COPD
Obstructive disease
- Characterised by an increase in the resistance to airflow owing to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchiole
- The major diseases are emphysema, chronic bronchitis, bronchiectasis and asthma
- Reduced FEV1
Restrictive disease
- Characterised by reduced expansion of the lung parenchyma with decreased total lung capacity
- Two types of disorder;
- Chest wall disorders in the presence of normal lungs e.g. neuromuscular disease, obesity, pleural disease, kyphoscoliosis
- Acute or chronic interstitial disease e,g, pneumoconiosis, interstitial fibrosis
Emphysema
- Characterised by permanent enlargement of the airspaces distal to the terminal bronchiole e.g. the acini, accompanied by wall destruction but no fibrosis
- Emphysema can be classified according to the anatomical distribution within the lobule. There are 4 types;
- Centriacinar
- Panacinar
- Distal acinar (paraseptal)
- Irregular (airspace enlargement with fibrosis)
- Centriacinar
Centriacinar Emphysema
- Constitutes 95% of case
- Destruction and enlargement of the central or proximal parts of the acinus, formed by the respiratopry bronchioles but sparing the distal alveoli
- Predominant involvement of the upper lobe and apices
- Occurs predominantly in smokers and often associated with chronic bronchitis
Panacinar emphysema
- Uniform destruction and enlargement of the acinus from the level of the respiratory bronchiole to the terminal alveoli
- Predominance in lower basal zones and in the anterior margins of the lung
- Associated with α1-antitrypsin deficiency
Distal acinar
- Involves mostly the distal acinus
- Typically near the pleura and adjacent to areas of fibrosis or scarring
- It is usually more severe in the upper half of the lung
- Frequently the underlying lesion in spontaneous pneumothorax in young adults
Irregular (airspace enlargement with fibrosis)
- Irregular acinar involvement with scarring
- May be the most common form of emphysema but is generally asymptomatic
Aetiology
- Tobacco smoke
Pathogenesis
- COPD is characterised by a mild chronic inflammation throughout the airways, parenchyma and pulmonary vasculature
- The protease-antiprotease hypothesis holds that alveolar wall destruction results from imbalances between pulmonary proteases and their inhibitors
- Individuals with hereditiary deficiency of α1-antitrypsin (major elastase inhibitor) invariably develop emphysema and it develops younger if they smoke
- Experimental pulmonary instillation of proteolytic enzymes including neutrophil elastase causes emphysema
- Tobacco smoke contributes to this by;
- Activating macrophages which in turn can recruit neutrophils to the lung
- Enhaving macrophage and neutrophil elastase activity
- Inactivating α1-antitrypsin, via oxidants in the smoke if by free radicals released from neutrophils
- Activating macrophages which in turn can recruit neutrophils to the lung
- There is also an accumulation of CD8 T cells which may participate in disease by causing apoptosis of alveolar epithelial cells or recruiting macrophages
- Centriacinar emphysema can be explained by the impaction of smoke particles at the bifurcation of the respiratory broncioles resulting in a influx of neutrophils and macrophages both of which secrete proteases
- The panacinar emphysema associated with α1-antitrypsin deficiency reflects the total lack of antiprotease throughout the acinus and the susceptibility to chornic low level proteolysis from neutrophils in transit through the lung circulation. This explains the predominant lower lobe distribution, when perfusion and neutrophil numbers are greatest
Morphology
- With diffuse disease the lungs can become voluminous and overlap the heart – generally seen in the panacinar form
- Microscopically the alveolar spaces are large with thin septa and the septal capillaries are compressed and bloodless
- Alveolar wall rupture can produce large airspaces called blebs or bullae. This is more common in irregular and distinal emphysema
- There may also be chronic bronchitis or bronchiolitis
Clinical
- Clinical manifestations only appear after at least 1/3 of the lung parenchyma has been damaged
- Patient is generally barrel chested and dysnoeic - pink puffers
- Development of cor pulmonale and eventual congestive heart failure related to secondary pulmonary hypertension is associated with poor prognosis
- Death in most patients with COPD is due to;
- Respiratory acidosis and coma
- Right sided heart failure
- Massive collapse of the lungs secondary to pneumothorax
- Respiratory acidosis and coma
Chronic bronchitis
- Clinically defined as persistent cough with sputum production for at least three months in at least 2 consecutive years
- Simple chronic bronchitis – patients have a productive cough but no physiological evidence of airflow obstruction
- Chronic asthmatic bronchitis – patients with hyperactive airways with intermittent bronchospasm and wheezing
- Obstructive chronic bronchitis – chronic airflow obstruction usually with evidence of associated emphysema
Pathogenesis
- Initiating factor is the chronic irritation of the airways by inhaled substances e.g. tobacco smoke
- Bacterial and viral infections are important for triggering an acute exacerbation
- Occurs most frequently in middle aged men
- The irritants cause;
- Mucus hypersecretion and mucous gland hypertrophy in the trachea and bronchi, stimulated by proteases release from neutrophils
- Goblet cell metaplasia in small airways – contributes to airway obstruction
- Bronchiolitis
- The role of infection appears to be secondary and maintains and promotes smoking mediated injury
- Mucus hypersecretion and mucous gland hypertrophy in the trachea and bronchi, stimulated by proteases release from neutrophils
Morphology
- Hyperaemia and oedema of the lung mucous airways
- Mucinous secretions and casts filling airways
- Increased mucous gland size
- Bronchial or bronchiolar mucus plugging, inflammation and fibrosis
- Squamous metaplasia or dysplasia of bronchial epithelium
Clinical
- Persistent productive cough is the cardinal symptom
- With time hypoxia, hypercapnia and mild cyanosis can develop
- Long standing chronic bronchitis can lead to cor pulmonale and right sided heart failure