Arthur DuBois
The earth and its atmosphere provide environments that are compatible with an extraordinary number of diverse life forms, each adapted to its particular ecologic niche. However, not all the earth’s surface is equally friendly for human survival, let alone comfort and function. Mountain climbers and deep sea divers know the profound effects of barometric pressure (PB) on human physiology, and astronauts quickly learn how the physically equivalent forces of gravity and acceleration affect the body. Humans can adapt to changes in PB and gravity up to a point, but survival under extreme conditions requires special equipment; otherwise, our physiological limitations would restrict our occupancy of this planet to its lowland surfaces.
Much can be learned from exposure to extreme environmental conditions. Although most people do not seek out these extreme environments, the same physiological responses that occur under extreme environmental conditions may also occur, to a lesser extent, in everyday life. In this chapter, I first discuss general principles of environmental physiology and then focus on extreme environments encountered in three activities: deep sea diving, mountain climbing, and space flight.
THE ENVIRONMENT
Voluntary feedback-control mechanisms can modulate the many layers of our external environment
Chapter 1 describes Claude Bernard’s concept of the milieu intérieur (basically, the extracellular fluid in which cells of the organism live) and his notion that “fixité du milieu intérieur” (the constancy of this extracellular fluid) is the condition of “free, independent life.” Chapters 2 through 57 focus mainly on the interaction between cells and their extracellular fluid. In this chapter, I consider how the milieu extérieur, which physically surrounds the whole organism, affects our body functions and how we, in turn, modify our surroundings when it is necessary to improve our comfort or to extend the range of habitable environments.
The milieu extérieur, in fact, has several layers: the skin surface, the air that surrounds the skin, clothing that may surround that air, additional air that may surround the clothing, a structure (e.g., a house) that may surround that air, and finally a natural environment that surrounds that structure. As we interact with our multilayered environment, sensors monitor multiple aspects of the milieu intérieur, and involuntary physiological feedback-control mechanisms—operating at a subconscious level—make appropriate adjustments to systems that control a panoply of parameters, including blood pressure, ventilation, effective circulating volume, gastric secretions, blood glucose levels, and temperature.
The sensory input can also rise to a conscious level and, if perceived as discomfort, can motivate us to take voluntary actions that make the surroundings more comfortable. For example, if we sense that we are uncomfortably hot, we may move out of the sun or, if indoors, turn on the air conditioning. If we then sense that we are too cool, we may move into the sun or turn off the air conditioning. Such conscious actions are part of the effector limb in a complex negative feedback system that includes sensors, afferent pathways, integration and conscious decision making in the brain, efferent pathways to our muscles, and perhaps inanimate objects such as air conditioners.
For a voluntary feedback system to operate properly, the person must be aware of a signal from the surroundings and must be able to determine the error by which this signal deviates from a desirable set-point condition. Moreover, the person must respond to this error signal by taking actions that reduce the error signal and thereby restore the milieu intérieur to within a normal range. Humans respond to discomfort by a wide variety of activities that may involve any layer of the environment. Thus, we may adjust our clothing, build housing, and eventually even make equipment that allows us to explore the ocean depths, mountain heights, and outer space.
Physiological control mechanisms—involuntary or voluntary—do not always work well. Physicians are acutely aware that factors such as medication, disease, or the extremes of age can interfere with involuntary feedback systems. These same factors can also interfere with voluntary feedback systems. For example, turning on the air conditioning is a difficult or even impossible task for an unconscious person, a bedridden patient, or a perfectly healthy baby. In these situations, a caregiver substitutes for the voluntary physiological control mechanisms. However, to perform this role effectively, the caregiver must understand how the environment would normally affect the care recipient and must anticipate how the involuntary and voluntary physiological control mechanisms would respond. (See Note: Role of a Caregiver)
Environmental temperature provides conscious clues for triggering voluntary feedback mechanisms
Involuntary control mechanisms—discussed in Chapter 60—can only go so far in stabilizing body core temperature in the presence of extreme environmental temperatures. Thus, voluntary control mechanisms can become extremely important.
As summarized in Table 60-1, the usual range of body core temperature is 36°C to 38°C. At an environmental temperature of 26°C to 27°C and a relative humidity of 50%, a naked person is in a neutral thermal environment (see Chapter 60), feeling comfortable and being within the zone of vasomotor regulation of body temperature. At 28°C to 29°C, the person feels warm, and ~25% of the skin surface becomes wet with perspiration. At 30°C to 32°C, the person becomes slightly uncomfortable. At 35°C to 37°C, one becomes hot and uncomfortable, ~50% of the skin area is wet, and heat stroke (see the box on heat stroke in Chapter 60) may be possible. The environmental temperature range of 39°C to 43°C is very hot and uncomfortable, and the body may fail to regulate core temperature. At 46°C, the heat is unbearable, and heat stroke is imminent—the body heats rapidly, and the loss of extracellular fluid to sweat may lead to circulatory collapse and death (see Chapter 60).
At the other extreme, we regard environmental temperatures of 24°C to 25°C as cool and 21°C to 22°C as slightly uncomfortable. At temperatures of 19°C to 20°C, we feel cold, vasoconstriction occurs in the hands and feet, and muscles may be painful. (See Note: Temperature Sensations and Computer Models)
Room ventilation should maintain PO2, PCO2, and toxic substances within acceptable limits
Ventilation of a room (
Room) must be sufficient to supply enough O2 and to remove enough CO2 to keep the partial pressures of these gases within acceptable limits. In addition, it may be necessary to increase Room even more, to lower relative humidity and to reduce odors. As outlined in Table 26-1, dry air in the natural environment at sea level has a PO2 of ~159 mm Hg (20.95%) and a PCO2 of ~0.2 mm Hg (0.03%).
Acceptable limits for PO2 and PCO2
The acceptable lower limit for PO2 for work environments is 148 mm Hg in dry air, which is 19.5% of dry air at sea level. The environmental atmosphere of a submarine may be kept at this slightly low PO2 to minimize the chance of fires, yet retain the mental capacity of the occupants.
