ENVIRONMENTAL PATHOLOGY . environment includes; -outdoor -indoor -occupational -personal, (tobacco, alcohol, drugs, diet) . environmental pathology deals with diagnosis, treatment, and prevention of injuries and illnesses resulting from exposure to exogenous chemical or physical agents, such exposure may occur in -working place -people may voluntarily expose themselves to these hazards TOBACCO USE .use of tobacco products, (cigarettes, cigars, pipes, and snuff) is associated with more mortality and morbidity than any other personal, environmental, or occupational exposure.mainstream cigarette smoke consists of -particulate phase -gas phase .contains more than 4000 constituents, including ======-43 carcinogens, ======-43 carcinogens, (polycyclic aromatic hydrocarbons, polonium 210, (polycyclic aromatic hydrocarbons, polonium 210, 4- aminobiphenyle, 2-naphthylamine, arsenic, nickel, N-Nitrosonornicotine cadmium, chromium) 2-naphthylamine, arsenic, nickel, N-Nitrosonornicotine cadmium, chromium) ====-potential promoters (acetaldehyde and phenol) ====-potential promoters (acetaldehyde and phenol) === -irritants (NO2, CO) . Nicotine==== is an alkaloid that crosses the blood- brain barrier and stimulates nicotine receptors in the brain -responsible for acute pharmacologic effects, most likely mediated by catecholamines -responsible for tobacco addiction. Nicotine==== is an alkaloid that crosses the blood- brain barrier and stimulates nicotine receptors in the brain -responsible for acute pharmacologic effects, most likely mediated by catecholamines -responsible for tobacco addiction . the inhaled agents in cigarette smoke -may act directly on mucous membrane -may be swallowed in saliva -may be absorbed into blood stream.most of the deaths attributable to cigarette smoking are due to -lung cancer -ischemic heart disease -chronic obstructive lung disease.these dangers are dose related.cessation of smoking reduces the risks of these disorders Adverse effects of smoking . smoking may contribute to cardiac arrest by -increasing platelets adhesion and aggregation -increasing platelets adhesion and aggregation -triggering arrhythmia -triggering arrhythmia -causing an imbalance between demand for O2 and supply to the myocardium -causing an imbalance between demand for O2 and supply to the myocardium .the fetus is especially vulnerable to the consequences of maternal smoking -fetal hypoxia>low birth weight, prematurity -increased incidence of spontaneous abortion.complications at the time of delivery - premature rupture of membranes - placenta previa -abruptio placentae .hazard of cigarette smoking at work place -smokers have higher rates of accidental injuries -smoke may act as a vector to transport other hazardous agents into the lungs, such as radon gas in miners cigarette smoke is synergistic with radon decay products in causing lung cancer . tobacco exacerbates.bronchitis.asthma.pneumoconiosis associated with exposure to silica, coal dust, cotton dust, and welding fumes.tobacco use also increases prevalence of peptic ulcers . hazards associated with exposure to side-stream smoke (passive smoking, or environmental tobacco smoke, ETS) -increase incidence of lung cancer and ischemic heart disease -hazardous for infants and children -maternal smoking increases the incidence of sudden infant death syndrome -young children suffer from increased incidence of respiratory and ear infections and exacerbation of asthma ALCOHOL ABUSE .blood concentration of mg/dl is the legal definition for driving under the influence of alcohol. in occasional drinkers, a blood alcohol level of 200 mg/dl produces inebriation; with coma and death, and respiratory arrest at mg/dl. habitual drinkers can tolerate blood alcohol levels up to 700 mg/dl . chronic use results in psychological and physical dependence, genetic factors may be involved.metabolism of ethanol is directly responsible for most of its toxic effects.effects of ethanol on various organs could also be attributed to specific vitamin deficiency .effects of ethanol on various organs -nervous system =================.acute depression, and addiction.chronic alcoholism > thiamine deficiency > degeneration of nerve cells, reactive gliosis, and