Ch9-Environmental and Nutritional diseases.ppt

ENVIRONMENT AL & NUTRITIONAL PATHOLOGY  Environmental and Nutritional Pathology Environment and Disease Common Exposures Environmental Occupational Nutrition and Disease  Today Environmental Pathology Environmental (out/indoor pollution, meta...

ENVIRONMENT AL & NUTRITIONAL PATHOLOGY  Environmental and Nutritional Pathology Environment and Disease Common Exposures Environmental Occupational Nutrition and Disease  Today Environmental Pathology Environmental (out/indoor pollution, metals as pollutant, espec lead & mercury) Occupational Lifestyle : Tobacco / Alcohol Medications : OC, Paracetamol, Aspirin Physical agents: mech / thermal / electric / ionizing Nutrition and Disease  Environmental diseases is conditions caused by exposure to chemical or physical agents in the ambient, workplace & personal environment, including diseases of nutritional origin. 2 key issues global health 1 global burden of disease 2 health effects of climate change  GLOBAL BURDEN OF DISEASE undernutrition→ health loss Ischemic heart disease & CVA → leading cause of death Emerging infectious disease Newly evolved strains (MDR TB, malaria) Pathogens endemic in other species (SARS) Health effects climate change Global climate change → due to ‘greenhouse effect”( CO2, methane & ozone) Cardiovasc, cerebrovasc & respiratory diseases by heat waves & air pollution GE-itis & infectious disease epidemics Vector borne infectious disease ( dengue virus) Malnutrition, due to disruption crops  Toxicity of chemical & physical agents “toxicology” = science of poison studies distribution, effects & mechanisms of actions of toxic agents Mechanisms of Toxicity Threshold effect Absorption at portals of entry ingestion inhalation skin contact Distribution within the body Metabolism and Excretion Toxic effects  Environmental pollution Air pollution (outdoor/indoor ) Metals (lead, mercury, arsenic, cadmium)  Outdoor Air Pollution Sulfurdioxide Carbon Monoxide CO Ozone “SMOG” Nitrogen Dioxide NO = 2 smoke & fog Lead Partikels (soot)  Ozone UV radiation + O2 = O3 (ozone) Protects life on earth by absorb. UV radiation from sun (ozone layer stratosphere) Recently holes in ozone layer due to chlorofluorocarbons ( ned: CFK’s) Ground level; ozone = pollutant  Non-irratating Colorless Tasteless Odorless gass Due to incompl oxidation carbonaceous material Sources: engines, industrial proces using fossil fuels, wood, charcoal & cigarette smoke Important cause for suicide  Carbon monoxide CO Effect Systemic asphyxiant Kills by inducing CNS depression Morph CO poisoning: Cherry-red skin color & mucous membranes ► due to carboxyhemoglobi ne  Indoor Air Pollution Tobacco smoke Carbon Monoxide CO Nitrogen Dioxide NO 2 Wood Smoke Formaldehyde Radon (radioactive gas) Manufactured Mineral Fibers Bioaerosols (microbiological agens)  Metals as environmental pollutants Lead Mercury Arsenic Cadmium  Lead heavy metal high levels ->disturbances in CNS adult &children. Adult mainly periph. neuropathy Neurotoxic effect attributed to inhibition of neurotransmitters.  Effects of Lead Competition with calcium ions As a divalent cation, lead competes with calcium and is stored in bone. Inhibits healing of fractures It also interferes with nerve transmission and brain development. Inhibition of enzymes δ-aminolevulinic acid dehydratase & ferrochelatase. Ferrochelatase incorporate iron in protoporphyrin. Inhibition ►heme deficiency ► microcytic hypochromic anemia.  