Chapter 11. The Respiratory System under Stress

The reader uses the knowledge he or she gained from the preceding chapters to predict the response of the respiratory system to 4 physiologic stresses: exercise, ascent to altitude, diving, and sleep.

• Identifies the physiologic stresses involved in exercise.
• Predicts the responses of the respiratory system to acute exercise.
• Describes the effects of long-term exercise programs (training) on the respiratory system.
• Identifies the physiologic stresses involved in the ascent to altitude.
• Predicts the initial responses of the respiratory system to the ascent to altitude.
• Describes the acclimatization of the cardiovascular and respiratory systems to residence at high altitudes.
• Identifies the physiologic stresses involved in diving.
• Predicts the responses of the respiratory system to various types of diving.
• Identifies the physiologic stresses involved in sleep.
• Relates the alterations that occur in the respiratory system during sleep to the pathophysiology of obstructive sleep apnea.

This chapter is mainly intended to be a review of the preceding chapters of the book. The responses of the respiratory system to 4 physiologic stresses are examined as they relate to the material already covered; the discussions of the responses to each stress will therefore be brief and rather superficial. For a more complete discussion of each stress, consult the Suggested Readings at the end of this chapter.

Acute Effects

The effects of exercise in an untrained person are mainly a function of an increase in the cardiac output coupled with an increase in alveolar ventilation.

Control of Breathing

As discussed at the end of Chapter 9, both the tidal volume and the breathing frequency are increased during exercise. The causes of the increased alveolar ventilation during exercise were discussed in that section.

Mechanics of Breathing

The work of breathing is increased during exercise. Larger tidal volumes result in increased work necessary to overcome the elastic recoil of the lungs and chest wall during inspiration because the lungs are less compliant at higher lung volumes and because the elastic recoil of the chest wall is inward at high thoracic volumes. Of course, the greater elastic recoil tends to make expiration easier, but this is offset by other factors. The high airflow rates generated during exercise result in a much greater airways resistance component of the work of breathing. Greater turbulence and dynamic compression of airways secondary to active expiration combine to greatly increase the work of breathing. (Recall that during turbulent airflow

Alveolar Ventilation

In normal adults, the resting minute ventilation (

As discussed in Chapter 9, at less strenuous levels of exercise, the increase in ventilation is accomplished mainly by increasing the tidal volume. During strenuous exercise, the tidal volume usually increases to a maximum of about 50% to 60% of the vital capacity of a normal subject, or about 2.5 to 3.0 L in an average-sized man. This increase in tidal volume appears to occur mainly at the expense of the inspiratory reserve volume, with the expiratory reserve volume somewhat less affected. An increase in the central blood volume (caused by increased venous return) may decrease the total lung capacity slightly. The residual volume and functional residual capacity may be unchanged or slightly elevated. The vital capacity may be slightly decreased or unchanged. The breathing frequency may increase to 40 to 50 breaths/min in healthy adults (and as high as 70 breaths per minute in children) with strenuous exercise.

The anatomic dead space may increase slightly in inspiration during exercise because of airway distention at high lung volumes; any alveolar dead space present at rest normally decreases as cardiac output increases. As a result, there is little change in physiologic dead space during exercise. Because the tidal volume does increase, however, the ratio of physiologic dead space to tidal volume (VD/VT) decreases.

The arterial

The regional differences in alveolar ventilation seen in upright lungs (which were discussed in Chapter 3) are probably slightly attenuated during exercise. The larger tidal volumes, occurring at the expense of both the inspiratory and expiratory reserve volumes, indicate that alveoli in more dependent regions of the lung are more fully inflated. However, these alveoli may also suffer airway collapse during active expirations. Similarly, alveoli in upper portions of the lung (with respect to gravity) should deflate more fully during expiration, resulting in greater ventilation of upper parts of the lung.

