High altitude and flying

Key points

Low inspired oxygen partial pressure at altitude causes immediate hyperventilation, which increases further with acclimatization to produce hypocapnia and improve oxygen levels.
The rate of ascent and altitude achieved are determinants of altitude-related illnesses, which vary from mild acute mountain sickness to potentially lethal high-altitude pulmonary oedema.
High-altitude populations have adaptations to their environment such as lesser degrees of hyperventilation compensated for by a greater lung surface area for gas exchange.
Commercial aircraft cabins are pressurized to an equivalent altitude of less than 2400 m (8000 ft), representing a level of hypoxia similar to breathing 15% oxygen at sea level.

With increasing altitude the barometric pressure falls, but the fractional concentration of oxygen in the air (0.21) and the saturated vapour pressure of water at body temperature (6.3 kPa or 47 mmHg) remain constant. The P o ₂ of the inspired air is related to the barometric pressure as follows:

Inspired gas P o ₂ = 0.21 × (Barometric pressure – 6.3) kPa

Inspired gas P o ₂ = 0.21 × (Barometric pressure – 47) mmHg

The influence of the saturated vapour pressure of water becomes relatively more important until, at an altitude of approximately 19 000 m or 63 000 ft, the barometric pressure equals the water vapour pressure, and alveolar P o ₂ and P co ₂ become zero.

Table 16.1 is based on the standard table relating altitude and barometric pressure. However, there are important deviations from the predicted barometric pressure under certain circumstances, particularly at low latitudes. At the summit of Everest, the actual barometric pressure was found to be 2.4 kPa (18 mmHg) greater than predicted, and this was crucial to reaching the summit without oxygen. The uppermost curve in Figure 16.1 shows the expected P o ₂ of air as a function of altitude, whereas the crosses indicate observed values in the Himalayas that are consistently higher than expected.

Equivalent oxygen concentration

The acute effect of altitude on inspired P o ₂ may be simulated by reduction of the oxygen concentration of gas inspired at sea level ( Table 16.1 ). This technique is extensively used for studies of hypoxia and for clinical assessment of patients before flying (see later), but there are theoretical reasons why the same inspired P o ₂ at normal and low barometric pressure may have different physiological effects. These include the density of the gas being breathed and different P n ₂ values in the tissues.

Up to 10 000 m (33 000 ft), it is possible to restore the inspired P o ₂ to the sea-level value by an appropriate increase in the oxygen concentration of the inspired gas (also shown in Table 16.1 ). Lower inspired P o ₂ values may be obtained between 10 000 and 19 000 m, above which body fluids boil.

Respiratory system responses to altitude

Ascent to altitude presents three main challenges to the respiratory system, resulting from progressively reduced inspired P o ₂ , low relative humidity and, in outdoor environments, extreme cold. Hypoxia is by far the most important of these and requires significant physiological changes to allow continuation of normal activities at altitude. The efficiency of these changes depends on many factors such as the normal altitude at which the subject lives, the rate of ascent, the altitude attained and the health of the subject.

Physiological effects of exposure to altitude

Transport technology now permits altitude to be attained quickly and without the exertion of climbing. Within a few hours, rail, air, cable car or motor transport may take a passenger from near sea level to as high as 4000 m (13 100 ft).

Ventilatory changes

At high altitude the decrease in inspired gas P o ₂ reduces alveolar, and therefore arterial, P o ₂ . The actual decrease in alveolar P o ₂ is mitigated by hyperventilation caused by the hypoxic drive to ventilation. However, on acute exposure to altitude, the ventilatory response to hypoxia is very short-lived because of a combination of the resultant hypocapnia and hypoxic ventilatory decline (page 52 and Fig. 4.7 ). During the first few days at altitude, this disadvantageous negative feedback is reversed by acclimatization (see later).

Signs and symptoms

Visual impairment is the earliest sign of altitude hypoxia, and at 2400 m (8000 ft) under mesopic (twilight) light conditions there is impairment of both contrast acuity and chromatic sensitivity. Under scotopic conditions (night vision) impairment may occur at altitudes of only 1200 m (4000 ft) because of the greater sensitivity to hypoxia of rods compared with cones in the retina. However, the most serious aspect of exposure to altitude is impairment of mental performance, which is of particular relevance to aviation personnel. Although difficult to study, there is evidence of impaired memory, cognitive flexibility and reaction times at altitude, but fortunately these tend to occur at higher levels than the cabin altitude (page 214) of commercial aircraft. Impaired cognitive function as a result of hypoxia is because of both a direct effect of hypoxia on brain tissue and cerebral vasoconstriction from the resulting hypocapnia.