An acceptable upper limit for PCO2 in working environments is 3.8 mm Hg, or 0.5% of dry air at sea level. This level of CO2 would increase total ventilation by ~7%, a hardly noticeable rise. Exposures to 3% CO2 in the ambient air—which initially would cause more substantial respiratory acidosis—could be tolerated for at least 15 minutes, by the end of which it would nearly double total ventilation. With longer exposures to 3% CO2, the metabolic compensation to respiratory acidosis (see Chapters 28 and 39) would have already begun to increase plasma [HCO−3] noticeably. (See Note: Physical Work and the Conscious Control of Body Core Temperature)
Measuring Room Ventilation Two approaches are available for determining Room. The first is a steady-state method that requires knowing (1) the rate of CO2 production (CO2) by the occupants of the room and (2) the fraction of the room air that is CO2. The equation is analogous to the one introduced for determining alveolar ventilation, beginning with Equation 31-9:
We could use a similar equation based on PO2 and the rate of O2 extraction by the occupants. (See Note: Steady-State Method for Computing “Room Ventilation”)
In the exponential decay method, the second approach for determiningRoom, one monitors the washout of a gas from the room. The approach is to add a test gas (e.g., CO2) to the room and then measure the concentrations of the gas at time zero (Cinitial) and—as Room washes out the gas over some time interval (Δt)—at some later time (Cfinal). The equation for exponential decay is as follows: (See Note: Exponential Decay Method for Determining “Room Ventilation”)
For example, imagine that we wish to measure the ventilation of a room that is 3 × 3 × 3 m—a volume of 27 m3 or 27,000 L. Into this room, we place a tank of 100% CO2 and a fan to mix the air. We then open the valve on the tank until an infrared CO2 meter reads 3% CO2 (Cinitial = 3%), at which point we shut off the valve on the tank. Ten minutes later (Δt = 10 minutes), the meter reads 1.5% (Cfinal = 1.5%). Substituting these measured values into Equation 61-2 leads to the following: (See Note: Effect of Disease on the Acute Response to Hypercapnia)
This approach requires that the incoming air contain virtually no CO2 and that the room contain no CO2 sources (e.g., people).
Carbon Monoxide More insidious than hypoxia, and less noticeable, is the symptomless encroachment of carbon monoxide (CO) gas on the oxyhemoglobin dissociation curve (see Chapter 29). CO—which can come from incomplete combustion of fuel in furnaces, charcoal burners, or during house fires—suffocates people without their being aware of its presence. Detectors for this gas are thus essential for providing an early warning. CO can be lethal when it occupies approximately half of the binding sites on hemoglobin (Hb), which occurs at a PCO of ~0.13 mm Hg or 0.13/760 ≅ 170 parts per million (ppm). However, the half-time for washing CO into or out of the body is ~4 hours. Thus, if the ambient CO level were high enough to achieve a 50% saturation of Hb at equilibrium, then after a 2-hour exposure (i.e., one half of the half-time), the CO saturation would be ½ × ½ × 50% or 12.5%. The symptoms at this point would be mild and nonspecific and would include headache, nausea, vomiting, drowsiness, and interference with night vision. Victims with limited coronary blood flow could experience angina. After a 4-hour exposure (i.e., one half-time), the CO saturation would be ½ × 50%, or 25%. The symptoms would be more severe and would include impaired mental function and perhaps unconsciousness. (See Note: Calculating the Lethal Partial Pressure of Carbon Monoxide; Other Gases That Bind to Hemoglobin; Effects of Carbon Monoxide Poisoning in Patients with Reduced Coronary Blood Flow)
Threshold Limit Values and Biological Exposure Indices Threshold limit values (TLVs) are reasonable environmental levels of toxic substances or physical agents (e.g., heat or noise) to which industrial workers can be exposed without causing predictable harm. Rather than depending on concentrations measured in air or food, we can use biological exposure indices (BEIs) to limit exposure to toxic substances by measuring the effects of these substances on animals and humans. The changes detected in the body are called biomarkers of exposure and correlate with the intensity and duration of exposure to toxic substances. (See Note: Threshold Limit Values and Biological Exposure Indices)
Tissues must resist the G force produced by gravity and other mechanisms of acceleration
Standing motionless on the earth’s surface at sea level, we experience a gravitational force—our weight—that is the product of our mass and the acceleration resulting from gravity (g = 9.8 ms−2): (See Note: The Laws of Motion)
In a particular condition, we may experience a different acceleration (a) from that caused by gravity. The G force is a dimensionless number that describes force (m · a) that we experience under a particular condition, relative to the gravitational force (m · g):
Thus, we normally experience a force of +1G that would cause us to fall with an acceleration of 9.8 ms−2 if we were not supported in some way.
Accelerations besides that caused by gravity also affect physiology. An accelerometer, placed on a belt, would show that we can jump upward with an acceleration of ~3G. It would also show that, on landing, we would strike the ground with a force of 3G—a force that our bones and other tissues must be able to tolerate. Later, we discuss G forces from the perspective of air and space flight.
At +1G, each cm2 of the cross section of a vertebral body, for example, can withstand the compressive force generated by a mass of ~20 kg before the trabeculae begin to be crushed. Thus, at +1G, a vertebral body with a surface area of 10 cm2 could support the compressive force generated by a mass of ~200 kg, far more than enough to support 35 kg, the mass of the upper half of the body of a 70-kg person. In fact, this strength would be adequate to withstand a G force of a (200 kg)/(35 kg) = +5.7G—provided the backbone is straight. However, if the backbone is not straight, the tolerance could be +3G, or approximately the acceleration achieved by jumping upward and landing on the feet with the back curved. When a pilot ejects from an aircraft, the thrust of the explosive cartridges accelerates the seat upward, and this can crush a vertebral body unless the pilot keeps the back straight. (See Note: Forces Supported by Vertebral Body)
With increasing age, our bones tend to demineralize (see Chapter 60), a process that weakens them and also causes us to grow shorter because of the demineralization of the vertebrae. Stepping off a curb, an elderly person with demineralized bones may fracture the neck of the femur or crush a vertebra. Demineralization also occurs with immobilization and space flight. In one study, a 6- to 7-week period of immobilization from bed rest led to losses of 14 g of calcium from bones, 1.7 kg of muscle cytoplasm, 21% in the strength of the gastrocnemius muscle, and 6% in average blood volume. The subjects became faint when they were suddenly tilted on a board, head above feet. Although the changes were reversible after these subjects resumed ambulation, it took 4 weeks for muscle strength to return to normal during remobilization.
The partial pressures of gases—other than water—inside the body depend on barometric pressure
As discussed in the next two major sections of this chapter, extremely high or extremely low values of PB create special challenges for the physiology of the body, particularly the physiology of gases. Dalton’s law (see Chapter 26for the box on this topic) states that PB is the sum of the partial pressures of the individual gases in the air mixture. Thus, in the case of ordinary dry air (see Table 26-1), most of the sea level PB of 760 mm Hg is the result of N2(~593 mm Hg) and O2 (~159 mm Hg), with smaller contributions from trace gases such as argon (~7 mm Hg) and CO2 (~0.2 mm Hg). As PB increases during diving beneath the water, or as PB decreases during ascent to high altitude, the partial pressure of each constituent gas in dry ambient air changes in proportion to the change in PB. At high values of PB, this relationship is especially important for ambient PN2 and PO2, which can rise to toxic levels. At low values of PB, this relationship is important for ambient PO2, which can fall to levels low enough to compromise the O2 saturation of Hb (see Chapter 31) and thus the delivery of O2 to the tissues. (See Note: Gas Laws)
The proportionality between PB and the partial pressure of constituent gases breaks down in the presence of liquid water. When a gas is in equilibrium with liquid water—as it is for inspired air by the time it reaches the trachea (see Chapter 26)—the partial pressure of water vapor (PH2O) depends not on PB but on temperature. Thus, at the very high pressures associated with deep sea diving, PH2O becomes a negligible fraction of PB, whereas PH2O becomes an increasingly dominant factor as we ascend to altitude.