Pulmonary Blood Flow

As already mentioned, the cardiac output increases linearly with oxygen consumption during exercise. This normally occurs more as a result of an autonomically mediated increase in heart rate than from an increase in stroke volume. An increased venous return, due to deeper inspiratory efforts (in addition to extravascular compression by the exercising muscles and by a decrease in venous capacitance), also contributes to the increase in cardiac output. Mean pulmonary artery and mean left atrial pressures increase, but the increase is not as great as the increase in pulmonary blood flow. This indicates a decrease in pulmonary vascular resistance. As discussed in Chapter 4, this decrease occurs passively by recruitment and distention of pulmonary vessels. Much of the recruitment of pulmonary blood vessels occurs in upper regions of the lung, thus tending to decrease the regional inhomogeneity of pulmonary blood flow discussed in Chapter 4. The expected effect of the deeper tidal volumes and active expirations that occur during exercise is to increase pulmonary vascular resistance. During active expiration the extraalveolar vessels should be compressed; during inspiration the alveolar vessels should be stretched. Mean pulmonary vascular resistance decreases, so the effects of recruitment and distention must be greater than the effects of stretching vessels and extravascular compression.

Ventilation-Perfusion Relationships

The more uniform regional perfusion that occurs during exercise results in a much more uniform matching of ventilation and perfusion throughout the lung. Studies done on normal subjects engaged in exercise in the upright position have demonstrated a greatly increased perfusion of upper regions of the lung, resulting in improved matching of ventilation and perfusion. Because in moderate to severe exercise ventilation increases more than perfusion, the whole lung ventilation-per-fusion ratio (

Diffusion through the Alveolar-Capillary Barrier

The diffusing capacities for oxygen and carbon dioxide normally increase substantially during exercise. Some studies have shown a nearly linear increase in diffusing capacity as oxygen uptake increases, although the diffusing capacity may reach a maximum level before the

Another related factor, less dependent on the increased cardiac output, that helps increase diffusion during exercise is that the mixed venous

The total effect on diffusion through the alveolar-capillary barrier of the increased surface area and the better maintenance of the alveolar-capillary partial pressure gradients may be seen by reviewing Fick law for diffusion:

The thickness of the alveolar-capillary barrier may also be affected during exercise, but the net effect may be either an increase or a decrease. At high lung volumes, the alveolar vessels are stretched and the thickness of the barrier may decrease. On the other hand, high cardiac outputs may be associated with vascular congestion, increasing the thickness of the barrier.

The alveolar-arterial oxygen difference increases during exercise. This is probably because of a number of factors, including

Oxygen and Carbon Dioxide Transport by the Blood

The loading of carbon dioxide into the blood and the unloading of oxygen from the blood are enhanced in exercising muscles. Oxygen unloading is improved because the

Acid-Base Balance

Exercise strenuous enough to cause a significant degree of anaerobic metabolism results in metabolic acidosis secondary to the increased lactic acid production. As discussed previously, the hydrogen ions generated by this process stimulate the arterial chemoreceptors (especially the carotid bodies) and cause a further compensatory increase in alveolar ventilation, maintaining arterial pH near the normal level.

The responses of the normal respiratory system to acute exercise are summarized in Table 11–1.

Training Effects

The ability to perform physical exercise increases with training. Most of the changes that occur as a result of physical training, however, are a function of alterations in the cardiovascular system and in muscle metabolism rather than changes in the respiratory system. The maximal oxygen uptake increases with physical training. This increase appears to be mainly a result of an increased maximal cardiac output. As stated earlier in this chapter, the maximal cardiac output is probably a limiting factor in exercise. Physical training lowers the resting heart rate and increases the resting stroke volume. The maximal heart rate does not appear to be affected by physical training, but the heart rate of a trained person is lower than that of an untrained person at any level of physical activity. Stroke volume is increased. The arterial hemoglobin concentration and the hematocrit do not appear to change with physical training at sea level, but the arteriovenous oxygen content difference does appear to increase with physical training. This is probably a function of the increased effects of local pH,

Physical training increases the oxidative capacity of skeletal muscle by inducing mitochondrial proliferation and increasing the concentration of oxidative enzymes and the synthesis of glycogen and triglyceride. These alterations result in lower concentrations of blood lactate in trained subjects than those found in untrained people, reflecting increased aerobic energy production. Nevertheless, blood lactate levels during maximal exercise may be greater in trained athletes than in untrained people.

Maximal ventilation and resting ventilation do not appear to be affected by physical training, but ventilation at submaximal loads is decreased, probably because of the lower lactic acid levels of the trained person during submaximal exercise. The strength and endurance of the respiratory muscles appear to improve with training. Total lung capacity is not affected by training; vital capacity may be normal or elevated. Pulmonary diffusing capacity is often elevated in athletes, probably as a result of their increased blood volumes and maximal cardiac outputs.

