnective tissueBleeding, fractures,gingival swelling,peridontal disease, poorwound healing