DIVING PHYSIOLOGY
For every 10 m of depth of immersion, barometric pressure increases by 1 atm, thereby compressing gases in the lungs
The average PB at sea level is 760 mm Hg. In other words, if you stand at sea level, the column of air extending from your feet upward for several tens of kilometers through the atmosphere exerts a pressure of 1 atmosphere (atm). In a deep mine shaft, over which the column of air is even taller, PB is higher still. However, it is only when diving under water that humans can experience extreme increases in PB. A column of fresh water extending from the earth’s surface upward 10.3 m exerts an additional pressure of 760 mm Hg—as much as a column of air extending from sea level to tens of kilometers skyward. The same is true for a column of water extending from the surface of a lake to a depth of 10.3 m. For seawater, which has a density ~2.5% greater than that of fresh water, the column must be only 10 m to exert 1 atm of pressure. Because liquid water is virtually incompressible, PB increases linearly with the height (weight) of the column of water (Fig. 61-1). Ten meters below the surface of the sea, PB is 2 atm, 1 atm for the atmospheric pressure plus 1 atm for the column of water. As the depth increases to 20 m and then to 30 m, PBincreases to 3 atm, then 4 atm, and so on.
Figure 61-1 Pressures at increasing depth of immersion. The pressure at the surface of the ocean is 1 atm and increases by 1 atm for each 10 m of immersion in sea water.
Increased external water pressure does not noticeably compress the body’s fluid and solid components until a depth of ~1.5 km. However, external pressure compresses each of the body’s air compartments to an extent that depends on the compliance of the compartment. In compliant cavities such as the intestines, external pressure readily compresses internal gases. In relatively stiff cavities, or those that cannot equilibrate readily with external pressure, increases of external pressure can distort the cavity wall, with resulting pain or damage. For example, when the eustachian tube is blocked, the middle ear pressure cannot equilibrate with external pressure, and blood fills the space in the middle ear or the tympanic membrane ruptures.
According to Boyle’s law, pressure and volume vary inversely with each other. Thus, if the chest wall were perfectly compliant, a breath-holding dive to 10 m below the surface would double the pressure and compress the air in the lungs to half its original volume. Aquatic mammals can dive to extreme depths because rib flexibility allows the lungs to empty. Whales, for example, can extend a breath-hold dive for up to 2 hours and can descend to depths as great as 900 m (91 atm) without suffering any ill effects. The human chest wall does not allow complete emptying of the lungs, and, indeed, the human record for a breath-hold dive is 160 m below the surface. (See Note: Gas Laws)
In a breath-hold dive that is deep enough to double PB, alveolar PCO2 could also double to 80 mm Hg. Because this value is substantially higher than the PCO2 of mixed venous blood at sea level (46 mm Hg), the direction of CO2diffusion across the blood-gas barrier reverses, and alveolar CO2 enters pulmonary capillary blood and increases arterial PCO2. In time, metabolically generated CO2 accumulates in the blood and eventually raises mixed venous PCO2 to values higher than alveolar PCO2 so CO2 diffusion again reverses direction, and CO2 accumulates in the alveoli. The increase in arterial PCO2 can reduce the duration of the dive by increasing ventilatory drive (see Chapter 32). During the ascent phase of the dive, the fall in PB leads to a fall in alveolar PCO2 and PO2, promoting the exit of both gases from the blood, and thus a fall in arterial PCO2 and PO2. The fall in arterial PO2 can lead to shallow water blackout. (See Note: Decrease in Lung Volume with Depth of Immersion)
Divers breathe compressed air to keep their lungs normally expanded
Technical advances have made it possible for divers to remain beneath the water surface for periods longer than permitted by a single breath-hold. One of the earliest devices was a diving bell that surrounded the diver on all sides except the bottom. Such a bell was reportedly used by Alexander the Great in 330 BC and then improved by Sir Edmund Halley in 1716 (Fig. 61-2). By the early 19th century, pumping compressed air from above the water surface through a hose to the space underneath the bell kept water out of the bell. In all these cases, the diver breathed air at the same pressure as the surrounding water. Although the pressures both surrounding the diver’s chest and inside the airways were far higher than at sea level, the pressure gradient across the chest wall was normal. Thus, the lungs were normally expanded. (See Note: The Diving Bell)
Figure 61-2 Diving bell. Between 1716 and 1721, Halley, the astronomer who gave his name to the comet, designed and built a wooden diving bell with an open bottom. Because the bell was at a relatively shallow depth (~12 m), the water level rose only partly into the bell. In Halley’s system, the air was replenished from a barrel that was open at the bottom and weighted with lead to sink beneath the diving bell. Thus, the air pressure in the barrel was higher than in the bell. The diver used a valve to regulate airflow into the bell. This design was in use for a century, until a practical pump was available for pumping air directly from the surface. The lower part of the figure illustrates what would have happened if Halley’s bell had been lowered to much greater depths. The greater the depth, the greater the water pressure. Because the air pressure inside the bell must be the same as the water pressure, the air volume progressively decreases at greater depths, and the water level rises inside the bell. (See Note: The Diving Bell)
The conditions are essentially the same in a modern-day caisson, a massive, hollow, pressurized structure that functions like a large diving bell. Once again, the pressure inside the caisson (3 to 4 atm) has to be high enough to prevent water at the bottom of the caisson from entering. Several workers (“sand hogs”) at the bottom of the caisson may excavate material from the bottom of a river for constructing tunnels or foundations of bridges.
Technical advances also extended to individual divers, who first wore diving suits with spherical helmets over their heads (Fig. 61-3A). The air inside these helmets was pressurized to match exactly the pressure of the water in which they were diving. In 1943, Jacques Cousteau perfected the self-contained underwater breathing apparatus, or SCUBA, that replaced cumbersome gear and increased the mobility and convenience of an underwater dive (Fig. 61-3B). (See Note: Diving Helmets and the Scuba System)
Figure 61-3 Devices for breathing under water. A, Compressed air, pumped from the surface to the diver, keeps the pressure inside the helmet slightly higher than that of the surrounding water. B, SCUBA is an acronym for self-contained underwater breathing apparatus.
Although the foregoing techniques permit deep dives for extended periods of time, they require training and carry the risk of drowning secondary to muscle fatigue and hypothermia. Air floatation and thermal insulation of the diving suit lessen these hazards. For reasons that will become apparent, use of any of these techniques while breathing room air carries additional hazards, including nitrogen narcosis, O2toxicity, and problems with decompression.