atrophy of the cerebellum and peripheral nerves (Wernicke syndrome and Korsakoff psychosis) .cardiovascular system =========================== -cardiomyopathy -hypertension. gastrointestinal tract acute gastritis -chronic users are vulnerable to acute and chronic pancreatitis.liver fatty change -acute alcoholic hepatitis -cirrhosis . skeletal muscles -injure muscles.reproductive system, chronic effects -testicular atrophy and hypo-fertility both in men and women -effect on pregnancy spontaneous abortion. fetal alcohol syndrome -growth defects -developmental defects . ethanol and cancer -association with cancers of, (oral cavity, pharynx, liver, esophagus, possibly breast) -association with cancers of, (oral cavity, pharynx, liver, esophagus, possibly breast) -acetaldehyde may act as a tumor promoter -acetaldehyde may act as a tumor promoter -ethanol inhibits detoxification of chemical carcinogens THERAPEUTIC DRUGS.adverse drug reaction is defined as a toxic or undesired response to a drug used at therapeutic doses to prevent, diagnose, or treat disease. predictive reactions are based on the known toxicity or mechanism of action of a drug (dose related).idiosyncratic reactions are rare and unpredictable, consequences may be severe or even fatal Oral Contraceptives their use is not associated with an increased risk of breast cancer..they decrease the risk of endometrial and ovarian cancers.their use by HIV-infected women, increased risk of cervical cancer.uncommon adverse effects, (venous thrombosis, cardiovascular disease liver adenoma). Anabolic Steroids.synthetic versions of testosterone used by athletes to improve performance.adverse effects, (dose times of therapeutic dose) -in adolescents, (stunted growth) -in males, (acne, gynecomastia, testicular atrophy) -in females, (growth of facial hair, menstrual disturbance) -psychiatric problems -premature heart attack Hormone Replacement Therapy estrogen therapy.risks include -increased risk of breast cancer if used for at least 5 years -venous thrombosis -cholecystitis Aspirin.==================== overdose is accidental in children, and suicidal in adults.respiratory alkalosis>metabolic acidosis.chronic aspirin toxicity in persons who take 3 gm or more daily for years.acute erosive gastritis>ulceration.aspirin mixed with other analgesics > analgesic nephropathy Outdoor Air Pollution .major sources -combustion of fossil fuels.mobile sources (motor vehicles).stationary sources (power plants factories, barbecues and fireplaces) -photochemical reactions.oxides of nitrogen and volatile hydrocarbons interact in the atmosphere to produce ozone (O3) as a secondary pollutant -power plants, (sulfur oxide, particulates), aerosolized acid sulfates contribute to acid rains -waste incinerators, industry and smelters, (acid aerosols metals, mercury vapors, organic compounds). lungs are the major targets of outdoor air pollution, especially vulnerable are -children -asthmatics -people with chronic lung or heart disease .major air pollutants Ozone major component of smog that accompanies summer heat waves.it oxidizes polyunsaturated lipids to hydrogen peroxide and lipid aldehydes, (irritants to mucus membranes) Nitrogen Dioxide----dissolves in water in the respiratory airways passages > nitric and nitrous acids > damage epithelium Sulfur Dioxide.soluble in water> resp.airways irritation Acid Aerosols in the atmosphere sulfur and nitrogen dioxides are oxidized to sulfuric and nitric acids respectively, which are dissolved in water droplets or adsorbed to particulates, (both are irritants to the airways epithelium and alter mucocilliary clearance) Particulates deposition and clearance of particulates inhaled into the lungs depend on their size, (less than 0.1 micron in diameter, are more hazardous) adverse effects are due to.systemic cytokine release.increased blood viscosity.autonomic changes associated with variable heart rates and arrhythmias Indoor Air Pollution Carbon Monoxide By product of burning of gasoline, oil, wood, and natural gas, and tobacco.effects of CO indoor pollution -reduces exercise capacity -aggravate myocardial ischemia -causes headache, dizziness, loss of motor control, and coma Nitrogen Dioxide produced by gas