Lead poisoning Major changes : bone marrow, nervous system, Gitract & kidneys Blood & bone marrow: ringed sideroblasten, microcytic hypochromic anemia with punctate basophilic stippling of RBC Brain damage prone to children Adults : periph demyelinating neuropathy (wrist & footdrop) Kidneys: prox tubular damage with intranucl inclusions  Mercury 3 forms Metallic mercury (elemental) Inorganic mercury (mercuric chloride) Organic mercury (methyl) Source: contaminated fish (goldmining)/ vapors in dental amalgams Lipid soluble facilites accumulation in brain Sx: disturb neuromotor, cognitieve and behavarioral functions.  Occupational health risks Global disease attributed to occupat.expos.: 13% COPD 9% longca. 2% leukemias  Occupational health risks Organic solvents : chloroform & carbon tetrachloride Sx: hoge D: dizziness/confusion / CNS depression / COMA lage D: liver & kidney toxicity benzeen ► ↑ risk leukemias  Occupational health risks Polycyclic carbons: Sources: combustion of fossil fuels (steel industry) present in tar & soot (chimneysweepers ► scrotal cancers) most potent carcinogens industrial exposures implicated in lung& bladder carc.  Occupational health risks Organochlorines ( & halogenated organic compounds) : Sources: Pesticides (DDT) most causes endocrine disruption with anti-estrogenic & anti- androgenic activity  Occupational health risks Inhalation of mineral dusts causes chronic non neoplast. lung disease or pneumoconioses. Common causes: Coal dust (mining hard coal) Silica (sandblasting & stone cutting) Asbestos (mining,fabrication. Insulation work) Vinyl chloride ►liver angio sarcoma Occupational health risks  CASE STUDY A 54-year-old male was evaluated in the emergency room for chest pain. He had a history of hypertension and a 30 pack-year smoking history. He complained of chest pain since a week. His usual angina lasted 10- 15 minutes and was relieved by nitroglycerine. In the hour prior to his admission he consumed a large meal after which he complained of severe chest pain, nausea, and dyspnea. There had been severe unrelenting pain for 45 minutes, and it had not been relieved by nitroglycerine. Vital signs: HR 105, BP 100/50 (his usual BP was about 155/95). He was diaphoretic (sweating profusely) with pale skin and labored respirations. Rales (rhonchi) were heard over both lung fields.  CASE STUDY What is your diagnosis? myocardial infarction What are the risk factors for this patient? Tobacco smoking & high blood pressure Tobacco smoking is related with which vascular disorder? Atherosclerosis  CASE STUDY Are other organs effected by tobacco smoking? Give 5 examples.  Effects of Tobacco Worldwide 5 million deaths/yr 440,000 premature deaths/yr in USA cancer cardiovascular disease respiratory disease cerebrovascular disease By far the most preventable cause of death. The effects of smoking on survival. The study compared age-specific death rates for current cigarette smokers with that of individuals who never smoked regularly (British Doctors Study). Measured at age 75, the difference in survival between smokers and nonsmokers is 7.5 years. Tobacco and Cancer 90% of lung cancers Cessation reduces: overall mortality risk of death by cardiovasc disease lungcancer mortality Tobacco: 2000-4000 substances > 60: carcinogens  Nicotine Alkaloid in tobacco leaves Addictive Binds to R in brain ► catecholamines release ►acute effects of smoking (↑ HR & BP, ↑ cardiac contractility & output) Diseases caused by tobacco  Smoking & lungcancer Effect of agents in smoke : direct irritant effect on respiratory mucosa (bronchitis) leuco’s recruitment in lung → ↑elastase prod. → lung injury → emphysema polycyclic hydrocarb. & nitrosamines → carcinogens → lungcancer  Smoking & other diseases tobacco & alcohol: laryngeal cancer Atherosclerosis → myocardial infarction Spontaneous abortions / preterm births  Organ-Specific Carcinogens in Tobacco Smoke Organ Carcinogen Lung, larynx Polycyclic aromatic hydrocarbons 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-buta-none (NNK) Polonium 210 Esophagus N'-Nitrosonornicotine (NNN) Pancreas NNK (?) Bladder 4-Aminobiphenyl, 2-naphthylamine Oral cavity (smoking) Polycyclic aromatic hydrocarbons, NNK, NNN Oral cavity (snuff) NNK, NNN, polonium 210 Data from Szczesny LB, Holbrook JH: Cigarette smoking. In Rom WH (ed): Environmental and Occupational Medicine, 2nd ed. Boston, Little, Brown, 1992, p. 1211.  