Increasing alveolar PN2 can cause narcosis
Descending beneath the water causes the inspired PN2—nearly 600 mm Hg at sea level (see Table 26-1)—to increase as PB increases. According to Henry’s law (see Chapter 26 for the box on this topic), the increased PN2 will cause more N2 to dissolve in pulmonary capillary blood and, eventually, the body’s tissues. The dissolved [N2] in various compartments begins to increase immediately but may take many hours to reach the values predicted by Henry’s law, as discussed later. Because of its high lipid solubility, N2 dissolves readily in adipocytes and in membrane lipids. A high PN2 reduces the ion conductance of membranes, and therefore neuronal excitability, by mechanisms that are similar to those of gas anesthetics. Diving to increased depths (e.g., 4 to 5 atm) while breathing compressed air causes nitrogen narcosis. Mild nitrogen narcosis resembles alcohol intoxication (e.g., loss of psychosocial inhibitions). According to “Martini’s law,” each 15 m of depth has the effects of drinking an additional martini. Progressive narcosis occurs with increasing depth or time of the dive and is accompanied by lethargy and drowsiness, rapid onset of fatigue, and, eventually, loss of consciousness. Because it develops insidiously, nitrogen narcosis poses a potentially fatal threat to divers who are not aware of the risks.
Increasing alveolar PO2 can lead to O2 toxicity
At sea level, dry inspired air has a PO2 of 159 mm Hg. However, the alveolar PO2 of a healthy person at sea level air is ~101 mm Hg, reduced from 159 mm Hg by humidification in the airways and removal of O2 by gas exchange with the blood (see Chapter 31). Arterial PO2 at sea level is very close to alveolar PO2 (within ~10 mm Hg) and nearly saturates Hb, to yield an arterial O2 content of ~20 mL/dL blood (Fig. 61-4, red curve). As PB—and therefore arterial PO2—increases at greater depths, the O2 bound to Hb increases very little. However, according to Henry’s law (see Chapter 26 for the box on this topic), the O2that is physically dissolved in the water of blood increases linearly (Fig. 61-4, black line). Thus, the increment of total O2 content at depth reflects dissolved O2 (Fig. 61-4, blue curve).
Figure 61-4 O2 content of blood at high pressures. The red curve is the same Hb-O2 dissociation curve as that in Figure 29-3, except the range is extended to very high values of PO2.
During a breath-hold dive to 5 atm, or in a hyperbaric chamber pressurized to 5 atm, arterial PO2 increases to ~700 mm Hg, slightly higher than breathing 100% O2 at sea level. Exposure to such a high PO2 has no ill effects for up to several hours. However, prolonged exposure damages the airway epithelium and smooth muscle and causes bronchiolar and alveolar membrane inflammation and, ultimately, pulmonary edema, atelectasis, fibrin formation, and lung consolidation. These effects are the result of inactivating several structural repair enzymes and oxidizing certain cellular constituents.
A prolonged, elevated PO2 also has detrimental effects on nonpulmonary tissues, including the central nervous system (CNS). Exposure to an ambient PO2 of ~1500 mm Hg (e.g., breathing room air at ~10 atm) for as little as 30 to 45 minutes can cause seizures and coma. Preliminary symptoms of O2 toxicity include muscle twitching, nausea, disorientation, and irritability. The toxic effects of O2 occur because O2 free radicals (e.g., superoxide and peroxide free radicals) oxidize the polyunsaturated fatty acid component of cell membranes as well as enzymes that are involved in energy metabolism. At the more modest PO2levels that normally prevail at sea level, scavenger enzymes (see Chapter 62) eliminate the relatively few radicals formed.
Using helium to replace inspired N2 and O2 avoids nitrogen narcosis and O2 toxicity
Several occupations—including deep mining caisson work and deep diving—require people to spend extended periods at a PB greater than that at sea level. During an extended dive or other exposure to high pressure (one exceeding several hours), the body’s tissues gradually equilibrate with the high-pressure gases that one has been breathing. This equilibrated state is referred to by the misnomer saturation. At sea level, the human body normally contains ~1 L of dissolved N2, equally distributed between the body’s water and fat compartments. As PN2 rises, the N2 equilibrates only slowly with the body’s lipid stores because adipose tissue is relatively underperfused. Although a deep dive of several minutes does not provide sufficient time to equilibrate the fat with N2, one of several hours’ duration does. At equilibrium—as required by Henry’s law—the volume of N2 dissolved in the tissues is proportional to alveolar PN2. Thus, if the body normally dissolves 1 L of N2 at a PB of 1 atm, it will ultimately dissolve 4 L of N2 at a PBof 4 atm. These same principles apply to O2, although the degree to which O2 dissolves in various tissues, and the speed at which equilibration takes place, is different. (See Note: High-Pressure Occupations)
The adverse effects of N2 and O2 depend on the amount of gas that is dissolved in tissues. The amount, in turn, increases with the dive’s depth (i.e., partial pressure of the gas) and duration (i.e., how close the gas is to achieving equilibrium with various tissues). Thus, the length of time that a diver can spend safely underwater is inversely proportional to the depth of the dive.
To prevent nitrogen narcosis in saturation diving conditions, divers must partly or completely replace N2 with another inert gas. Helium is the replacement gas of choice for four reasons: (See Note: Properties of Helium)
1. Helium has only a fraction of the narcotizing effect of N2.
2. Helium dissolves in the tissues to a lesser extent than N2.
3. Helium has a lower density than N2, and this lowers effective airway resistance. However, the low density of helium facilitates convective “air” cooling around the body, thereby increasing heat loss. Thus, ambient temperature must be higher in a high-helium compression chamber.
4. During the decompression phase of a dive, helium diffuses out of the tissues more rapidly than does N2 and thereby alleviates most of the problems associated with decompression.
To prevent O2 toxicity in saturation diving conditions, divers must reduce the fraction of inspired air that is O2 in the compressed gas mixture. Thus, at a PB of 10 atm, a mixture of 2% O2 in helium will provide the same inspired PO2 as room air does at sea level (i.e., ~20% O2 at a PB of 1 atm).
Following an extended dive, a diver must decompress slowly to avoid decompression sickness
Although I have focused on problems divers face while at great depths, serious difficulties also arise if—after a deep saturation dive—the diver returns to the surface too quickly. At the end of a saturation dive, PN2 is at the same high value in the alveoli and most tissues. As PB falls during ascent, alveolar PN2 will fall as well, thus creating a PN2 gradient from the mixed venous blood to the alveolar air. Washout of N2 from the blood creates a PN2 gradient from tissues to blood. To allow enough time for the dissolved N2 to move from tissues to blood to alveoli, a diver must rise to the surface slowly (no faster than ~3 m/hr). Because N2 exits from water much faster than it does from fat, the total elimination of N2 has two components: some compartments empty quickly (e.g., blood), and some empty slowly (e.g., joints, fat, eyeballs). (See Note: Nitrogen Washout: The Oxygen Window)
Too rapid an ascent causes the N2 in the tissues—previously dissolved under high pressure—to leave solution and to form bubbles as PB falls. This process is identical to the formation of gas bubbles when one opens a bottle of a carbonated beverage that had been capped under high pressure. Similar problems can occur in pilots who bail out from a pressurized aircraft at high altitude or in divers who ascend to altitude or become aircraft passengers (i.e., exposed to a lower-than-normal PB) too soon after completing a dive that, by itself, would not cause difficulties.
