MUNI MED Respiratory system & Lung diseases 1 Respiratory system Points -Ventilation - Diffusion - Perfusion 2 Respiratory system MUNI MED Breathing - Lung ventilation can be considered in two parts: - the mechanical process of inspiration and expiration - the control of respiration to a level appropriate for the metabolic needs. 3 Respiratory system MUNI MED Neurotonic tohrtary corfnil Chnmicjil facton AnsrttylySittiA Hindi 4 Respiratory system © Elsevier Suente Lid A Physiological deadspace Ventilation with reduced perfusion VA/$= >1 Causes. Pulmonary embolism Pulmonary arteritis Necrosts or fibrosis (loss of capillary bed} B Normal Ventilation and perfusion i C Physiological Perfusion with reduced ventilation *a/0 < 1 Blood vessels Causes Arrway limitation {asthma and COPD) Lung colfapse or consolidation Loss of elastic tissue (emphysema) Disease of the chest wall © ElMsvier Science Ltd 6 Respiratory system so 2 £ 3 Inspiratory Reserve Volume [IRV] Tidal Volume [TVorVT] Expiratory Reserve Volume [ERV] Respiratory system Normal respiration Forced respiration [Deep breath] Normal respiration Residual Volume (RV3 Inspiratory Capacity tie) Functional Residual Capacity (FRO Vital Capacity [VC] Total Lung Capacity [TLC] Residual Volume [RV] Lung Volume Patterns - Obstructive Disease: Characterized by hyperinflation and gas trapping (increased TLC and RV/TLC) - asthma, chronic COPD (bronchitis, emphysema) - Restrictive Disease: Characterized by generalized reduction in lung volume (decreased TLC, RV and FRC) - interstitial lung diseases (pulmonary fibrosis, sarcoidosis), pneumothorax, lung resection 8 Respiratory system MUNI MED Obstructive pulmonary diseases □ They are characterized by airway obstruction that is worse with expiration. □ Either more force (i.e., use of accessory muscles of expiration) is required to expire a given volume of air or emptying of the lungs is slowed or both. □ The unifying symptom of obstructive disease is dyspnea, the unifying sign is wheezing. □ The most common obstructive diseases are asthma, chronic bronchitis and emphysema. □ Because many individuals have both bronchitis and emphysema, they are often called COPD 9 Respiratory system Spectrum of Obstructive Lung Disease Syndromes I Emphysem I irreversible A----— ~------- revers ible Airway obstruction caused by emphysema, chronic bronchitis, and asthma Normal lung Bronchitis Most eel □sympathetic nerve Smooth - _ ^ muscle onchioles---. Respiratory -bronchioles Mucus, accumulation Mucus, plug inflation -of alveoli tPulmonary artery ___Cartilage Submucosal gland ^Epithelium Goblet cell Alveoli Enlarged , submucosal gland Inflammation of epithelium Emphysema Asthma Norma alveoi D Degranu lotion of mast cell Smooth muscle ~ constriction / Mucus I 1 1 plug Hyperinflation t i i — Mucus accumulation of alveoli 11 Respiratory system Asthma bronchiale > Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. > The chronic inflammation causes an associated increase in airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. > These episodes are usually associated with widespread but variable airway obstruction that is often reversible either spontaneously or with treatment. 12 Respiratory system Asthma Pathogenesis Airway Irritants Gender Ozone M. pneumoniae C. pneumoniae Airway Hyper reactivity Exercise Viruses Chronic Airway Inflammation GERD Rhino-sinusitis IgE Cold air 13 Respiratory system Types of asthma Allergic asthma IgE-mediated _asthma 14 Respiratory system Non-allergic asthma IgE non-mediated asthma Allergie asthma Asthma response Early phase Late phase 15 Respiratory system ^ Altergen mi t«W5V?t Mast cell Early-phase response Bionchospasm Fibroblasts Disrupted elastic fibrils Late-phase response Eosinophil Lymphocyle Macrophage ok Acute inflammation, hyperresponsiveness Continued exposure Chronic irreversible lung dseasc 16 Respiratory system Asthma classification based on severity □ Mild intermitent □ Mild persistent □ Moderate persistent □ Severe persistent 17 Respiratory system Determining Asthma Severity Symptoms Daytime Symptoms Nocturnal FEVi PEFR Variability Severe Persistent Continuous > 2 nights/wk <60% pred >30% Moderate Persistent Daily 1 or 2 nights/wk 60-80% pred >30% Mild Persistent >2 days/wk > 2 nights/mo >80% pred 20-30% Mild Intermittent <2 days/wk < 2 nights/mo >80 % pred <20 % 18 Respiratory system Asthma - clinical manifestations □ During full remision ■ Individuals are asymptomatic and pulmonary function tests are normal. □ During partial remision There are no clinical symptoms but pulmonary function tests are abnormal □ During attacks ■ Individuals are dyspneic and respiratory effort is marked ■ Breath sounds are ecreased except for considerable wheezing, dyspnea, non-productive coughing, tachycardia and tachypnea occur 19 Respiratory system Asthma - pulmonary function - Spirometry shows decreases in expiratory flow rate, forced expiratory volume (FEV), and forced vital capacity (FVC) - FRC and total lung capacity (TLC) are increased. - Blood gas analysis shows hypoxemia with early respiratory alkalosis or late respiratory acidosis. 20 Respiratory system MUNI MED Treatment Goals: ■ To reverse of acute attacks ■ To control recurrent attacks ■ To reduce bronchial inflammation and the associated hyperreactivity ■ + elimination of allergens (if it is possible) Drugs: ■ Allergen's immunotherapy ■ Bronchodilator (Beta agonists, Anticholinergic agents, Theophylline) ■ Immunosuppressant (corticosteroids) ■ Others (Leukotriene modifiers, antihistamine, e.g.) 21 Respiratory system Chronic obstructive pulmonary disease (COPD) □ COPD is defined as pathologic lung changes consistent with emphysema or chronic bronchitis. □ It is syndrome characterized by abnormal tests of expiratory airflow that do not change markedly over time, and without a reversible response to pharmacological agents. □ 5-20% adult population □ Most frequently in men □ The fifth leading cause of death 22 Respiratory system The complex, heterogenous overlapping of the three primary diagnoses include under diseases of air flow limitation is present on the next picture: Chronic Obstructive Pulmonary Disease 1. Chronic bronchitis □ Chronic bronchitis is defined as hypersecretion of mucus and chronic productive cough that continues for at least 3 months of years for at least 2 consecutive years. □ Incidence is increased in smokers (up to twentyfold) and even more so in workers exposed to air pollution. □ It is a major health problem for the elderly population. Repeated infections are common. 