The total barometric pressure decreases at greater altitudes because the total barometric pressure at any altitude is proportional to the weight of the air above it. There is a greater change in barometric pressure per change in altitude closer to the earth’s surface than there is at very great altitudes because air, which is attracted to the earth’s surface by gravity, is compressible.

The fractional concentration of oxygen in the atmosphere does not change appreciably with altitude. Oxygen constitutes about 21% of dry ambient air, and so the

The alveolar

The inspired

The alveolar

The advantage of hypoxic stimulation of the arterial chemoreceptors causing the hyperventilation described in the previous paragraph can be understood by looking at Figure 11–2 and considering the alveolar air equation. As the alveolar

Acute Effects

An unacclimatized person would suffer a deterioration of nervous system function if he or she ascended rapidly to great heights. Similar dysfunctions occur if cabin pressure is lost in an airplane. The symptoms are mainly due to hypoxia and may include sleepiness, laziness, a false sense of well-being, impaired judgment, blunted pain perception, increasing errors on simple tasks, decreased visual acuity, clumsiness, and tremors. Severe hypoxia, of course, may result in a loss of consciousness or even death.

If an unacclimatized person ascends to a moderate altitude (8000–10,000 ft or 2400–3000 m above sea level), he or she may suffer from a group of symptoms known collectively as acute mountain sickness.

Control of Breathing

The decreased alveolar and arterial

Mechanics of Breathing

The increased rate and depth of breathing increase the work of breathing. Greater transpulmonary pressures are necessary to generate greater tidal volumes and also to overcome the possible effects of vascular engorgement and increased interstitial fluid volume of the lung, which may also decrease the vital capacity during the first 24 hours at altitude. High ventilatory rates may be accompanied by active expiration, resulting in dynamic compression of airways. This airway compression, coupled with a reflex parasympathetic bronchoconstriction in response to the arterial hypoxemia, results in elevated resistance work of breathing. More turbulent airflow, which is likely to be encountered at elevated ventilatory rates, may also contribute to elevated resistance work. Maximum airflow rates may increase because of decreased gas density.

Alveolar Ventilation

The anatomic dead space may decrease slightly at altitude because of the reflex bronchoconstriction or increase slightly because of the opposing effect of increased tidal volumes. In any event the ratio of dead space to tidal volume falls with greater tidal volumes. A more uniform regional distribution of alveolar ventilation is also expected at altitude because of deeper inspirations and fuller expirations. Previously collapsed or poorly ventilated alveoli will be better ventilated.

Pulmonary Blood Flow

There is an increase in cardiac output, heart rate, and systemic blood pressure at altitude. These effects are probably a result of increased sympathetic stimulation of the cardiovascular system secondary to arterial chemoreceptor stimulation and increased lung inflation. Alveolar hypoxia results in pulmonary vasoconstriction— hypoxic pulmonary vasoconstriction (HPV). The increased cardiac output, along with hypoxic pulmonary vasoconstriction and sympathetic stimulation of larger pulmonary vessels, results in an increase in mean pulmonary artery pressure and tends to abolish any preexisting zone 1 (which is alveolar dead space) by recruiting previously unperfused capillaries. Undesirable consequences of these effects include vascular distention and engorgement of the lung secondary to the pulmonary hypertension, which may lead to “high-altitude pulmonary edema” and a greatly increased right ventricular workload. Some climbers seem particularly susceptible to high-altitude pulmonary edema; it is possible that they do not have as extensive or responsive intrapulmonary arteriovenous shunts (described in the exercise section earlier) as those climbers less susceptible to high-altitude pulmonary edema. People who are more susceptible to high-altitude pulmonary edema also seem to have greater HPV responses than less susceptible individuals. Furthermore, their pulmonary blood flow appears to be more heterogeneous during hypoxia, which may be a result of uneven HPV. Analysis of the fluid from high-altitude pulmonary edema shows that it contains high-molecular-weight proteins, which indicates that the edema is caused by increased capillary permeability as well as increased capillary hydrostatic pressure. The increased capillary permeability may result from capillary stress failure caused by high pulmonary artery pressure and blood flow and by altered release of cytokines or other mediators.