During a too-rapid decompression, bubble formation can occur in any tissue in which N2 has previously dissolved. Decompression sickness (DCS) is the general term for the clinical disorder. The pathologic process has three general causes: (1) local formation of bubbles in tissue; (2) bubbles that form emboli in blood; the blood can carry them along until they become wedged in and obstruct a vessel, and a patent foramen ovale can allow bubbles to enter the arterial circulation; and (3) arterial gas embolization; if air is trapped behind an obstructed bronchus, expansion can cause it to tear the lung tissue, enter a pulmonary vein and then a systemic artery, and lodge in the brain or other organ. (See Note: Dysbarism)
Clinicians recognize three categories of DCS. Mild or type I DCS can include short-lived mild pains (“niggles”), pruritus, a skin rash, and deep throbbing pain (“bends”) resulting from bubbles that form in muscles and joints. Serious or type II DCS can include symptoms in the CNS, lungs, and circulatory system. The CNS disorder—most commonly involving the spinal cord—reflects bubble formation in the myelin sheath of axons that compromises nerve conduction. Symptoms may range from dizziness (“staggers”) to paralysis. Pulmonary symptoms (“chokes”)—resulting from gas emboli in the pulmonary circulation—include burning pain on inspiration, cough, and respiratory distress. In the circulatory system, bubbles can not only obstruct blood flow but also trigger the coagulation cascade and lead to the release of vasoactive substances. Hypovolemic shock is also a part of this syndrome. The third category is arterial gas embolization, in which large gas emboli can have catastrophic consequences unless the victim receives immediate recompression treatment.
Figure 61-5 shows how long a diver can spend at various depths—breathing room air—without having to undergo a decompression protocol during the ascent. For example, a dive to 8 m can last indefinitely without any ill effects during the ascent. A dive of 25 minutes’ duration will not provide sufficient time to saturate the tissues unless the dive exceeds 40 m. However, a longer dive at 40 m will require a decompression program. For instance, a 20-minute dive to a depth of 90 m requires nearly 3 hours of decompression time. Thus, the rate at which a diver should ascend to avoid DCS depends on both the depth and the duration of the dive. Divers use detailed tables to plan their rate of ascent from a deep dive.
Figure 61-5 The need for decompression as a function of depth and duration of dive. If the dive is sufficiently brief or sufficiently shallow, no decompression is required (teal area). For deeper depths or longer durations, a decompression protocol is required (salmon area). (Data from Duffner GJ: Ciba Clin Symp 1958; 10:99-117.)
The best treatment for DCS is to recompress the diver in a hyperbaric chamber. Recompression places the gases back under high pressure and forces them to dissolve again in the tissues, a process that instantly relieves many symptoms. Once the diver is placed under high pressure, decompression can be carried out at a deliberate and supervised pace.
HIGH-ALTITUDE PHYSIOLOGY
Barometric pressure and ambient PO2 on top of Mount Everest are approximately one third of their sea level values
Unlike a column of water, which is relatively noncompressible and has a uniform density, the column of air in the atmosphere is compressible and has a density that decreases exponentially ascending from sea level. Half of the mass of the earth’s atmosphere is contained in the lowest 5500 m. Another fourth is contained in the next 5500 m (i.e., 5500 to 11,000 m of altitude). In other words, at higher and higher altitudes, the number of gas molecules pressing down on a mountain climber also falls exponentially; PB falls by half for each ~5500 m of ascent (Fig. 61-6).
Figure 61-6 Altitude dependence of PB and PO2 in dry air.
Everest Base Camp At an altitude of 5500 m—which also happens to be the altitude of the first base camp used in most ascents of Mount Everest—PB is half the value at sea level (PB ≅ 380 mm Hg), as is the ambient PO2 (PO2 ≅ 80 mm Hg). At this altitude, arterial O2 delivery (arterial blood O2 content × cardiac output) can still meet O2 demands in most healthy, active persons, even during mild physical activity. However, the body’s compensatory responses to reduced ambient PO2 at high altitude vary among different people. Thus, exposure to an altitude of 5500 m is problematic for a significant portion of the population.
Peak of Mount Everest The peak of Mount Everest—8848 m above sea level—is the highest point on earth. PB at the peak is ~255 mm Hg, approximately one third that at sea level, and the ambient PO2 is only ~53 mm Hg. For a climber at the peak of Mount Everest, the PO2 of the humidified inspired air entering the alveoli is even lower because of the effects of water vapor (PH2O = 47 mm Hg at 37°C). Therefore, the inspired PO2 = 21% × (255 − 47) = 44 mm Hg, compared with 149 mm Hg at sea level (see Table 26-1). Hypoxia is thus a major problem at the summit of Mount Everest.
Air Travel Pressurized cabins in passenger planes maintain an ambient pressure equivalent to ~1800 m of altitude (~79% of sea level pressure) in cross-continental flights, or ~2400 m of altitude (~74% of sea level pressure) in transoceanic flights. Considering that most people do not need supplemental O2 in the inspired air at Denver (~1500 m) or at some ski resorts (~3000 m), most airline passengers are not bothered by the slight reduction in arterial O2saturation (89% saturation at 3000 m) associated with these airline cabin pressures. However, passengers with chronic obstructive pulmonary disease may need to carry supplemental O2 onto the plane even if they do not require it at sea level.
Up to an altitude of ~3000 m, arterial O2 content falls proportionally less than PB because of the shape of the hemoglobin-O2 dissociation curve
Although PB and ambient PO2 decrease by the same fraction with increasing altitude, the O2 saturation of Hb in arterial blood decreases relatively little at altitudes up to ~3000 m. The reason is that, at this altitude, arterial PO2 is 60 to 70 mm Hg, which corresponds to the relatively flat portion of the O2-Hb dissociation curve (see Fig. 29-3), where almost all the O2 in blood is bound to Hb. Decreasing arterial PO2has relatively little effect on arterial O2 content until arterial PO2 falls to less than this flat portion of the curve. Thus, the characteristics of Hb protect the arterial O2 content, despite modest reductions of PO2. At higher altitudes, aviators are advised to breathe supplemental O2.
