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High-altitude gastric disorders: insights into maladaptation pathophysiological mechanisms, disease spectrum and
Huihui Shang1, Rong Zhang2, Youbang Xie3
1Department of Health Medicine, The 991st Hospital of the Joint Logistic Support Force of the People's Liberation Army, Xiangyang, Hubei, China.
Abstract:
High-altitude environments are characterized by hypoxia (low oxygen levels), low atmospheric pressure, and intense ultraviolet radiation. Researchers have identified these factors as key contributors to gastric damage. Environmental stressors compromise the gastric mucosal barrier by causing direct damage, oxidative stress, inflammatory responses, and tight junction disruption. Furthermore, gastrointestinal hormones and motility dysfunction, neuroendocrine disturbances, and gut microbiota dysbiosis increase intestinal permeability and immune imbalance. These factors can trigger gastric diseases and multi-organ dysfunction. This article highlights the role of bidirectional regulation of the HIF signaling pathway and its metabolic reprogramming cascades in high-altitude gastric diseases. While previous reviews have primarily focused on intestinal damage, this review centers on the stomach, elucidating the pathophysiological mechanisms of gastric damage caused by failed hypoxia acclimatization to high altitudes. It covers the progression from acute damage to chronic lesions (e.g., gastric damage associated with high-altitude polycythemia (HAPC)) and the pathophysiological mechanisms of malignant transformation. It also discusses associated diseases such as acute gastric mucosal injury, peptic ulcers (which carry an increased risk of bleeding and perforation), and an elevated prevalence of gastroesophageal reflux disease (GERD). Long-term exposure may also increase the risk of gastric cancer. Prevention and standardized treatment of high-altitude gastric disorders are of critical importance.
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