Introduction
The first time I read about high-altitude illness was a handful of years ago while studying for my FP-C. I immediately (and naively) built a mental association between these conditions and places like Mount Everest and stored it in my “Makes No Difference to Me” folder. Since then, I’ve developed a habit for outdoor recreation and light versions of mountaineering, which led me to realize that altitude illness can occur in much less extreme conditions than I’d previously thought and that these pathophysiologies might actually be relevant to those of us not living in Nepal. My hope is that if you’re studying for your certification exams, have a soft spot for wilderness medicine, or even if you like to spend your time off outside, this discussion on high-altitude illness will provide some relevant and exciting information.
Background
The human body relies predominantly on aerobic (oxygen-facilitated) cellular respiration to meet energy demands. The end result of aerobic respiration is the production of adenosine triphosphate (ATP) via the interaction between oxygen molecules and a biological molecule called pyruvate. The body requires a specific pressure gradient to diffuse oxygen molecules across cell membranes and into the tissues where the reaction occurs to facilitate cellular respiration. The pressure needed depends on tissue type, capillary density, overall oxygen demand, and perfusion. As we know, an individual’s energy demands change based on factors such as physical exertion, hydration status, and overall health.
The amount of dissolved oxygen available within the tissues not only depends on the aforementioned intrinsic factors, but also on extrinsic environmental factors like barometric pressure, the temperature, humidity, and – drum roll, please – altitude. As altitude increases, atmospheric pressure decreases. Low atmospheric pressure causes the partial pressure of environmental oxygen to decrease, which simplistically means that although atmospheric oxygen concentration remains stable at 21%, fewer individual oxygen molecules are available in a fixed volume of air relative to the same volume at sea level. In other words, oxygen molecules become less condensed and more difficult to find.
For those of you who are visual learners, the diagram below may be helpful in understanding this concept. On the left-hand side, we have a hiker at sea level. The triangular area in front of them is (arbitrarily) the area from which they can draw air into their lungs. The small blue dots represent individual oxygen molecules; you can see many available within that space. Alternatively, the hiker to the right is at the top of Mount Shasta, which is 4,173m (14,180ft) above sea level. In the same amount of space, far fewer oxygen molecules are available for the hiker to breathe in.
The decreased partial pressure of oxygen (PO2) in the atmosphere also reduces driving pressure in the lungs, hindering gas exchange. Compromised gas exchange decreases PO2 in the tissues, limiting the oxygen available for cellular respiration. Over time, the body can adapt to these changes through a process known as acclimatization, which occurs primarily through hyperventilation and erythropoiesis. However, adults and children traveling to high altitudes are at risk for high-altitude illness without adequate acclimatization.
High Altitude Illness
There are three defined conditions under the altitude illness umbrella: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Acute mountain sickness and HACE are often discussed together, as the two have the same pathophysiologic process with varying degrees of severity. HAPE is a separate condition that may can occur alone or simultaneously with AMS or HACE.
The Wilderness Medical Society (WMS) stresses that a high index of suspicion should be applied to any traveler with relevant symptoms at high altitude, regardless of their reason for being there. Simply put, associating altitude illness with mountaineers exclusively may lead to a missed diagnosis in a businessman from Florida traveling to a mountaintop Colorado resort for a conference. Retrospective studies and expert experience suggest that unacclimatized travelers ascending to altitudes as low as ~2000m (6561ft) may be at risk for high-altitude illness.
Acute Mountain Sickness
Acute mountain sickness is the most common and least severe type of high-altitude illness. Regardless, early recognition is essential as AMS can progress to the point of becoming debilitating or precede HACE (less than 1%). It occurs in up to 25% of unacclimatized travelers above 3000m (9842ft), and incidence increases with altitude. Symptom onset is generally 6-12 hours after traveling to altitude but can occur within as little as 1-2 hours. Symptoms often resolve without intervention within 24-48 hours as the body acclimatizes.
AMS is a clinical diagnosis encompassing several non-specific symptoms, so recognition can be complex and often relies on relevant history taking and exclusion of differentials. The classic finding in AMS is a headache, sometimes creatively referred to as a high-altitude headache (HAH). Other symptoms include appetite loss, nausea, vomiting, insomnia, dizziness, and fatigue while at rest. Facial and/or extremity edema and retinal hemorrhage may also occur but are uncommon. Clinical diagnosis requires the presence of HAH and at least one other associated symptom.
Again, AMS typically resolves on its own without descent or treatment. However, severe or debilitating cases do require intervention. The most important step in resolving AMS is immediate descent. Target altitude will be variable, and descent should proceed until symptoms resolve. Supplemental oxygen can resolve symptoms over time without changes in altitude. Patients may also receive corticosteroids to treat vasogenic edema. The Wilderness Medical Society recommends 2mg of dexamethasone administered PO/IV/IM every 6 hours.
High Altitude Cerebral Edema
High-altitude cerebral edema is generally regarded as late- or end-stage acute mountain sickness. However, it is important to be aware that not all HACE cases are preceded by identifiable symptoms of AMS. HACE is the least common form of altitude sickness but is a severe, life-threatening emergency that can lead to death within 12-24 hours if untreated. Symptoms often appear after two days at altitudes >4300m (14,000 ft) but have been seen at lower altitudes and within shorter windows. HACE is a clinical diagnosis in the presence of AMS symptoms plus neurological symptoms.