Although the amount of O2 in the blood leaving the lung is important, even more important is the amount of O2 taken up by systemic tissues. This uptake is the product of cardiac output and the arteriovenous (a-v) difference in O2content (see Chapter 29). At sea level, arterial PO2 is ~100 mm Hg, corresponding to an Hb saturation of ~97.5%, whereas the mixed venous PO2 is ~40 mm Hg, corresponding to an Hb saturation of ~75%. The difference between the arterial and the venous O2 contents is ~22.5% of Hb’s maximal carrying capacity for O2. However, at an altitude of 3000 m, arterial PO2 is only ~60 mm Hg, which may correspond to an Hb saturation of only 88%. This reduction in blood O2 content is called hypoxemia. Assuming that everything else remains the same (e.g., O2 utilization by the tissues, hematocrit, 2, 3-diphosphoglycerate levels, pH, cardiac output), then the mixed a-v difference in Hb saturation must still be 22.5%. Thus, the mixed venous blood at 3000 m must have an Hb saturation of 88% − 22.5% = 65.5%, which corresponds to a PO2 of ~33 mm Hg. As a result, the a-v difference of PO2 is much larger at sea level (100 − 40 = 60 mm Hg) than at 3000 m (60 − 33 = 27 mm Hg), even though the a-v difference in O2 content is the same. The reason for the discrepancy is that the O2-Hb dissociation curve is steeper in the region covered by the PO2 values at high altitude. (See Note: Capillary Tissue PO2Gradients)
At very high altitudes, still another factor comes into play. The uptake of O2 by pulmonary capillary blood slows at high altitudes and thereby reflects the smaller O2 gradient from alveolus to blood (see Fig. 30-10D). As a result, at sufficiently high altitudes, particularly during exercise, O2 may no longer reach diffusion equilibrium between alveolar air and pulmonary capillary blood by the time the blood reaches the end of the capillary. Thus, at increasing altitude, not only does alveolar PO2—and hence the maximal attainable arterial PO2—fall in a predictable way, but also the actual arterial PO2 may fall to even a greater extent because of a failure of pulmonary capillary blood to equilibrate with alveolar air.
During the first few days at altitude, compensatory adjustments to hypoxemia include tachycardia and hyperventilation
A reduction in arterial PO2 stimulates the peripheral chemoreceptors and causes an immediate increase in ventilation. Increased ventilation has two effects. First, it brings alveolar PO2 (and thus arterial PO2) closer to the ambient PO2. Second, hyperventilation blows off CO2, the effect of which is respiratory alkalosis that inhibits the peripheral but especially the central chemoreceptors and decreases ventilatory drive (see Chapters 31 and 32). Thus, total ventilation during an acute exposure to 4500 m is only about twice that at sea level, whereas the hypoxia by itself would have produced a much larger stimulation. Accompanying the increased ventilatory drive during acute altitude exposure is an increase in heart rate, probably owing to the heightened sympathetic drive that accompanies acute hypoxemia (see Chapter 23). The resultant increase in cardiac output enhances O2 delivery.
During the next few days to weeks at an elevation of 4500 m, acclimatization causes ventilation to increase progressively by about the same amount as the acute response. As a result, PO2 continues to improve, and PCO2 falls. Two mechanisms appear to cause this slower phase of increased ventilation. First, the pH of the cerebrospinal fluid (CSF) decreases, an effect that counteracts the respiratory alkalosis induced by the increase in ventilation and thus offsets the inhibition of central chemoreceptors. However, the time course of the pH increase in CSF does not correlate tightly with the time course of the increase in ventilation. The pH at the actual site of the central chemoreceptors may fall with the appropriate time course. Long-term hypoxia appears to increase the sensitivity of the peripheral chemoreceptors to hypoxia, and this effect may better account for acclimatization.
In the second mechanism for acclimatization, the kidneys respond over a period of several days to the respiratory alkalosis by decreasing their rate of acid secretion (see Chapter 39) so blood pH decreases toward normal (i.e., metabolic compensation for respiratory alkalosis). Another result of this compensation is spillage of HCO−3 into the urine that leads to osmotic diuresis and production of alkaline urine. The consequence of reducing both CSF and plasma pH is to remove part of the inhibition caused by alkaline pH and thus allow hypoxia to drive ventilation to higher values.
An extreme case of adaptation to high altitude occurs in people climbing very high mountains. In 1981, a team of physiologists ascended to the peak of Mount Everest. Although on their way up to the summit the climbers breathed supplemental O2, at the summit they obtained alveolar gas samples while breathing ambient air—trapping exhaled air in an evacuated metal container. The alveolar PCO2 at the summit was a minuscule 7 to 8 mm Hg, or ~20% of the value of 40 mm Hg at sea level. Thus, assuming a normal rate of CO2 production, the climber’s alveolar ventilation must have been 5-fold higher than normal (see Chapter 31). Because the work of heavy breathing and increased cardiac output at the summit (driven by hypoxia) would increase CO2 production substantially, the increase in alveolar ventilation must have been much greater than 5-fold.
The climbers’ alveolar PO2 at the peak of Mount Everest was ~28 mm Hg, which is marginally adequate to provide a sufficient arterial O2 content to sustain “resting” metabolic requirement at the summit. However, the term restingis somewhat of a misnomer, because the work of breathing and the cardiac output are markedly elevated.
Long-term adaptations to altitude include increases in hematocrit, pulmonary diffusing capacity, capillarity, and oxidative enzymes
Although the increases in ventilation and cardiac output help to maintain O2 delivery during acute hypoxia, they are costly from an energy standpoint and cannot be sustained for extended periods. During prolonged residence at a high altitude, the reduced arterial PO2 triggers profound adaptations that enhance O2 delivery to tissues at a cost that is lower than that exacted by short-term compensatory strategies. Many of these adaptations are mediated by an increase in hypoxia-inducible factor 1 (HIF-1), a transcription factor that activates genes involved in erythropoiesis, angiogenesis, and other processes.
Hematocrit Red blood cell (RBC) mass slowly increases with prolonged hypoxemia. The Hb concentration of blood increases from a sea level value of 14 to 15 g/dL to more than 18 g/dL, and hematocrit increases from 40% to 45% to more than 55%. Normally, the body regulates RBC mass within fairly tight limits. However, renal hypoxia and norepinephrine stimulate the production and release of erythropoietin (EPO) from fibroblast-like cells in the kidney (see p. 453 for the box on EPO). EPO is a growth factor that stimulates production of proerythroblasts in bone marrow and also promotes accelerated development of RBCs from their progenitor cells. (See Note: Erythropoietin)
Pulmonary Diffusing Capacity Acclimatization to high altitude also causes a 2- to 3-fold increase in pulmonary diffusing capacity. Much of this increase appears to result from a rise in the blood volume of pulmonary capillaries and from the associated increase in capillary surface area available for diffusion (see Chapter 30). This surface area expands even further because hypoxia stimulates an increase in the depth of inspiration. Finally, right ventricular hypertrophy raises pulmonary arterial pressure and increases perfusion to the upper, well-ventilated regions of the lungs (see Chapter 31).
Capillary Density Hypoxia causes a dramatic increase in tissue vascularity. Tissue angiogenesis (see Chapter 20) occurs within days of exposure to hypoxia, triggered by growth factors released by hypoxic tissues. Among these angiogenic factors are vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and angiogenin.
Oxidative Enzymes Hypoxia promotes expression of oxidative enzymes in the mitochondria and thereby enhances the tissues’ ability to extract O2 from the blood (see Chapter 60). Thus, acclimatization to high altitude increases not only O2 delivery to the periphery, but also O2 uptake by the tissues.
