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