Effects of Alcohol >10 million chronic alcoholics in the USA 100,000 deaths/year due to alcohol abuse (US). 1.8 million worldwide. Deaths by accidents (drunken driving) homicides suicides livercirrhosis  Definition of Alcoholism ? Many people living in denial (i.e., alcoholics) are violently opposed to defining alcoholism at >2* drinks per day, so probably the TRUEST definition of alcoholism is subjective but involves impairment and degradation of family and social relationships. Most alcoholics living in denial devote most of their brilliant brain power proving to themselves and the world that they are NOT alcoholic. *2 beers, 2 wines, 2 shots Microsomal ethanol-oxidizing system Effects of Blood Alcohol Levels in the Absence of Tolerance Blood Level, mg/dL Usual Effect 20 Decreased inhibitions, a slight feeling of intoxication 80 Decrease in complex cognitive functions and motor performance 200 Obvious slurred speech, motor incoordination, irritability, and poor judgment 300 Light coma and depressed vital signs 400 Death Harrison Internal Med,  Adverse ethanol effects Acute alcoholism CNS effects: effects subcort. structures→ brainstem reticular formation stimulates & disorders cortical, motor& intellectual behavior high levels : depression cortical neurons & medullary centers → respiratory arrest Hepatic & gastric changes (reversible if discontinued) acute gastritis/ulceration fatty change/hepatic steatosis  Adverse ethanol effects Chronic alcoholism liver ( hepatitis/cirrhosis) GI tract (bleeding due to ulcus/gastritis/esoph varices) thiamine deficiency (periph neuropathy/Wernicke-Korsakoff syndrome) cardiovasc system (cardiomyopathy) Pancreas (acute/chronic pancreatitis) fetal alcohol syndrome ( microcephaly/growth retard./facial abnorm./↓ mental fx) cancer (oral cavity/esophagus/liver& breast in female) malnutrition & vit B deficiency  Wernicke Korsakoff Esophagus varices syndrome Cardiomyopathy Hepatitis Cirrhosis Gastritis/ulcus GI bleeding Cancer Fetal Alcohol Syndrome Mucosal irritation Cancer Pancreatitis  Alcohol and the Liver Fatty Change in > 90% of binge & chronic drinkers liver is enlarged but patient is asymptomatic Changes reversible with cessation of drinking macrosteatosis w/o inflammation or necrosis Alcohol hepatitis Only 10 - 15% of alcoholics will develop alcoholic hepatitis may have systemic symptoms and jaundice hepatocellular necrosis with Mallory bodies and PMNs (central hyaline sclerosis) thought to be a precursor of cirrhosis Alcoholic cirrhosis shrunken nodular liver with uniform small nodules (micronodular cirrhosis) Neurologic Manifestations of Alcoholism Wernicke syndrome confusion, ataxia, and diplopia from ophthalmoplegia damage to mammillary bodies, cerebellum and periaqueductal gray matter of the midbrain due to thiamine deficiency may respond to prompt thiamine replacement Korsakov syndrome memory loss and confabulation results from thiamine deficiency and direct toxicity  Mechanisms of Disease Caused by Ethanol Abuse Organ System Lesion Mechanism Liver Fatty change Toxicity Acute hepatitis Alcoholic cirrhosis Nervous system Wernicke syndrome Thiamine deficiency Korsakoff syndrome Toxicity and thiamine deficiency Cerebellar degeneration Nutritional deficiency Peripheral neuropathy Thiamine deficiency Cardiovascular Cardiomyopathy Toxicity system Hypertension Vasopressor  Mechanisms of Disease Caused by Ethanol Abuse Organ System Lesion Mechanism Gastrointestinal