The High Altitude Sickness - Epidemiology, Pathophysiology, Symptoms, Prevention and Treatment

Abstract

High altitude sickness encompasses three overlapping syndromes—acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE)—triggered when ascent outpaces acclimatization to hypobaric hypoxia. With more than 100 million people ascending above 2,500 m annually, these conditions represent a significant yet largely preventable burden in travel medicine. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, clinical presentation, prevention, and treatment of acute altitude illness. Relevant literature was identified through PubMed/MEDLINE and Google Scholar, prioritizing recent authoritative syntheses, Cochrane systematic reviews of preventive interventions, consensus diagnostic statements, and primary mechanistic studies. No formal quality scoring or meta-analysis was performed. AMS is the most common form, with prevalence ranging from 15% to 80% depending on absolute altitude, ascent rate, and individual susceptibility; prior history is the strongest predictor. HACE and HAPE are rarer but potentially fatal, the latter being the leading cause of altitude-related death. All forms originate from hypobaric hypoxia: the cerebral syndromes reflect hypoxic vasodilation and blood-brain barrier disruption with vasogenic edema, whereas HAPE arises from exaggerated, heterogeneous hypoxic pulmonary vasoconstriction causing capillary stress failure. Emerging research highlights roles for HIF and VEGF signaling, oxidative stress, and microglial activation. Prevention rests on graded ascent—particularly controlling nightly gains in sleeping altitude—supplemented by acetazolamide, dexamethasone, or nifedipine in higher-risk individuals. Treatment is anchored by descent, complemented by oxygen and targeted pharmacotherapy. Early recognition of ataxia and resting dyspnea remains the single most important determinant of survival.