7. Obstructive Pulmonary Diseases

Question 1

Definition of obstructive pulmonary diseases

Answer 1

Obstructive airway diseases characterized by an increase in resistance to airflow due to partial or complete obstruction at any level; pulmonary function test usually show a decreased expiratory function (decreased maximal airflow rates during forced expiration) & an increase in total lung volume (barrel chest)

Question 2

Types of obstructive pulmonary diseases

Answer 2

1. Bronchiectasis
2. Bronchial asthma
3. Emphysema
4. Chronic bronchitis

Question 3

Definition of bronchiectasis

Answer 3

A chronic necrotizing inflammation of the bronchi & bronchioles leading to or associated with abnormal permanent dilation of these airways

Question 4

Causes of bronchiectasis

Answer 4

1. Congenital or hereditary conditions
   - Cystic fibrosis
   - Intralobar pulmonary sequestration
   - Kartagener syndrome (aka immotile ciliary syndrome or primary ciliary dyskinesia; autosomal recessive disorder resulting in a defect in the action of cilia lining the respiratory tract & fallopian tubes; presents with triad of bronchiectasis, chronic sinusitis & situs inversus – congenital condition whereby major visera are mirrored from their normal positions)
2. Post-infection conditions
   - Post-pneumonia
   - Post-pulmonary tuberculosis
3. Bronchial obstruction
   - Due to tumour, foreign bodies etc
   - Bronchiectasis in such cases will be isolated to the
   obstructed lung segment
4. Immune-mediated
   - Rheumatoid arthritis, SLE, inflammatory bowel disease, post-transplantation

Question 5

Pathogenesis of bronchiectasis

Answer 5

1. Obstruction coupled with infection produces necrotizing
   inflammatory reactions
   - Destroys smooth muscle & elastic tissue
   - Weakens bronchial wall
   - Leads to permanent dilation of the bronchi & bronchioles involved
2. Bronchiectasis may be generalized or localized:
   - Localized bronchiectasis: mechanical obstruction of an airway, childhood bronchopulmonary infections
   - Generalized bronchiectasis: inherited conditions, acquired impairment of host defences against respiratory infections

Question 6

Morphology of bronchiectasis

Answer 6

1. [Gross]
   - Saccular, cylindrical or irregular dilation of bronchi
   - Bronchi contain thick mucopurulent secretions
2. [Histology]
   - Loss of bronchial wall smooth muscle & elastic tissue
   - Inflammation, lymphoid aggregates
   - Goblet cell metaplasia & squamous metaplasia of bronchial epithelium
   - Fibrosis of parenchyma

Question 7

Pathological Effects & complications of bronchiectasis

Answer 7

1. Cor pulmonale
2. Chronic suppurative inflammation
3. Lung abscess
4. Pyemia predisposing to brain abscess
5. Systemic amyloidosis

Question 8

Clinical features of bronchiectasis

Answer 8

1. Persistent cough, foul-smelling sputum
2. Dyspnea, orthopnea
3. Fever
4. Clubbing

Question 9

Definition of bronchial asthma

Answer 9

Chronic inflammatory disorder of the airways that is characterized by increased airway responsiveness to a variety of stimuli, resulting in episodic small airway obstruction due to reversible bronchoconstriction, inflammation of the bronchial walls & increased mucus secretion

Question 10

Forms of asthma

Answer 10

1. Allergic/Atopic Asthma (extrinsic)
2. Non-atopic Asthma (intrinsic)
3. Occupational Asthma (extrinsic)

Question 11

Allergic/Atopic Asthma (extrinsic)

Answer 11

1. Type I hypersensitivity reaction (IgE-mediated)
2. Most common in children, typically with a personal or family history of allergy
3. Triggered by allergens (e.g. pollen, dust)

Question 12

Non-atopic Asthma (intrinsic)

Answer 12

1. Caused by prior airway inflammation (non-allergic)
   which is postulated to lower the threshold of the subepithelial vagal receptors to irritants, hence resulting in a state of hyperirritability
2. Triggered by respiratory viral infections, inhalation of environmental pollutants (SO2, NO2, O3), stress, cold, exercise

