The atmosphere surrounding the earth is a vast mixture of gases and trace quantities of liquids and solids held earthward by gravity. The gases that make up the greatest percentage of the atmosphere are nitrogen and oxygen. The percentage or ratio of oxygen to nitrogen is constant up to an altitude of approximately 60 miles (96 kilometers) where layering begins. Water vapour varies with time, location and meteorological conditions as well as with altitude, since the presence of water vapour is governed by temperature. The primary particles, which make up cosmic radiations, are photons, neutrons, alpha particles and heavy nuclei.

The atmosphere has been classically considered as being divided into several concentric “shells” around the Earth, each with its own characteristics. These shells are Troposphere, Stratosphere, Ionosphere and Exosphere. The innermost shell is the troposphere, which extends from ground level to 9144 m (30,000 ft) at the poles and 18,288 m (60,000 ft) at the Equator. Conventional aircraft operates in this region. It is characterized by a relatively constant decline in temperature with increasing altitude at a rate of 1.98°C/305 m (1000 ft) ascent. Air is compressed by gravity. Therefore, atmospheric pressure is greatest at sea level and declines logarithmically with ascent.

The troposphere has constant composition containing 21% oxygen, 78% nitrogen, and 1% other gases (including argon and carbon dioxide, the latter being present at a concentration of 0.03%). It is the fall in the partial pressure of oxygen as total pressure declines on ascent that can give rise to hypobaric hypoxia, not a change in its percentage in air. Boyle's law predicts that, as pressure falls on ascent, there will be an inversely proportional increase in gas volumes. This affects body parts where gases are trapped, including the middle and inner ear, sinuses, and intestines. The same effect occurs in the lungs. The volume of a gas is also related to temperature, but the temperature of gases trapped in the body stays constant at 37°C.

To understand how the flight influences physiology and occasionally pathology, it is useful to consider the physiological properties of the atmosphere environment and changes that occur on ascent to altitude.

The aerospace environment, it is the human's relation to that environment which is of primary concern. Therefore, it is useful to consider physiological responses at various levels of the atmosphere, and to divide the atmosphere into three physiological zones as follows:- (4)

1. Physiological zone. The region of the atmosphere to which humans are adapted physiologically extends from sea level (SL) to 10,000 feet. The oxygen (O2) level within this zone is sufficient to keep a normal, healthy person physiologically fit without the aid of special protective equipment. The changes in pressure encountered with rapid ascents or descents within this zone can produce ear or sinus difficulties.

2. Physiologically deficient zone. This zone extends from 10,000 ft to about 50,000 ft (FL 500). Because of reduced atmospheric pressure, this is the zone in which O2 deficiency becomes an ever-increasing problem. Supplemental O2 is required when flying above 10,000 ft. Trapped gas in the intestinal tract, lung and evolved gas problems occur within this zone. In addition, protection must be provided against decreasing temperature.

3. Space-equivalent zone. From a physiological viewpoint this zone begins when 50,000 ft is reached since supplemental O2 (100%), even when supplied under pressure, no longer protects one from the problem of hypoxia. The means of protecting a person above 50,000 ft are such that they will also offer protection in true space (i.e., pressure suits, sealed cabins). The only additional physiological problems occurring within this zone, which extends from 50,000 ft to 120 miles, are possible radiation effects and the boiling of body fluids in an unprotected individual. Boiling of body fluids will occur when the total barometric pressure (PB) is less than the vapor pressure of water at 37 o C (47 mmHg), which is reached at 63,500 ft (Armstrong's Line).

Aerospace hypobaric exposures, including operation of jet aircraft and airplane travel, often involve rapid changes in total PB, partial pressures of gases, and acceleration forces that entail risks for barotrauma, decompression sickness, and other manifestations. Terrestrial hypobaric exposures, such as mountain climbing, usually involve a slower rate of change in conditions; permitting acclimatization to lower partial pressure of O₂, but often involve longer exposure, and variable temperature. (6)

The barometric pressure of ambient air declines in a nonlinear manner as altitude above SL increases. Table (I) shows the international standard atmosphere for elevations above SL and PB. These values represent average conditions. Local weather conditions can cause significant deviations from the standard atmosphere. Although the fraction of inspired O₂ (FiO₂) remains constant, at 20.9%, as altitude increases, the partial pressure of O₂ in ambient air declines progressively in proportion to declining barometric pressure. (6)

