Much of the clinical education related to aerospace pressure effects concerns hyperbaric or increased pressure exposures. Human exposure to increased pressure occurs while diving and during hyperbaric oxygen therapy. Hypobaric (reduced pressure) exposures occur on commercial plane flights where the cabin pressure equals about 2438.4 meters (8000 feet); however, professional aviators, particularly military personnel, mountain climbers, research subjects, and astronauts are exposed to much greater extremes in low-pressure environments. The two main concerns about hypobaric exposure relate to absolute pressure upon the human body and the total oxygen available to the body.[1][2][3]

An understanding of the gas laws is foundational to understanding how pressure changes affect humans. The gas laws describe the relationship between temperature, volume, and pressure for a given amount of gas. For example, Charle's law states that for a given pressure, the volume is proportional to the temperature. Therefore, a gas expands when heated as long as the pressure is allowed to remain the same. However, if gas cannot expand such as when trapped inside the middle ear or a nasal sinus, the pressure will increase.  For a given volume the pressure will vary with the temperature of the gas.  The thermoregulatory system in the human body does not typically allow for more than a few degrees Celcius variance in body temperature.  Boyle's law states that for a given temperature the volume is inversely proportional to the pressure. This law explains why sinuses or middle ear (which are normally fixed volume gas-filled spaces) may hurt when during altitude or pressure changes.  Finally, Dalton's law notes the total pressure of a mixture of gases equals the partial pressure exerted by each gas. This concept is important given that the air humans breathe is a mixed gas of nitrogen (approximately 78%), oxygen (approximately 21%), and trace other gases.

If the human body is exposed to a low enough absolute pressure, then surface fluids (tear film, saliva, and the air-exposed surface of alveoli) will begin to boil at normal body temperature. This occurs at around an altitude of 60,000 feet (approximately 11.4 miles or 18.3 kilometers) depending on exact atmospheric conditions. This altitude has been named "Armstrong's limit" or "Armstrong's line" and is named after an early American aerospace medicine physician, Harry G. Armstrong. When blood boils, this is called "ebullism" and is the trapping of gases released from blood under the skin. Ebullism is painful but recoverable to full function as human experience has shown.

Reduced oxygen levels in the body can occur for various reasons. Hypoxia is the general term for low oxygen content in the blood or at the tissue level. Hypoxic hypoxia is hypoxia secondary to low alveolar oxygen exchange in the lungs and can be caused by either a low oxygen availability or due to low surface area for the gas exchange. In this article, "hypoxia" means hypoxic hypoxia due to low oxygen availability in the environment.  While the percentage of oxygen remains a constant 21% as one increases in elevation, the total pressure of oxygen decreases because the total pressure of all gases combined decreases. The barometric pressure at sea level is around 760 mm Hg with some variation depending on the weather.  Therefore at sea level, oxygen is only 21% of that total or 160mm Hg.  Inside the lungs and alveoli, the temperature remains approximately 37 degrees Celsius (98.6 degrees Fahrenheit).  As one ascends in altitude, the total atmospheric pressure goes down which necessarily means the oxygen available for breathing goes down as well.

While there is some variation from person to person, the effects of hypoxia are accepted to begin at 3048 meters (10,000 feet). These effects include reduced light reception and decreased ability to distinguish colors. As a person ascends in altitude, their body compensates with increased depth of respiration, increased rate of respiration, and increased heart rate in an attempt to maintain oxygen delivery to the tissues. Further ascent leads to extreme fatigue and reduced mental capacity. Exposure to atmospheric conditions in approximately 7620 to 10,363 meters (25,000 to about 34,000 feet) results in death if supplemental oxygen is not used. Under 34,000 ft 100% oxygen in a tight-fitting mask will deliver near ground level oxygen to the tissues. Pressure suits or pressurized cockpits must be used beyond this level to maintain near sea level oxygenation to the tissues.[4][5][6]

Hypoxia can occur without the subject being aware of its effects. Slow loss of cabin pressure or loss of the oxygen source during flight may lead to a gradual onset of the effects of hypoxia. This occurs occasionally and is a perilous situation for pilots as the early symptoms of hypoxia are mild but, if not corrected, they will become disabling. For some, early hypoxia leads to euphoria and an inability to recognize the hazard. For a pilot or other aircrew, if the symptoms of hypoxia are not recognized the problem may culminate in a crash.  

Because of this potentially subtle problem, flight systems are designed to recognize hypoxia hazardous situations and alert pilots to the potential danger so they may take action and correct the situation. Additionally, military air forces require hypoxia training either through altitude exposure in low-pressure chambers or via normal pressure/reduced oxygen gas exposures. The FAA does not require hypoxia training in commercial aviation but it is highly encouraged, and many companies educate their aircrew through one of the hypoxia training systems mentioned above.

Sudden loss of pressure is not a subtle event when there is a significant pressure difference between the inside and the outside of an aircraft. Pilots are required to have "quick-don" masks readily available while piloting in these situations. While this is a dangerous situation overall, it does not pose the subtle threat of a slow loss of pressure.  However, with a sudden and dramatic reduction in oxygen, one may lose consciousness in a few minutes.  The time between sudden decompression and loss of the ability to perform a useful activity is called the "time of useful consciousness" or TUC.  Beyond this time period, one can no longer perform actions to save either themselves or others, i.e. they are unconscious.  Any action to correct the situation must occur before the TUC runs out.  Commercial airliners routinely fly in the above 10,000 meters.  At these altitudes, the TUC is less than one minute.  This is why pilots are required to have "quick don" masks which will greatly extend the TUC.[7][8]

For the loss of cabin pressure at high altitude, the treatment for hypoxia is 100% oxygen.  In large, multiplace aircraft, aircrew are to wear masks and breathe 100% oxygen.  Passengers in passenger planes should put on the deployed yellow masks when there is a loss of cabin pressure. Symptoms will resolve almost immediately.  The aircrew should simultaneously return to below 3048 meters (10,000 feet) as fast and safely possible.  In small military tactical aircraft, aircrews wear masks all the time, and when the need arises, they switch to 100% oxygen. These small aircraft also will descend to 10,000 feet or less if the situation allows.

Mountain climbers also risk altitude-related illness. High altitude illness (HAI) is a term used to describe pathologic conditions that occur when unacclimated individuals are exposed rapidly to elevations above 2500 meters (8000 feet). "Rapid" means a change that happens within a few hours. Change that takes days will allow one to acclimate to the new altitude and prevents high-altitude illnesses. Illnesses associated with altitude exposure include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Definitive treatment of these conditions is moving to a lower altitude, but this may not be necessary in mild AMS or HAPE cases. Prophylactic use of acetazolamide has been shown to decrease the risk of AMS.  AMS may be treated with rest, hydration, NSAIDs, and not moving any higher until symptoms have resolved. AMS is considered an early form of HACE. If AMS worsens or if one suspects HACE then an immediate descent of 762 to 914.4 meters (2500 to 3000 feet) or more is extremely important to avoid severe consequences. HACE and HAPE have caused death and should be treated as soon as the condition is suspected. Additionally, there are portable, inflatable hyperbaric chambers available and utilized by professional organizations that can be used when the descent is not possible. Pharmacologic therapy of HACE and HAPE differs and is beyond the scope of this article.[9][10][11][12]