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CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Chronic Obstructive Pulmonary Disease (COPD). Chronic Obstructive Airway disease (COAD). DEFINITION.
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Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Airway disease (COAD)
DEFINITION COPD is a disease state characterized by increase in resistance to airflow due to partial or complete obstruction of airway at any level from the trachea to respiratory bronchiole. Changes are usually irreversible esp. in chronic bronchitis and emphysema. - Predominant symptom; Dyspnoea - Predominant cause; Smoking
Pulmonary function tests show : 1-Increased pulmonary resistance 2- Limitation of maximal expiratory flow rates (reduced FEV1).
EMPHYSEMA CHRONIC BRONCHITIS ASTHMA BRONCHIECTASIS
Emphysema. -Abnormal permanent enlargement of the distal air spaces due to destruction of the alveolar walls and loss of respiratory tissue. -“Obstruction” is caused by lack of elastic recoil.
Etiology: 1-Most common cause is smoking: produces combination of emphysema and chronic inflammation 2- Genetic deficiency of alpha1 antitrypsin (Pi locus on chromosome 14) ; alpha-1-antitrypsin deficiency produces almost pure emphysema
Pathogenesis: 1- Protease-antiprotease imbalance: . Alpha1 antitrypsin present in serum, tissue fluids, macrophages . Inhibitor of proteases (esp. elastase secreted by neutrophils during inflammation) .Stimulus--TNF,IL8--Increased neutrophils--Release of proteases(elastase,proteinase-3,cathepsin-G)--Elastic lung tissue destruction
Pathogenesis • 2- Oxidant-antioxidant imbalance: Smoking--Free O2 radicals--Deplete Antioxidant in lung (superoxide dismutase, glutathione)—Damage of lung tissue
Types of Emphysema1-Centroacinar (Centrilobar) Emphysema -- Affects central (proximal) parts of the acini (respiratory bronchioles) but spares the distal alveoli. - More severe in upper lobes, especially apical segments .
Causes: -Smoking -Coal dust
2-Panacinar (Panlobar) Emphysema -- Uniform enlargement of the acini in a lobule. - May not necessarily involve entire lung - Predominantly lower lobes. - Alpha -1- antitrypsin deficiency is prototype.
3-Paraseptal (Distal Acinar) Emphysema -- Proximal acinus normal, distal part involved - Most prominent adjacent to pleura and along the lobular connective tissue septa. - Probably underlies spontaneous pneumothorax in young adults.
4-Bullous Emphysema -- Any form of emphysema which produces large subpleural blebs or bullae (> 1cm). - Localized accentuation of any one of the type.
5-Interstitial Emphysema Air penetration into the connective tissue stroma of the : - lung - mediastinum or - subcutaneous tissue.
6-Compensatory “Emphysema” - Dilatation of alveoli in response to loss of lung substance elsewhere. - Actually hyperinflation since no destruction of septal walls.
7-Senile “Emphysema” - Change in geometry of lung with larger alveolar ducts and smaller alveoli. - No loss of lung tissue; hence not really an emphysema.
Chronic Bronchitis - Clinical definition: persistent cough with sputum production for at least three months in at least two consecutive years. - Can occur with or without evidence of airway obstruction - Smoking is the most important cause.
: • Basic Mechanism: Hypersecretion of mucus • Histology -Increased numbers of goblet cells in small airways as well as large airways. -Increased size of submucosal glands in large airways (Reid index: ratio of thickness of mucosal glands to thickness of wall between epithelium and cartilage) -Peribronchiolar chronic inflammation.
Bronchiectasis - Permanent abnormal dilation of bronchi and bronchioles, - Usually associated with chronic necrotizing inflammation - Patients have fever, cough, foul–smelling sputum. - More common in left lung, lower lobes.
Causes: Obstruction (tumor, mucus) Congenital Intralobar sequestration Cystic fibrosis Immotile cilia syndrome Necrotizing pneumonia Kartaganer’s Syndrome
Asthma - Increased responsiveness of tracheobronchial tree to various stimuli, leading to paroxysmal airway constriction - Unremitting attacks (status asthmaticus) can be fatal.
Etiology : 1- Extrinsic Factors (atopic, allergic); most common 2- Intrinsic Factors (idiosyncratic); now recognize mixed.
Basic Mechanism - Bronchial plugging by thick mucous plugs containing eosinophils, whorls of shed epithelium (Curschmann’s spirals), and Charcot – Leyden crystals (Eosinophil membrane protein); - Distal air- spaces become over distended.
Histology: -Thick basement membrane -Edema and infiltration of the bronchial walls by inflammatory cells with prominence of eosinophils, - Hypertrophy of bronchial wall muscle.
Therapeutic agents are aimed at increasing cAMP levels either by : - increasing production (ß-agonists, e.g epinephrine) or - decreasing degradation (Methyl xanthines, e.g theophylline). - Cromolyn sodium prevents mast cell degranulation.
Allergic Bronchopulmonary Aspergillosis Occur in chronic asthmatics; hypersensitivity to non – invasive Aspergillus. Bronchocentric granulomatous inflammation, mucus impaction of bronchi, eosinophilic pneumonia. Distinctive promixal bronchiectasis (?Pathgnomonic)
Burden of Asthma • Prevalence increasing in developed countries more than developing or underdeveloped countries affecting 10 -15% of population. • The number of children with asthma has increased six-fold in the last 25 years • Between 100 and 150 million people around the globe • 5.1 million people in the UK have asthma • In South Asia (including Pakistan) rough estimates indicate a prevalence of between 10% and 15%
Burden of Asthma • World-wide, the economic costs associated with asthma are estimated to exceed those of TB and HIV/AIDS combined. • In the United States, for example, annual asthma care costs (direct and indirect) exceed US$6 billion. • At present Britain spends about US$1.8 billion on health care for asthma and because of days lost through illness
1999 2011 2010 Target Burden of Asthma Age-adjusted death rate per million Under 5 years 5-14 years 15-34 years 35-64 years 65 years and over 0 20 40 60 80 Deaths per Million
CLASSIFICATION OF ASTHMA • EXTRINSIC Implying a definite external cause Atopic individuals Positive skin prick test More common Early onset in childhood • INTRINSIC OR CRYPTOGENIC Late onset (middle age)