Altitude causes mild symptoms in most people and acute or chronic mountain sickness in susceptible individuals
Symptoms of Hypoxia The first documented evidence of the ill effects of high altitude was in 35 BC, when Chinese travelers called the Himalayas the “Headache Mountains.” Recreational mountain climbing became popular in the mid-19th century, and with modern transportation, many people can now travel rapidly to mountain resorts. In fact, it is possible to ascend passively from sea level to high altitude in a matter of minutes (e.g., in a balloon) to hours. A rapid ascent may precipitate a constellation of relatively mild symptoms: drowsiness, fatigue, headache, nausea, and a gradual decline in cognition. These uncomfortable effects of acute hypoxia are progressive with increasing altitude. They occur in some people at altitudes as low as 2100 m and occur in most people at altitudes higher than 3500 m. Initially, these symptoms reflect an inadequate compensatory response to hypoxemia that results in reduced O2 delivery to the brain. In the longer term, symptoms may stem from mild cerebral edema, which probably results from dilation of the cerebral arterioles, thus leading to increased capillary filtration pressure and enhanced transudation (see Chapter 20).
Acute Mountain Sickness Some people who ascend rapidly to altitudes as seemingly moderate as 3000 to 3500 m develop acute mountain sickness (AMS). The constellation of symptoms is more severe than those described in the previous paragraph and includes headache, fatigue, dizziness, dyspnea, sleep disturbance, peripheral edema, nausea, and vomiting. The symptoms usually develop within the first day and last for 3 to 5 days. The primary problem in AMS is hypoxia, and the symptoms probably have two causes. The first is thought to be a progressive, more severe case of cerebral edema. The second cause of the symptoms is pulmonary edema, which occurs as hypoxia leads to hypoxic pulmonary vasoconstriction (see Chapter 31), which, in turn, increases total pulmonary vascular resistance, pulmonary capillary pressure, and transudation. Certain people have an exaggerated pulmonary vascular response to hypoxia, and they are especially susceptible to AMS. Cerebral or pulmonary edema can be fatal if the exposure to hypoxia is not rapidly reversed, first by providing supplemental O2 to breathe and then by removing the individual from the high altitude.
Although being physically fit provides some protection against AMS, the most important factor is an undefined constitutional difference. Persons who are least likely to develop symptoms ventilate more in response to the hypoxia and therefore tend to have a higher PO2 and a lower PCO2. The higher PO2 and lower PCO2 lead to less cerebral vasodilation, and the higher PO2 minimizes pulmonary vasoconstriction.
Chronic Mountain Sickness After prolonged residence at high altitude, chronic mountain sickness may develop. The cause of this disorder is an overproduction of RBCs—an exaggerated response to hypoxia. In such conditions, the hematocrit can exceed 60% (polycythemia), thereby dramatically increasing blood viscosity and vascular resistance and increasing the risk of intravascular thrombosis. The combination of pulmonary hypoxic vasoconstriction and increased blood viscosity is especially onerous for the right side of the heart, which experiences a greatly increased load. These conditions eventually lead to congestive heart failure of the right ventricle. (See Note: High-Altitude Diseases)
FLIGHT AND SPACE PHYSIOLOGY
Acceleration in one direction shifts the blood volume in the opposite direction
To accelerate a rocket from rest, we must apply enough force to overcome its inertial force (i.e., its weight, the product of its mass, and the acceleration caused by gravity), as well as the frictional forces of the environment. This requirement is merely a restatement of Newton’s second law of motion. With the rocket accelerating vertically, astronauts inside experience an inertial G force, as required by Newton’s third law, a force that presses the astronauts into their seats in the direction opposite that of the rocket’s acceleration. (See Note: The Laws of Motion)
Before liftoff, an astronaut experiences only the force of gravity, +1G. As a rocket blasts off from earth, the astronaut experiences higher G forces. In early rockets, astronauts sometimes experienced G forces as high as +10G. Maximal G forces in the space shuttle are only ~+4G (Fig. 61-7). Similarly, pilots of high-performance aircraft experience positive G forces as they pull out of a dive, and we all experience negative G forces when an aircraft hits turbulence, suddenly loses altitude, and lifts us out of our seats. Although G forces can frequently have potentially large effects on aircraft pilots, they affect astronauts only during the liftoff and re-entry phases of space flight. To ensure that acceleration effects have a minimal influence on body function, astronauts sit with their backs perpendicular to the direction of the accelerating force, so the G force acts across the chest from front to back. (See Note: Effects of Acceleration on Astronauts)
Figure 61-7 G forces during ascent into space on the space shuttle. Before liftoff, astronauts experience +1G, the acceleration that results from the earth’s gravity. After liftoff, the solid rockets burn for ~2 minutes, during which time the G force increases to slightly more than +3G. After the solid-rocket burn, the G force falls back to +1G. Thereafter, the main engine gradually builds up the G force to ~+4G before engine cut-off. These G-force data were generated in a human centrifuge to simulate the profile of a shuttle launch. (Data from Buckey JC, Goble RL, Blomqvist CG: Med Instrum 1987; 87:238-243.)
G forces propel the body’s tissues in the direction opposite that of acceleration; these forces compress soft tissues against underlying structural elements (e.g., bone) or pull these tissues away from overlying structural elements. In addition, G forces tend to shift the blood volume away from the direction of acceleration, thereby adding to the other component forces that determine blood pressure (see Chapter 17).
In high-performance aircraft, the rapid motions associated with changes in flight direction or altitude produce G forces that can be considerable for several minutes, exceeding 8Gs. Even in relatively primitive aircraft, aerobatic maneuvers can shift blood volume away from the head and can result in transient reductions in cerebral blood flow and O2 delivery. If these reductions are sufficiently large, they can result in loss of consciousness. The early warnings of such an event are narrowing of the visual field (i.e., loss of peripheral vision) and loss of color perception as the retina is deprived of O2, a phenomenon called gray-out. The term blackout describes a total loss of consciousness that occurs during acceleration that lasts for tens of seconds or minutes. Pilots experiencing gray-out or blackout are at extreme risk. As early as World War II, fighter pilots used G-suits that provided counterpressure to the lower extremities during repeated tight maneuvers during dogfights. The counterpressure opposed the pooling of blood in the extremities and maintained sufficient cardiac filling, cardiac output, and blood flow to the brain, thereby eliminating the tendency toward gray-out.
“Weightlessness” causes a cephalad shift of the blood volume
An astronaut in an orbiting spacecraft experiences “weightlessness,” a state of near-zero G force, also called a microgravity environment. Although an astronaut at an altitude of 200 km still experiences ~94% of the force of the earth’s gravity at sea level (i.e., the astronaut truly has weight), the centrifugal force of the spacecraft’s orbital trajectory balances the earth’s gravitational force, and the astronaut experiences no net acceleration forces and thus has the sensation of weightlessness. This weightlessness, however, differs from the true near-zero-gravity environment in “outer space.”