Ventilation-Perfusion Relationships

The increase in pulmonary blood flow seen acutely at high altitude, coupled with the more uniform alveolar ventilation, would be expected to make regional

Diffusion through the Alveolar-Capillary Barrier

At high altitude, the partial pressure gradient for oxygen diffusion is decreased because the alveolar

Oxygen and Carbon Dioxide Transport by the Blood

Oxygen loading in the lung may be compromised at alveolar

Cerebral Circulation

The response of the cerebral circulation to high altitude is complex. Hypocapnia is a strong cerebral vasoconstrictor. The brain therefore receives not only blood with a low oxygen content but could also receive reduced blood flow. On the other hand, hypoxia causes cerebral vasodilation and can cause hyperperfusion and distention of cerebral vessels.

Hypoxic stimulation of the arterial chemoreceptors causes hypocapnia and respiratory alkalosis, as already discussed. Cerebral arterial hypocapnia not only could cause constriction of the cerebral blood vessels, but would also cause alkalosis of the cerebrospinal fluid (as discussed under Control of Breathing above; see also Figure 9–8). Most of the central nervous system symptoms of acute mountain sickness could be attributed to cerebral hypoperfusion, alkalosis, or both. However, it appears that in most cases the symptoms of acute mountain sickness result from cerebral hyperperfusion and edema. This hyperperfusion is mainly a result of vasodilation, which is the direct effect of hypoxia on the cerebral blood vessels. As the cerebral arterioles dilate, the hydrostatic pressure in the cerebral capillaries increases, increasing the tendency of fluid to leave the cerebral capillaries and cause cerebral edema. The hyperperfusion and cerebral edema elevate intracranial pressure, compressing and distorting intracranial structures. This may lead to a general increase in sympathetic activity in the body, increasing the possibility of pulmonary edema and promoting renal salt and water retention.

Acid-Base Balance

As already mentioned, the increased alveolar ventilation at altitude results in hypocapnia and respiratory alkalosis.

Prevention of Acute Mountain Sickness

Acetazolamide, a carbonic anhydrase inhibitor, taken for a few days before ascending to altitude can prevent the symptoms of acute mountain sickness in many people. The mechanism by which it does this is unclear because acetazolamide has several actions that may help prevent acute mountain sickness. It decreases reabsorption of bicarbonate by the proximal tubule of the kidney. This may lead to a moderate metabolic acidosis systemically and in the brain that may partly offset the respiratory alkalosis and therefore also help stimulate ventilation. Acetazolamide is also a diuretic, so it may help prevent fluid retention and edema. Therefore, acetazolamide may act to prevent acute mountain sickness by preventing fluid retention. It is likely that both proposed mechanisms are involved. Acetazolamide may also inhibit HPV.

Acclimatization

Longer-term compensations to the ascent to high altitude begin to occur after several hours and continue for days or even weeks. The immediate responses to the ascent and the early and late adaptive responses are summarized in Table 11–2.

Renal compensation for respiratory alkalosis begins within a day: Renal excretion of base is increased, and hydrogen ions are conserved.

Hypoxic stimulation of the arterial chemoreceptors persists indefinitely, although it may be somewhat diminished after prolonged periods at high altitude. A more immediate finding is that the ventilatory response curve to carbon dioxide shifts to the left. That is, for any given alveolar or arterial

Resolution of the cerebral edema and increased intracranial pressure probably also occurs at about the same time as the alleviation of central nervous system symptoms. This probably occurs because of increased reabsorption of cerebrospinal fluid, autoregulation of cerebral blood flow, and a sympathetically mediated vasoconstriction that for some reason takes several days to develop. It is also possible that the cerebral vessels produce less nitric oxide, which probably mediates the cerebral vasodilation in response to hypoxia.

The elevated cardiac output, heart rate, and systemic blood pressure return to normal levels after a few days at high altitude. This probably reflects a decrease in sympathetic activity or changes in sympathetic receptors. Nevertheless, HPV and pulmonary hypertension persist (along with increased blood viscosity), increasing right ventricular afterload, leading to right ventricular hypertrophy and sometimes chronic cor pulmonale (right ventricular failure secondary to pulmonary hypertension) in those who live at high altitude for extended periods. In addition, chronic exposure to hypoxia increases the smooth muscle content of small pulmonary arteries. Similar changes occur in chronically hypoxic and hypercapnic patients, such as those with chronic obstructive pulmonary disease or obstructive sleep apnea.

