Adobe Systems Respiratory system & Lung diseases Respiratory system 1 Adobe Systems Points ̶Ventilation ̶Diffusion ̶Perfusion Respiratory system 2 Adobe Systems 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. ̶ Respiratory system 3 S25798-14-f03 Respiratory system 4 S25798-14-f10 Respiratory system 5 Respiratory system 6 Adobe Systems 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 ̶ ̶ Respiratory system 7 Obstructive pulmonary diseases oThey are characterized by airway obstruction that is worse with expiration. oEither 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. oThe unifying symptom of obstructive disease is dyspnea, the unifying sign is wheezing. o oThe most common obstructive diseases are asthma, chronic bronchitis and emphysema. oBecause many individuals have both bronchitis and emphysema, they are often called COPD o Respiratory system 8 Spectrum of Obstructive Lung Disease Syndromes copdvenn Asthma Emphysema Chronic Bronchitis Respiratory system 9 Airway obstruction caused by emphysema, chronic bronchitis, and asthma obr7a obr7b Normal lung Emphysema obr7c Bronchitis obr7d Asthma Respiratory system 10 Asthma bronchiale ØAsthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Ø ØThe 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. Ø ØThese episodes are usually associated with widespread but variable airway obstruction that is often reversible either spontaneously or with treatment. Respiratory system 11 Asthma Pathogenesis Airway Hyper- reactivity Chronic Airway Inflammation Rhino- sinusitis IgE GERD Viruses M. pneumoniae C. pneumoniae Ozone Cold air Airway Irritants Exercise Gender Respiratory system 12 Types of asthma Allergic asthma Non-allergic asthma IgE-mediated asthma IgE non-mediated asthma Respiratory system 13 obr4 Asthma response Early phase Late phase Allergic asthma Respiratory system 14 obr8a obr8b Respiratory system 15 oMild intermitent o oMild persistent o oModerate persistent o oSevere persistent Asthma classification based on severity Respiratory system 16 Determining Asthma Severity Respiratory system 17 Asthma – clinical manifestations q During full remision nIndividuals are asymptomatic and pulmonary function tests are normal. q During partial remision There are no clinical symptoms but pulmonary function tests are abnormal q During attacks nIndividuals are dyspneic and respiratory effort is marked nBreath sounds are ecreased except for considerable wheezing, dyspnea, non-productive coughing, tachycardia and tachypnea occur Respiratory system 18 Adobe Systems ̶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. Asthma - pulmonary function Respiratory system 19 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.) Respiratory system 20 Chronic obstructive pulmonary disease (COPD) oCOPD is defined as pathologic lung changes consistent with emphysema or chronic bronchitis. oIt is syndrome characterized by abnormal tests of expiratory airflow that do not change markedly over time, and without a reversible response to pharmacological agents. o o5-20% adult population oMost frequently in men oThe fifth leading cause of death n Respiratory system 21 obr2 The complex, heterogenous overlapping of the three primary diagnoses include under diseases of air flow limitation is present on the next picture: Respiratory system 22 1. Chronic bronchitis qChronic 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. qIncidence is increased in smokers (up to twentyfold) and even more so in workers exposed to air pollution. qIt is a major health problem for the elderly population. Repeated infections are common. Respiratory system 23 bronchitis Chronic bronchitis - etiology oIt is primarily caused by cigarette smoke, both active and passive smoking have been implicated o oOther risk factors: - profesional exposition - air pollution - repeated infections of airways - genetics o Respiratory system 24 Chronic bronchitis - morphology oInspired irritants not only increase mucus production but also increase the size and number of mucous glands and goblet cells in airway epithelium oThe 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. oCiliary function is impaired, reducing mucus clearance further. The lung´s defense mechanisms are tehrefore compromised, increasing susceptibility to