Emphysema: Presentation & Pathogenesis (PDF)

Emphysema Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls & without obvious fibrosis Incidence: Common  50% of autopsies and cause of death in 6.5%  Sex: M > F  Clear cut association betwee...

Emphysema Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls & without obvious fibrosis Incidence: Common  50% of autopsies and cause of death in 6.5%  Sex: M > F  Clear cut association between cigarette smoking and emphysema, environmental air pollution  Genetic & familial predisposition (+) 1  PATHOGENESIS OF EMPHYSEMA: Exposure to toxic substances such as tobacco smoke and inhaled pollutants  Ongoing inflammation with accumulation of neutrophils, macrophages and lymphocytes in the lung. Release of pro-inflammatory cytokines(including leukotriene B4, IL-8, TNF, and others) 2 PATHOGENESIS OF EMPHYSEMA: Elastases, cytokines (including IL-8) and oxidants are released causing epithelial injury, a proteolysis of the extracellular matrix (ECM)  Elastin degradation products further increase the inflammation. 3  Protease-anti-protease imbalance  Patients with a genetic deficiency of the antiprotease α1-antitrypsin Markedly enhanced tendency to develop pulmonary emphysema Severity compounded by smoking.  α1-antitrypsin is normally present in serum, tissue fluids, and macrophages Major inhibitor of proteases(elastase, proteinase 3, cathepsin G) secreted by neutrophils during inflammation. 4  Sequence of events 1. Neutrophils release cellular proteases 2. Oxidative stress  Increases the number of leukocytes  Increases proteolytic activity 3. Low levels of serum α1-antitrypsin  Unchecked elastase tissue destruction  Emphysema * Thus, emphysema is seen to result from the destructive effect of high protease activity in subjects with low antiprotease activity. 5 Oxidant-antioxidant imbalance Natural Antioxidants in lung keep oxidative damage to a minimum. Tobacco smoke contains abundant reactive oxygen species (ROS) (free radicals) ROS deplete these antioxidant mechanisms Induce tissue damage 6 7 8 9 Other types of Emphysema : i. Compensatory emphysema – Dilation of alveoli in response to loss of lung substance elsewhere Hyper expansion of residual lung parenchyma following surgical removal of a diseased lung or lobe. ii. Bullous emphysema: Large subpleural blebs or bullae Can occur in any form of emphysema. These localized accentuations of emphysema occur near the apex, sometimes near old tuberculous scarring. Rupture of the bullae may give rise to pneumothorax. 10 iii. Obstructive over inflation: Common cause is subtotal obstruction of the airways by a tumor or foreign object. Congenital lobar overinflation in infants, resulting from hypoplasia of bronchial cartilage Occurs because of the obstructive agent acts as ball valve, allowing air on inspiration while preventing its exodus on expiration Occurs as collaterals bring in air behind the obstruction. These collaterals consist of the pores of Kohn and other direct accessory bronchioloalveolar connections (the canals of Lambert). iv. Interstitial emphysema Entrance of air into the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue In most instances, alveolar tears causes it, secondary to raised intra-aveolar 11 Depend on form & severity of emphysema. PANACINAR TYPE : ( well developed ) Pale and voluminous lung, overlapping Heart Emphysematous lobes ( lower zones ) - uniformly pale due to compression of blood supply. CENTRIACINAR TYPE : May not appear pale or voluminous unless disease is well developed. Upper 2/3 of lung is more severely affected. IRREGULAR EMPHYSEMA: Apical blebs / bullae , Secondary to scarring 12 13 Centriacinar Panacinar 14  Histological Morphology  Destruction of alveolar walls without fibrosis, leading to enlarged air space  Abnormally large alveoli separated by thin septa  Loss of attachment of alveoli to outer wall of small airways  Severe cases - alveoli fuse & form BLEBS or BULLAE.  Alveolar capillaries - diminished 15 Abnormal large alveoli with destruction of the wall Normal alveoli Histology: Thinning and destruction of alveolar walls. Large air spaces found. Alveolar loss. Most of alveolar capillaries are diminished. Fibrosis of respiratory bronchioles +. Loss of attachments of alveoli to the 16 outer walls of smaller airways. Clinical features of Emphysema:  Only when 1/3 of lung function is incapacitated  Panacinar type is most disabling.  DYSPNOEA - 1st symptom, begin insidiously & progressive.  COUGH + EXPECTORATION – variable & depend on extent of associated bronchitis  WHEEZING  WEIGHT LOSS 17  On clinical examination:  Barrel chested & dyspnoeic  Prolonged expiration, hunched over & slowing of forced expiration.  Pinched face & breath through pursed lips  Patient is overventilated & well oxygenated “PINK PUFFERS” 18  Diagnosis of Emphysema:  Chest Radiograph: Hyper translucent lung with small Heart Pulmonary function test  Reduced FEV1(forced expiratory volume)  Normal FVC (forced vital capacity) ,ratio of FEV1 to FVC is reduced  High Resolution CT Scan  Detection, characterization and quantification of emphysema & bullae 19