Acute exposure to high altitude ultimately leads to loss of consciousness, which usually occurs at altitudes in excess of 6000 m (about 20 000 ft). The time to loss of consciousness varies with altitude, and is of great practical importance to pilots in the event of loss of pressurization ( Fig. 16.2 ). The shortest possible time to loss of consciousness (about 15 seconds) applies at greater than 16 000 m (52 000 ft), and is governed by lung-to-brain circulation time and the capacity of high energy phosphate stores in the brain (page 273).

• Fig. 16.2, Symptoms of acute and chronic exposure to altitude.

Acclimatization to altitude

Acclimatization refers to the processes by which tolerance and performance are improved over a period of hours to weeks after an individual who normally lives at relatively low altitude ascends to a higher area. Acclimatization never returns blood gases or performance back to sea-level values but can achieve impressive physiological results. For example, Everest has been climbed without oxygen by well-acclimatized lowlanders, although the barometric pressure on the summit would cause rapid loss of consciousness without acclimatization ( Fig. 16.2 ). Adaptation to altitude (described later) refers to physiological differences in permanent residents at high altitude and is quite different from acclimatization.

Earlier studies of acclimatization took place in the attractive, although somewhat hostile, environment of high-altitude expeditions in many mountain ranges. Technical limitations in these conditions led to two experiments, named Operation Everest II and III, in which volunteers lived in a decompression chamber in which an ascent to the summit of Everest was simulated. These conditions permitted extensive physiological research to be undertaken at rest and during exercise.

Ventilatory control

Prolonged hypoxia results in several complex changes in ventilation and arterial blood gases which are shown in Figure 16.3 . The initial hypoxic drive to ventilation on acute exposure is short-lived, and after about 30 mintues ventilation returns to only slightly above normoxic levels, with P co ₂ just below control levels ( Fig. 16.3 ). This poor ventilatory response causes significant arterial hypoxaemia and results in many of the symptoms seen during the first few hours and days at altitude. Over the next few days, ventilation slowly increases, with an accompanying reduction of P co ₂ and matching increase in arterial P o ₂ . This increase in P o ₂ is of relatively small magnitude and can never correct P o ₂ to normal (sea-level) values, but it does seem to be enough to ameliorate most of the symptoms of exposure to acute altitude.

• Fig. 16.3, Effects of prolonged hypoxia (equivalent to 4300 m, 14 100 ft) on ventilation and blood gases. The first section of the graph shows the acute hypoxic response and hypoxic ventilatory decline described in Chapter 4 . Acclimatization then takes place, partially restoring P o 2 by means of long-term hyperventilation and hypocapnia, a situation that is maintained indefinitely while remaining at altitude. Individuals who reside throughout life at this altitude maintain similar P o 2 values with lesser degrees of hyperventilation, but still have a minute ventilation greater than sea level normal.

There are significant differences between species in the rate at which acclimatization takes place, being just a few hours in most animals, and several days or weeks in humans. Both the rate of ascent and the altitude attained influence the speed at which ventilatory acclimatization occurs, but in humans most subjects are fully acclimatized within 1 week.

There are many possible mechanisms to explain the ventilatory changes seen with acclimatization. In spite of the low blood P co ₂ , stimulation of the central chemoreceptors almost certainly plays a part in the hyperventilation that occurs with acclimatization. It was first suggested, in 1963, that the restoration of cerebrospinal fluid (CSF) pH, by means of bicarbonate transport, might explain this acclimatization of ventilation to altitude. However, the time course of changes in CSF pH does not match changes in ventilation, and most studies showed a persistent increase in CSF pH at altitude. CSF pH therefore is unlikely to represent an important mechanism of acclimatization. Other studies, mainly in animals, indicate that acclimatization represents an increase in the responsiveness of the respiratory centre to hypoxia from both direct effects of prolonged hypoxia on the central nervous system and prolonged maximal afferent input from the peripheral chemoreceptors. This increased responsiveness may be mediated by alterations in the sensitivity to neurotransmitters involved in respiratory control (see Fig. 4.4 ). For example, increased sensitivity to glutamate will directly increase ventilation, or decreasing γ–aminobutyric acid (GABA) sensitivity will effectively reduce hypoxic ventilatory decline (page 52).

In addition to changes affecting the central chemoreceptors, there is evidence that peripheral chemoreceptor sensitivity is increased during prolonged hypoxia, contributing to the progressive hyperventilation seen with acclimatization. In humans, the acute hypoxic ventilatory response is increased during the first few days at altitude and for several days after return to sea level. The mechanism of this increased sensitivity to hypoxia is not known, but is independent of changes in P co ₂ , and may reside either with increased sensitivity of the carotid bodies or with the increased responsiveness of the respiratory centre described in the previous paragraph.