pulmonary infection and injury. oThe bronchial walls become inflamed and thickened from edema and accumulation of inflammatory cells. o Respiratory system 25 oInitially chronic bronchitis affects only the larger bronchi, but eventually all airways are involved. oThe thick mucus and hypertrophied bronchial smooth muscle obstruct the airways and lead to closure, particularly during expiration, when the airways are narrowed. oThe airways collapse early in expiration, trapping gas in the distal portions of the lung. oObstruction eventually leads to ventilation-perfusion mismatch, hypoventilation (increased PaCO2) and hypoxemia. obr1b Respiratory system 26 Chronic bronchitis – clinical manifestations oIndividuals usually have a productive cough („smoker´s cough“) and evidence of airway obstruction is shown by spirometry oBronchitis 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. o o 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) o o Respiratory system 27 Adobe Systems ̶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 Chronic bronchitis – evaluation and treatment Respiratory system 28 Adobe Systems Chronic bronchitis: low-flow oxygen therapy ̶It is administered with care to individuals with severe hypoxemia and CO2 retention ̶Because of teh chronic elevation of PaCO2, 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 PaO2. ̶Peripheral chemoreceptors do not stimulate breathing if the PaO2 is much more than 60 mmHg. ̶Therefore, if oxygen therapy causes PaO2 to exceed 60 mmHg, the stimulus to breathe is lost, PaCO2 increases, and apnea results. ̶If inadequate oxygenation cannot be achieved without resulting in respiratory depression, the individual must be mechanically ventilated) ̶ Respiratory system 29 Adobe Systems ̶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. 2. Emphysema Respiratory system 30 Types of emphysema oThree 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. Respiratory system 31 obr3 Respiratory system 32 Adobe Systems ̶Primary emphysema: - it is commonly linked to an inherited deficiency of the enzyme a1-antitrypsin that is a major component of a1-globulin, a plasma protein. - Normally it inhibits the action of many proteolytic enzymes. - Individuals with deficiency of this enzyme (AR) have an increased likelihood of developing emphysema because proteolysis in lung tissues is not inhibited. ̶Secondary emphysema: - It is also caused by an inability of the body to inhibit proteolytic enzymes in the lung. It results from an insult to the lungs from inhaled toxins, such as cigarette smoke and air pollution. Types of emphysema Respiratory system 33 Adobe Systems Pathophysiology of emphysema ̶Emphysema begins with destruction of alveolar septa ̶It is postulated that inhaled oxidants, such as those in cigarette smoke and air pollution, tip the normal balance of elastases (proteolytic enzymes) and antielastases (such as a1-antitrypsin) such that elastin is destroyed at an increased rate ̶Expiration becomes difficult because loss of elastic recoil reduces the volume of air that can be expired passively. ̶Hyperinflation of alveoli causes large air spaces (bullae) and air spaces adjacent to pleura (blebs) to develop. ̶The combination of increased RV in the alveoli and diminished caliber of the bronchioles causes part of each inspiration to be trapped in the acinus. Respiratory system 34 Mechanisms of air trapping in emphysema Damaged or destroyed alveolar walls no longer support and hold open the airways, and alveoli lose their property of passive elastic recoil. Both of the se factors contribute to collapse during expiration. obr5 Respiratory system 35 Adobe Systems ̶Patients with emphysema are able to maintain a higher alveolar minute ventilation than those with chronic bronchitis. Thus they tend to have a higher PaO2 and lower PaCO2 and have classically been referred to as „pink puffers“ ̶Physical examination often reveals a thin, tachypneic patient using accessory muscles and pursed lips to facilitate respiration. The thorax is barrel-shaped due to hyperinflation. ̶There is little cough and very little sputum production (in „pure“ emphysema) Emphysema – clinical manifestations Respiratory system 36 Adobe Systems ̶Pulmonary function tests: - indicate obstruction to gas flow during expiration - airway collapse and air trapping lead to a decrease in FVC and FEV1 and an increase in FRC, RV, and TLC. - diffusing capacity is decreased because destruction of the alveolocapillary membrane ̶Arterial blood gas measurements are usually normal until latge in the disease Emphysema – evaluation Respiratory system 37 Adobe Systems Emphysema – approach to therapy ̶Smoking cessation is the most important intervention ̶Inhaled anticholinergic agets ̶b2-adrenergic agonists ̶Steroids ̶Low-flow oxygen therapy in selected individuals ̶Lung transplant can be considered Respiratory system 38 obr1a Respiratory system 39 obr1c Respiratory system 40 Adobe Systems Cyansis ̶Reduced hemoglobin higher than 50 g/l ̶ ̶Hemoglobin ̶ Normal – 120-160 g/l (F), 130-180 g/l (M) ̶ Anemia – less than 110 g/l, Severe anemia – less than 79 g/l S25798-14-f07 Respiratory system 42 Adobe Systems Hypoxic drive ̶Traditional theory, obsolete ̶Global respiratory insufficieny (hypoxemia + hypercapnia) disables stimulation based on pCO2 ̶Respiration stimulated by hypoxemia ̶Administration of oxygen may cause depression of the respiratory center (leading to critical hypercapnia) Adobe Systems Ventilation-perfusion mismatch ̶Current theory ̶Low pO2 causes pulmonary vasoconstriction (redistribution of perfusion to a ventilated area) ̶Administration of oxygen will reverse pulmonary vasoconstriction, however, a poorly ventilated alveolus does not ventilate CO2 ̶Oxygen also leads to a shift of the dissociation curve to the right (release of CO2 from hemoglobin – Haldane effect), which is not ventilated, increasing pCO2 ̶Oxygen administration is safe if oxygenation is titrated to reach 88%-92% saturation Interstitial lung diseases oThere are a large number of diseases that affect the interstitium of the lung ß it is connective tissue present between the alveolar epithelium and capillary endothelium oSome of these diseases have known etiology, e.g. occupational diseases o oOthers are diseases of unknown etiology - most frequent of these are idiopatic pulmonary fibrosis (diffuse interstitial fibrosis), pulmonary fibrosis associated with collagen-vascular diseases, and sarcoidosis. Respiratory system 45 Nozological units Idiopatic pulmonary fibrosis oDiseases unknown etiology, non-specific fibrotic change in lung. The diagnosis is to some extent one of exclusion. Sarcoidosis oOne of the most common. It is multi-systém granulomatous disease that involves lung, lymph nodes, salivary glands, and liver. Specific type is called erythema nodosum Occupational intersticial diseases oExposure to occupational and environmental inhalants for a long time can lead to develop lung disease. Workers in industries with heavy exposure to silica dust, asbestos particles, and welding fumes are generally aware of the risk of their occupation. Respiratory system 46 Occupational diseases Diseases Cause Welder´s lung Farmer´s lung Lung of breeder of birds Coal Azbestos particlesl Silica dust Welding fumes Azbestosis Aspergilosis Berryliosis Pneumoconiosis Silicosis Birds´ antigens Grain´s mould Berrylium´s compouds Mould - Respiratory system 47 Clinical manifestations Subjective symptoms odyspnoe ocough Objective signs otachypnoe ocrackles oclubbing ocyanosis ocor pulmonale Laboratory findings oDecrease PaO2 onormal PaCO2 oECG- cor pulmonale oSpirometry - restrictive pattern ( VC, normal ratio FEV1/FVC) oDecrease diffusion capacity of the lung for carbon monooxide Respiratory system 48 Therapy oIt depends on etiology (if it is known) o oStopping the occupational exposure oAntibiotics oDiseases of unknown etiology (sarcoidosis, idiop. pulmonary fibrosis) corticosteroids oOxygen therapy Respiratory system 49 Adobe Systems Spirometry Respiratory system 50 Respiratory system 51 Adobe Systems Types of spirometers f3p8 Respiratory system 52 Mild Obstruction Flow Volume Mild Obstruction Volume Time Curve Graphs Volume-time Flow-volume Expiration Inspiration FEV1 Respiratory system 53 Adobe Systems Lung Volume Patterns ̶Obstructive Disease: Characterized by hyperinflation and gas trapping (increased TLC and RV/TLC) ̶ ̶Restrictive Disease: Characterized by generalized reduction in lung volume (decreased TLC, RV and FRC) Flow-volume graphs Normal Restrictive Obstructive Respiratory system 55 Respiratory system 56