Question 13

Occupational Asthma (extrinsic)

Answer 13

1. Due to a variety of mechanisms depending on inciting agent (e.g. Type I hypersensitivity reaction, direct liberation of bronchoconstricting substances)
2. Triggered by inhalation of organic & chemical dusts, fumes, & other chemicals

Question 14

Pathogenesis of allergic asthma

Answer 14

1. Type I hypersensitivity reaction (2 phases)
   - Early phase reaction due to induction of TH2 cells which secrete a variety of cytokines which results in bronchoconstriction & mucus secretion
   - Late phase reaction due to recruitment of leukocytes which secrete more factors & cytokines to cause another bout of epithelial damage and airway narrowing
2. Airway remodelling
   - Due to repeated bouts of allergen exposure &
   immune reactions which result in structural changes
   of the bronchial wall
   - Hypertrophy & hyperplasia of bronchial smooth
   muscle, epithelial injury, increased airway vascularity, subepithelial mucus gland hypertrophy & hyperplasia, deposition of subepithelial collagen

Question 15

Morphology of bronchial asthma

Answer 15

[Gross]

1. Mucosal & submucosal edema
2. Leukocytic infiltrate (eosinophils, mast cells, lymphocytes)
3. Epithelial cell necrosis
4. Bronchial wall fibrosis

[Histology]

1. Charcot-leyden crystals: Derived from eosinophil granules (galectin-10, a lysophospholipase binding protein)
2. Curschmann spirals: Mucous plugs from small airways containing whorls of shed epithelium
3. Creola bodies: Clusters of epithelial cells

Question 16

Pathological effects & complications of bronchial asthma

Answer 16

Status asthmaticus

• A state of unremitting attacks which can persist for days to weeks, leading to respiratory insufficiency & eventual death
• Such patients typically have a long history of asthma

Question 17

Definition of emphysema

Answer 17

Permanent dilation of air spaces distal to the terminal bronchiole (acinus) with destruction of their walls, without fibrosis; clinically grouped with Chronic Bronchitis and collectively referred to as “Chronic Obstructive Pulmonary Disease” (COPD)

Question 18

Types of emphysema

Answer 18

1. Centriacinar (Centrilobular) Emphysema
2. Panacinar (Panlobular) Emphysema
3. Distal Acinar (Paraseptal) Emphysema
4. Other Emphysemas (loose use of the term)
   - Compensatory emphysema
   - Scar emphysema

Question 19

Centriacinar (Centrilobular) Emphysema

Answer 19

1. Central/proximal parts of acinus affected (affects proximal respiratory bronchioles, spares alveoli)
2. Usually occurs in the apical regions of upper lobes
3. Found in smokers, often in associated with chronic bronchitis

Question 20

Panacinar (Panlobular) Emphysema

Answer 20

1. Acinus is uniformly enlarged, from the respiratory bronchiole to the terminal alveoli (affects both respiratory bronchioles & alveoli)
2. Usually occurs in the lower zones & anterior margins of the lung
3. Found in individuals with alpha1-antitrypsin deficiency

Question 21

Distal acinar (paraseptal) emphysema

Answer 21

1. Distal parts of the acinus affected (affects alveoli,
   spares respiratory bronchioles)
2. Usually occurs in the upper half of the lungs,
   adjacent to areas of fibrosis, scarring or atelectasis
3. May lead to sub pleural bull which can rupture, leading to spontaneous pneumothorax (commonly seen in adults)

Question 22

Compensatory emphysema

Answer 22

Dilation of alveoli without destruction of septal walls as a compensatory response to loss of lung substance elsewhere

