Altitude Hypoxia - Explained

What is Altitude Sickness?
Altitude sickness is a generic term for any condition directly related to the reduced oxygen levels of high altitude environments. The severity of these conditions varies from a minor headache to life threatening swelling of the brain and lungs. Because all altitude sickness is a result of low oxygen levels, treatment with supplemental oxygen or descent to low altitude rapidly reverses symptoms.

AMS Epidemiology
The two primary determinants of altitude sickness are the altitude at which one sleeps and the rate of ascent. Higher sleeping altitudes and faster rates of ascent are associated with increased incidence of altitude sickness. While in one study 22% of people visiting altitudes of 7,000 to 9,000 feet developed acute mountain sickness (AMS), 42% of those ascending above 10,000 feet got sick. Most ski resorts and mountain towns in the American west reside somewhere within this altitude range. This puts 30 million people at risk of developing acute mountain sickness each year.

Anyone flying directly to high altitudes or ascending very quickly is even more susceptible to altitude illness. Two thirds of climbers ascending Mount Rainier (14,411 feet) within two days of arrival at altitude developed acute mountain sickness. Prior exposure to high altitude mitigates the risk of altitude illness while residence below 3,000 feet exacerbates the risk. Fitness does not protect against altitude sickness.

Little is known about the interaction between altitude and underlying diseases. Hypertension, coronary artery disease, mild chronic obstructive pulmonary disease, diabetes, and pregnancy do not alter susceptibility to altitude sickness. Smoking and physical fitness are also unrelated to the incidence of altitude illness. Obesity and other cardiopulmonary diseases seem to increase susceptibility to altitude illness. People over 50 show lower incidence of altitude illness than all other age groups. Women are more susceptible to acute mountain sickness but less so to pulmonary edema. Additional large scale trials are needed to untangle the web linking common diseases to incidence of altitude sickness.

AMS Presentation
Acute mountain sickness is a set of nonspecific symptoms that typically develop in unacclimatized people ascending above 8,000 feet. Rapid ascent, overexertion, and the use of respiratory depressants can produce acute mountain sickness in partially acclimatized people. The defining characteristic of mountain sickness is a headache with fatigue, dizziness, anorexia, or nausea. Headache normally develops within 6 to 10 hours of arrival at altitude. It is typically a throbbing sensation located near the temple region. The feeling mimics an alcohol hangover. Afflicted persons have trouble sleeping and may feel a deep inner chill that is more intense than typical exposure to cold temperatures. Most people are pale, irritable, and weary.

AMS Pathophysiology
Decreased oxygen in the blood is the stimulus that starts the common path toward acclimatization or altitude sickness. In response to reduced oxygenation, the endothelium (the lining of blood vessels) releases a cascade of signaling molecules that cause dilation of blood vessels within the brain and increase blood brain barrier permeability. This change helps to maintain oxygen delivery to the brain but it also increases cerebral blood pressure. Activation of the sympathetic nervous system causes the kidneys to retain water. The end result of these changes is brain swelling. Brain swelling is a normal and universal response to altitude. Therefore, it is the degree of swelling that differentiates someone with AMS. The brain minimizes swelling by displacing excess fluid into the central canal of the spinal cord. People with a history of acute mountain sickness are less able to buffer the increased swelling due to smaller intracranial and intraspinal capacities. This continued swelling is likely responsible for most of the mountain sickness symptoms.

AMS Treatment
Treatment of acute mountain sickness should focus on increasing blood oxygen levels. When caught early, conservative measures rapidly reverse symptoms but if left untreated, the condition can be fatal. The first step is to remain at the same altitude until symptoms disappear. This gives the body time to adapt to the lower oxygen levels. Adaptation can be accelerated with a prescription drug called acetazolamide (Diamox). Ibuprofen and aspirin are the best treatments for headache, promethazine for nausea and vomiting. Alcohol and other respiratory depressants should be avoided to prevent dangerously low oxygen levels during sleep. If symptoms do not respond to rest and over-rhe-counter drugs, descent below the altitude where the symptoms began is advised. When descent is not possible, a portable hyperbaric chamber (Gamov bag) or supplemental oxygen should be used. If neither descent nor supplemental oxygen is a possibility, then treatment with dexamethasone is the best option.

AMS Prevention
The key to preventing AMS is a gradual ascent that allows for adequate acclimatization. Travel from sea level to 10,000 feet or more should include a rest day at a moderate altitude (5,000 to 6,000 feet). If this is not possible, then acetzolamide or dexamethasone prophylaxis should be considered. Combining the two drugs is more effective than either alone. Ginkgo biloba has also shown promise in accelerating acclimatization. Once above 8,000 feet sleeping altitude should be increased no more than 2,000 feet per day. In addition, a rest day with no change in sleeping altitude should be taken for every 4,000 foot gain.

