Slide 1American Lung AssociationHistoryRespiratory TractPulmonary defense mechanismsSlide 6FunctionsSlide 8Defense mechanismSlide 10Slide 11Slide 12VentilationSlide 14Slide 15RespirationTypes of inhalable toxicantsSlide 18Large particles (> 10 mm)Pulmonary EffectsLocal IrritationCellular DamageFibrosis (Pneumoconiosis)AsbestosAsbestos usesAllergic ResponseLung cancerEmphysemaParaquatOther agentsTesting procedureObservationsMorphological changesTestsInhalation ToxicologyDavid Shubert Ph.D.125 Sherman Annex [email protected] Lung Association•Lung disease is the number three killer (behind heart disease and cancer) in the United States, responsible for one in six deaths.•An estimated 438000 Americans die each year from diseases directly related to cigarette smoking, including heart and lung diseases.•Lung disease costs the U.S. economy $ 95 billion in direct health-care expenditures every year, plus indirect costs of $ 59 billion—a total of $ 154 billionHistory•Bernardino Ramazzini – Italian physician (father of occupational medicine )•1713 he provided detailed accounts of ailments in miners (they breathe particles in the mine; they weren’t in an open environment) (he compared the people in close env and in open env.)•Concept of exposure•Compared workers who shovel, melt and cast compared to minersRespiratory Tract•Nasopharynx•Stratified-squamous epithelium, Nonciliated epithelium, Ciliated epithelium, Olfactory epithelium•Tracheal•Bronchial tract•Pulmonary acini•Respiratory bronchioles•Alveolar ducts•AlveoliPseudostratified epithelium containing:Ciliated cells : to clean the air in respiratory system. (pushes the mucus up)Nonciliated cells: Mucous cellsSerous cells : water fluidPulmonary defense mechanisms•Upper respiratory tract – constant temperature and humidification, traps and removes foreign materials•Nasal hairs – trap some bacteria and noxious gases•Mucus blanket – traps foreign materials•Cilia – propel mucus and trapped particles toward oropharynx (swallowed or expectorated) •Alveolar macrophages – important if you inhale any bacteria •Irritant receptors – in nostrils tigger sneeze reflex (defense mechanism)Functions•Oxygen and carbon dioxide exchange •Blood and Air•Pulmonary acini•Alveoli•Lined with epithelial cells Type 1•Thin cytoplasm (0.1-0.2 mm)•Large surface area (2,290 mm2)•Regulates blood concentrations (important for blood pressure) •Angiotensin converting enzyme (angiotensin II)•Biogenic amines (HISTAMINE, NORADRENALINE AND DOPAMINE)•Prostaglandins ( inflammation, immune responses)•Excretion (gases)•MetabolismDefense mechanism•Trachea and Bronchi•Ciliated epithelium •Thin layer of mucus•Squamous epithelial cells (Type I)•Gas exchange, structure•Great alveolar cells (Type II)•Pulmonary surfactant; lowers surface tension ( providing area for gas exchange)•Macrophage•Destroy foreign material•Clara Cells •Cytochrome P450 system (drug metoblism) •Detoxify •ActivateVentilation•Total lung capacity – approximately 5700 cm3 •Residual volume – left after maximum expiration 1200 cm3•Vital capacity – amount of air moved into and out of the lung with maximum inspiration and expiration•Tidal volume – amount of air moved into and out of the lung under resting conditions 500 cm3•FVC – forced vital capacity •FEV1- forced expiration value after 1 sec•FEV/FVC- forced expiration value after 1 sec as a percentage of forced vital capacity•Normal values depend on age, gender, and heightRespiration•Respiratory frequency – number of breath per minute 12-20•Exercise – •Increase in tidal volume•Increase in respiratory frequency•Perfusion – lung receives entire output from the right ventricle 70-80 cm3 blood per heartbeat•Diffusion – contact to airborne toxin occurs over the entire alveolar surface (140 m2) intestine 250 m2 skin 1.75 m2•Thicken the alveolar septum and affect diffusion of oxygen•Liquid in alveolar space•Thickening of the pulmonary epitheliumTypes of inhalable toxicants•Gases•Vapors•Liquid droplets•Solid particulate matter•>10 mm•1-3 mm•<0. 1 mm•Systemic effects•Local effects•Affect respiratory tract after other routesLarge particles (> 10 mm)•Mainly deposited in the nasal passages•Nickel subsulfide•Nickel oxide•Hyperplasia•Ulceration•Squamous or transitional cell metaplasia•CarcinomaPulmonary Effects•Local irritation •Cellular damage and edema•Fibrosis•Allergic reaction•Lung CancerLocal Irritation•Ammonia & Chlorine•Acute•Bronchial constriction•Edema•Dyspnea – shortness of breath•Chronic•Effects are rareCellular Damage•Ozone & oxides of nitrogen•Peroxidation of membranes•Damaged membrane•Edema •Fluid accumulates in the airway•Cellular damage •Affects type I cells in the aveoli•Proliferation of type II cells•Differentation into type I •Extensive damage•Neutrophils, debris, eventually fibrous tissueFibrosis (Pneumoconiosis)•Silicosis•Crystalline forms of silica (silicon dioxide)•Quartz most stable but on heating, volcanc eruption become more fibrogenic•Tridymite•Cristobalite•Mechanism- rupture of the lusosomal membrane in a macrophages, the released lysosomal enzymes digests the macrophage, and this process in turn releases the silica from lysed macrophage.Asbestos•Mineral fiber containing hydrated silicates of magnesium, calcium, and others •Crocidolites (blue asbestos)•Bronchogenic carcinoma•mesothelioma•Chrysotile (white)•Potency•Fibers 5 mm length and 0.3 mm diameterAsbestos uses•Fixes retardant material•Building materials•Side walls•Roof material•Floor material •Insulation-Asbestos cement water pipes and sewer pipes-Added to concrete for strength and flexibility-Canada still sells asbestos to third world countriesAllergic Response•Pollens, spores of mold, bacterial contaminants, and cotton dust•Toluene diisocyanate (TDI)•Used in the plastic industry•Mechanism•Reactive chemical binds to proteins•Antigen•Antibodies•Bronchoconstriction triggered by interactions•Long term•Chronic bronchitis and fibrosisLung cancer•Cigarette smoke (lung cancer deaths, 90% in men and 80% in women)•Carcinogens•Cocarcinogens•Irritants•Oxidative stress•Free radicals•Hydroquinones - redox cycle•Asbestos•Increased in smokersEmphysema•Lung compliance – measure of