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COPD (Definitions + Pathology) Dr.Mohsen SHAHEEN Pneumologist 1 2 COPD High Morbidity Mortality 3 A common respiratory disease Chronic Inflammation Small + Large Airways Fixed Airflow Limitation 4 COPD affects more than the population 5% of It is the third-ranked cause of death in the US Killing more than 120,000 individuals each year COPD is a High Chronic and Prevalence Disease The impact of COPD High Medical resource utilization Frequent clinician office visits The impact of COPD Frequent hospitalization s due to acute exacerbations The impact of COPD Need for chronic therapy Supplemental oxygen therapy Medications 11 12 Symptoms (especially dyspnea) Frequency and severity of exacerbations Health status Exercise capacity Prolong survival Definition of COPD 13 14 15 common Preventable and treatable disease Non Curable 16 Exposure Toxic particles + Gazes Chronic Inflammation S m a l l + L a rge a i r way s Lung Progressive airflow limitation Chronic Bronchitis Emphysema Chronic Bronchitis 18 Chronic Productive Cough For 3 months in each of two successive years In a patient in whom other causes of chronic cough (eg, bronchiectasis) have been excluded Emphysema Conducting Zone Trachea Primary Bronchus (BR) Bronchioles (BL) Terminal bronchioles (TBL) 21 Source: From Weibel 360 Respiratory Zone Respiratory bronchioles (RBL) Alveolar ducts (AD) Alveolar sacs (AS) Alveoli (300 million) Definition of Emphysema Abnormal and permanent Enlargement of the airspaces distal to the terminal bronchioles 24 Destruction of the airspace walls without obvious fibrosis 25 Types of Emphysema 1. Pure emphysema 2. Emphysema + Mild Fibrosis 3. Interstitial Pneumonias + Emphysema 4. Emphysema Moderate or severe airflow obstruction ( more common) 5. Emphysema + Normal pulmonary Function Pathology of COPD Airways Pathology COPD Lung parenchyma Pulmonary vasculature COPD Is a Disease Characterized by Inflammation Cigarette smoke Epithelial cells Macrophage/Dendritic cell Neutrophil Monocyte Fibroblast CD8+ Tc cell Proteases Fibrosis Obstructive bronchiolitis Emphysema Mucus hypersecretion Airway inflammation in COPD Neutrophilic inflammation Numbers of Macrophages CD8+ T-lymphocytes Neutrophilic inflammation 33 Neutrophils Key effector cells in COPD Increasing cell numbers correlate with declining lung function Neutrophils Infiltrating Bronchial Glands in COPD Release mediators involved in neutrophil, monocyte and CD8+ cell to the lung Contribute to structural lung damage 39 Are generated in the thymus and express the T-cell receptor 41 Orchestrate inflammatory process Effector cells that attract and enhance inflammatory function, e.g. in neutrophils and macrophages Increasing cell numbers correlate with loss of lung function 42 Release multiple inflammatory mediators 43 Inflammatory Mediators in COPD proteases, TNF- , IL-8 Neutrophils IL-8, IL-6 Macrophages IFN-, TNF- CD8+ T-cell IL-8 Epithelial cell Small airways 44 Small airways are usually defined as Noncartilaginous airways with an internal diameter < 2mm • These airways are located from approximately the eight generation of airways down to the alveoli Emphysema Loss Of alveolar attachments Peripheral airway collapse Normal Small Air way Reduction in the number of small airways Mucus Plugging Obstructs Small Airways in COPD Normal COPD Mucus Plug numbers of: Goblet cells Mucus gland hyperplasia Reproduced from The Lancet, Vol 364, Hogg JC. "Pathophysiology of airflow limitation in chronic obstructive pulmonary disease", pp709-721. Copyright © 2004, with permission from Elsevier. 49 Lung Parenchyma 50 Paraseptal Emphysema Distal Acinar 51 Paraseptal Emphysema Paraseptal Emphysema Distal Acinar 53 alpha-1 antitrypsin deficiency Panlobular Emphysema Panacinar emphysema 54 55 Panlobular Emphysema Centrilobular emphysema Proximal ac inar emphysema 56 Emphysema centrilobular = upper lobes = apical region 58 Pulmonary vascular remodelling Pulmonary vascular remodelling Begin early during the course of the disease Pulmonary vascular remodelling 1. Thickening of the vessel wall 2. Endothelial dysfunction 3. increased vascular smooth muscle 4. infiltration of the vessel wall by inflammatory cells: o Macrophages o CD8+ o T lymphocytes 5. There is collagen deposition 6. Emphysematous destruction of the capillary bed 64 Pulmonary vascular Remodeling Local hypoxia Pulmonary vasoconstriction (Chronic Hypoxemia) Reduction of the pulmonary vascular bed Blood hyperviscosity Pulmonary Hypertension in COPD Pulmonary vascular resistance Pulmonary vascular Remodelling Cor Pulmonale Pulmonary Hypertension + Right Ventricular Dysfunction