Environmental Pathology PDF

→ The air people breathe, the food and water they consume, OUTLINE and the toxic agents they are exposed to are major I. Objectives VI. Indoor Air Pollution II. Environmental Patholog...

→ The air people breathe, the food and water they consume, OUTLINE and the toxic agents they are exposed to are major I. Objectives VI. Indoor Air Pollution II. Environmental Pathology A. Radon determinants of health A. Environment & B. Lead Environmental disease - conditions caused by exposure to Disease VII. Radiation chemical or physical agents in the ambient, workplace, and B. Mechanisms of VIII. Injury by Physical Agent personal environment, including diseases of nutritional origin Toxicity A. Mechanical Trauma Table 1. Reported Occupational Diseases in the US C. Xenobiotics B. Thermal Injury Disease Number Percentage III. Effects of Tobacco C. Electrical Injury Repeated trauma 276,600 64% A. Tobacco IX. Injury Related to Skin disorders 57,900 13% B. Tobacco & Cancer Atmospheric Pressure Lung conditions due to 20,300 5% C. Cigarettes & The X. References toxin exposure Physical injury 16,600 4% Workplace XI. Appendix Poisoning 5,100 1$ IV. Effects of Alcohol Lung disease due to 2,900 1% A. Alcohol You may click the contents of the dust B. Alcohol & The Liver outline to navigate. All other illnesses 50,600 12% C. Neurologic 🙁 Total 430,300 100% Click “GPATHO1 - LEC” on the Manifestations *Source was not provided by Doc lower left part of the page to return V. Injury by Therapeutic to the first page. Drugs B. MECHANISMS OF TOXICITY Threshold Effect ❗️ Remember 📣 Lecturer 📖 Book 📝 Previous Trans → “An agent is considered toxic when upon a sufficient dose 50% of the exposed population manifests signs and I. OBJECTIVES symptoms of toxicity” To know and understand, at a basic level, the etiologic agents → The point where the agent reaches toxicity present in the environment that are responsible for disease → Similar concept to Toxic/Lethal Dose (TD50/LD50) from manifestations and the occurrence of tumors. Pharmacodynamics II. ENVIRONMENTAL PATHOLOGY Portals of entry for a toxic agent → Ingestion A. ENVIRONMENT AND DISEASE → Inhalation 📖 KEY CONCEPTS [Robbins & Cotran, 10th ed] ENVIRONMENTAL DISEASES AND ENVIRONMENTAL → Skin contact Toxins may act at the site of entry or at other sites following POLLUTION transport through the blood Environmental diseases are conditions caused by exposure to Toxins follow the principles of Pharmacokinetics (ADME) chemical or physical agents in the ambient, workplace, → Absorption and personal environments. → Distribution Exogenous chemicals known as xenobiotics enter the body → Metabolism through inhalation, ingestion, and skin contact and can either → Excretion be eliminated or accumulate in fat, bone, brain, and other tissues. → Xenobiotics can be converted into nontoxic products or activated to generate toxic compounds through a two-phase reaction process that involves the cytochrome P-450 system. The most common and important air pollutants are ozone (which in combination with oxides and particulate matter forms smog), sulfur dioxide, acid aerosols, and particles less than 10 μm in diameter. C. XENOBIOTICS CO poisoning is an important cause of death from accidents and suicide Xenobiotics - substances foreign to living systems → it binds hemoglobin with high affinity, leading to systemic → Exogenous chemicals in the environment in air, water, food, asphyxiation associated with CNS depression and soil that may be absorbed into the body A variety of pollutants including smoke, bioaerosols, radon, and Most solvents, drugs, and xenobiotics are metabolized to form formaldehyde may accumulate in indoor air and cause disease. inactive water-soluble products (detoxification) or are activated to form toxic metabolites Many diseases are caused