Pathophysiology of hypoxaemic pulmonary vascular diseases

Abstract

Chronic alveolar hypoxia whether due to living at high altitude or to lung disorders, such as chronic obstructive lung disease (COLD), leads to development of pulmonary arterial hypertension (PAH). Sustained PAH is the principal cause of right ventricular hypertrophy (RVH) and failure. The majority of high altitude residents, in spite of having moderate PAH and hypoxemia with some degree of RVH, manage to live actively and productively through acclimatization. Although the processes of acclimatization decrease the magnitude of oxygen (O2) pressure drop at each step of the O2 tension cascade, O2 pressures in the tissue capillaries and mixed venous blood are lower than those at sea level. Since the cardiac output and O2 consumption in residents at high altitude have been shown to be comparable to those of sea level residents, the importance of adaptive changes at the tissue level to facilitate diffusion and utilization of O2 must be emphasized. In patients with COLD and hypoxaemia, most of the adaptive changes that have been shown to operate in high altitude residents do not occur, or have not been observed consistently. At present, only long-term O2 therapy has been shown to improve survival and lower pulmonary artery pressure (Ppa), but the changes of the latter are generally too modest to explain the former. It may be that the improved survival is mainly achieved by correcting hypoxaemia, thereby improving tissue oxygenation, rather than lowering Ppa.