Respiratory alkalosis at altitude is counteracted, over the course of a few days, by renal excretion of bicarbonate, resulting in a degree of metabolic acidosis that will tend to increase respiratory drive (see Fig. 4.6 ). This was formerly thought to be the main factor in the ventilatory adaptation to altitude, but it now appears to be of minor importance compared with the changes in the central and peripheral chemoreceptors.

Blood gases

Figure 16.3 shows the time course of blood gas changes during acclimatization, and Figure 16.1 shows changes in alveolar gas partial pressures with altitude in fully acclimatized mountaineers. Alveolar P o ₂ is unexpectedly well preserved at extreme altitude, and at greater than 8000 m (26 000 ft) tends to remain close to 4.8 kPa (36 mmHg). Operations Everest II and III found arterial P o ₂ values of 3.6 and 4.1 kPa (27 and 31 mmHg) at a pressure equivalent to the summit of Everest ( Table 16.2 ), with an alveolar/arterial P o ₂ difference of less than 0.3 kPa (2 mmHg) at rest. The Caudwell Extreme Everest expedition in 2007 obtained arterial blood samples at 8400 m (27 559 ft) with an average P o ₂ of 3.3 kPa (25 mmHg). There was also a significant alveolar to arterial P o ₂ difference of 0.7 kPa (5 mmHg), which the authors suggested may have resulted from a diffusion barrier to oxygen at such low levels, possibly as a result of subclinical pulmonary oedema.

TABLE 16.2

Cardiorespiratory Data Obtained at Rest and During Exercise at Extreme Reduction of Ambient Pressure During the Simulated Ascent of Everest in a Low-Pressure Chamber

	Sea-Level Equivalent		Extreme Altitude Equivalent
Ambient pressure (kPa)	101		33.7
(mmHg)	760		253
Haemoglobin concentration (g.L ⁻¹ )	135		170
o _2peak (mL.min ⁻¹ , STPD)	3980		1170
State	Rest	Exercise	Rest	Exercise
Exercise intensity (watts)	0	281	0	90
Ventilation (L.min ⁻¹ , BTPS)	11	107	42.3	157.5
o _2peak (mL.min ⁻¹ , STPD)	350	3380	386	1002
Ventilation equivalent	31	32	110	157
Arterial P o ₂ (kPa)	13.2	12.0	4.0	3.7
(mmHg)	99.3	90.0	30.3	27.7
Arterial P co ₂ (kPa)	4.5	4.7	1.5	1.3
(mmHg)	33.9	35.0	11.2	10.1
Arterial/venous O ₂ content difference (mL.dL ⁻¹ )	5.7	15.0	4.6	6.7
Mixed venous P o ₂ (kPa)	4.7	2.6	2.9	1.9
(mmHg)	35.1	19.7	22.1	14.3
Cardiac output (L.min ⁻¹ )	6.7	27.2	8.4	15.7
Pulmonary arterial pressure (mean, mmHg)	15	33	33	48

Actual ambient pressure at simulated high altitude was 32 kPa (240 mmHg), but leakage of oxygen from masks worn by investigators had caused the oxygen concentration in the chamber to rise to 22%, the equivalent of 33.7 kPa at 21%, which is equivalent to the summit of Everest.

BTPS, body temperature and pressure, saturated STPD, standard temperature, pressure and dry.

Haemoglobin concentration and oxygen affinity

An increase in haemoglobin concentration was the earliest adaptation to altitude to be demonstrated. Initially caused by a reduction in plasma volume, erythropoietin levels are raised within a few hours at altitude, and haemoglobin mass begins to increase within a few days, reaching a plateau after about three weeks. ^, Data from subjects at 8400 m (27 559 ft) reported an increase from 148 to 193 g.L ⁻¹ , which, at the resting value of 54% saturation, maintained an arterial oxygen content of almost 15 mL.dL ⁻¹ .

The haemoglobin dissociation curve at altitude is affected by changes in both pH and 2,3-diphosphoglycerate (DPG) concentration (page 146). DPG concentrations are generally increased at high altitude, displacing the curve to the right, whereas pH is invariably high because of hyperventilation, displacing the curve to the left. Conflicting reports of the P ₅₀ (page 146) at altitude therefore exist, with differences resulting from the population studied (high-altitude natives or lowlanders), the degree of acclimatization, altitude of the study, and so on. However, it is generally thought that the pH effect predominates, and that altitude causes a left shift of the curve; and in vivo data at 3600 m (12 000 ft) support this, indicating that oxygen loading in the lung takes priority over maintaining P o ₂ at the point of release.

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