When one is breathing pure O₂ at 33,700 ft, the partial pressure of O₂ in the alveoli is the same as the pressure at SL when breathing air. Above 34,000 ft, the partial pressure of O₂ in the lungs begins to fall below the pressure at SL, even though 100 % O₂ is breathed. At altitudes greater than 40,000 ft, the partial pressure of O₂ decreases rapidly and falls below the limit that maintains the body in a physiologically safe condition. (6)

It is generally recognized that the most serious danger for the aircrew member is the decreased partial pressure of oxygen encountered at low barometric pressures. Without the proper use of oxygen equipment and cabin pressurization, hypoxia can quickly lead to incapacitation or death, depending on the altitude. (5)

Combination exposures, such as air travel followed by mountain climbing or skiing, frequently occur. Patients may seek medical supervision to accelerate acclimatization by pharmacologic means or to prepare for treatment of altitude sickness if it develops. The mountain climbing or air travel carries increased risk for decompression sickness. (6)

Figure 1

Table (I): Pressure equivalents at various altitudes above sea level

Cabin pressurization in modern aircraft ensures that the effective altitude to which occupants are exposed is much lower than that at which the aircraft is flying. Commercial aircraft are not pressurized to sea level but to a relatively modest intermediate cabin altitude. This allows the aircraft to fly at much higher altitudes, which is fuel efficient for jet engines and more comfortable since it avoids much turbulence. Aircraft cabin altitude can thus approach 2438 m (8000 ft) while the aircraft is flying at 11,582 m (38,000 ft). Therefore, a pressure differential exists across the cabin wall, commonly of up to 9 pounds per square inch (psi). International aviation regulations stipulate that, at a plane's maximum cruising altitude, the cabin pressure should not exceed 2438 m (8000 ft). This may be exceeded in emergencies. (5)

In the event of failure of the cabin pressurization system at high altitude, all occupants would require supplemental oxygen to prevent an unacceptable degree of hypoxemia. Commercial aircraft are thus equipped with an emergency oxygen system for passengers, demonstrated before each flight in accordance with civil aviation regulations. However, some passengers with impaired respiratory function may be unusually susceptible to the effects of ascent even to normal cabin altitudes. (6)

Moderate altitude is defined as 5,000-10,000 ft above SL. As the altitude increases, the barometric pressure (PB) decreases. This fall in the PB affects the available PO₂. The O₂% remains stable at about 21%. At sea level, the partial pressure of O₂ available in the environment is equal to 0.21 times the PB (760 mm Hg), or 159 mm Hg. After saturation with water and expired CO₂, the partial pressure of alveolar O₂ (PAO₂) is 103 mm Hg, as calculated by the following equation: PAO₂ = FiO₂ (PB - PH₂O) - PaCO₂ [FiO₂ + (1 - FiO₂/R)]

(PB is the ambient barometric pressure, PH₂O is the pressure exerted by water vapor at body temperature, FiO₂ is the fraction of inspired oxygen, PaCO₂ is the alveolar carbon dioxide pressure, and R is the respiratory exchange quotient.)

Although the O₂% in inspired air is constant at different altitudes, the fall in atmospheric pressure at higher altitude decreases the partial pressure of inspired oxygen and hence the driving pressure for gas exchange in the lungs. An ocean of air is present up to the ends of troposphere layer. The weight of air above us is responsible for the atmospheric pressure, (100 kPa at SL). This atmospheric pressure is the sum of the partial pressures of the constituent gases, oxygen and nitrogen, and also the partial pressure of water vapour (6.3 kPa at 37°C). (8)

The decrease in PB with increasing altitude results in a fall in the PaO₂. Atmospheric pressure and inspired oxygen pressure fall roughly linearly with altitude to be 50% of the SL value at 5500 m and only 30% of the SL value at 8900 m (the height of the summit of Everest). For example, the PaO₂ decreases from 103 mm Hg at SL to 81 mm Hg in Denver, Colo (5,280 ft, 1,610 m), and 48 mm Hg at the top of Pikes Peak (14,110 ft, 4,300 m). (9)

