Update: High altitude pulmonary edema
Recent high altitude studies with pulmonary artery (PA) catheterization and broncho-alveolar lavage (BAL) in early high altitude pulmonary edema(HAPE) have increased our understanding of the pathogenetic sequence in HAPE. High preceding PA and pulmonary capillary pressures lead to a noninflammatory leak of the alveolar-capillary barrier with egress of red cells, plasma proteins and fluid into the alveolar space. The mechanisms accounting for an increased capillary pressure remain speculative. The concept that hypoxic pulmonary vasoconstriction (HPV) is uneven so that regions with less vasoconstriction are over-perfused and become edematous remains compelling but unproved. Also uncertain is the role and extent of pulmonary venoconstriction. With disruption of the normal alveolar-capillary barrier, some individuals may later develop a secondary inflammatory reaction. A high incidence of preceding or concurrent respiratory infection in children with HAPE has been used to support a causative role of inflammation in HAPE. However, alternatively even mild HPV may simply lower the threshold at which inflammation-mediated increases in alveolar capillary permeability cause significant fluid flux into the lung. Other major questions to be addressed in future research are: 1.) What is the mechanism of exaggerated hypoxic pulmonary vasoconstriction? Is there a link to primary pulmonary hypertension? Several observations suggest that susceptibility to HAPE is associated with endothelial dysfunction in pulmonary vessels. This has not yet been studied adequately. 2.) What is the nature of the leak? Is there structural damage, i. e. stress failure, or does stretch cause opening of pores? 3.) What is the pathophysiologic significance of a decreased sodium and water clearance across alveolar epithelial cells in hypoxia? 4.) What is the role of exercise? Do HAPE-susceptible individuals develop pulmonary edema when exposed to hypoxia without exercise? Answers to these questions will increase our understanding of the pathophysiology of HAPE and also better focus research on the genetic basis of susceptibility to HAPE.
Keywordsgoals for research pathophysiology inflammation hydrostatic edema capillary pressure
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- 6.Bartsch P, Haeberli A, Nanzer A, et al. High altitude pulmonary edema: Blood coagulation. In: Sutton JR, Houston CS, and Coates G (eds.), Hypoxia and molecular medicine. Burlington: Queen City Printers Inc, 1993, pp. 252–258.Google Scholar
- 8.Busch T, Bartsch P, Pappert D, Grünig E, Elser H, Falke KJ, and Swenson ER. Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high altitude pulmonary edema. Am J Respir Cht Care Med 163: 368–373, 2001.Google Scholar
- 14.Frank JA, Wang Y, Osorio O, and Mathhay MA. β-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J Appl Physiol S9: 1255–1265,2000.Google Scholar
- 28.Hultgren NH. High altitude pulmonary edema. Lung Water and Solute Exchange: 237–269, 1978.Google Scholar
- 39.Ritter M, Jenni R, Maggiorini M, Grimm J, and Oelz O. Abnormal left ventricular diastolic filling patterns in acute hypoxic pulmonary hypertension at high altitude. Am J Noninvas Cardiol 7: 33–38, 1993.Google Scholar
- 42.Roos CM, Rich GF, Uncles DR, Daugherty MO, and Frank DU. Site of vasodilatation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs. J Appl Physiol 11: 51–57, 1994.Google Scholar
- 47.Sugita M, Ferraro P, Yamagata T, Poirier C, and Berthiaume Y. Effects of 3-hour preservation and reperfusion on transalveolar fluid transport mechanism in a canine single lung transplant model (Abstract). Am J Respir Crit Care Med 161: A415, 2000.Google Scholar
- 48.Swenson ER, Mongovin S, Gibbs S, Maggiorini M, Greve I, Mairbäurl H, and Bärtsch P. Stress failure in high altitude pulmonary edema (HAPE) (abstract). Am J Resp Crit Care Med 161: A418, 2000.Google Scholar
- 51.West JB, Colice GL, Lee Y-J, Namba Y, Kurdak SS, Fu Z, Ou L-C, and Mathieu-Costello O. Pathogenesis of high-altitude pulmonary oedema: Direct evidence of stress failure of pulmonary capillaries. Eur RespirJ 8: 523–529, 1995.Google Scholar