We are adapted to life at +1G, and arteriolar tone in the lower extremities prevents pooling of blood in the capacitance vessels (see Chapter 25), thereby ensuring adequate venous return to the right heart. The acute effects of microgravity on the circulatory system are exactly what you would expect for a system designed to oppose the effect of gravity in a standing person: blood volume redistributes toward the head. This cephalad shift of blood volume—away from the capacitance vessels of the legs—expands the central blood volume, increases the cardiac preload, and increases the filtration of plasma water into the interstitium of the facial region. The resulting edema explains the dramatically bloated facial appearance of astronauts in microgravity within 24 hours of the launch. From this discussion, you would think that the central venous pressure (CVP) is higher in space. However, such an increase in CVP has been difficult to confirm.
In laboratory studies involving prolonged head-down tilt (i.e., a model intended to simulate microgravity exposure), the cephalad shift of blood volume produces the expected increase in CVP and rapid reflex responses to the apparent volume overload. First, the increased stretch on the right atrium causes release of atrial natriuretic peptide (ANP). Second, stimulation of the low-pressure baroreceptors inhibits secretion of arginine vasopressin or antidiuretic hormone from the posterior pituitary (see Chapter 23). These two events increase excretion of salt and water by the kidneys (see Chapter 40). They also correct the perceived volume overload and explain the tendency for astronauts to remain relatively underhydrated during space flight.
In orbiting spacecraft, the cephalad shift of blood volume, even without an increase in CVP, causes a small increase in cerebral arterial pressure and thus in blood flow to the brain. Such regional alterations in blood volume and flow do not substantially affect total peripheral resistance in space. Thus, mean arterial pressure and cardiac output are not significantly different from their values on the earth’s surface.
Space flight leads to motion sickness and to decreases in muscle and bone mass
Despite training (e.g., in three-dimensional motion simulators), more than half of all astronauts experience motion sickness during the initial days of microgravity. Motion sickness (i.e., nausea and vomiting) results from conflicting sensory input to the brain regarding the position of the body. In space flight, motion sickness is the consequence of altered inertial stimulation of the vestibular system in the absence of normal gravitational forces. Nearly all cases of motion sickness resolve within the first 96 hours of microgravity exposure as the vestibular system or the CNS accommodates to the novel input.
The increased cerebral blood flow and blood volume in microgravity, accompanied by increased capillary filtration of fluid from the intravascular space, contribute to the increased incidence of headache, nausea, and motion sickness, at least during the transition period to microgravity. These symptoms reduce performance. Astronauts attempt to minimize these effects by restricting water intake before launch.
Numerous other changes occur during prolonged residence in microgravity, many of which are related to the markedly diminished aerobic power output in space, where the force of gravity does not oppose muscle contraction. The major physiological alterations include reductions in body water content, plasma and RBC volume, total body N2 stores, muscle mass, and total body Ca2+ and phosphate (associated with a loss in bone mass). The bone loss appears to be continuous with time in a weightless environment, whereas the other changes occur only during the first weeks in space. The reductions in plasma and RBC volumes result in a marked decrease in maximum cardiac output, a determinant of maximal aerobic power. The reduction of muscle mass decreases the maximal force developed by muscle. The reduction in bone mass similarly decreases bone strength. Although these changes are appropriate adaptations to a microgravity environment, in which great strength and high aerobic capacity have little inherent value, they are decidedly disadvantageous on return to the earth’s surface.
Exercise partially overcomes the deconditioning of muscles during space flight
The intermittent loading of muscles, bone, and the cardiovascular system prevents—to some extent—the deconditioning effects of space flight on muscle mass and performance. Astronauts have used bungee (i.e., elastic) cords and ergometric (i.e., work-measuring) stationary bicycles to provide resistance against which to exert force. The most effective exercise regimen appears to be walking on a motor-driven treadmill with the lower body encased in a negative-pressure chamber. Reducing the chamber pressure to 100 mm Hg lower than ambient pressure creates transmural pressure differences—across the blood vessels in the feet—that are similar to pressure differences when standing upright on the earth’s surface. However, this arrangement greatly exaggerates transmural pressure differences near the waist. For this reason, these astronauts also wear positive-pressure pants that compress the tissues by 70 mm Hg at the level of the waist and—decrementally—by 0 mm Hg at the feet. The net effect of the negative-pressure chamber and the graded positive-pressure pants is to create a physiological toe-to-waist gradient of transmural pressures across the blood vessels of the lower body. The aerobic activity, the impact of the feet on the treadmill, and the generation of physiological transmural pressure gradients appear to be sufficient to simulate exercise at +1G. This regimen can reduce or even eliminate the deconditioning effects of space flight.
Return to earth requires special measures to maintain arterial blood pressure
The problems associated with re-entry reflect a return to full gravity on earth’s surface. The most dramatic effects result from reduced blood volume and decreased tone of the leg vessels. Both factors contribute to reductions in cardiac preload, orthostatic tolerance, and exercise capacity. It has been common practice to shield astronauts from public view immediately after return to the earth’s surface, until they have regained a good orthostatic response.
In recent years, astronauts have employed various strategies just before re-entry to counter the adaptations to microgravity. The countermeasure to orthostatic intolerance is restoration of blood volume before re-entry. One means of attenuating the reduction of blood volume in space flight is an exercise program. Even a brief period (e.g., 30 minutes) of intense exercise expands plasma albumin content and increases plasma oncotic pressure and plasma volume by 10% within 24 hours. The problems with exercise programs are difficulties in logistics and the astronauts’ lack of motivation. A second means of minimizing the reduced blood volume is increasing salt and fluid intake. However, this practice has proven difficult to implement because of the consequent increase in urine flow. Currently, astronauts are educated about the effects of prolonged space flight and are then maintained under continuous scrutiny after re-entry until they have regained a normal orthostatic response. This usually occurs within hours, and certainly within 1 day, of re-entry.
REFERENCES
Books and Reviews
Bunn HF, Poyton RO: Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 1996; 76:839-885.
Crystal RG, West JB: The Lung. New York: Raven Press, 1991.
Duffner GJ: Medical problems involved in underwater compression and decompression. Ciba Clin Symp 1958; 10:99-117.
Krakauer J: Into Thin Air. New York: Anchor Books–Doubleday, 1997.
Monge C: Chronic mountain sickness. Physiol Rev 1943; 23:166-184.
West JB: Man in space. News Physiol Sci 1986; 1:189-192.
Journal Articles
Buckey JC, Goble RL, Blomqvist CG: A new device for continuous ambulatory central venous pressure measurement. Med Instrum 1987; 87:238-243.
Cain SM, Dunn JE II: Low doses of acetazolamide to aid the accommodation of men to altitude. J Appl Physiol 1966; 21:1195-1200.
Schoene RB, Lahiri S, Hackett PH, et al: Relationship of hypoxic ventilatory response to exercise performance on Mount Everest. J Appl Physiol 1984; 56:1478-1483.
West JB: Human physiology at extreme altitudes on Mount Everest. Science 1984; 223:784-788.