Pathology of Asthma and COPD

Question 1

What is COPD?

Answer 1

• Chronic Obstructive Pulmonary Disease
• Umbrella term for:
• -> Emphysema (pink puffer)
• -> Chronic bronchitis (blue bloater)

Question 2

What is the shared aetiology for COPD?

Answer 2

• Cigarette smoking
• Marijuana smoke
• Atmospheric pollution
• Occupation dust exposure (e.g. factory work)

Question 3

How is spirometry used to show COPD?

Answer 3

• Monitoring lung function
• Lung function test
• How much air the patient can quickly expire

Question 4

How is an obstructive disease shown in spirometry?

Answer 4

• Amount of air in is normal

- Pathological expiration

Question 5

How is a restrictive disease shown in spirometry?

Answer 5

• Air breathed in is pathological

Question 6

What are the clinical syndromes of emphysema?

Answer 6

• Pink puffer
• Rapid, shallow breathing
• Thin
• Subjectively breathless
• Active effort used to maintain normal blood gases
• Often low BMI
• Not associated with lung infections- not hyper inflammatory
• Exercise intolerance

Question 7

What are the clinical syndromes of chronic bronchitis?

Answer 7

• Blue bloater
• Productive cough to produce sputum (clear, white or purulent)
• Obese and oedematous
• Hypoxic
• Polycythaemia
• Congestive cardiac failure
• Exercise intolerance
• Insufficiency respiratory drive (hypoxia and carbon dioxide retention)- leading to cyanosis
• Predisposition to infection

Question 8

What complications are involved with COPD?

Answer 8

• Bronchopneumonia (comorbidities mean that they may not make a full recovery)
• Cardiac failure (respiratory failure), right sided failure
• Pulmonary thromboembolism
• Increased risk of lung cancer

Question 9

Describe the epidemiology of COPD?

Answer 9

• Major worldwide cause of mobility and mortality due to respiratory insufficiency
• Current/former smokers
• 35 year+ onset
• Gender distribution matches that of smoking

Question 10

What is emphysema?

Answer 10

• Destructive process involving alveoli
• Lung-abnormal increase of air spaces (abnormally dilated)
• Space greater than 1cm = bulla
• Pathological inflation of affected tissue

Question 11

How does air trapping occur in emphysema?

Answer 11

• Air flow limitation due to atrophy/expiratory collapse of airways with decreased elastic recoil and less alveolar attachments
• Barrel chest phenotype and hyperinflation
• Reduced alveolar SA for GE- pathological enlargement of each alveolus
• May be associated with small airway disease, with inflammation and narrowing of bronchioles

Question 12

What are the morphological changes that occur due to smoke?

Answer 12

• Normal acinus contains respiratory bronchiole and alveolar ducts/alveoli
• Smoke particles deposited into respiratory bronchiole
• Centrilobular emphysema- alveoli surrounding bronchi dilated
• Panacinar emphysema- all alveoli enlarged

Question 13

What is the aetiology of emphysema

Answer 13

• Centracinar- cigarette smoking

- Primary panacinar- may also be due to genetic α-1-antitrypsin deficiency

Question 14

What happens with a genetic α-1-antitrypsin deficiency?

Answer 14

• May lead to early-onset emphysema
• Unopposed action leukocyte elastase on lung connective tissue (elastase breaks down elastin)
• too much breakdown results in loss of elastic recoil
• Autosomal recessive inheritance
• Association with hepatitis and cirrhosis

Question 15

How does cigarette smoking lead to emphysema?

Answer 15

• Activates alveolar macrophages
• Increased macrophages release proteolytic enzymes
• Neutrophil chemotactic factors
• Free radicals
• Reactive oxygen species

Question 16

What is the protease/anti-protease hypothesis?

Answer 16

• Protease causes damage to lung tissue, inflammatory response in response
• May also cause inhibition through free radicals

Question 17

What is chronic bronchitis?

Answer 17

• Hypersecretory process involving conducting airways
• Airflow limitation due to inflammation of wall and intermittent mucous plugging
• Persistent/ recurrent excess of bronchial secretion on most days for at least 3 moths in the year, over at least 2 years

Question 18

What is the pathogenesis of chronic bronchitis?

Answer 18

• Directly actin irritants cause mucus hypersecretion
• Neural reflexes activated by sensory nerve endings in airways further promote this effect
• Up-regulation of mucin genes and epidermal growth factor
• Increase in acidic muffins, leading to more viscous and thick sputum

Question 19

What does bronchial asthma?

Answer 19

• Inflammatory condition of airways associated with bronchial hyperresponsivess with reversible airways obstruction
• Affects 5% of population
• Prevalence is increasing
• Manageable condition with inhalers but it can also be fatal

Question 20

What is bronchoconstriction in bronchial asthma?

Answer 20

• Narrowed passages conducting air from trachea to alveoli

Question 21

What does episodic mean in bronchial asthma?

Answer 21

• No symptoms between attacks (normal lung function)

Question 22

What does reversible mean in bronchial asthma?

Answer 22

• Bronchoconstriction can be reversed with appropriate treatment

Question 23

What is the aetiology of bronchial asthma?

Answer 23

• Inhaled substance (e.g. pollen, animal dander, house dust, food, drugs etc.)
• Exacerbating factos of asthma:
• -> Lung infections
• -> Exercise
• -> Emotional stress
• -> Cold air

Question 24

What is the relationship between bronchial asthma and IgE?

Answer 24

• Low conc in plasma, bound to receptor on mast cell and basophil leukocyte membranes
• Synthesis depends on genetic background, cytokine milieu, nature and timing of allergen exposure
• Cross-linkage of receptors by allergen causes mast cell degranulaiton

Question 25

Describe the effects of type 1 hypersensitivity in asthma

Answer 25

• Presented by dendritic cells to Th2 cells (which promote IgE production)
• Stimulated specific receptors on B cells, which become plasma cells secreting IgE specific for allergen

Question 26

What does subsequent exposure cause?

Answer 26

• Mast cell degranulation
• Antigen presented to Th2 cells by dendritic cells
• Release of cytokines to activate B cells
• B cells differentiate to plasma cells and produce IgE
• IgE attaches to mast cells causing degranulation

Question 27

What acute changes occur to the bronchi in asthma?

Answer 27

• Mast cell degranulation via IgE (release of granule-derived mediators, leukotriene C4, prostaglandin D2 and cytokines)
• T cell activation (Th2)
• Cytokine release
• Eosinophil leukocyte recruitment
• Epithelial cell damage

Question 28

What chronic changes occur to the bronchi in asthma?

Answer 28

• Epithelial damage
• Thickening of airway wall
• Increased vascularity
• Smooth muscle hypertrophy and hyperplasia
• Mucus gland hyperplasia

Question 29

What are the causes of airway obstruction in asthma?

Answer 29

• Smooth muscle contraction
• Vascular congestion
• Oedema of airway wall
• Mucus secretion
• Epithelial damage

Question 30

What is the pathogenesis of asthma?

Answer 30

• Increase contraction of smooth muscle in airways
• Increased mucus production
• Increased vascular permeability (collection of oedema fluid)

Question 31

What happens to smooth muscle in asthma?

Answer 31

• Hyperplastic or hypertrophic
• Enlarged
• Increased contraction

Question 32

What happens to mucous glands in asthma?

Answer 32

• Hyperplasia

- Increased mucous production