A fall in inspired O₂ pressure reduces the driving pressure for gas exchange in the lungs and in turn produces a cascade of effects right down to the level of the mitochondria, the final destination of the O₂. (8)

The lungs are a delicate interface between the atmosphere and our bodies across which O₂ diffuses from the air we breathe to the blood. In healthy lungs at SL where there is a surfeit of O₂, this process occurs easily, whereas, in lungs with disease it becomes a task, which may not be fully successful and hypoxemia may ensue or worsen. At high altitude where the PB and thus the supply of O₂ is lower, the job of getting O₂ to the blood, even in the healthy lung is more difficult, and in the diseased lung it may be impossible. (10)

Hypoxic ventilatory response

Stages of Hypoxia (8)

Hypoxia of high altitude may be divided into four stages related to the altitudes, and the O₂ saturations of the blood. This is illustrated in table (II):

Figure 2

Table (II): Stages of hypoxia

In the Critical stage, there is loss of consciousness. It may be the result of circulatory failure (“fainter”) or a central nervous system failure (“non-fainter,” unconsciousness with maintenance of blood pressure). The former is more common with prolonged hypoxia, the latter with acute hypoxia. With either type there may be convulsions and eventual failure of the respiratory center.

Hypoxia during flying most often results from depletion of compressed air supplies and other types of equipment failure. The manifestations of hypoxia begin when dry inspired PO₂ declines below 0.14 ATA (equivalent to 14% oxygen at SL). Tachycardia, increased systemic blood pressure, tachypnea, and cyanosis typically occur. Other manifestations include inability to concentrate on task, loss of coordination, loss of color vision, drowsiness, generalized weakness, incapacitation (0.11 ATA O₂), loss of consciousness (< 0.1 ATA O₂), and death. (6)

The appearance of the signs and the severity of the symptoms of acute hypoxic hypoxia depend on the following variables:-

a. Altitude level.
b. Rate of ascent.
c. Duration at altitude.
d. Ambient temperature.
e. Physical activity.
f. Individual factors:-
Inherent tolerance.
Physical fitness.
Emotional state.
Acclimatization.

The treatment for hypoxia consists in giving 100% O₂ by inhalation. The aviator recognizing hypoxia must immediately switch to 100 % O₂ and emergency. If respiration has deceased, artificial respiration along with simultaneous use of 100% O₂ is indicated. If peripheral circulatory failure persists, the type must be determined and treated accordingly.

Recovery from hypoxia is rapid when sufficient O₂ is supplied. An individual on the threshold of unconsciousness may regain full faculties within 15 seconds after receiving an abundance of oxygen.

Time of useful consciousness (TUC) is the period of time from the interruption of the O₂ supply or exposure to an oxygen-poor environment, to the time when useful function is lost. The individual is no longer capable of taking proper corrective and protective action. It is not the time to total unconsciousness. A rapid decompression can reduce the TUC by up to 50% caused by the forced exhalation of the lungs during decompression and the extremely rapid rate of ascent. (6)

a) Neuromuscular. The increased sensitivity and irritability of neuromuscular tissue, due to an elevation in blood pH, gives rise to a superficial tingling of the extremities (this tingling is not limited to the extremities, but is usually encountered there). The tingling usually precedes muscular spasm (i.e., a fixation of the hand wherein the fingers are drawn back toward the wrist). In severe cases facial muscles will be tetanically contracted, and the face will give an appearance of being pulled downward. The most dire and dramatic reaction is the “stiffening” of the entire body due to generalized muscular tetany. It is believed that a reduction in the partial pressure of alveolar CO₂ to 24-30 mmHg is the critical level for the onset of these symptoms.

b) Psychomotor. Deterioration of muscular control and coordinated activity is invariably seen during severe hyperventilation. Performance deterioration is encountered whenever the partial pressure of alveolar CO₂ is reduced below 25 mmHg. As the value falls below this level, performance deterioration becomes more marked.

Voluntary reduction in the rate or depth or both of respiration of the individual affected is the most effective method of treatment, when applicable. It is conceivable, however, that an extremely apprehensive person would not respond to directions to slow respiration.