Gastritis Toxicity tract Pancreatitis Toxicity Skeletal muscle Rhabdomyolysis Toxicity Reproductive Testicular atrophy ? system Spontaneous ? abortion Fetal alcohol Growth retardation Toxicity syndrome Mental retardation Birth defects  Injury by Therapeutic Drugs Injury by Physical Agents Injury by Therapeutic Drugs ADVERSE DRUG REACTIONS Oral Contraceptives (OCs) Hormone Replacement Therapy (HRT) Anabolic steroids Acetaminophen Aspirin  Hormone Replacement Therapy (HRT = estrogen & progesterone)) Cancer increases risk of breast cancer in women who used HRT combined therapy for 5-8 years Thromboembolic events increases risk venous thromboembolism, more pronounced first 2 y. Cardiovascular disease 60y: NO PROTECTION  Oral Contraceptives (OCs) Thromboembolism 3 x ↑ risk venous thrombosis & pulm.thromboembolism Risk further ↑ in carriers of prothrombin & factor V Leiden mutations Mech: acute phase respons leads to : ↑ C-reactive protein & coagulation factors (F VII,IX,X,XII & XIII) Reduction anticoagulants (prot.S & anti-thrombin III) Cardiovascular disease M.I. risk increases regardless of age in smoking ♀ & > 35 y in nonsmoking ♀ Cancers reduces risk endometrial & ovarian cancer No risk breast cancer Liver tumors benign hepatic adenomas in older ♀ with prolonged OC use  Acetaminophen (Tylenol/ Paracetamol) no effect on cyclo-oxygenase, so bleeding associated with aspirin does not occur has analgesic and antipyretic actions but no anti-inflammatory action large doses may produce hepatic necrosis do not exceed recommended dose (4 grams/day) adult toxic dose 15 -25 gm  Aspirin Overdose ( kids:2-4gr, adults 10-30gr) respiratory alkalosis (stim. respiratory center medulla region) → metabolic acidosis → ┼ fatal Chronic aspirin toxicity (salicylism, >3gm/day) headache, dizziness, ringing in ears (tinnitus), mental confusion, drowsiness, nausea, vomiting, & diarrhea CNS changes → convulsions & coma Inhibits cyclo-oxygenase (COX 1 & 2) Erosive gastritis (block thromboxane A2) → GI bleeding  Injury by drugs of abuse DRUG ABUSE Cocaine Heroin Amphetamines Marijuana others  Cocaine Coca plant → cocaine hydrochloride Use: snorted dissolved in water & injected SC/IV Effects: intense euphoria & stimulation acute overdose: seizures/arrhythmias/respiratory arrest Cocaine inhibits reuptake neurotransmitters dopamine & norepinephrine Myoc infarction due to coron. art. vasoconstriction enhanced platelet aggregation thrombus formation  Cocaine Effects: On pregnancy: decrease blood Q placenta→ fetal hypoxia & spontaneous abortion impaired neurologic development Other: nasal septum perforation decreased lung diffusing capacity dilated myocardiopathy  Heroin Opiod related to morfine Use: iv/smoked/snorted Effects: euphoria/hallucinations/somnolence &sedation Adverse effect related to: pharmacologic action reaction to cutting agents hypersensitivity reactions needle use  Heroin Important adverse effect: sudden death (drug purity unknown. Mech: RDS, arrhythmia, cardiac arrest & pulm.oedema) pulmonary injury (oedema, septic embolism, lung abscess, opportunistic infections, foreign body granulomas due to talc) infections (skin, subcutis, heart valves, liver & lungs) skin (abscess, cellulitis, ulcerations) Kidney ( amyloidosis, focal glomerulosclerosis)  Amphetamines Metamphetamine Aka ”speed” Mech: dopamine release in brain → inhibits presyn neurotransmission. Effects: strong CNS effects Euphoria followed by “CRASH”  Ampheta mines MDMA (3,4 methylenedioxyme thamphetamine) Aka “ ecstasy” Oral use Effect: euphoria hallucinogen like feeling ↑serotonin  Marijuana Cannabis sativa plant →Tetrahydrocannabinol Use: joint Effect: Acute (clear in 4-5h) distorts sensory perception (artist) impairs motor coordination Progress to cognitive & psychomotor impairments