RESP: Pathophysiology of respiratory diseases 2

Question 1

What is COPD?

Answer 1

Umbrella term for mixture of chronic bronchitis, emphysema, ‘small airways disease’. It encompasses a long-term, progressive, and accelerated decline in respiratory function.

(Emphysema is a condition in which airsacs of lung are damaged and enlarged, causes breathlessness)

90% COPD associated with long-term tobacco smoke exposure

30% long term smokers develop COPD

Other factors = genetics (e.g. alpha-1 antitrypsin deficiency) and environmental (e.g. pollution)

Question 2

How does smoking reduce respiratory function and lead to COPD?

Answer 2

• Tobacco smoke leads to inhalation of noxious chemicals and reactive oxygen species
• This leads to to tissue damage directly but also leads to antiprotease inactivation, which increases protease burden, leading to tissue damage. Antiproteases are needed to prevent structural proteins being degradd, maintaining airway structure.
• Long term tissue damage leads to tissue remodelling, which itself can cause decreased respiratory function
• Tissue remodelling and tissue damage leads to impaired mucociliary clearance which ⬆️respiratory infections, which leads to inflammatory response, leading to secretion of IL-8 and TNF-alpha. This causes macrophage activation and neutrophil activation and trafficking, which leads to increased protease burden, which leads to tissue damage which then has the affects listed above.
  
  • Immune cells (macrophages, neutrophils) are attracted to tissues damaged by smoking due to acute local inflammation brought on by the chemicals. When immune cells infiltrate the areas, they release proteolytic enzymes that breakdown dead cells and kill invading organisms. Due to chronic exposure, these mechanisms become pathological.

Question 3

What are the key pathological features observed within the airways of COPD patients?

Answer 3

• Cilia damage
• Mucus hypersecretion (⬆️goblet cells + ⬆️mucus gland activation)
• Inflamed, swollen airway tissue + oedema
• Weakened airway structure (loss of elastin) & loss of patency (airway collapse)
  
  • Impaired mucociliary clearance = increased risk of infection = recurrent infection
  • Irritation of sensory neurones = cough
  • Decreased luminal area = increased airway resistance and airway obstruction

Question 4

What is chronic bronchitis?

Answer 4

Chronic, excessive sputum production, coughing and airway obstruction. Coughing and mucus production consequence of inflammation within airway tissue, activates sensory neurones, stimulates mucus glands.

Question 5

What causes chronic bronchitis?

Answer 5

• Airway lumen size decreased by excessive mucus secretion, tissue swelling, degradation of overall airway structure (resulting in airway collapsing when under excessive pressure)
• Increased airway resistance

Question 6

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

Answer 6

• Hypoxia results in hypoxic vasoconstriction (⬆️ pulmonary vascular resistance), pulmonary hypertension, increased right ventricular afterload-> RV hypertrophy, and eventually right heart failure

Chronic alveolar hypoxia also results is hypercapnia, hypoxaemia, acidemia, leads to decreased exercise tolerance, fatigue, and a decreased quality of life.

Question 7

What is pneumonia?

Answer 7

Infection of lung parenchyma, resulting in inflammation and oedema

Classified according to:

• Pathogen (bacteria, virus, fungi)
• Tissues affected, e.g. lobar, bronchial, interstitial
• Where infection was acquired (community or hospital)

Question 8

What is the pathophysiology of pneumonia?

Answer 8

Induced acute lung injury (by pneumonia) :

• Weakening of host defence (e.g. following viral infection, damage to epithelium, immune suppression)
• Colonisation of alveoli by pathogens
• Activation of macrophages and cytokines release (IL-6, IL-8, TNF-alpha)
• Recruitment of neutrophils into alveolar space, release of proteases and ROS
• Injury to alveolus and surrounding structures
  
  • Deposition of dead cells and proteins in alveolar wall (’hyaline membrane’ formation) → Impaired gas exchange → Hypoxaemia - Hypercapnia typically avoided due to a reflex increase in ventilation, including better-functioning parts of lungs. However, due to VQ mismatch, hypoxaemia remains
  • Disruption of endothelium and basement membrane disruption, fluid accumulates in alveoli (oedema) and/or interstitium → Impaired gas exchange → Hypoxaemia → Also causes crackly lung sounds. Can be seen as opacity on X-ray

Question 9

Compare asthma, COPD and viral pneumonia with their characteristics, pathology, impact and changes in respiratory function

Answer 9

Allergic asthma - Eosinophils, Th2, Mast cells, IL-4, IL-5, IL-13, ROS, LTs, PGs. Pathology site = small airways, causes ASM contraction, mucus hyper secretion. Results in dyspnoea, airway obstruction potentially leading to impaired ventilation (⬆️ PaCO2, ⬇️ PaO2, if pathology severe and ventilation impaired)

COPD - Neutrophils + macrophages, IL-8, TNF-alpha, proteases. Pathology site= Large + small airways. Causes mucus hyper secretion in large airways, and in small airways, structural degradation and loss of patency. In alveoli = airspace enlargement/reduced surface area. Results in impaired ventilation (type 2 respiratory failure) + ⬇️ gas exchange, ⬆️ PaCO2, ⬇️ PaO2. Long term impact on CVS (pulmonary hypertension, right ventricular hypertrophy, right heart failure)

Viral pneumonia - Neutrophils + macrophages, IL-6, IL-8, TNF-alpha, proteases, ROS. Pathology = Predominantly lungs (alveoli + interstitial tissue), potentially terminal bronchi. Causes hyaline membrane formation, oedema of alveoli and interstitial tissue (potential V/Q mismatch). Can result in acute lung injury and ARDS. Reduced gas exchange (type 1 respiratory failure), ⬇️ PaO2. Potentially normal PaO2 if normal ventilation rate maintained.

Question 10

How does respiratory failure affect other organs?

Answer 10

Respiratory failure places further burden on other organs and tissues, such as the CVS.

Chronic hypoventilation of alveoli results in prolonged and widespread hypoxic vasoconstriction. Constriction of pulmonary vascular increases vascular resistance, in turn increasing the force required to pump blood through the system and pressure of blood within it (pulmonary hypertension). Requires heart to work harder to maintain normal blood flow against increased resistance, resulting in right heart hypertrophy and worsening efficiency.