W5 Molecular Pathophysiology of COPD

Question 1

State some factors that describe COPD:

Answer 1

Chronic Obstructive Pulmonary Syndrome
- Airflow obstruction that is not fully reversible
- Does not change markedly over several months
- Usually progressive
- General term encompassing a number of disease esp chronic bronchitis and emphysema

Question 2

What is the general definition of COPD?

Answer 2

“A disease state characterised by the presence of chronic bronchitis and/or emphysema associated
with airflow obstruction: air flow obstruction is often accompanied by airway hyperreactivity and may be partially reversible

Question 3

What is Chronic Bronchitis?

Answer 3

Lung damage and inflammation in large airways (bronchi)
Chronic Cough
Sputum production (purulent)
(3 months of the year – 2 consecutive years)
Haemoptysis (sometimes)- coughing up blood
Initially mild dyspnea- SOB
Cyanosis (resulting in blue tinge to skin and lips) due to Hypoxemia
Peripheral oedema (cor pulmonale)

Question 4

What is Emphysema?
What are the symptoms?

Answer 4

Lung damage and inflammation of alveoli
Enlargement of the air spaces distal to the
terminal bronchioles

Dyspnea- not being able to breathe fast enough
Minimal Cough
Pink flush in the face, pursed lip breathing (Effort for breathing)
Hyperinflation, barrel chest (accessory muscle
use)
Tachypnea (fast shallow breathing)

Question 5

What are the functional changes of COPD? (7)

Answer 5

*Airway obstruction
*Air trapping
*Hyperinflation
*Mucus hypersecretion
*Ciliary dysfunction
*Gas exchange impairment
*Pulmonary hypertension

Question 6

Epidemiology of COPD:
(for info)

Answer 6

• Approximately 90% of COPD patients are smokers
  -although only 15% of smokers develop COPD
• In the 10% of non-smokers who suffer from COPD, causative factors include environmental factors (passive smoking, pollutants, inhalation of other toxins) and
  developmental lung changes
• COPD increase with age and are higher in men
• Inflammation dominated by neutrophil invasion of the lung tissue
• The most important identified genetic risk factor for the evolution of COPD is deficiency of α1-protease (α1-antitrypsin) inhibitor

Question 7

COPD: Disease progression
(for info)

Answer 7

• Inflammatory and structural changes persist even after cessation of smoking
• Lung function never returns to the normal rate of decline in those who
  cease smoking and are susceptible to the effects of smoking
• Although lung function decreases naturally with age, this deterioration is amplified if a person smokes and is susceptible to its effects.

Question 8

When to diagnose COPD:

Answer 8

“The diagnosis of chronic obstructive pulmonary disease (COPD) depends on thinking of it as a cause of breathlessness or cough. The diagnosis is suspected on the basis of
symptoms and signs and is supported by spirometry.”
A diagnosis of COPD should be considered in patients:
* Over the age of 35
* Who have a risk factor (generally smoking)
* And who present with:
exertional breathlessness
chronic cough
regular sputum production frequent winter ‘bronchitis’ or wheeze.

Question 9

What are some pathophysiological changes in COPD?
in the alveoli?
in the bronchioles?

Answer 9

In the alveoli:
Loss of elastic fibres, Decreased SA so leads to collapsed alveoli

In the bronchioles
Smooth muscle contraction
Mucus Hyperpigmentation

Question 10

COPD - pathophysiology
Theory: Mechanisms

Answer 10

• Theory: Mechanisms
• Associated with chronic airway inflammation
• Prolonged cigarette smoke (and other toxins)
• Create an inflammatory response
• This response can be normal, protective response.
• Amplified in COPD
• Increased number of neutrophils, activated macrophages and activated T-lymphocytes
• Chemokines
• Cytokines
• Epithelial cells
  -fibrosis
• Macrophages epithelial cells:
• Cytokines/chemokines
• Attract immune cells
• Release proteases
• (proteases) that break down elastin in the alveolar walls (e.g. neutrophile lastase),

Question 11

What is Alpha-1antitrypsin deficiency (AATD)?

Answer 11

• α1-antitrypsin is also known as α1-protease inhibitor.
• AATD is a genetic condition whereby there is a deficiency of the protease inhibitor
• This proteases breaks down the elastases, which enhance the destruction of lung tissue.
• Deficiency of the inhibitor to balance this

Question 12

Emphysema: Pathophysiology

Answer 12

• Alveoli walls damaged:
• Surface area for gas exchange is reduced
• Leads to
  -increased physiological dead space and
  -poor diffusing capacity.
• Lung tissue is not affected uniformly therefore the lung is
  not evenly ventilated
• leading to V/Q mismatch,
• hypoxaemia and hypercapnia (Currie, 2011).
• Loss of elastic recoil and increased lung compliance
  -increasing risk of hyperinflation and pneumothorax (Fischer et al.2011).
• leading to ‘floppy’ airways where airway resistance is increased and FEV1/FVC ratio is reduced

Question 13

Chronic bronchitis:
Pathophysiology

Answer 13

• Increase in Neutrophil levels
  -levels in sputum generally correlate with disease severity
• Neutrophil elastase (protease) causes mucous hypersecretion
• TGFbeta released by epithelial cells/ macrophages
  -stimulates fibroblast proliferation and
  -cause fibrosis of the small airways
• Prolonged inflammation leads to permanent changes within the airways
  -Hypertrophy of mucous glands, hyperplasia of Goblet cells and reduced cilia motion,
  -Which increase mucous production and secretion, and reduce its clearance.

Question 14

Treatment of COPD
What are some treatments? (6)

Answer 14

1. Corticosteroids (benefit?)
2. Long acting Beta-agonists (LABA) e.g. Formoterol
   -SABA may also be given
3. Anticholinergics
   - ipratropium, tiotropium
4. Oxygen
5. Avoid respiratory infections (immunisation)
6. Smoking cessation – the only measure that reduces rate of decline of airway function