High altitude pulmonary edema is caused by stress failure of pulmonary capillaries

Int J Sports Med. 1992 Oct;13 Suppl 1:S54-8. doi: 10.1055/s-2007-1024594.


The pathogenesis of high altitude pulmonary edema (HAPE) is disputed. We propose that the mechanism is stress failure of pulmonary capillaries. The main features to be accounted for are the strong association with pulmonary hypertension, the high permeability characteristics of the edema, and the presence of inflammatory markers in the lung lavage fluid. When the capillary pressure is raised to about 40 mmHg in anesthetized rabbits, ultrastructural damage to the capillary walls is seen including breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. This results in a high permeability form of edema with the escape of high molecular weight proteins and blood cells into the alveolar spaces. In addition the basement membrane of the endothelial layer is frequently exposed, and we suggest that this highly reactive surface attracts and activates platelets and neutrophils. The result is the formation of small thrombi which are frequently seen in HAPE, and the presence of inflammatory markers such as leukotriene B4 and the complement fragment C5a in the lung lavage fluid. Hypoxic pulmonary vasoconstriction raises the pressure in some capillaries because the constriction is uneven. Since HAPE has its origin in the high pulmonary artery pressure, the objective of treatment should be to reduce the pressure by descent, administering oxygen, or giving drugs such as calcium channel blockers (e.g. nifedipine) which relax pulmonary vasoconstriction. Stress failure of pulmonary capillaries satisfactorily accounts for the features of HAPE.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Altitude Sickness / etiology*
  • Altitude Sickness / physiopathology
  • Animals
  • Basement Membrane / ultrastructure
  • Capillaries / physiology
  • Capillaries / ultrastructure
  • Capillary Permeability / physiology
  • Hypertension, Pulmonary / complications
  • Pulmonary Circulation / physiology*
  • Pulmonary Edema / etiology*
  • Pulmonary Edema / physiopathology
  • Pulmonary Wedge Pressure / physiology
  • Rabbits
  • Vasoconstriction / physiology