From the Guidelines
Pathophysiology of Acute Mountain Sickness (AMS)
The pathophysiology of acute mountain sickness (AMS) involves a complex interplay of hypoxia, inflammation, and vascular dysfunction, triggered by rapid ascent to high altitudes 1.
- Hypoxia leads to increased pulmonary artery pressure, causing fluid leakage into the lungs and brain, resulting in symptoms such as headache, nausea, and fatigue.
- The condition is thought to be mediated by the release of various cytokines and chemokines, which contribute to the development of high-altitude pulmonary edema and high-altitude cerebral edema.
- The activation and sensitisation of the trigemino-vascular system by both mechanical and chemical factors may cause headaches, and in rare cases, high-altitude cerebral edema may result from dysfunction or disruption of the blood–brain barrier 1.
- Sympathetic activation accompanied by a rise in heart rate and cardiac output, and pulmonary vasoconstriction and elevated pulmonary arterial pressure (PAP) are also key physiological responses to acute high-altitude exposure 1. The risk of AMS steeply rises when unacclimatised individuals are exposed to increasing altitude, affecting more than 50% of them at altitudes above 4500 m 1.
Key Factors
- Adequate acclimatisation and slow ascent speed are crucial in preventing AMS 1.
- Preventive medication, such as acetazolamide, can also help alleviate symptoms and prevent progression of the disease 1.
- Sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women 1.
From the Research
Pathophysiology of Acute Mountain Sickness (AMS)
The pathophysiology of AMS is complex and involves multiple factors, including:
- Hypoxia-induced changes in cerebral blood volume and inflammation 2, 3, 4
- Disruption of the blood-brain barrier, leading to increased permeability and edema 3, 4
- Activation of the trigeminovascular system, contributing to headache and other symptoms 4
- Increased levels of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-8 2
- Elevated levels of vascular endothelial growth factor (VEGF), which may play a role in the development of AMS 2, 5
- Changes in hypoxia-related hormones, including HIF-1, Endothelin-1, and Orexin-A 5
Key Factors Contributing to AMS
Some key factors that contribute to the development of AMS include:
- Rapid ascent to high altitude 6, 4
- Individual susceptibility, which may be influenced by genetic factors, physical condition, and pre-existing medical conditions 6, 4
- Inadequate acclimatization, which can lead to increased risk of AMS 6, 4
- High-altitude exposure, which can trigger a range of physiological responses, including changes in blood oxygen saturation, heart rate, and blood pressure 5, 4
Molecular Mechanisms Underlying AMS
The molecular mechanisms underlying AMS are not fully understood, but research suggests that:
- Hypoxia-inducible factor-1 (HIF-1) plays a key role in the response to hypoxia, regulating the expression of genes involved in angiogenesis, inflammation, and metabolism 5
- VEGF is involved in the regulation of angiogenesis and may contribute to the development of AMS 2, 5
- Other hypoxia-related hormones, such as Endothelin-1 and Orexin-A, may also play a role in the pathophysiology of AMS 5