HACE Presentation
Untreated acute mountain sickness develops into a potentially fatal condition called high altitude cerebral edema (HACE). Altered consciousness and loss of coordination (ataxia) are the hallmarks of this cerebral edema. Victims are confused, disoriented, and show impaired judgment. This renders them unable to care for their basic needs, such as eating and dressing themselves. Within a day of losing coordination, high altitude cerebral edema victims slip into a coma and death results without proper medical care.   

HAPE Epidemiology
The incidence of HAPE is primarily related to sleeping altitude and the rate of ascent. As with AMS, higher elevations and faster ascents are associated with increased susceptibility. Cold temperatures are an additional risk factor for HAPE development since they increase pulmonary artery pressures. HAPE typically develops during the second night at altitude and rarely after the fourth. It is more common among those climbing in extremely cold temperatures such as Denali (2%) or in those making rapid ascents to high altitude (15%) than in the more moderate elevations seen in the mountain communities of the American west (0.01%). Despite this relatively low incidence, HAPE is still the most common altitude related cause of death. A previous case of HAPE predisposes one to develop symptoms upon subsequent exposure. Studies suggest that 60% of previous HAPE victims will redevelop the condition upon rapid ascent.

HAPE Presentation
HAPE typically strikes young, fit men who quickly ascend from sea level to altitudes greater than 8,000 feet. The earliest signs are decreased exercise performance and increased recovery time. Victims feel overly fatigued and breathing becomes more difficult when walking uphill. A dry cough also develops but these nonspecific symptoms are often attributed to a bad day. The hallmarks of AMS (headache, anorexia, and lassitude) are present about half the time. Heart rates and ventilation typically increase while lips and nail beds turn blue. Difficulty breathing at rest and audible chest congestion signal a serious deterioration in one’s condition. The clinical diagnosis of HAPE is based on two findings. Arterial oxygen tensions of 30 to 40 mmHg suggest HAPE. Patchy lung infiltrates with a normal sized heart and full pulmonary arteries confirm the diagnosis.

HAPE Pathophysiology
As with AMS, the root cause of HAPE is decreased blood oxygenation. This activates the sympathetic nervous system and starts the pathological progression. Pulmonary artery pressures increase in all people traveling to altitude but HAPE victims show an exaggerated increase. This is likely a function of uneven pulmonary vasoconstriction that produces areas of relative strength and weakness. Constricted areas are protected against the increased pulmonary pressures while less constricted areas are susceptible to damage and subsequent leakage as pulmonary blood pressures increase. Patchy vasoconstriction could be due to individual anatomical differences or to loss of the vasoconstrictor response in severely hypoxic lung regions. If pulmonary pressures remain elevated, the lung vessels weaken and eventually rupture. This causes the lungs to swell and is responsible for breathing difficulties in HAPE victims.

HAPE Treatment
Treatment of HAPE is aimed at increasing blood oxygen levels and normalizing pulmonary artery pressures. Breathing supplemental oxygen or descent quickly reduces pulmonary artery pressures and stops capillary leakage. Exertion should be minimized during descent to avoid making symptoms worse. Immediate descent and hospitalization are indicated if high flow oxygen does not increase arterial oxygen saturation above 90% within 5 minutes. Otherwise, rest with 2 to 3 days of supplemental oxygen is sufficient to completely reverse the condition. If neither oxygen nor descent is a possibility, nifedipine is the treatment of choice but its effectiveness is much less pronounced. More work is needed to determine whether beta-agonists are effective for treating HAPE. With any of these treatments, the victim must be kept warm since cold temperatures increase pulmonary pressures and thus exacerbate the symptoms.

HAPE Prevention
As with AMS, a gradual ascent that allows for acclimatization is critical. Travel from sea level to 10,000 feet should include a rest day at a moderate altitude (5,000 to 6,000 feet). If this is not possible, then nifedipine, acetzolamide, or dexamethasone prophylaxis should be considered.  Once above 8,000 feet sleeping altitude should be increased no more than 2,000 feet per day. In addition, a rest day with no change in sleeping altitude should be taken for every 4,000 foot gain in elevation.
Previous HAPE victims should ascend more slowly and descend at the first sign of HAPE.  Nifedipine, acetzolamide, or dexamethasone prophylaxis is strongly recommended. Anyone experiencing repeated HAPE or HAPE below 2,500 feet should consult a doctor to rule out intracardiac or intrapulmonary shunts, preexisting pulmonary hypertension, mitral valve stenosis, and other conditions that increase pulmonary vascular resistance.  

Reentry Pulmonary Edema
HAPE develops in some long term high altitude residents after they return from a trip at low altitude. This is called reentry pulmonary edema. High altitude residents returning to altitude are more likely to develop pulmonary edema than low altitude residents coming to altitude. As with any altitude sickness, a faster ascent leads to more problems. Reentry HAPE is most common in places, such as Peru, where rapid travel from low to very high altitude is possible.