Studies have shown that people native to high altitudes in the Andes can get chronic mountain sickness, but people who live at similar altitudes in the Himalayas don’t. This suggests that there may be a genetic component to the disorder.

Response to Extreme Altitude

Many of the predicted responses of the respiratory system to chronic and acute altitude may be seen in the data obtained from 1 of 2 medical scientist climbers who made it to the summit of Mount Everest without supplemental oxygen in 1981. They were members of the American Medical Research Expedition and had undergone lengthy periods of acclimatization at somewhat less severe high altitudes. Total barometric pressure on top of Mount Everest was 253 mm Hg. This was about 17 mm Hg higher than expected and was explained by local weather conditions and because barometric pressure is higher at lower latitudes. The alveolar

The scientist’s arterial hemoglobin concentration was elevated to 18.4 g/100 mL of blood, and his extremely high levels of 2,3-BPG should have shifted his oxyhemoglobin dissociation curve to the right, with a P50 of 29.6 at a pH of 7.40. However, his respiratory alkalosis actually shifted the curve to the left, resulting in a P50 of 19.4. This leftward shift allowed sufficient loading at the summit to saturate 75% of his hemoglobin with oxygen.

Similar results were obtained under the more controlled conditions of a simulated 40-day “ascent” (in a decompression chamber) to a maximum altitude of 29,028 ft. Arterial blood samples taken from 5 subjects at the simulated summit had a mean

A recent study (2009) analyzed arterial blood samples obtained at an altitude of 27,559 ft (8440 m) from 4 acclimatized climbers descending from the summit of Mt. Everest. They breathed ambient air for 20 minutes before the blood samples were taken. Barometric pressure at 8440 was 272 mm Hg. Their mean alveolar

Physical Principles

The pressure at the bottom of a column of liquid is proportional to the height of the column, the density of the liquid, and the acceleration of gravity. For example, for each 33 ft of seawater (or 34 ft of fresh water) ambient pressure increases by 1 atmosphere (atm). Thus, at a depth of 33 ft of seawater, total ambient pressure is equal to 2 atm or 1520 mm Hg.

The tissues of the body are composed mainly of water and are therefore nearly incompressible, but gases are compressible and follow Boyle’s law. Thus, in a breath-hold dive the volume of gas in the lungs is inversely proportional to the depth attained. At 33 ft of depth (2 atm) lung volume is cut in half; at 66 ft (3 atm) it is one third the original lung volume. As gases are compressed, their densities increase.

As the total pressure increases, the partial pressures of the constituent gases also increase, according to Dalton’s law. The biologic effects of gases are generally dependent on their partial pressures rather than on their fractional concentrations. Also, as the partial pressures of gases increase, the amounts dissolved in the tissues of the body increase, according to Henry’s law.

Effects of Immersion Up to the Neck

Merely immersing oneself up to the neck in water causes profound alterations in the cardiovascular and pulmonary systems. These effects are mainly a result of an increase in pressure outside the thorax, abdomen, and limbs.

Mechanics of Breathing

The pressure outside the chest wall of a person standing or seated in neck-deep water is greater than atmospheric, averaging about 20 cm H2O. This positive pressure outside the chest opposes the normal outward elastic recoil of the chest wall and decreases the functional residual capacity by about 50%. This occurs at the expense of the expiratory reserve volume, which may be decreased by as much as 70%. The intrapleural pressure is less negative at the functional residual capacity because of decreased outward elastic recoil of the chest wall. The work that must be done to bring air into the lungs is greatly increased because extra inspiratory work is necessary to overcome the positive pressure outside the chest. Nonetheless, the vital capacity and total lung capacity are only slightly decreased. As was already pointed out, the expiratory reserve volume is decreased by neck-deep immersion, and the inspiratory reserve volume is therefore increased. The residual volume is slightly decreased because of an increase in pulmonary blood volume. Immersion up to the neck in water results in an increase in the work of breathing of about 60%.

The hydrostatic pressure effects of water outside the chest prevent a submerged person who is trying to breathe through a tube that is communicating with the air above the surface of the water from descending more than about 3 ft. This is true even if the increased airways resistance offered by the tube were negligible and if the person avoided increasing the effective dead space by occluding the mouth end of the tube and exhaling directly into the water (or by using a one-way valve). The reason is that the maximal inspiratory pressure that normal individuals can generate with their inspiratory muscles is about 80 to 100 cm H2O (ie, intrapleural pressures of −80 to −100 cm H2O). Because 100 cm is 1 m, or 39.37 in, the maximum depth a person can attain while breathing through a tube in this manner is a little more than 3 ft.

