HAPE is a non-cardiogenic pulmonary edema triggered by exaggerated hypoxic pulmonary vasoconstriction (HPV) at altitudes above 2500 metres. Uneven vasoconstriction creates regional overperfusion of unprotected capillary beds, leading to stress failure of pulmonary capillaries. The resulting high-permeability leak fills alveoli with protein-rich, hemorrhagic edema fluid. Impaired alveolar sodium transport reduces fluid reabsorption from the alveolar space. Inflammatory mediators are secondary to the mechanical capillary injury, distinguishing HAPE from other forms of ARDS. Individuals with a brisk HPV response or reduced pulmonary vascular bed (prior pneumonectomy, congenital absence of pulmonary artery) are particularly susceptible.