stoves and kerosene space heaters.impairs lung defenses>infection Wood smoke complex mixture of nitrogen oxides, particulates, and polycyclic aromatic hydrocarbons.respiratory infections in children Formaldehyde highly soluble, volatile chemical used in the manufacture of textiles, pressed wood, furniture, and insulation ---- causes acute irritation of the eyes and upper respiratory tract and exacerbation of asthma Radon ---- a decay product of uranium, widely distributed in the soil causes lung cancer in miners Asbestos Fibers.non-friable and un-disturbed fibers have low indoor levels Bioaerosols Legionella pneumonia > pneumonia allergens associated with pets, dust mites, cockroaches, fungi, and molds can cause allergic rhinitis,asthma RADIATION INJURY forms of radiation ---waves 1--long wavelengths, low frequency 2--short wave lengths, high frequency ---particles approximately 80% of radiation is derived from natural sources -cosmic radiation -ultraviolet light -natural radioisotopes (radon gas) forms of radiation ---waves 1--long wavelengths, low frequency 2--short wave lengths, high frequency ---particles approximately 80% of radiation is derived from natural sources -cosmic radiation -ultraviolet light -natural radioisotopes (radon gas) remaining 20% is derived from manufactured sources -instruments used in medicine - consumer products that emit radio waves or microwaves -nuclear power plants non-ionizing radiations have long wave lengths and low frequencies, (electric power, radio waves, microwaves, infra- red and ultraviolet lights), cause vibration and rotation of atoms in biological molecules ionizing radiations have short wave lengths and high frequency, (X- rays, gamma rays, cosmic rays), can ionize biologic molecule and eject electrons particulate radiation include, (electrons, protons, nutrons, mesons, deuterons) Ionizing Radiation.the dose is measured in several units, (roentgen, rad, gray, rem, Sievert ).these measurements do not directly quantify energy transferred per unit of tissue and therefore do not predict the biologic effects of radiation factors influence the biologic effects of ionizing radiation.physical properties and dose of radiation.rate of radiation.rapidly dividing Versus quiescent cells.single dose V regional doses.cells in G2 and M phases are most sensitive.type of cell involved.enhancement of damage by O2 cellular changes of radiation injury. 1---acute changes -necrosis -damage to DNA, if DNA damage is severe or cannot be repaired > cell cycle arrest > apoptosis. 2---chronic changes -fibrosis -mutation > cancer after years Morphologic features of radiation injury Clinical Manifestations Of Exposure To Ionizing Radiation depend on -dose -duration -mode of exposure Acute Whole-Body Exposure 4 syndromes are recognized 1--sub-clinical or prodromal syndrome (less than 200 rem) mild nausea and vomiting,lymphocytes less than 1500/ml survival is 100% 2---hematopoietic syndrome ( rem) intermittent nausea and vomiting, petechiae and hemorrhage, maximum neutrophil and platelet depression in 2 weeks, lymphocytes less than 1000/ml.infections, patient may require bone marrow transplantation 3-gastro-Intestinal syndrome ( rem).nausea, vomiting, diarrhea,hemorrhage.infection.severe neutrophil and platelet depression.lymphocytes less than 500/ml.death in days 4---central nervous system syndrome (more than 1000rem).intractable nausea and vomiting,confusion, convulsions, coma in 15 min- 3hrs.lymphocytes absent.death in 14-36hrs Effects Of Radiation Therapy external radiation is delivered to cancers at fractionated doses with shielding of adjacent tissues, radiation when delivered to the chest or abdomen > acute radiation sickness.patients treated with radiation may have -sterility -secondary cancer -delayed radiation injury Delayed Radiation Injury.arteries, fibrosis of wall>narrowing of lumen.capillaries, thrombosis or ectatic.heart, restrictive pericarditis, myocardial ischemia > fibrosis Artery, radiation injury (subintimal fibrosis) .skin -epidermis (desquamation>atrophy) -dermis (dilated vessels, fibrosis) -radiation dermatitis (impaired healing, increased susceptibility to infection, ulceration) -skin cancer, as long as 20 years later.brain (focal