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Pathogenesis of Obstructive Airways Disease
© McGill Molson Medical Informatics Project 2002
Obstructive vs. Restrictive
• OBSTRUCTIVE:– Airflow obstruction with normal or hyper-expansion of lungs
• COPD
• RESTRICTIVE:– Reduced expansion of the lung (e.g. due to fibrosis or oedema)
• Chest wall disorders • Acute or chronic interstitial & infiltrative diseases
• Different pulmonary function tests
Obstructive Airways Disease
Spectrum of disorders associated with airflow
obstruction:
• Chronic bronchitis– Chronic bronchiolitis (small airways disease)
• Emphysema• Asthma• Bronchiectasis
All characterized by airflow limitation, but involve differentmechanisms and parts of the respiratory tract.
BRONCHIAL LEVEL: Chronic bronchitis - hypersecretory & obstructive
ACINAR LEVEL: Emphysema - destructive
Frequently co-exist and overlap:
• ‘CHRONIC OBSTRUCTIVE PULMONARY DISEASE’ (COPD)
COPD = Chronic Bronchitis &/or emphysema +/- asthma
• Cigarette smoking in majority (10% non-smokers)
• 4th leading cause of morbidity & mortality (USA)
• Classically 2 clinical syndromes based on mechanism - but frequent overlap:
– “BLUE BLOATER vs. PINK PUFFER”
Chronic Obstructive Pulmonary Disease (COPD)
Emphysema predominates* Chronic bronchitis predominates*
• Definition– Persistent cough with sputum production for:– at least 3 months,– in at least 2 consecutive years.
• Middle-aged & elderly, M > F
• Mucoid sputum (initally - progressive)
• Cigarette smoke, air pollution, dust exposure – cadmium, smog
Chronic Bronchitis
• Pathology– Irritants– Release of proteases from neutrophils– Hypersecretion of mucus in large airways
• Hyperplasia & hypertrophy of mucus producing cells
• Small airways initially affected (Chronic Bronchiolitis):– Goblet cell metaplasia - mucus plugging– Chronic inflammation & fibrosis - focal stenosis– Squamous metaplasia– Hypoxic pulmonary vasoconstriction – hypertension – cor pulmonale
Chronic Bronchitis
Obstructive Airways Disease
Normal
Chronicbronchitis
Bronchialmucusglandhyperplasia
Acute on Chronic Bronchitis
Loss of airway ‘tapering’ in chronic bronchitis
• Clinical Features
– Early Stages: Chronic cough with sputum– Later Stages: Progressively more severe
– Right heart failure (cor pulmonale) or respiratory failure
• Complications
– Recurrent infections / acute exacerbations– Malignancy (SCC)
Chronic Bronchitis
• Definition:– Destructive, permanent enlargement of the airspaces
distal to the terminal bronchioles, without obvious fibrosis
• Airflow limitation is due to premature closure of airways because of diminished elastic recoil
• Reduced surface area for gas exchange
Emphysema
• Pathogenesis: Proteases vs. Antiproteases
– Neutrophils & macrophages - sources of elastase – increased in smokers / infection / inflammation
– Smoking stimulates release and enhances activity of elastase
– Oxidants in cig smoke inhibit native 1-AT activity
1-AT deficiency - unopposed elastase activity
Emphysema
• 3 main types of Emphysema
– CENTRIACINAR• Destruction of central portion with
sparing of distal airways• Upper lobes > lower• Cause: smoking
– PANACINAR• Uniform injury• Lower lobes > upper• Cause: 1-antitrypsin deficiency
– PARASEPTAL• Destruction of distal portion;
normal proximal portion of acinus (septal / subpleural)
• Upper lobes > lower• Incidental / Spontaneous
pneumothorax
Normal acinarunit
Centriacinaremphysema
Panacinaremphysema
NeutrophilsAlpha-1-AT
Centriacinar Emphysema Paraseptal Emphysema
• Large solitary bullae
• May grow large enough to cause respiratory failure by compressing adjacent ‘normal’ lung. • Corrective bullectomy or ‘lung reduction’ may return pulmonary function to normal
Paraseptal Emphysema
Panacinar Emphysema
• Commonly co-exists with COPD• Hyper-reactive airways
– Increased responsiveness of the tracheobronchial tree to various stimuli
– Episodic, reversible bronchconstriction
• Extrinsic / Atopic / Allergic– Allergy to exogenous substances
• Intrinsic / Non-atopic– No exogenous factors identified
Bronchial Asthma
Bronchiectasis• Permanent dilatation of
bronchi & bronchioles
• Caused by destruction of muscle & elastic tissue secondary to recurrent inflammation
– Fibrosis in the surrounding parenchyma
– Obliteration of smaller bronchioles
• Congenital/Hereditary:– Cystic fibrosis– Primary ciliary dyskinesia– Kartagener’s syndrome
• Acquired (post-infective, post-obstructive):
– Children - Whooping cough, pneumonia & measles
– Adults - Necrotizing pneumonias (e.g. TB), bronchial obstruction (e.g. tumour, foreign body)
Bronchiectasis
• Usually lower lobes, bilateral
• May be sharply localised with tumour or foreign body obstruction
• Gross examination: – Dilated bronchi exending to pleural surface (characteristic),
surrounding scarring
• Microscopy: – Mucosal ulceration, submucosal CI & granulation tissue, adjacent
organising pneumonia
Bronchiectasis
Bronchiectasis
• Clinical:– Fever– Severe, persistent cough (foul sputum)– Haemoptysis– Recurrent infections– Paroxysmal cough
• Worse in morning due to drainage into bronchi of collected pus
Bronchiectasis
• Complications:– Depend on severity & co-existent disease
• Recurrent infections (common)– H. influenzae & Pseudomonas
• Rare: Cor pulmonale, metastatic brain abscesses & amyloid