High-Altitude Pulmonary Vascular Diseases

Abstract

More than 140 million people permanently reside in high-altitude regions of Asia, South America, North America, and Africa. Another 40 million people travel to these places annually for occupational and recreational reasons, and are thus exposed to the low ambient partial pressure of oxygen. This review will focus on the pulmonary circulatory responses to acute and chronic high-altitude hypoxia, and the various expressions of maladaptation and disease arising from acute pulmonary vasoconstriction and subsequent remodeling of the vasculature when the hypoxic exposure continues. These unique conditions include high-altitude pulmonary edema, high-altitude pulmonary hypertension, subacute mountain sickness, and chronic mountain sickness.

Long‐term chronic intermittent hypoxia: a particular form of chronic high‐altitude pulmonary hypertension

“…4 This condition is observed in subjects who are chronically exposed to hypobaric hypoxia due to hypoxic pulmonary vasoconstriction and subsequent vascular structural remodeling. 3,12,13 Epidemiology of HAPE and HAPH HAPE is a high-altitude disorder which occurs during the first day of acute exposure to hypoxia. It is a consequence of acute pulmonary hypertension along with impaired alveolar clearance, which manifests as uneven pulmonary patches of pulmonary edema that, if not treated, can lead to death.…”

“…The clinical presentation of individuals suffering from HAPH is not different from that of individuals suffering from any other type of pulmonary arterial hypertension: its features range from asymptomatic in some individuals to exertional dyspnea in the early stages, followed by general fatigue, intolerance to exercise, chest pain, mental alterations, dizziness, syncope, and ultimately cor pulmonale. 12,17,19,26 Different mPAPs are found depending on altitude, and individual variations should be considered 3 ; in addition, the potential contributory role of sleep apnea in HAPH, either central or obstructive, cannot be ignored, since the former is rather common and the latter is aggravated at high altitude. 27 Functional capacity impairments (determined according to the New York Heart Association (NYHA) Functional Classification criteria and 28 the six-minute walking test) are observed in people with HAPH, but there is still some disagreement.…”

“…Concurrently, there is a reduction in the diffusive barriers between the lungs and tissue capillaries. 12 Moreover, at the cellular level, there are changes in capillary and mitochondrial density as well as metabolic efficiency. [38][39][40] Most of these responses are elicited by the stabilization of hypoxia-inducible factors (HIFs).…”

“…7,48,49 As has commonly been observed in the clinical setting, most responses are physiologically useful; however, in some cases, these beneficial responses are excessive and can be the source of a pathological response. The main examples of such cases are exaggerated polycythemia or CMS under chronic hypoxia and HPV leading to HAPH 12 (Fig. 1).…”

“… 4 This condition is observed in subjects who are chronically exposed to hypobaric hypoxia due to hypoxic pulmonary vasoconstriction and subsequent vascular structural remodeling. 3 , 12 , 13 …”