Severe pulmonary hypertension increases right ventricular afterload and eventually leads to the clinical syndrome of right heart failure with systemic congestion and inability to adapt right ventricular output to peripheral demand at exercise. Many patients with advanced COPD present with ankle edema but normal right atrial pressures (at rest). This apparent paradox has stimulated speculation that edema in COPD might be a renal rather than a right ventricular problem .
However, it is now better realized that edema in COPD is likely to be initially caused by repeated stretching of the right atrium from increased right ventricular diastolic pressures at exercise or conceivably with oxygen desaturation during sleep, causing increased sympathetic nervous system tone and activation of the renin-angiotensin-aldosterone system, with resultant renal salt and water retention.
Renal salt and water retention may be aggravated by hypercapnia, which directly increases proximal tubular reabsorption of sodium, but also activates the sympathetic nervous system and the renin-angiotensin-aldosterone system, which causes additional distal tubular sodium reabsorption through amiloride-sensitive sodium channels.
In summary, and as summarized in , systemic congestion in COPD is caused by right heart failure, involving mechanisms that are very similar to those accounting for systemic and pulmonary congestion in left heart failure, but with an important additional contribution of hypercapnia .