Abstract
Altitude is an environmental state of elevation > 760m (~2500 ft) above sea level, and has a continuous physiologic stressor of hypobaric hypoxia. Altitudes are subdivided into very high (3,500-5,500 m or ~11,500-18,000 ft), and extreme (> 5,500 m or > 18,000 ft). Forty million people peer year travel to altitudes >2500 m (~8000 ft) (Plant and Aref-Adib 2008), and many or more work in mines, military or border operations, etc. at high altitude. Clinical disorders are associated with acclimatization by the travelers, workers and migrants yet settlers illustrate adaptations to lifetime residence and populations with millennia of residence. Hypoxemia (FIO2 equivalent to ~17% O2 at 2500m, down to ~8% O2 at the summit of Everest) causes the physiologic responses and illnesses. Birthweights are generally lower and the rate of small-for-gestational-age babies and congenital heart defects are higher than in lowland populations (West 2012). With a hurried ascent, ~80% of lowlanders will report a transient headache (high altitude headache or HAH), and some will develop an acute high altitude illness: Acute Mountain Sickness (AMS), fewer will develop high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE) (Eide and Asplund 2012, West 2012). AMS and HAH are annoying and interfere with activity and work, however, HACE and HAPE can be fatal with mortality rates approaching 30% (Basnyat, Gertsch et al. 2003, Gallagher and Hackett 2004, Schoene 2008). Some residents at altitude exhibit chronic mountain sickness (CMS) and right ventricular hypertrophy, developing over months to years of residence at altitude. Cold air, and extreme exercise may also contribute to illness. Other environmental features may include UV radiation, trauma, and infections, which are not covered in this chapter. Finally, managing illness in a remote altitude location can be challenging as evacuation to a lower altitude as a primary treatment may be limited or not feasible.
Considerations of Exposure and Timecourse
Individual responses to hypobaric hypoxic may be conceptualized along a time continuum of interrelated phases: acute (immediate to 3-5 days in which acute illnesses present), sub-acute (over weeks leading towards acclimatization), chronic (years), and lifelong residence (Figure 1). The reduction in environmental oxygen as result of altitude exposure lowers the oxygen available for gas exchange in the lungs (PAO2), arterial oxygen (PaO2), and cellular oxidative phosphorylation for adenosine triphosphate (ATP) production.
Single cell and multicellular organisms have been exposed to oxygen since the origins of life; over the past 600 million years, oxygen levels have varied from as low as ~12% to as high as ~30% (Farquhar, Huiming et al. 2000, Stolpera, Revsbechb et al. 2010). All multicellular organisms have genetically encoded oxygen homeostasis pathways, meaning that there are interacting feedback control of cellular and organ system adaptations to oxygen availability and need. Archaic responses to hypoxia appeared several billion years ago, and elements continued, some with adaptations, to contribute to physiology and altitude fitness in modern living organisms, as well as the human ancestral tree. People moved to live at high altitudes in the past 100,000 years, and in three continents evolutionary forces have resulted in different strategies of adaptation in different indigenous populations (Beall 2007).
Altitude is an environmental state of elevation > 760m (~2500 ft) above sea level, and has a continuous physiologic stressor of hypobaric hypoxia. Altitudes are subdivided into very high (3,500-5,500 m or ~11,500-18,000 ft), and extreme (> 5,500 m or > 18,000 ft). Forty million people peer year travel to altitudes >2500 m (~8000 ft) (Plant and Aref-Adib 2008), and many or more work in mines, military or border operations, etc. at high altitude. Clinical disorders are associated with acclimatization by the travelers, workers and migrants yet settlers illustrate adaptations to lifetime residence and populations with millennia of residence. Hypoxemia (FIO2 equivalent to ~17% O2 at 2500m, down to ~8% O2 at the summit of Everest) causes the physiologic responses and illnesses. Birthweights are generally lower and the rate of small-for-gestational-age babies and congenital heart defects are higher than in lowland populations (West 2012). With a hurried ascent, ~80% of lowlanders will report a transient headache (high altitude headache or HAH), and some will develop an acute high altitude illness: Acute Mountain Sickness (AMS), fewer will develop high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE) (Eide and Asplund 2012, West 2012). AMS and HAH are annoying and interfere with activity and work, however, HACE and HAPE can be fatal with mortality rates approaching 30% (Basnyat, Gertsch et al. 2003, Gallagher and Hackett 2004, Schoene 2008). Some residents at altitude exhibit chronic mountain sickness (CMS) and right ventricular hypertrophy, developing over months to years of residence at altitude. Cold air, and extreme exercise may also contribute to illness. Other environmental features may include UV radiation, trauma, and infections, which are not covered in this chapter. Finally, managing illness in a remote altitude location can be challenging as evacuation to a lower altitude as a primary treatment may be limited or not feasible.
Considerations of Exposure and Timecourse
Individual responses to hypobaric hypoxic may be conceptualized along a time continuum of interrelated phases: acute (immediate to 3-5 days in which acute illnesses present), sub-acute (over weeks leading towards acclimatization), chronic (years), and lifelong residence (Figure 1). The reduction in environmental oxygen as result of altitude exposure lowers the oxygen available for gas exchange in the lungs (PAO2), arterial oxygen (PaO2), and cellular oxidative phosphorylation for adenosine triphosphate (ATP) production.
Single cell and multicellular organisms have been exposed to oxygen since the origins of life; over the past 600 million years, oxygen levels have varied from as low as ~12% to as high as ~30% (Farquhar, Huiming et al. 2000, Stolpera, Revsbechb et al. 2010). All multicellular organisms have genetically encoded oxygen homeostasis pathways, meaning that there are interacting feedback control of cellular and organ system adaptations to oxygen availability and need. Archaic responses to hypoxia appeared several billion years ago, and elements continued, some with adaptations, to contribute to physiology and altitude fitness in modern living organisms, as well as the human ancestral tree. People moved to live at high altitudes in the past 100,000 years, and in three continents evolutionary forces have resulted in different strategies of adaptation in different indigenous populations (Beall 2007).