Physiology
High altitude is considered to be heights between 1,500 and 3,500 m (4,921 to 11,483 feet (ft)), very high altitude is between 3,500 and 5,500 m (11,483 to 18,045 ft) and extreme altitude is greater than 5,500 m (18,045 ft) [1]. No matter how high you climb, the percentage of oxygen in the air remains roughly 21%. What changes as you climb is the density of the air molecules. At sea level, the air molecules are densely packed together from the weight of the air above them. As you climb, there is less pressure on the air molecules and so they are more dispersed. This air pressure is called barometric pressure or atmospheric pressure.
Air molecules that are more dispersed translate into fewer molecules taken in with each breath. Thus, a breath at 3,500 m contains about 60% as much oxygen as at sea level. The concentration of the oxygen is still 21%, but there are fewer oxygen molecules available. At 5,000 m (the altitude of Everest Base Camp), each breath has about half the oxygen available at sea level and at 8,848 m (Mount Everest summit), each breath takes in about one-third as much as at sea level. As the level of inhaled oxygen decreases, the body responds with altitude acclimatization.
Many physiological changes occur as the human body is subjected to the stress of high altitude. Erythropoietin is released from the kidneys once hypoxic conditions are sensed. This hormone stimulates bone marrow to increase red blood cell production. Within 2 hours of ascent, erythropoietin can be measured [2]. Within 4–5 days, new red blood cells are in circulation. Over a period of weeks to months, red blood cell mass increases in proportion to the degree of hypoxia, allowing for an improved oxygen uptake and delivery.
The lungs respond by utilizing normally unused portions. As the human body ascends to altitude, breathing is deeper and faster. Sensing a fall in pO2, the carotid bodies located within the carotid artery signal the central respiratory center in the medulla to increase the rate of pulmonary ventilation. Increased ventilation decreases alveolar and blood concentrations of carbon dioxide, while trying to maintain a normal oxygen concentration. As carbon dioxide continues to fall, pH becomes alkalotic. This alkalosis will reach a maximum threshold in which the central respiratory center limits further increase in ventilation so as to prevent severe alkalosis.
Within 24–48 hours of persistent alkalosis, the kidneys begin to excrete bicarbonate in the urine. Bicarbonate diuresis reverses alkalosis and returns the body’s pH to a normal physiological level. This adjusted pH stimulates the cycle to begin again as the ventilatory response again increases, resulting in alkalosis, which prompts the kidneys to excrete bicarbonate. Ventilatory compensation reaches a maximum after 4–7 days at the same altitude [3]. For each increase in altitude, the cycle of pulmonary-renal events recurs.
Other physiological changes at altitude include dehydration, edema, and periodic breathing. The lower humidity and air pressure cause the skin and lungs to lose water through evaporation at a faster rate, resulting in dehydration if meticulous attention is not paid to fluid intake. As water is lost, the body tries to maintain fluid balances by minimizing the excretion of water and sodium. Fluid leaks from capillaries into tissues, causing edema. Most noticeable in the face, hands, and feet, high altitude edema seems to affect women more commonly than men. The edema usually worsens with ascent and resolves with descent. Periodic breathing is common at high altitude. As the body attempts to regulate oxygen and carbon dioxide, breathing may fall into a cycle of decreased breathing, followed by complete apnea for 3–15 seconds. Once the paCO2 has built up again, breathing resumes.
The circulatory system responds to altitude with an increase in sympathetic activity, which causes a mild increase in blood pressure. After 24 hours, bicarbonate diuresis begins to decrease pH as well as stroke volume. Fortunately, this decrease in blood volume rarely causes myocardial strain as echocardiographic studies demonstrate a lack of myocardial stress with a decreased stroke volume [4]. Additionally, with acclimatization, resting heart rate returns to normal, except at extreme altitudes. Paradoxical pulmonary hypoxic vasoconstriction shunts blood away from poorly aerated, injured, or diseased lung alveoli to healthy alveoli so as to maintain adequate oxygenation. When exposed to a high altitude environment, this phenomenon occurs throughout the lungs, leading to complete pulmonary vasoconstriction and mild pulmonary hypertension which is usually managed well by the body. Cerebral blood flow depends on the overall balance of hypoxic vasodilation and hypocapnia-induced vasoconstriction. This balance is rigorously tested in high altitude hypoxic environments. One study demonstrated a cerebral blood flow increase of 24% on abrupt ascent to 3,810 m and subsequent return to normal over 3–5 days [5]. With severe hypoxia at high altitude, this delicate autoregulation of vasodilation and vasoconstriction becomes impaired, leading to several pathophysiological states discussed below.
Acute mountain sickness
Pathophysiology
Acute mountain sickness (AMS) is the most common of the attitude illnesses. AMS has been described in altitudes as low as 2,500–2 700 m [1]. We do not fully understand the exact pathophysiology of AMS but it is thought that genetics may play a role. The pathophysiology of AMS includes minor hypoventilation, interstitial edema, and increased sympathetic drive [6,7].
Several theories regarding the cause of AMS are circulating. One theory suggests that AMS results from mild brain swelling. A study using brain imaging of patients with moderate-to-severe AMS showing white matter edema with an elevated intracranial pressure (ICP) supports this concept [8]. However, those with mild AMS do not have cerebral edema [9–14]. Hence, this hypothesis only partially explains AMS. Other investigators have postulated that an increase in ICP causes AMS. Although some studies demonstrate an increase of ICP in AMS using optic nerve sheath diameter and lumbar puncture pressure, other studies demonstrate no change in pressure [14–17]. Thus, evidence that ICP is elevated in mild AMS remains limited. A third hypothesis, known as the tight fit hypothesis, theorizes that persons with smaller intracranial and intraspinal cerebral spinal fluid capacity are predisposed to develop AMS, because they cannot tolerate brain swelling compared to those who have more room to accommodate [18].
Symptoms
Most unacclimatized persons traveling to high altitude experience a mild form of AMS. The most common complaint is headache followed by fatigue, anorexia, and dizziness [14,19]. Headache is described as throbbing, bitemporal, and worse at night. Additionally, Valsalva maneuvers or bending over exacerbate the headache. Anorexia and nausea are common. Frequent waking from sleep, periodic breathing, and a feeling of suffocation are exaggerated in patients with AMS. Symptoms are often described as similar to an alcohol hangover [1]. Additionally, persons with AMS may complain of a deep inner chill, vomiting, dyspnea on exertion (although pulmonary symptoms vary widely), and lassitude. Symptoms typically begin within 24–48 hours of reaching altitude and resolve in 3–5 days at the same altitude.
There are no pathognomonic physical exam findings associated with AMS. Pulse may range from bradycardia to tachycardia [7,14,20]. Blood pressure may range from normal to postural hypotension. Rales may be present and oxygen saturation changes correlate poorly in the diagnosis of AMS [21]. Fundoscopic examination may reveal venous dilation as well as retinal hemorrhages, but are not diagnostic. Finally, a decrease in urine output demonstrating poor alkalotic diuresis may also be an early finding of AMS. It is always key to remember that there are no neurological deficits associated with AMS [14,22–25].