It should be noted that the symptoms of hypoxia and hyperventilation are virtually indistinguishable. The individual must treat for both simultaneously. If either occurs, a decrease in the respiratory rate and breathing 100% O₂, will correct the condition. In the presence of hypoxia, if other disturbances coexist, or in more severe cases, it is imperative to return to ground level before more serious developments occur.

In the systemic circulation hypoxia acts as a vasodilator, but in the pulmonary circulation it is a vasoconstrictor. The purpose of hypoxic pulmonary vasoconstriction is unclear. It may help match ventilation and perfusion within the lung, but in hypoxia of altitude the reflex leads to pulmonary hypertension and is associated with high altitude pulmonary oedema (HAPE). (8)

An estimated 20% of the general population responds to a hypoxic stimulus with a marked increase in the pulmonary vascular resistance. These individuals are referred to as hyper-reactors. Clinically significant increases in the right ventricular pressure can be seen in such individuals who have an elevated pulmonary vascular resistance secondary to the hypoxic environment of a higher altitude. This can be exacerbated by acute pulmonary disease, exercise, upper airway obstruction, or congenital heart defects associated with an increase in pulmonary blood flow or restriction to pulmonary venous return. (13)

An increase in pulmonary vascular resistance is seen in normal subjects during hypoxic breathing at SL, in acclimatized lowlanders and in high-altitude natives. Hypoxic pulmonary hypertension in all these circumstances is most generally moderate, except in high-altitude natives at exercise. Pulmonary hypertension may become severe during HAPE, during infantile or adult forms of subacute mountain sickness, and during chronic mountain sickness. Subacute and chronic mountain sickness may be associated with a right heart failure that would be the human counterpart of brisket disease described in cattle. (13)

Susceptible subjects will present with HAPE with a slight increase in pulmonary vascular resistance at rest and at exercise, and often with an enhanced pulmonary vascular reactivity to hypoxia compared to normal person. Noninvasive echo-Doppler studies of the pulmonary circulation at sea level are of little predictive value of tolerance to altitudes on an individual basis. (13)

At SL gaseous diffusion is probably limited by ventilation/perfusion matching in the lung. At high altitude, however, the alveolar-arterial difference for O₂ is higher than would be predicted from the measured ventilation/perfusion inequality. This is because the decreased driving pressure for O₂ from alveolar gas into arterial blood is insufficient to fully oxygenate the blood as it passes through the pulmonary capillaries. This is more evident on exercise as cardiac output increases and blood spends less time at the gas- exchanging surface (diffusion limitation). (9)

The heart works remarkably well at altitude. Initially there is an increase in cardiac output in relation to physical work but later this settles to SL values. At all times there is increased heart rate and decreased stroke volume for a given level of work, though the maximum obtainable heart rate falls as higher altitudes are reached. (8)

Hypoxia has progressive effects on the functioning of the central nervous system. Accidents that occur at extreme altitude on Everest and other mountains may be due to poor judgment as a consequence of hypoxic depression of cerebral function. More worrying is that these effects on cerebral function may be permanent. The American Medical Research Expedition to Everest studied its climbers a year after return to SL and found some enduring abnormalities of cognitive function and ability to perform fast repetitive movements, although most functions tested had returned to pre-expedition values. (8)

Initially on traveling to altitude, hemoglobin concentrations rise through a fall in the plasma volume due to dehydration. Later, hypoxia stimulates production of erythropoietin by the juxtaglomerular apparatus of the kidney so hemoglobin production increases and hemoglobin concentrations may rise to 200 g/l. The increased viscosity of the blood coupled with increased coagulability increases the risk of stroke and venous thromboembolism. Some authors advocate regular venesection in high altitude climbers; others recommend prophylactic aspirin. Neither has been shown scientifically to reduce the incidence of venous or arterial thrombosis. (14)

The chronic hypoxia associated with moderate altitudes can affect the fetus. Birth weights are smaller, uterine blood flow is decreased, placental morphology may be different, and the incidence of prematurity and pregnancy-induced hypertension is increased at higher altitudes. Maternal smoking at high altitudes can have an additive effect. Travel of pregnant women from a low to a high altitude and vice versa has the potential to initiate premature labor caused by the changing PB on the amniotic sac. No difference in hematocrit levels has been reported in neonates born at higher altitudes compared with those born at SL. (15)