Question 23

Scar emphysema

Answer 23

Irregular involvement of acini, associated with scarring

Question 24

Causes of emphysema

Answer 24

1. Cigarette smoking
2. Atmospheric pollution
3. Chronic bronchitis
4. Pneumoconiosis
5. alpha1-antitypsin deficiency

Question 25

Pathogenesis of emphysema

Answer 25

1. Normal connective tissue modeling is governed by a delicate protease-antiprotease balance - Neutrophil proteases (e.g. elastase) are released at sites of inflammation - Serum alpha1-antitrypsin is a major inhibitor of proteases 2. Inflammation due to various causes results in an increase in proteases liberated locally 3. Decreased levels of alpha1-antitrypsin results in impaired inhibition of proteases - Congential deficiency of alpha1-antitrypsin - Acquired functional deficiency of alpha1-antitrypsin (inactivated by reactive oxygen species, produced as a result of inflammation or directly from cigarette smoke) 4. Additionally, alveolar macrophages also release macrophage elastase (which is not inhibited by alpha1-antitrypsin) during the inflammatory process 5. Collectively, increased protease liberation & decreased alpha1-antitrypsin levels results in destruction of elastic tissue, which results in: - Destruction of alveolar walls, resulting in fusion of alveoli into large abnormal air spaces (if near pleural surface, appears grossly as blebs & bullae) - Premature collapse of bronchioles during expiration (as they are usually tethered by elastic recoil of the lung, which diminishes with elastic tissue destruction), resulting in air-trapping

Question 26

Morphology of emphysema

Answer 26

[Gross] - Voluminous (due to air trapping) - Pale (due to vessel compression) - Blebs & bullae (air-filled spaces) [Histology] - Dilation of alveolar spaces - Destruction of septal walls - Fusion of alveoli - Compression or distortion of bronchioles & vasculature by large abnormal air spaces

Question 27

Pathological effects & complications of emphysema

Answer 27

1. Cor pulmonale (due to destruction of vasculature with the destruction of the alveolar walls & compression of remaining vasculature by large abnormal air spaces) 2. Respiratory failure 3. Pneumothorax (due to rupture of bullae) 4. Increased incidence of peptic ulcer (postulated to be secondary to hypercapnia which induces increased gastric acid secretion)

Question 28

Clinical features of emphysema

Answer 28

1. “Pink puffers” 2. Barrel-chested (due to air trapping) 3. Dyspneic, with obviously prolonged expiration 4. Breaths through pursed lips (to help maintain positive airway pressure)

Question 29

Definition of chronic bronchitis

Answer 29

Clinically defined as persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause; clinically grouped with Emphysema and collectively referred to as “Chronic Obstructive Pulmonary Disease” (COPD)

Question 30

Causes of chronic bronchitis

Answer 30

1. Cigarette smoking (main cause) 2. Air pollution 3. Toxic industrial inhalants 4. Respiratory infections

Question 31

Pathogenesis of chronic bronchitis

Answer 31

1. Mucus hypersecretion as a result of: - Stimulation by neutrophil proteases - Mucus gland hypertrophy - Marked increased in goblet cells in small airways 2. Mucus plugs then produce airway obstruction 3. Role of infection appears to be secondary - Not responsible for initiation of chronic bronchitis - But probably significant in maintaining & exacerbating it

Question 32

Morphology of chronic bronchitis

Answer 32

1. Hypertrophy & hyperplasia of mucous gland layer, resulting in an increased ratio of thickness of the mucous gland layer to that of the entire bronchial wall (Reid index, normally = 0.5) 2. Excess mucus in the airways 3. Increase in the number of goblet cells 4. Increased amount of smooth muscle 5. Lymphocytic infiltrate 6. May exhibit squamous metaplasia & dysplasia

Question 33

Pathological Effects & complications of chronic bronchitis

Answer 33

1. Respiratory failure 2. Cor pulmonale (as air trapping in obstructed segments produce increased pressure which compressed pulmonary vessels) 3. Respiratory infections (due to accumulation of mucus) 4. Malignancy (due to atypical metaplasia & dysplasia)

Question 34

Clinical features of chronic bronchitis

Answer 34

1. “Blue bloaters” 2. Mild cyanosis, dyspnea 3. Persistent productive of sputum