Respiratory System Drugs Respiration o A process designed to provide o A continuous oxygen supply to bodily and o The removal of gaseous waste products carbon dioxide o Normal blood values PaCO2 36 44 mm Hg PaO2 80 100 mm Hg pH 7 36 7 44 7 4 Three definitions of Respiration o Pulmonary ventilation the movement of and out of the lungs o Gas transport the exchange of gases across tissues mainly air in various phase barriers via diffusion from the air to lung cells from lung cells across capillaries into the pulmonary blood from the blood across capillaries into the interstitial fluid from interstitial fluid across plasma membrane into the cells and the reverse of this process o Cellular respiration the biochemical enzymatic reactions that use oxygen to extract energy from cellular nutrients the aerobic catabolism of glucose to yield ATP Pulmonary capillaries very short and alveoli are intermeshed so as to create a moving sheet of blood General Structure o Alveoli around the gas exchange surfaces 50 100 square meters Where gas exchange takes place o Airway The passage way from the outside into the lungs all the way down to the alveoli where the process of gas exchange with the pulmonary blood begins the air is warmed humidified and cleared of harmful substances particles lung tissue where NO gas exchange occurs o Dead space practically anywhere there aren t alveoli some diseases damage the air passage way but not the alveoli some diseases degrade the respiratory gas exchange surface increase dead space Respiratory tract secretions o The inner surface of the tracheobronchial tree is lined with ciliated columnar epithelial cells interspersed with goblet these cells produce the gelatinous mucus gel layer mucopolysaccharides proteins cells o Goblet cells o Bronchial glands o These two cells combine to produce the Gel Sol film watery mucus sol layer AKA mucociliary blanket o Alveolar cells stability of alveoli during the numerous changes in pressure gradients one type of these cells produce surfactant e g dipalmitoyl phosphatidyl choline that confers greater Keeping it clean o In the trachea and bronchi Mucokinesis process of moving mucus along the tracheobronchial tree by the action of the ciliated cells Healthy adults produce about a liter of mucous per day but swallow most of it unconsciously o In the alveoli Macrophages are the primary means of removing debris that gets into the alveoli These cells migrate over the inner surface and engulf foreign matter Bronchial smooth muscle o Powerfully modulated by the autonomic nervous system o Nerve supply to the actual lung tissue is the autonomic nervous system ANS o The somatic nervous system that operates the diaphragm and rib muscles skeletal muscles for actual breathing o CONSTRICTION Ca2 influx cyclic GMP phosphatidyl inositol turnover IP3 second messengers parasympathetic acetylcholine from the vagus stimulates muscarinic acetylcholine receptors increases mucosal secretions induces contraction of bronchial smooth muscles bronchoconstriction o Constricting hormones drugs a1 receptor stimulation histamine PGF2a serotonin Leukotrienes b2 receptor blockade non selective beta blockers like propranolol o DILATION cyclic AMP is the second messenger sympathetic epinephrine from the adrenal medulla stimulates b2 b1 adrenergic receptors induces relaxation of bronchial smooth muscles bronchodilation o Dilating hormones drugs PGE2 PGI prostacyclin muscarinic acetylcholine receptor blockade many drugs Respiratory Control o CNS respiratory rhythm is controlled in the medulla o CNS depressant drugs cause respiratory depression opiates barbiturates ethanol benzodiazepines esp in combo o Peripheral NS Carbon dioxide and blood pH regulate respiration via chemosensors in the aorta Low pH low bicarbonate or high CO2 increase respiration rate and depth The reverse of these conditions decreases rate and depth of respiration Altered by fear pain stress blood pressure body temperature Oxygen has no great effect until it falls below normal then stimulates chemoreceptors to increase respiration Respiratory Diseases o Asthma hyper reactive bronchial passages inflammatory process that increases the resistance to air flow outflow Triggers but often idiopathic dust animal dander plants fungi vagal input psychological stress allergies pollen eggs chocolate drugs ASA emotions enhanced sensitivity to muscarinic stimuli infections exertion environmental irritants usually due to viruses but bacterial too especially in cold dry air air pollution saw dust etc Causes bronchoconstriction and mucus plugs o Chronic bronchitis excessive mucus production due to chronic inflammation mucus thins the airways increase resistance plugs can also form an outright block damage is initially reversible but less so with extended time o COPD emphysema Chronic Obstructive Pulmonary Disease two conditions with similar overlapping symptoms disease begins years before symptoms show up slowly progressive with intermittent acute exacerbations similar treatment regimens Characteristics of COPD emphysema Destruction of alveoli blown up enlarged become dead space Decreased pulmonary elasticity cannot expel air well air pollutants smoking inhibits macrophage and ciliary function Risk factors for COPD Emphysema o hypertrophy and hyperplasia of mucus glands fibrosis to replace damaged cells genetic factors alpha 1 anti trypsin a small glycoprotein that inhibits many proteases such as trypsin collagenase elastase and others from bacteria and the WBCs present o Low anti trypsin is responsible for 5 COPD cases infections most often viruses are risk factors o alcoholism diabetes anemia can all make these problems worse o Cystic fibrosis a primary genetic defect in the transport of chloride ions across epithelial cells Not enough Cl goes out too few Na ions follow decreased water flow into lumen increased viscosity of the mucus layer gets too thick cilia are unable to work properly Affected tissues lung reproductive tract pancreas sweat glands Mediators of Inflammation o Rhinitis inflammation of nasal mucosal membranes viruses and hypersensitivity o Histamine made stored in high amounts in the lungs skin and GI tract in mast cells basophils Found in highest concentrations in tissues in contact with external environment release triggers cold viruses bacteria trauma toxins drugs allergens Histamine is broken down and inactivated by tissues but at a limited rate slow minimal release often causes a limited