Abstract
High-altitude pulmonary oedema (HAPE) is a potentially fatal altitude illness affecting individuals within 2–4 days of rapid ascent to altitudes above 3,000 m. Although a minority of high-altitude travellers develop HAPE 1, there is some suggestion that many develop subclinical fluid accumulation without overt alveolar flooding 2. The inciting mechanism of the injury to the lung in HAPE still generates some controversy. However, there is an ever-growing body of evidence that mechanical injury to the pulmonary capillaries induced by high transmural pressures starts a cascade of events that ultimately results in the development of HAPE. This injury, termed “stress failure” described by West et al. 3, refers to mechanically induced breaks in the blood-gas barrier, and these have been suggested to be important the pathophysiology of a number of human diseases 4. In animals, when pulmonary capillaries are subjected to increased transmural pressure, ultrastructural changes consisting of discrete areas of damage to the blood–gas barrier, with rupture of the capillary endothelium, extracellular matrix and the alveolar epithelium, interspersed with large areas of structurally intact blood–gas barrier are observed 5. Accompanying this is increased permeability of the lung to protein and red blood cells, as measured by increased concentrations in bronchoalveolar lavage fluid 6. Leukotriene (LT)B4 concentration is also increased in bronchoalveolar lavage fluid 6, perhaps representing cellular activation by exposed basement membrane. Similar findings are observed in some humans following maximal exercise in normoxia 7 where bronchoalveolar lavage fluid contains increased concentrations of red cells, protein and LTB4 thought to result from high pulmonary capillary pressures. In both of these instances, the blood–gas barrier retains sieving function for large molecular weight proteins 6. However, in established HAPE, permeability to macromolecules is increased 8, and an inflammatory response of the lung to …
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