The earliest sign of HACE is usually ataxia (loss of coordination). As cerebral edema worsens, patients exhibit lethargy, altered mental status, speech difficulties, seizures, and eventually coma and/or death. Like AMS, the curative treatment for HACE is immediate descent until symptom resolution which typically occurs after a 1-3000ft decrease in altitude. Supportive therapies should not delay descent and should be administered only while awaiting or concurrently with patient evacuation. Supportive treatment options outlined by the Wilderness Medical Society include one 8mg dose of dexamethasone followed by 4mg doses every 6 hours, supplemental oxygen to maintain SpO2 >90%, and if possible, portable hyperbaric therapy. The latter is equipment- and labor-intensive but may save a patient’s life in remote areas where evacuation is significantly delayed. Care providers should expect symptoms to return after the patient is removed from the hyperbaric chamber.
High Altitude Pulmonary Edema
High-altitude pulmonary edema (HAPE) may occur independently or simultaneously with AMS or HACE. In fact, HACE may occur secondarily to severe hypoxia caused by HAPE. HAPE is fairly uncommon but is the most fatal of the three defined altitude illness diagnoses, occurring in 1 out of 10,000 Colorado skiers and in ~1 per 100 climbers over 4300m (14,000ft) with a mortality rate of about 50%. Symptom onset usually occurs between day 1-5 at high altitude and progresses over 24-48 hours.
Early indications of HAPE are increased dyspnea with exertion and a dry cough, which rapidly progresses to dyspnea at rest and a productive cough. These primary symptoms may be accompanied by tachycardia, tachypnea, fever, low SpO2 relative to other travelers at the same altitude, and crackles. If left untreated, respiratory arrest and death can occur within 24 hours. Like other types of high altitude illness, immediate descent is the most important treatment measure. However, descent can be especially complicated with HAPE as physical exertion is likely to worsen symptoms. Supportive treatment guidelines from the WMS include 30mg of Nifedipine for reduction of pulmonary hypertension if evacuation is delayed or unavailable, supplemental oxygen, or portable hyperbaric chamber. There is limited data behind the efficacy of CPAP for treating HAPE, but it can be considered as an adjunctive treatment and may improve V/Q mismatch.
General Assessment
Thorough history taking is crucial when treating patients with possible high altitude illness. Beyond normal medical history, information such as a roughly estimated altitude change and the length of time over which the change occurred can aid in proper diagnosis. A detailed interview and physical exam will help you identify classic signs and symptoms of such as high altitude headache, dyspnea, abnormal fatigue, cough, etc. Tachycardia can be an incredibly nonspecific finding, especially in those who have been hiking/skiing/whatever, but may indicate an underlying problem if sustained while at rest. It is important to note that during acclimatization periods, it is not abnormal for SpO2 to drop to 88-91% due to decreased PO2.
Risk Factors and Prophylaxis
Rapid ascent (defined by the WMS as ascent >1500 ft per day for altitudes more than 3000m/10,000ft above sea level) is generally regarded as the biggest risk factor for high-altitude illness. Interestingly, the altitude at which the traveler sleeps is considered to be more important than the maximum altitude reached in a 24-hour period. This is thought to be related to the slow, periodic breathing pattern adopted by the body during sleep contributing to relative hypoventilation. Other risk factors include heavy physical exertion, alcohol consumption, dehydration, and existing co-morbidities that may affect acclimatization such as coronary artery disease, COPD, hypertension, obesity, and sickle cell trait/anemia. Predisposition is believed to have a genetic link, but no screening test currently exists. Severe high altitude illness occurs more frequently in young adult males, which is attributed to their relative likelihood to sustain heavy physical exertion for longer periods of time and to ignore early signs/symptoms. Finally, previous occurrence of high altitude illness is a significant predictor for recurrence.
The most effective prophylaxis for high-altitude illness is gradual ascent. Pharmacological prophylaxis does exist but is generally reserved for those with previous diagnoses of high-altitude illness or other high-risk individuals. Acetazolamide is the only drug clinically proven to facilitate acclimatization and does so by triggering bicarbonate diuresis and thereby inducing metabolic acidosis. To compensate, the body enters a state of hyperventilation and ultimately draws in more oxygen. Known side effects include increased urinary output and an increased risk of dehydration. While seemingly irrelevant for acute medical stabilization, knowing whether or not the patient has been treated with acetazolamide is an important part of history taking and might aid in building differential diagnoses. Other prophylactic medications include dexamethasone, nifedipine, and tadalafil, but none of these promote acclimatization and are generally only seen in patients with a history of HACE (dexamethasone) or HAPE (nifedipine & tadalafil) or those at exceptionally high risk, like search-and-rescue personnel who are airlifted to high altitudes.
Summary
Thanks to modern technology, unconditioned/inexperienced recreationists can travel from sea level to high altitude faster and easier than ever before. Medical personnel working in and traveling to high-altitude regions should keep a high index of suspicion and be able to recognize the signs of AMS, HACE, and HAPE.
Although rare, high-altitude illness can result in death if not appropriately recognized and treated.
High altitude illness is most common at altitudes >3000m (~10,000 ft), but has been diagnosed at much lower altitudes. Therefore, the Wilderness Medical Society stresses that altitudes <3000m should not exclude altitude illness from your differentials.
Immediate descent is the only curative treatment for severe high-altitude illnesses such as HACE and HAPE. Supportive treatments should never delay descent.
References
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