24 Respiratory system Chronic bronchitis - etiology □ It is primarily caused by cigarette smoke, both active and passive smoking have been implicated □ Other risk factors: - profesionál exposition - air pollution - repeated infections of airways - genetics 25 Respiratory system Chronic bronchitis - morphology □ Inspired irritants not only increase mucus production but also increase the size and number of mucous glands and goblet cells in airway epithelium □ The mucus produced is thicker and more tenacious than normal. This sticky mucus coating makes it much more likely that bacteria, such as H. influenze and S. pneumoniae, will become embedded in the airway secretions, there they reproduce rapidly. □ Ciliary function is impaired, reducing mucus clearance further. The lung's defense mechanisms are tehrefore compromised, increasing susceptibility to pulmonary infection and injury. □ The bronchial walls become inflamed and thickened from edema and accumulation of inflammatory cells. 26 Respiratory system □ Initially chronic bronchitis affects only the larger bronchi, but eventually all airways are involved. □ The thick mucus and hypertrophied bronchial smooth muscle obstruct the airways and lead to closure, particularly during expiration, when the airways are narrowed. □ The airways collapse early in expiration, trapping gas in the distal portions of the lung. □ Obstruction eventually leads to ventilation-perfusion mismatch, hypoventilation (increased PaC02) and hypoxemia. Air movement during inspiration Air movement during expiration 27 Respiratory system Chronic bronchitis - clinical manifestations □ Individuals usually have a productive cough („smoker's cough") and evidence of airway obstruction is shown by spirometry □ Bronchitis patients are often described as „blue bloaters" due to their tendency to exhibit both hypoxemia and right heart failure with peripheral edema in spite of only moderate obstructive changes on pulmonary functional tests. □ Acute episodes (e.g. after infection) result in marked hypoxemia that leads to polycytemia and cyanosis (blueness) associated with an increase in pulmonary artery pressure, impairing right ventricular function, and significant jugular venous distension and ankle edema (bloated) 28 Respiratory system Table 32-4 Obstructive Lung Disease Clinical Manifestations Productive cough Dyspnea Wheezing History of smoking Barrel chest Prolonged expiration Cyanosis Chronic hypoventilation Polycythemia Cor pulmonale Bronchitis Classic sign Late in course Intermittent Common Occasionally Always present Common Common Common Common Emphysema Late in course with infectioi Common Minimal Common Classic Always present Uncommon Late in course Late in course Late in course Chronic bronchitis - evaluation and treatment - Diagnosis is made on the basis of physical examination, chest radiograph, pulmonary function tests and blood gas analyses. The best „treatment" is prevention, because pathological changes are not reversible. - If the individuals stops smoking, disease progression can be halted - Therapy: - bronchodilators - expectorans - chest physical therapy - steroids - antibiotics MUNI 30 Respiratory system . . _ _ Chronic bronchitis: low-flow oxygen therapy - It is administered with care to individuals with severe hypoxemia and C02 retention - Because of teh chronic elevation of PaC02, the central chemoreceptors no longer act as the primary stimulus for breathing. - This role is taken over by the peripheral chemoreceptors, which are sensitive to changes in Pa02. - Peripheral chemoreceptors do not stimulate breathing if the Pa02 is much more than 60 mmHg. - Therefore, if oxygen therapy causes Pa02 to exceed 60 mmHg, the stimulus to breathe is lost, PaC02 increases, and apnea results. - If inadequate oxygenation cannot be achieved without resulting in respiratory depression, the individual must be mechanically ventilated) 31 Respiratory system UNI ED 2. Emphysema - It is abnormal permanent enlargement of gas-exchange airways (acini) accompanied by destruction of alveolar walls and without obvious fibrosis. - In emphysema, obstruction results from changes in lung tissues, rather than mucus production and inflammation, as in chronic bronchitis. - The major mechanism of airflow limitation is loss of elastic recoil. 32 Respiratory system MUNI MED Types of emphysema □ Three distinctive types of alveolar destruction have been described, according to the portion of the acinus first involved with disease: 1) Centrilobular (centriacinar): - septal destruction occurs in the respiratory bronchioles and alveolar ducts, usually in the upper lobes of the lung. The alveolar sac (alveoli distal to the respiratory bronchiole) remains intact. It tends to occur in smokers with chronic bronchitis. 2) Panacinar (panlobular): - It involves the entire acinus with damage more randomly distributed and involving the lower lobes of the lung. It tends to occur in patients with a1-antitrypsin deficiency. 3) Distal acinar (subpleural): - It is typically seen in a young adult with a history of a spontaneous pneumothorax. 33 Respiratory system A. Ccntrilobular Emphysema B. Panacinar Emphysema C Distal Acinar Emphysema 34 Respiratory system Types of emphysema - Primary emphysema: - it is commonly linked to an inherited deficiency of the enzyme