This comprehensive review of the biology, history and physiology of high elevation starts with a fatal hot air balloon ride that happened in 1875. The passengers went past 8,000 meters, or over 26,000 feet and lost consciousness. The balloon failed and fell to the ground but not until after the altitude related hypoxia killed two out of the three passengers. Currently the legal limit in many parts of the world for how high a hot air balloon can fly is around 3,000 feet.

The pressure the atmosphere exerts on our bodies, the barometric pressure, that is the pressure of all gasses including oxygen, decreases as we go higher in altitude. As seen in the graph below, the higher you go, the less barometric pressure. This leads to a decrease in the partial pressure of oxygen. The percentage of air that contains oxygen is 21% at any height. However, the oxygen molecules are less dense higher up so with every breath our bloodstream gets less oxygen which is called hypoxemia. Our tissues then get less oxygen as well which is called hypoxia.

Our bodies go through a process called acclimatization to help us adjust to these changes at altitude. The first change we see is increased ventilation. The decrease in oxygen stimulates chemoreceptors in our aorta and carotid which then regulate the depth and rate of our breathing, making our breaths deeper and faster to try and get more oxygen in. This involuntary action is called the hypoxic ventilatory response (HVR). There is an inverse relationship between carbon dioxide and oxygen in the alveoli of our lungs. Since we breathe deeper and faster at altitude we breathe out more carbon dioxide, hence increasing the partial pressure of oxygen. Discussions about carbon dioxide, how it affects the kidneys, what happens to hemoglobin, cardiac output, are very helpful for a deeper understanding of what happens in the body at altitude.

There are three major illnesses that can occur when our bodies do not go through acclimatization properly: acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). AMS is the most common. It is seen within 4-12 hours of ascending to altitudes higher than 2500 meters. A headache is needed to diagnose AMS in most scoring systems used for diagnosis, other symptoms include GI symptoms, dizziness, fatigue, and sleep disturbances. HACE is a progression of these symptoms. It is dangerous since as the name implies it is cerebral edema or swelling. There may be signs of altered mental status, ataxia, and can progress to coma and death within 24 hours. According to the blog there is not much understanding/consensus of which part of the acclimatization process goes wrong to cause these potentially fatal  outcomes, nor is there a clear answer about whether you can have one without the other. The onset of HAPE is slower, occurring between 1-5 days, rarely after a week. There are more pulmonary symptoms as the name suggests such as excessive shortness of breath, chest tightness, cough, sputum production. The podcast discusses in detail theories about the causes of HAPE.

The history of altitude sickness goes back to Ancient Chinese, Greek and Roman medical texts. “The ancients also observed that the rarity of the air on the summit of Olympus was such that those who ascended it were obligated to carry sponges moistened with vinegar and water and to apply them now and then to their nostrils as the air was not dense enough for their respiration.” This suggested they believed there was no water vapor in the air at high altitudes making it difficult to breathe. Some other texts mentioned “headache mountains” suggesting the naming of mountains based on side effects they experienced at these high altitudes.

The podcast hosts reviewed landmark experiments showing the effects of hypoxia on people and animals. Robert Boyle and Robert Hooke’s experiments using an air pump to investigate an animal’s response to different air pressures. Results showed that survival was shortened at lower pressures. Hook also created a decompression chamber so humans could test low pressure effects. He personally sat in there for 15 minutes at 570 torr, the equivalent of 7,800 ft (2400 m), and experienced some hearing loss. Anton Lavoisier performed another experiment, he compared blood that passed through the lungs with fresh air with venous blood. Freshly ventilated blood was bright red and venous blood was darker red, suggesting something changes in our blood when having contact with fresh air. Another scientist, Mayow, put a mouse on a stool inside of a bowl of water then covered it with a glass bell, creating a sealed environment. The same thing was done with a candle.

Results were that the water levels inside the bell rose as the animal breathed or as the candle burned, suggesting the mouse or the flame was consuming some part of the air which the water came in to fill. He demonstrated there must be at least two different components in air, one of them being necessary for both animal respiration and combustion. Later on he also suggested this “component” is taken up by the lungs and passed into the blood where it is involved during heat production and muscle movement, explaining why breathing increases during exercise, as we need more of this substance in the air to move.

Mountaineering and hot air balloons led to further understanding during the 1700 and 1800s. Paul Bert used animals in hypobaric chambers, simulating the low pressure of high altitude. He found that illness and death always occurred at a certain level of blood oxygen. The same thing happened when air pressure was kept at sea level but the overall oxygen concentration was lowered. Bert also suspected that people and animals at high altitude produce more red blood cells for increased oxygen absorption. Now we know this is true. Plasma volume drops 15-25% which causes a rise in the concentration of hemoglobin. This occurs within around 1-2 days of ascent to altitude. This triggers erythropoietin which stimulates red blood cell production. However, this occurs over days or weeks. So if you are at high altitude for less time your body will not get to this step. (Read “Red Flags At Altitude blog about lab values seen in the patient portal).

To understand altitude effects many researchers now study small animals.  The highest mammal is the yellow-rumped leaf-eared mouse, at 21,000 ft, studied by Jay Storz and colleagues. North American deer mice are the only mammals above tree line in the Rocky Mountains.  University of Denver Assistant Professor of Biology Jon Velotta does studies comparing these high dwellers to their lower altitude cousins. With colleagues Catie Ivy andGraham Scott they were able to show that the breathing rate, red blood cells and hemoglobin increase proportionately to decreasing partial pressures of oxygen.

Anyone interested in the nitty gritty of altitude will learn from this podcast, as well as many other medical topics covered by Colorado-based hosts Erin Allmann Updike MD, PhD and epidemiologist and Erin Welsh PhD disease ecologist and epidemiologist.  Each podcast is accompanied by original recipes for a themed cocktail and nonalcoholic drink.

Claudia Ismerai Reyes is a PA student at Red Rocks Community College in Arvada, Colorado. She grew up in Phoenix, Arizona and went to Arizona State University to get her bachelor’s degree in biology. The first in her family to graduate college. She moved to Colorado a little over five years ago and worked as a CNA at Denver Health for over two years before getting into PA school. In her free time, she likes to watch movies with her husband, trying new places to eat, or playing board games at home.