Respiratory: Pathology - Obstructive airways disease

Question 1

What is the difference between obstructive and restrictive airways disease?

Answer 1

Obstructive: increased resistance to airflow due to obstruction
Restrictive: decreased expansion of lung parenchyma (decreased total lung capacity)

Question 2

Give four examples of obstructive lung diseases

Answer 2

1. Chronic bronchitis*
2. Emphysema*
3. Asthma
4. Bronchiectasis

• COPD is a clinical grouping of chronic bronchitis and emphysema

Question 3

What is emphysema?

Answer 3

Chronic obstructive lung disease charactered by irreversible airspace enlargement distal to terminal bronchioles, with destruction of their walls

Question 4

Give three risk factors for emphysema

Answer 4

1. Heavy cigarette smoking
2. Female sex
3. African American

Question 5

What % of emphysema sufferers do not smoke?

Answer 5

10%

Question 6

What are the four classifications of emphysema?

Answer 6

1. Centriacinar
2. Panacinar
3. Paraseptal (distal acinar)
4. Irregular (airspace enlargement with fibrosis)

Question 7

Describe the pathological changes seen in centriacinar emphysema

Answer 7

Destruction of central or proximal parts of acini, with sparing of distal alveoli

Question 8

Describe the pathological changes seen in panacinar emphysema

Answer 8

Uniform enlargement of acini

Question 9

Describe the pathological changes seen in paraseptal emphysema

Answer 9

Enlargement of distal acini, sparing proximal
Multiple continuous enlarged airspaces 0.5 to >2cm in diameter
May form cyst-like structures

Question 10

Describe the pathological changes seen in irregular emphysema

Answer 10

Irregular involvement of acinus, with scarring

Question 11

What parts of the lung are predominantly affected in centriacinar emphysema?

Answer 11

Upper lobes and apices

Question 12

What parts of the lung are predominantly affected in panacinar emphysema?

Answer 12

Lower zones and anterior margins
Most severe at bases

Question 13

What parts of the lung are predominantly affected in paraseptal emphysema?

Answer 13

Areas adjacent to pleura, along lobular connective tissue septa, and lobule margins

Question 14

Which pattern of emphysema is typically seen in heavy smokers?

Answer 14

Centriacinar

Question 15

Which pattern of emphysema is usually caused by a1-antitrypsin deficiency?

Answer 15

Panacinar

Question 16

Which pattern of emphysema may be the underlying cause in spontaneous pneumothorax?

Answer 16

Paraseptal

Question 17

What is the typical clinical presentation seen with irregular emphysema?

Answer 17

Often asymptomatic, clinically insignificant

Question 18

Describe the pathogenesis of emphysema in smokers

Answer 18

Nicotine and reactive oxygen species from tobacco smoke cause “functional” a1-antitrypsin deficiency due to oxidative damage, and induce transcription of NF-κB
Results in release of chemoattractants for neutrophils and macrophages, which are then activated with subsequent release of proteases and elastase
May also see goblet cell metaplasia with mucus plugging, and peribronchial fibrosis

Question 19

Describe the concept of protease-antiprotease imbalance as it relates to emphysema

Answer 19

Hereditary deficiency of a1-antitrypsin (a major protease inhibitor) invariably results in emphysema
In these patients, unchecked proteolytic activity occurs in response to inflammatory stimulus, resulting in destruction of elastic tissue and leading to airway enlargement

Question 20

What % of all patients with emphysema have a1-antitrypsin deficiency?

Answer 20

1%

Question 21

Define chronic bronchitis

Answer 21

Persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in absence of any other identifiable cause

Question 22

What are some of the potential complications of chronic bronchitis?

Answer 22

1. COPD
2. Cor pulmonale
3. Respiratory epithelium metaplasia/dysplasia -> increased risk of cancer

Question 23

What % of chronic bronchitis sufferers are smokers?

