PULMONARY PATHOLOGY Prof Frank Carey

General Approach r Understanding mechanisms of disease r Emphasizing the role of the pathologist in diagnosis

Functional Classification of Lung Disease Distinctive clinical and physiological features define: r Obstructive lung disease r Restrictive lung disease

Airway Narrowing/Obstruction r Muscle spasm r Mucosal oedema (inflammatory or otherwise r Airway collapse due to loss of support r (Localised obstruction due to tumour or foreign body)

Main Categories of Obstructive Disease r Asthma r Chronic obstructive pulmonary disease (COPD/COAD/COLD)

Chronic Obstructive Disease r Chronic bronchitis r Emphysema Symptomatic patients often have both

Chronic Bronchitis Cough productive of sputum on most days for 3 months of at least 2 successive years r An epidemiological definition r Does not imply airway inflammation

Chronic Bronchitis r Chronic irritationdefensive increase in mucus production with increase in numbers of epithelial cells (esp goblet cells) r Poor relation to functional obstruction r Role in sputum production and increased tendency to infection

Chronic Bronchitis r Non-reversible obstruction r In some patients there may be a reversible (“asthmatic”) component

Normal vs. Chronic Bronchitis

Small airways in Chronic Bronchitis r More important than traditionally realised r Goblet cell metaplasia, macrophage accumulation and fibrosis around bronchioles may generate functional obstruction

Emphysema r Increase beyond the normal in the size of the airspaces distal to the terminal bronchiole r Without fibrosis The gas-exchanging compartment of the lung

Emphysema (types) r Centriacinar (centrilobular) r Panacinar r Others (e.g. localised around scars in the lung)

Emphysema r Difficult to diagnose in life (apart from in extremis) r Radiology (CT) can show changes in lung density r Correlation with function known from autopsy studies

Emphysema r “Dilatation” is due to loss of alveolar walls (tissue destruction) r Appears as “holes” in the lung tissue

Normal lung

Centriacinar emphysema

Panacinar emphysema 1

Panacinar emphysema 2

Emphysema How do these changes relate to functional deficit? r Poorly at macroscopic level r Better with microscopic measurement

Normal

Early emphysema

Emphysema Impairs Respiratory Function r Diminished alveolar surface area for gas exchange r Loss of elastic recoil and support of small airways leading to tendency to collapse with obstruction

Loss of surface area (emphysema)

Loss of support on bronchiolar walls

As disease advances…. Pa O 2 leads to: r Dyspnoea and increased respiratory rate r Pulmonary vasoconstriction (and pulmonary hypertension)

Epidemiology of COPD r Smoking r Atmospheric pollution r Genetic factors

Pathophysiology of Emphysema High rate of emphysema in the rare genetic condition of  1 antitrypsin deficiency r THE PROTEASE/ANTIPROTEASE HYPOTHESIS

Elastic Tissue r Sensitive to damage by elastases (enzymes produced by neutrophils and macrophages)   1 antitrypsin acts as an anti-elastase Imbalance in either arm of this system predisposes to destruction of elastic alveolar walls (emphysema)

Tobacco smoke….. r Increases nos. of neutrophils and macrophages in lung r Slows transit of these cells r Promotes neutrophil degranulation  Inhibits  1 antitrypsin

Bronchial Asthma A chronic inflammatory disorder characterised by hyperreactive airways leading to episodic reversible bronchoconstriction

Asthma r Extrinsic - response to inhaled antigen r Intrinsic - non-immune mechanisms (cold, exercise, aspirin)

Immunological Mechanisms Type  hypersensitivity - allergen binds to IgE on surface of mast cells r Degranulation (histamine) l muscle spasm l inflammatory cell influx (eosinophils) l mucosal inflammation/oedema r Inflammatory infiltrate tends to chronicity

Pathology r Narrowed oedematous airways r Mucus plugs r Inflammatory cells (lymphocytes, plasma cells, eosinophils) r Epithelial cell damage

Mucosal oedema

Mucus plugs

Mucus plug/inflammation

Inflammation

Inflammation/epithelial damage