necrosis and demyelination of the white matter).spinal cord, (transverse myelitis) Skin, chronic radiation dermatitis .lungs -acute lung injury -delayed radiation pneumonia -cancer as late complication. breast -diagnostic radiation during adolescence increases the incidence of breast cancer after years Ovaries>follicles degenerate acutely. urinary tract -kidneys (hypertension, atrophy) -urinary bladder (epithelial necrosis> submucosal fibrosis) -tumors of kidneys and urinary bladder. gastro-Intestinal tract === -esophagitis, gastritis, and entero-colitis -delayed injuries, (ischemic necrosis, fibrosis, strictures). testes, (infertility).eyes, (cataract) Ultraviolet Radiation. divided into A, B, and C ozone in the atmosphere is protective agent against ultraviolet radiation.chlorofluorocarbons interacts with and depletes ozone (increases incidence of skin cancer) .some protection from the effects of UV light is afforded by window glasses.sun-blocks and sunscreens offer greater protection. ======================================== effects of UV radiation =============================== -premature aging of the skin -skin cancer.acute effects of UVA and UVB are short-lived and reversible, (erythema, pigmentation) .tanning is due to -increase in number of melanocytes -elongation and extension of dendritic processes -transfer of melanin to keratinocytes Electromagnetic Fields.increased incidence of childhood leukemia at very high exposure. occupational exposures at higher levels have not been associated with an increased risk of cancer or neuro- degenerative disease OBESITY .is a disease of caloric imbalance resulting from excess intake of calories above their consumption by the body that lead to accumulation of adipose tissue of sufficient magnitude to impair health .assessment of obesity -body mass index (BMI).obese if BMI is above 30kg/sq. m.overweight if BMI is in the range of body weight -triceps skin-fold thickness -mid-arm circumference -ratio between waist hip circumferences .types of obesity -central (visceral), fat accumulation in trunk and abdominal cavity -peripheral, diffuse fat accumulation in subcutaneous tissue. associated diseases with obesity -type 2 diabetes -dyslipidemias -cardiovascular disease -hypertension -cancer .pathogenesis of obesity ============================= -peripheral (afferent system), generate signals from various sites.fat cells (leptin, adiponectin).stomach, ilium, colon (ghrelin, peptide).pancreas (insulin) - hypothalamic arcuate nucleus generates efferent signals -efferent system, carries hypothalamic signals to control food intake and energy expenditure Leptin.synthesized by fat cells,.stimulated when fat store is abundant,. It regulates -food intake -energy expenditure -pro-inflammatory cytokine -hematopoiesis and lymphopoisis.leptin resistance rather than deficiency may be prevalent in obesity Adiponectin ===.called fat burning molecule guardian angel against obesity produced mainly by adipocytes,.directs fatty acids to muscle for their oxidation General Consequences Of Obesity.obesity is the main driver for metabolic syndrome (visceral adiposity, insulin resistant hypertriglyceridemia, low HDL cholesterol), syndrome-associated diseases include -type 2 diabetes -coronary artery disease -fatty liver disease -cholelithiasis -Pickwickian syndrome -osteoarthritis Obesity And cancer.about 4% of cancers in men and 7% in women are associated with obesity, the risk of cancer is related to -hyperinsulinemia -insulin resistance.obesity and hyperinsulinemia have an effect on steroids that regulate cell growth and differentiation in different tissues .in men BMI is more than 25 kg/sq.m is strongly correlated with -adenocarcinoma of esophagus -thyroid cancer -colonic cancer -renal cancer.in women BMI of more than 25 kg/sq. m is strongly correlated with -adenocarcinoma of esophagus -endometrial cancer -gall bladder cancer -renal cancer DIET AND CANCER factors related to carcinogenesis.content of exogenous carcinogens (aflatoxin-hepatocellular carcinoma).endogenous synthesis of carcinogens from dietary components-- (nitrosamines and nitrosamides-gastric carcinoma).lack of protective factors (vitamins C and E, -carotenes, fibers, and selenium)