or influenced by environmental → This metabolic process to form non-toxic and toxic factors. metabolites occurs in two phases. Environment - encompasses the various indoor, outdoor, and ▪ Phase I reactions occupational settings in which human beings live and work. − Occurs in smooth endoplasmic reticulum GPATHO1 – LEC Trans no. 9 | Batch 2027 1 of 13  − Makes metabolites less lipophilic by adding a direct COMMON METHODS OF EXPOSURE polar group Personal o Decreases cellular uptake of these compounds Medications − Involves 3 chemical reaction: Outdoor & Indoor Air pollution o Hydrolysis Industrial Exposures o Reduction Agricultural Hazards o Oxidation Natural Toxins − Cytochrome P450 - most important catalyst of phase I Radiation Injury reactions Physical Injury ▪ Phase II reactions III. EFFECTS OF TOBACCO − Products of phase I reactions are often metabolized into water-soluble compounds through phase II 📖 KEY CONCEPTS [Robbins & Cotran, 10th ed] HEALTH EFFECTS OF TOBACCO reactions Smoking is the most prevalent preventable cause of human − Includes processes such as: death. o Glucuronidation Tobacco smoke contains more than 7000 compounds.Among o Sulfation these are nicotine, which is responsible for tobacco addiction, o Methylation and potent carcinogens—mainly, polycyclic aromatic o Conjugation with glutathione (GSH) hydrocarbons, nitrosamines, and aromatic amines. − Makes metabolites more readily to be excreted from → Nicotine also has other adverse effects, particularly on fetal the body development, and is associated with preterm birth and stillbirth. Approximately 90% of lung cancers occur in smokers. → Smoking is also associated with an increased risk of cancers of the oral cavity, larynx, esophagus, stomach, bladder, and kidney, some forms of leukemia, as well as liver and colorectal cancer. → Cessation of smoking reduces the risk of lung cancer. Smokeless tobacco use is an important cause of oral cancers. → Tobacco consumption interacts with alcohol in multiplying the risk of oral, laryngeal, and esophageal cancer and increases the risk of lung cancers from occupational exposures to asbestos, uranium, and other agents. Tobacco use is an important risk factor for development of atherosclerosis and myocardial infarction, peripheral vascular disease, and cerebrovascular disease. In the lungs, in addition to cancer, it predisposes to emphysema, chronic bronchitis, and chronic obstructive pulmonary disease. Maternal smoking increases the risk of spontaneous abortion, premature birth, and intrauterine growth retardation. A. TOBACCO 440,000 premature deaths/year in USA Figure 1. Mechanism of Xenobiotics [Doc Templo’s PPT, 2024] → Most common cause: Cancer Table 2. Contents of Toxic Waste Dumps ▪ Cancer related to tobacco: Lung CA Acetone DDT, DDE, DDD − Squamous Cell Carcinoma o Looks like squamous cell carcinoma, but Aldrin/Dieldrin 1,1 and 1,2-Dichloroethane non-smoker, probably not squamous, it may be Arsenic Lead 📣 poorly-differentiated type of tumor (this is Barium Mercury correlation) − Small Cell Carcinoma Benzene Methylene Chloride 📣 − Usually, you don’t diagnose these cancers if the patient 2-Butanone Nickel is non-smoker, second-guess your diagnosis Cadmium Pentachlorophenol → Cardiovascular disease → Respiratory disease Carbon tetrachloride Polychlorinated Biphenyls → Cerebrovascular disease Chlordance Tri- and Tetrachloroethylene $150 billion in health related costs Chloroform Toluene By far the most preventable cause of death in the United States Chromium Vinyl Chloride B. TOBACCO & CANCER Cyanide Zinc 70% of all lung cancers 📣 30% of all cancer Cancers related to smoking → Acute myeloid leukemia (AML) GPATHO1 - LEC Trans no. 9 | Environmental Pathology 2 of 13  ▪ Mouth and throat C. CIGARETTES AND THE WORKPLACE → ▪ Larynx Renal Cell CA Cancer is uncommon for person