Illnesses at high altitude

High-altitude illnesses have profound consequences on the health of many unsuspecting and otherwise healthy individuals who sojourn to high altitude for recreation and work. The clinical manifestations of high-altitude illnesses are secondary to the extravasation of fluid from the intravascular to extravascular space, especially in the brain and lungs. The most common of these illnesses, which can present as low as 2,000 m, is acute mountain sickness, which is usually self-limited but can progress to the more severe and potentially fatal entities of high-altitude cerebral edema and high-altitude pulmonary edema. This article will briefly review normal adaptation to high altitude and then more extensive reviews of the clinical presentations, prevention, and treatments of these potentially fatal conditions. Research on the mechanisms of these conditions will also be reviewed. A better understanding of these disorders by practitioners will lead to improved prevention and rational treatment for the increasing number of people visiting high-altitude areas around the globe. There will not be space for writing about high-altitude residents, medical conditions in low-altitude residents going to high altitude, or training for athletes at high altitude. These topics deserve another article.     

Kala-Azar at high altitude

Kala-azar or Visceral leishmaniasis (VL) is a disease of low altitude (approximately 500 meters mean sea level). In India, however cases have been reported from sub-Himalayan region (350-960 meters MSL) of Kumaon region of Uttaranchal. We present two patients of VL, natives of tribal district of Kinnnaur (2000-3000 meters MSL), Himachal Pradesh, who had never visited known endemic area for Leishmaniasis. These are probably first indigenous cases of VL being reported from an area situated at an altitude of 3000 meters and 2300 meters MSL.     

Immune suppression at high altitude

This paper is a review and interpretation of prior studies that have investigated the effects of hypoxia on immune function. A summary of current methods used to assess immune effector cell function in human beings is presented using in vitro models of mononuclear cell activation. Animal studies indicate that impaired host defenses against bacterial pathogens may be compromised, but that resistance to virus infections may remain intact. Data from human studies and animal models indicate that active immunization and B cell function are unimpaired, whereas T cell function is blunted following exposure to hypoxia. Mechanisms that may be responsible for alterations in normal immunoregulation are presented. The implications of altered immune function in subjects exposed to high altitude are discussed.     

Primary vasculitis at high altitude

We describe a 34-year-old mountaineer who presented with gut infarction from necrotizing vasculitis, probably due to Churg-Strauss syndrome. Subsequently, relapses occurred whenever he climbed to 4000 meters. We hypothesize that the effects of vasculitis were compounded by the physiological changes at high altitude. We suggest that patients with systemic vasculitis should be cautious about climbing and trekking at high altitude.     

Limits of respiration at high altitude

Under most conditions, the lungs compensate for the stresses of illness to ensure adequate acquisition of oxygen. Even with exposure to high altitude, the lungs' adaptations ensure that this process takes place. This process is challenged by global hypoxia, especially if there is impairment in the three processes needed for adequate tissue oxygenation: (1) intact ventilatory drive to breathe; (2) sufficient increase in alveolar ventilation, which is stimulated by that drive; and (3) intact gas exchange at the alveolar-capillary interface. This article reviews the mechanisms that make the study of high altitude relevant to patients who have heart or lung disease at low altitude.     

罗沙司他对急性高原低氧心脏功能适应的作用及其机制

目的 探讨PHD2抑制剂罗沙司他对模拟海拔5 000 m高原低氧环境小鼠心脏功能适应的作用及其机制。 方法 40只雄性C57BL/6J小鼠随机分为4组:常氧组、罗沙司他（100 mg/kg）+常氧组、低氧组、罗沙司他（100 mg/kg）+低氧组。低氧组小鼠置于ProOx-810L动物低压氧舱内饲养7 d;常氧组于常压常氧环境饲养。应用超声心动图、血常规、血生化综合评价高原低氧环境下小鼠心脏功能变化,Western Blotting分析HIF-1α和HIF-2α的表达水平。 结果 高原低氧暴露下,小鼠体质量增长显著减缓,罗沙司他对高原低氧暴露下的小鼠没有明显的毒副作用。高原低氧7 d后小鼠左室舒张末期内径（LVIDd）显著减小（P<0.05）,罗沙司他可增加LVIDd（P<0.05）,提高心脏适应能力。高原低氧导致红细胞生成素（EPO）明显升高,红细胞计数（RBC）、血红蛋白（Hb）和红细胞压积（Hct）增加（P<0.01）,该效应可被罗沙司他进一步增强[RBC（P<0.01）、Hb（P<0.01）和Hct（P<0.05）]。与常氧组比较,高原低氧可以显著增加小鼠心肌HIF-1α（P<0.05）、HIF-2α（P<0.01）和PHD2的蛋白表达水平（P<0.01）,此效应可被罗沙司他进一步增强[HIF-1α（P<0.01）、HIF-2α（P<0.01）和PHD2（P<0.05）]。低氧条件下心肌损伤相关的血清乳酸脱氢酶（LDH）水平显著增高（P<0.01）,罗沙司他可降低LDH水平,减轻低氧对心肌的损伤（P<0.01）。 结论 罗沙司他可通过抑制PHD2活性上调HIF-1α和HIF-2α的蛋白水平,同时减轻心肌损伤,进而促进高原低氧环境下小鼠心脏功能的适应。     

Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.

Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired.     

Gastrointestinal problems at high altitude.

Gastrointestinal (GI) problems at high altitude are commonplace. The manifestations differ considerably in short-term visitors, long-term residents and native highlanders. Ethnic food habits and social norms also play a role in causing GI dysfuntion. Symptoms like nausea and vomiting are common manifestations of acute mountain sickness and are seen in 81.4% short-term visitors like mountaineers. Anorexia is almost universal and has a mutifactorial causation including effect of hormones like leptin and cholecystokinin and also due to hypoxia itself. Dyspepsia and flatulence are other common symptoms. Diarrhoea, often related to poor hygiene and sanitation is also frequently seen especially among the short-term visitors. Peptic ulceration and upper gastro-intestinal haemorrhage are reported to be common in native highlanders in the' Peruvian Andes (9.6/10000 population per year) and also from Ladakh in India. A hig h incidence o f gastriccarcinoma is also reported, especially from Bolivia (138.2 cases per 10000 population per year). Megacolon and sigmoid volvulus are common lower GI disorders at high altitude. The latter accounted for 79% of all intestinal obstructions at a Bolivian hospital. Thrombosis of the portosystemic vascultature and splenic hematomas has been reported from India. Malnutrition is multifactorial and mainly due to hypoxia. Fat malabsorption is probably significant only at altitudes > 5000m. Neonatal hyperbilirubinemia was found to be four times more common in babies born at high altitude in Colorado than at sea level. Gall stones disease is common in Peruvian highlands. A high seroprevalence of antibodies to H pylori (95%) has been found in Ladakh but its correlation to the prevalence of upper gastro-intestinal disease has not been proven.     

Regulation of hepcidin expression at high altitude

Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis through the suppression of the iron regulatory hormone hepcidin. Hypoxia also suppresses hepcidin through a mechanism that is unknown. We measured iron indices and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high altitude (4340 m above sea level), with and without prior intravenous iron loading. Without prior iron loading, a rapid reduction in plasma hepcidin was observed that was almost complete by the second day at altitude. This occurred before any index of iron availability had changed. Prior iron loading delayed the decrease in hepcidin until after the transferrin saturation, but not the ferritin concentration, had normalized. We conclude that hepcidin suppression by the hypoxia of high altitude is not driven by a reduction in iron stores.