Environmental.pdf

Environmental and Nutritional Disease David Wagner, M.D. Associate Professor Department of Pathology at UNMC Email: [email protected] No financial interests to disclose Objectives Discuss the general pathophysiology of toxic effects of chemical and physical agents...

Environmental and Nutritional Disease David Wagner, M.D. Associate Professor Department of Pathology at UNMC Email: [email protected] No financial interests to disclose Objectives Discuss the general pathophysiology of toxic effects of chemical and physical agents Name some common air pollutants and discuss their pathophysiology Discuss mechanisms of toxicity of commonly encountered heavy metal toxins Identify some commonly encountered industrial and agricultural toxins and associated diseases Objectives Discuss the health effects and diseases associated with use of tobacco products and overuse of alcoholic beverages Describe some of the more commonly encountered adverse reactions to therapeutic drugs Describe the adverse health effects of the most commonly encountered drugs of abuse Name and define several types of traumatic injury Discuss classification and clinical considerations of burns, electrical injury, and radiation injury Toxicology Study of distribution, effects, and pathophysiology of toxic agents (poisons) Exogenous chemicals (xenobiotics) Physical agents ( e.g., radiation) heat Toxic levels of therapeutic drugs: poisons may only be poisons based on dosage Most chemical toxins are lipophilic The liver may alter drugs/toxins to turn them into metabolites or water soluble forms (detoxification); water soluble for excretion in urine Phase I – cytochrome P450; metabolism and drug conversion; influenced by genetics and other drugs/toxins Phase 2 – additional modifications Environmental Disease Caused by exposure to chemical or physical agents in the surroundings, workplace or personal space. Major disasters like nuclear reactor melt downs, contaminated water Chronic exposure to low level chemicals/toxins Toxin Exposure and Distribution Exposure Air Water/Food Soil Portals of Entry Skin Lungs Gut Distribution Bloodstream Disposition Excretion Accumulation Toxic effects Air Pollution Common Air Pollutants Ozone (O3) Sulfur dioxide (S02) Acid aerosols Particulate matter (50% of surface area likely fatal Can lead to shock from volume shifting Inhalation injury – airway obstruction Sepsis/organ failure – leading cause of death in burn patients (Pseudomonas) Clinical severity/prognosis related to: Depth of burn (first through fourth degree) Percentage of surface area (rule of nines) Associated injuries (inhalational, traumatic) Efficacy and promptness of treatment Fluid/electrolyte balance Prevention/control of infection Treatment of hypermetabolic state  Burn Depth First degree-epidermis Second degree-epidermis and upper dermis Third degree-epidermis and dermis Fourth degree-into subcutis Burn Percentage Rule of Nines  Electrical Injury Types of Injury Burns tetany Disruption of physiologic electrical impulses Cardiorespiratory failure Ventricular fibrillation Depends on amperage and path of electric current Amperage=voltage/resistance (Ohm’s Law) Radiation Injury Non-ionizing – does not displace electrons; UV light, microwaves, sounds Ionizing – enough energy to remove electrons; x- rays/CT-scans Sources of radiation Medical (cancer therapy, nuclear medicine, diagnostic imaging) Environmental (nuclear bombs, nuclear accidents, radon) Occupational (uranium miners) Measurement units: Curie (Ci)—exposure Centigray (cGy)—absorption (common unit for radiation therapy) Sievert (Sv)-dose; damage equivalent  Radiation Damage to Cells DNA damage Direct Indirect Leads to: Apoptosis Carcinogenesis Teratogenesis Damage to endothelial cells Hypoxia Fibrosis Other organs in the field Determinants of Radiation Injury Dose Rate of delivery (one event vs fractionation) Field size (whole body vs specific area) Type of tissue Radiation injury Clinical effects Rapidly dividing tissues/cells most severely affected Gonads Hematolymphoid tissue (esp. lymphocytes) Gut Radiation carcinogenesis Postradiation sarcomas Thyroid cancers Tumors in A-bomb and nuclear accident survivors Lung cancers (uranium, radon)