Cardiovasc: increase heart rate /BP / angina Lung: laryngitis, pharyngitis,bronchitis  Injury by Physical Agents MECHANICAL TRAUMA THERMAL INJURY ELECTRICAL INJURY IONIZING RADIATION INJURY  MECHANICAL TRAUMA TYPES: ABRASION CONTUSION LACERATION INCISED WOUND GUNSHOT WOUNDS  Physical Injury Abrasion basically a scrape superficial epidermis is torn off by friction or force regeneration without scarring usually occurs Laceration vs. Incision a laceration is an irregular tear in the skin produced by overstretching. The wound margins are frequently hemorrhagic and traumatized an incision is made by a sharp cutting object. The margins of the incision are usually relatively clean Contusion an injury caused by a blunt force that damages small blood vessels and causes interstitial bleeding, usually without disruption of the continuity of the tissue (cf ecchymosis) Abrasion Laceration Contusion Incision  THERMAL INJURY Thermal burns CLINICAL Sx depends on: Depth % of body surface involve Internal injuries caused by inhalation hot & toxic fumes Promptness & efficacy Classification burns: Superficial (1st degree burn) Partial thickness (2nd degree burn) Full thickness burns (3th degree)  Burns of 10% in children or 15% in adults (or greater) are potentially life threatenin g injuries  THERMAL INJURY Complications: Shock, sepsis, RDS Hypovolemic shock (particulary >20% body surface) Hypermetabolic state (excess heat lost) Opportun infections ( pseudomonas ) Injury airways & lungs  THERMAL INJURY Hyperthermia prolonged exp. ↑ temperatures: Heatcramps (electrolyte loss via sweat) Exhaustion (Water depletion and lack of cardiovasc. compensation) heat stroke (Extensive peripheral vasodilatation, i.e., “shocky”, very serious, T>106º, over 110º have been reported, high mortality) Hypothermia prolonged exp. ↓ temperatures: loss of consciousness bradycardia & atrial fibrillation  HYPO-THERMIA Oftenin setting of homelessness or alcoholism or both < 90º often fatal, assoc. w. BRADYCARDIA ATRIAL FIBRILLATION  ELECTRICAL INJURY Injuries burns ventricular fibrillation or cardiac & resp center failure  RADIATION INJURY NON-IONIZING : uv/ infrared/ microwave/ soundwave IONIZING: X-RAY & GAMMA rays Effects: Cancer treatment/diagnostics Therapeutic/diagnostic radioisotopes Adverse effects: fibrosis, mutagenesis, carcinogenesis & teratogenesis Overview of the major morphologic consequences of radiation injury. Early changes occur in hours to weeks; late changes occur in months to years. ARDS, acute respiratory distress syndrome. NUTRITIONAL DISEASES Dietary insufficiency Protein-energy malnutrition Anorexia nervosa & bulimia Vitamin deficiencies Obesity Diets,cancer & atherosclerosis  Dietary insufficiency Appropiate diet provides: Sufficient energy (carbs,fats, proteins) Building blocks for proteins & lipids (amino & fatty acids) Vitamins & minerals function as coenzyme or hormones (calcium & phospate) Dietary insufficiency  Dietary insufficiency Malnutrition 2 types: Primary malnutrition: one or all components are missing from diet Secondary malnutrition: adequate supply but malnutrition occurs due to insuff. intake malabsorption impaired utilization or storage excess loss increased need nutrients  Dietary insufficiency Causes leading to dietary insuff.: Poverty Infections Acute/chronic illness (↑basal metabolic rate) Chronic alcoholism Ignorance & failure diet supplementation Self imposed dietary restriction (anorexia & bulemie) Other causes (GI-diseases, malabsorption SD, genetic diseases, drug therapies & total parenteral nutrition)  Protein-energy malnutrition Often affecting children Common in low-income countries developed countries: elderly & debilitated patients in nursing homes & hospital Malnutrition determined by BMI(body mass index= weight/length2 )