Answer 23

90%

Question 24

Describe the pathogenesis of chronic bronchitis

Answer 24

Chronic airway irritation due to smoking or other inhaled irritants
Earliest feature is mucus hypersecretion and hypertrophy of submucosal glands in large airways (trachea, bronchi): this is stimulated by elastases and MMPs released by neutrophils
Subsequent metaplastic reaction with hyperplasia and hypertrophy of goblet cells of smaller airways (small bronchi, bronchioles), leading to airway obstruction

Question 25

Five morphological changes seen in chronic bronchitis

Answer 25

1. Hyperaemia and oedema of mucous membranes 2. Mucinous secretions or casts filling airways 3. Increased mucus gland size (increased Reid index, which is ratio of mucus gland layer to total wall thickness) 4. Bronchial/bronchiolar mucous plugging, inflammation and fibrosis 5. Squamous metaplasia/dysplasia of respiratory epithelium

Question 26

What is bronchiolitis obliterans?

Answer 26

Obliteration of small airway lumen seen in severe chronic bronchitis as a result of progressive airway fibrosis and narrowing

Question 27

Distinguish between predominant emphysema and predominant bronchitis patterns of COPD, in terms of appearance, age, dyspnoea, cough, infections, respiratory insufficiency, cor pulmonale, airway resistance, elastic recoil, and CXR changes

Answer 27

Question 28

What is asthma?

Answer 28

Chronic inflammatory disorder characterised by recurrent episodes of wheezing, breathlessness, chest tightness, and cough (often nocturnal and/or early morning)

Question 29

Three hallmarks of asthma

Answer 29

1. Increased airway responsiveness resulting in episodic bronchoconstriction 2. Inflammation of bronchial walls 3. Increased mucus secretion

Question 30

What are the four types of asthma? Which are most common?

Answer 30

1. Atopic (most common) 2. Intrinsic nonreagenic (also common) 3. Drug-induced 4. Occupational

Question 31

Describe the immediate and late phase components of the hypersensitivity reaction seen in atopic asthma. What mediates each and what are the features?

Answer 31

Acute phase: - Mediated by binding of Ag to IgE-coated mast cells - Features include bronchoconstriction, increased mucus secretion, vasodilation with increased vascular permeability Late phase: - Inflammation mediated by recruited leukocytes - Features persistent bronchospasm and oedema, leukocytic infiltration, loss of damaged epithelial cells

Question 32

Three cytokines of importance in atopic asthma

Answer 32

All secreted by TH2 cells: IL-4: IgE production IL-5: eosinophil activation IL-13: increased mucus secretion and IgE production

Question 33

What are three typical triggers for intrinsic nonreagenic asthma?

Answer 33

Respiratory tract infections Chemical irritants Drugs

Question 34

What causes drug-induced asthma?

Answer 34

Aspirin, likely related to effects of COX inhibition

Question 35

What causes occupational asthma?

Answer 35

Triggered by fume, organic and chemical dusts, gases, and other chemicals Usually due to repeated exposures

Question 36

Describe the histological findings seen in asthma

Answer 36

1. Curschmann spirals (whorled mucus plugs) 2. Eosinophilic infiltrate with crystalloid debris of their membranes (Charcot-Leyden crystals) 3. "Airway remodelling": - Thickening of airway wall with sub-basement membrane fibrosis - Hypervascularity - Submucosal gland hypertrophy, mucous metaplasia - Hypertrophy and/or hyperplasia of bronchial wall muscle

Question 37

What is bronchiectasis?

Answer 37

Disease charactered by permanent dilation of bronchi and bronchioles, caused by destruction of muscle and elastic tissue due to chronic necrotising infections

Question 38

Four types of causes of bronchiectasis with examples of each

Answer 38

1. Congenital/hereditary conditions (e.g. CF, primary ciliary dyskinesia) 2. Postinfectious conditions (e.g. TB, influenza, aspergillosis) 3. Bronchial obstruction (e.g. due to tumour or FB) 4. Other causes (e.g. RA, IBD, GVHD)

Question 39

What areas of the lung are predominantly affected in bronchiectasis?

Answer 39

Lower lobes May be localised if due to obstruction, otherwise typically bilateral

Question 40

What is typically grown on sputum culture in bronchiectasis?

Answer 40

Mixed flora