Pathophysiology of COPD

The above pathogenic mechanisms result in the pathological
changes found in COPD. These in turn result in physiological
abnormalities—mucous hypersecretion and ciliary dysfunction,
airflow obstruction and hyperinflation, gas exchange
abnormalities, pulmonary hypertension, and systemic effects.
Mucous hypersecretion and ciliary dysfunctionMucous hypersecretion results in a chronic productive cough.
This is characteristic of chronic bronchitis but not necessarily
associated with airflow obstruction, and not all patients with
COPD have symptomatic mucous hypersecretion. The
hypersecretion is due to squamous metaplasia, increased
numbers of goblet cells, and increased size of bronchial
submucosal glands in response to chronic irritation by noxious
particles and gases. Ciliary dysfunction is due to squamous
metaplasia of epithelial cells and results in an abnormal
mucociliary escalator and difficulty in expectorating.
Airflow obstruction and hyperinflation or air trappingThe main site of airflow obstruction occurs in the small
conducting airways that are < 2 mm in diameter. This is
because of inflammation and narrowing (airway remodelling)
and inflammatory exudates in the small airways. Other factors
contributing to airflow obstruction include loss of the lung
elastic recoil (due to destruction of alveolar walls) and
destruction of alveolar support (from alveolar attachments).
The airway obstruction progressively traps air during
expiration, resulting in hyperinflation at rest and dynamic
hyperinflation during exercise. Hyperinflation reduces the
inspiratory capacity and therefore the functional residual
capacity during exercise. These features result in breathlessness
and limited exercise capacity typical of COPD. The airflow
obstruction in COPD is best measured by spirometry and is a
prerequisite for its diagnosis.
Gas exchange abnormalitiesThese occur in advanced disease and are characterised by
arterial hypoxaemia with or without hypercapnia. An abnormal
distribution of ventilation:perfusion ratios—due to the
anatomical changes found in COPD—is the main mechanism
for abnormal gas exchange. The extent of impairment of
diffusing capacity for carbon monoxide per litre of alveolar
volume correlates well with the severity of emphysema.
Pulmonary hypertensionThis develops late in COPD, at the time of severe gas exchange
abnormalities. Contributing factors include pulmonary arterial
constriction (as a result of hypoxia), endothelial dysfunction,
remodelling of the pulmonary arteries (smooth muscle
hypertrophy and hyperplasia), and destruction of the
pulmonary capillary bed. Structural changes in the pulmonary
arterioles result in persistent pulmonary hypertension and right
ventricular hypertrophy or enlargement and dysfunction (cor
pulmonale).
Systemic effects of COPDSystemic inflammation and skeletal muscle wasting contribute
to limiting the exercise capacity of patients and worsen the
prognosis irrespective of degree of airflow obstruction. Patients
also have an increased risk of cardiovascular disease, which is
associated with an increase in C reactive protein.
Pathophysiology of exacerbationsExacerbations are often associated with increased neutrophilic
inflammation and, in some mild exacerbations, increased
numbers of eosinophils. Exacerbations can be caused by
infection (bacterial or viral), air pollution, and changes in
ambient temperature.
In mild exacerbations, airflow obstruction is unchanged or
only slightly increased. Severe exacerbations are associated with
worsening of pulmonary gas exchange due to increased
inequality between ventilation and perfusion and subsequent
respiratory muscle fatigue. The worsening ventilation-perfusion
relation results from airway inflammation, oedema, mucous
hypersecretion, and bronchoconstriction. These reduce
ventilation and cause hypoxic vasoconstriction of pulmonary
arterioles, which in turn impairs perfusion.
Respiratory muscle fatigue and alveolar hypoventilation can
contribute to hypoxaemia, hypercapnia, and respiratory
acidosis, and lead to severe respiratory failure and death.
Hypoxia and respiratory acidosis can induce pulmonary
vasoconstriction, which increases the load on the right ventricle
and, together with renal and hormonal changes, results in
peripheral oedema.