pathophysiology of COPD

Question 1

What is Chronic Obstructive Pulmonary Disease (COPD)?

Answer 1

It is an umbrella term used for a mixture of chronic bronchitis and emphysema, and encompasses a long-term, progressive and accelerated decline in respiratory function.

Question 2

Why does smoking damage the respiratory system?

Answer 2

The many harmful constituents of tobacco smoke cause acute damage to respiratory tissue, generating an inflammatory response.
With repeated exposure, the inflammation becomes pathological and generates chronic and irreversible dysfunction.

Question 3

How does the inflammation observed within the lungs of COPD patients develop due to tobacco smoke?

Answer 3

Tobacco smoke is inhalation of noxious chemicals and reactive oxygen species; which can lead to tissue damage. This tissue damage can lead to decreased respiratory function in many different way:

1. Direct tissue damage from noxious chemicals and reactive oxygen species causes tissue remodeling (local tissue injury)= decreased respiratory function
2. Tissue damage can impair mucociliary clearance which increased respiratory infections = inflammatory response  3. Tissue damage can initiate inflammatory response = macrophage and neutrophil activation and trafficking via IL-8 and TNF-A = increases protease burden = tissue damage = tissue remodeling and decreased respiratory function

Question 4

What pathological features are observed within the airways of COPD (chronic bronchitis) patients?

Answer 4

Symptoms:
• - impaired mucociliary clearance, leading to an increased risk of infection (and recurrent infections)
• - irritation of sensory neurons, leading to coughing
• - decreased luminal area, leading to increased airway resistance and obstruction

Physical observations of bronchi:
• Damage to cilia
• Mucus hypersecretion due to increased goblet cells and mucus gland activation
• Inflamed, swollen airway tissue and oedema
• Weakened airway structure (loss of elastic) and loss of patency (airway collapse)

Question 5

What pathological features are observed within the lungs of COPD (emphysema) patients?

Answer 5

• alveoli have decreased surface area and perfusion, leading to decreased gas exchange
• loss of elastin fibres, leading to increased compliance and decreased recoil
  AIRSPACE ENLARGEMENT

Question 6

What is the overall effect of COPD on respiratory function?

Answer 6

HYPOXAEMIA
Airway obstruction + trapping results in:
Less ventilation = alveolar hypoxia
Less lung recoil = greater expiratory effort

Question 7

Why is loss of airway patency problematic in COPD?

Answer 7

In healthy lungs, there is elastin surrounding the alveoli which provides radial traction to splint bronchioles against positive Palv. In COPD lungs, there is an obstruction meaning no radial traction and the bronchioles collapse.

Question 8

What are the effects of chronic respiratory failure on the body?

Answer 8

Chronic bronchitis:
	• Recurrent cough and increased sputum production 
	• Hypoxia 
	• Hypercapnia 
	• Respiratory acidosis 
	• Increased Hbg 
	• Increased respiratory rate
	• Cardiac enlargement 
	• Use of accessory muscles to breathe 
	• Leads to right sided failure 

Emphysema:
	• Increased CO2 retention 
	• Prolonged expiratory time 
	• Anxious 
Use of accessory muscles to breathe

Question 9

What are the signs of right sided heart failure (Cor Pulmonale)?

Answer 9

• Fatigue
  
  • Increased peripheral venous pressure
  • Ascites
  • Enlarged liver and spleen
  • Distended jugular veins
  • Anorexia and GI distress
  • Weight gain

Question 10

Describe how chronic respiratory failure can lead to right heart failure

Answer 10

1. Chronic alveolar hypoxia
   
   2. Hypoxic vasoconstriction = increased pulmonary vascular resistance
   3. Pulmonary hypertension
   4. Increased right ventricle afterload = RV hypertrophy (increase in size because has to work harder)
2. Right heart failure (Cor Pulmonale)

Question 11

How effective is smoking cessation in treating COPD patients?

Answer 11

Smoking cessation only halts the acceleration of decline - lung function doesn’t regenerate and the decline continues (just not as fast).

Question 12

How can the pathophysiology of COPD be modelled in animals?

Answer 12

1. Expose mice to tobacco smoke for a period of time
   
   2. Measure their:
      Lung function
      Airway resistance
      Airway compliance
   3. Cull animals and take bronchoalveolar and lung tissue samples
   4. Measure cytokine and leukocyte levels
2. Observe histological changes in lung