L57: Pathology Of Small Airway Obstruction

Question 1

Small airway vs Large airway pathologies

Answer 1

Small airway (<2mm, no cartilage, beyond terminal bronchioles): generalised effects and diffuse
—> Airflow obstruction

Large airway: regional effects
—> Infections, collapse, atelectasis

Question 2

Asthma

Answer 2

• Paroxysmal narrowing of airway
• Reversible
• FEV1/FVC ratio <70%, reversible with bronchodilators with >= 12% increase
• Risk factors: Host + Environmental
  Host: genetic, atopy, airway hyperresponsiveness to ACh
  Environmental: allergens, pollution, occupation

Question 3

Extrinsic asthma vs Intrinsic asthma

Answer 3

Extrinsic:

• Allergic condition: Type 1 hypersensitivity —> raised IgE level against antigens: dust mite (most important), pollens
• Aggravation: pollution, infection
• Childhood onset
• well-controlled may subside in adolescent

Intrinsic:

• unknown etiology
• adult onset

Question 4

Pathogenesis of asthma

Answer 4

Foreign antigen bind to igE on mast cell
—> mast cell degranulation
—> histamine, leukotriene, eosinophilic chemotactic factor

1. Bronchospasm —> thick muscle coat
2. Vascular dilatation
3. Oedema
4. Mucus production —> mucus plugs
5. Airway inflammation

Overall effect: obstruction —> increased airway resistance —> air trapping —> hyperinflated lungs

Question 5

Clinical features of asthma

Answer 5

1. Shortness of breath / dyspnea
2. Long expiration
3. Wheezing (turbulent air flow)
4. Episodic attack with recovery in between
5. Coughing (worse at night)

Question 6

Lung volume and Spirometry changes in asthma and COPD

Answer 6

Asthma and COPD

1. ↓ Tidal volume
2. ↓ Vital capacity
3. ↑ Residual volume

Spirometry:
Asthma: both FEV1, FVC ↓, but FEV1 decreases more —> ↓ FEV1/FVC ratio <70%

COPD: post-bronchodilator FEV1/FVC ratio <70%, indicate presence of airflow limitation that is not fully reversible

Question 7

COPD / COAD / COLD / CORD

Answer 7

• Chronic
• Progressive, not completely stopped by smoking cessation
• abnormal inflammatory response + bronchospasm
• Acute exacerbation by infections, pollution
• 3rd commonest cause of death, 5th commonest disability by 2020

Causes:

• Tobacco (80-95%)
• occupational (coal minding, welding)
• pollution
• genetics

Question 8

Pathogenesis of COPD

Answer 8

ROS, chemotactic substances, inflammatory mediators
—> Activated macrophage, neutrophil, lymphocyte
1. Mucus secretion
2. Chronic inflammation
3. Peribronchiolar fibrosis
4. Proteolytic enzyme (matrix metalloproteinase, elastase —> emphysema)

Question 9

Pathology of COPD (2 entities)

Answer 9

1. Chronic bronchitis

2. Emphysema

Question 10

Chronic bronchitis

Answer 10

Defined clinically:

• chronic productive cough with mucoid sputum
• at least 3 months per year for 2 consecutive years

1. Mucus secretion
   - excess mucus and chronic inflammation of small airway
   - increased mucus gland layer thickness
   - impaired ciliary clearance: mucus plugs, white mucoid sputum —> Infection
2. Chronic inflammation
   - mucosal oedema
   - muscle spasm
   - epithelial damage —> more inflammatory cells —> vicious cycle
3. Peribronchiolar fibrosis
   - irreversible, slow progressive narrowing of small airways
   - fibroblast proliferation
   - ECM collagen deposition in bronchial wall

Question 11

Emphysema

Answer 11

Defined pathologically:

Destruction of alveolar wall —> permanent enlargement of air spaces in small airways

• ↓ in anti-protease: smoking, Alpha 1 anti-trypsin deficiency
• ↑ in protease: smoking

Smoking: increase neutrophil, macrophage and ROS
—> ↑ proteolytic enzymes from neutrophil, macrophage
—> Apoptosis of cell + Degradation of ECM

TWO forms:

1. Centriacinar (proximal acinus / upper lobe): smoking-related —> panacinar in advanced case
2. Panacinar (entire lobe): alpha1 antitrypsin deficiency-related / smoking in advanced case

Question 12

Effects of loss of alveolar tissue

Answer 12

1. Loss of elastic recoil / radial traction
   —> Early closure of airway during expiration (scooped out appearance in Spirometry flow-volume loop)
   —> Air trapping
2. ↓ SA for gas exchange

Question 13

Long term complications of COPD

Answer 13

1. Hypoxia
2. Pulmonary hypertension (pulmonary systolic >= 30mmHg), irreversible pulmonary arterial narrowing due to chronic alveolar hypoxia
3. Cor pulmonale
4. Polycythaemia: ↑ erythropoietin —> ↑ RBC —> ↑ viscosity —> ↓ blood flow
5. Related to cancer: ROS, inflammatory mediators —> chronic inflammation —> DNA damage —> mutation

Question 14

Comparison between asthma and COPD

Answer 14

Similarity

1. Common signs and symptoms
   - SOB
   - cough with sputum
   - narrow airway —> turbulent flow —> expiratory wheeze
   - exacerbation
   - prolonged expiration
2. Common acute complications
   - Pneumothorax: air leakage in weak spots
   - Bacterial infection / pneumonia
   - Type 2 acute respiratory failure (ventilation failure)

Difference

1. Cause
   - allergy
   - smoking
2. Pathology
   - acute attack
   - chronic
3. Reversibility
   - reversible
   - irreversible