The different pathogenic mechanisms discussed above produce the pathological changes, which, in turn, give rise to the following physiological abnormalities in COPD: mucous hypersecretion and cilliary dysfunction, airflow limitation and hyperinflation, gas exchange abnormalities, pulmonary hypertension, and systemic effects.

Mucous Hypersecretion and Cilliary Dysfunction

These are typically the first physiological abnormalities in COPD.

The former is due to stimulated secretion from enlarged mucous glands. The latter due to squamous metaplasia of epithelial cells.

Airflow Limitation And Hyperinflation

Expiratory (largely irreversible) airflow limitation is the physiological hallmark of COPD.

The major site of the airflow limitation is in the smaller conducting airways <2 mm in diameter and is mainly due to airway remodelling (fibrosis and narrowing) [9, 26].

Other factors that also contribute include loss of elastic recoil (due to destruction of alveolar walls), destruction of alveolar support (alveolar attachments) [12], accumulation of inflammatory cells, mucous and plasma exudate in the bronchi, and smooth muscle contraction and dynamic hyperinflation during exercise. The latter is one of the major contributors to exercise limitation in these patients [27].

Airflow limitation in COPD is best measured by spirometry, which is key to the diagnosis of the disease.

Gas Exchange Abnormalities

These occur in advanced disease and are characterised by arterial hypoxaemia with or without hypercapnia.

An abnormal distribution of ventilation-perfusion ratios (due in turn to the anatomical alterations described above) is the main mechanism of abnormal gas exchange in COPD [28].

An abnormal diffusing capacity of carbon monoxide per litre of alveolar volume correlates well with the severity of the emphysema [29].

Pulmonary Hypertension

This occurs late in the course of COPD, normally after the development of severe gas exchange abnormalities.

Factors contributing to pulmonary hypertension in COPD include vasoconstriction (mostly of hypoxic origin), endothelial dysfunction, remodelling of pulmonary arteries and destruction of the pulmonary capillary bed. This combination of events may eventually lead to right ventricular hypertrophy and dysfunction (cor pulmonale) [19, 30].

Systemic Effects

COPD is associated with extrapulmonary effects, including systemic inflammation and skeletal muscle wasting. These systemic effects contribute to limit the exercise capacity of these patients and to worsen prognosis, independent of their pulmonary function [31].