Pulmonary Blood Flow

During neck-deep immersion, increased pressure outside the limbs and abdomen results in less pooling of systemic venous blood in gravity-dependent regions of the body. If the water temperature is below body temperature, a sympathetically mediated venoconstriction occurs, also augmenting venous return. The increased venous return increases the central blood volume by approximately 500 mL. Right atrial pressure increases from about −2 to +16 mm Hg. As a result, the cardiac output and stroke volume increase by about 30%. The increases in pulmonary blood flow and pulmonary blood volume probably result in elevated mean pulmonary artery pressure, capillary recruitment, an increase in the diffusing capacity, and a somewhat improved matching of ventilation and perfusion.

An additional effect of neck-deep immersion is “immersion diuresis.” Within a few minutes of immersion, the urine flow of a well-hydrated person increases 4- to 5-fold. Osmolal clearance increases only slightly. These findings are consistent with stimulation of stretch receptors in the left atrium and elsewhere in the heart and thoracic vessels by the increased thoracic blood volume. This, in turn, is believed either to decrease the secretion of antidiuretic hormone (ADH) by the posterior pituitary gland or to cause the release of natriuretic hormone from the atria, or both.

Breath-Hold Diving

During a breath-hold dive, the total pressure of gases within the lungs is approximately equal to ambient pressure. Therefore, the volume within the thorax must decrease proportionately and partial pressures of gases increase.

The Diving Reflex

Many subjects demonstrate a profound bradycardia (decreased heart rate), often with arrhythmias and increased systemic vascular resistance with face immersion (especially into cold water), as well as apnea. This “diving reflex” is initiated by as yet unknown sensors in the face or nose. A similar (but greater) response is seen when aquatic mammals such as whales and seals dive. The reflex decreases the workload of the heart and severely limits perfusion to all systemic vascular beds except for the strongest autoregulators—namely, the heart and brain. The cardiovascular effects of the diving reflex are similar to those produced by stimulation of the arterial chemoreceptors when no increase in ventilation can occur, except that the diving reflex also appears to cause the spleen to slowly contract, which releases erythrocytes stored in the spleen into the venous blood. This increases the oxygen-carrying capacity of the blood and therefore the oxygen content of the blood at the same arterial

Gas Exchange in the Lungs

Breath-hold divers usually hyperventilate before a dive so that typical alveolar

During ascent, the ambient pressure falls rapidly, lung volume increases, and alveolar gas partial pressures decrease accordingly. Alveolar

Most people can hold their breaths for 1 to 2 minutes, especially if they hyperventilate before the breath-hold. Competitive breath-holders have held their breaths for as long as 10 minutes, mainly by using a technique called glossopharyngeal insufflation or “lung packing.” They use their glossopharyngeal muscles to force air into their airways and alveoli, increasing the maximal volume of air in their lungs before an attempt by as much as 50% (if the volume were not compressed by increased pressure). They may also release small amounts of air from the lungs into the pharynx to use it to equalize the pressures in the middle ear and sinuses, which is called glossopharyngeal exsufflation. Some divers may be able to also decrease the residual volume during a dive by glossopharyngeal exsufflation.

The Use of Underwater Breathing Apparatus

Self-contained underwater breathing apparatus, or scuba gear, mainly consists of a tank full of compressed gas that can be delivered by a demand regulator to the diver when the diver’s mouth pressure decreases (during inspiration) to slightly less than the ambient pressure. Expired gas is simply released into the water as bubbles. Therefore, during a dive with scuba gear, gas pressure within the lungs remains close to the ambient pressure at any particular depth. The physiologic stresses on the respiratory system during scuba diving are therefore mainly a consequence of elevated gas densities and partial pressures.

Mechanics of Breathing

During scuba diving, the inspiratory work of breathing is not a great problem at moderate depths because gas is delivered at ambient pressures. Lung compliance may be slightly decreased as a result of increased blood volume, as discussed above. At very great depths, however, increased gas density becomes a problem because it elevates the airways resistance work of breathing during turbulent flow. For example, in long-term experiments done with subjects simulating dives of over 2000 ft inside hyperbaric chambers, all subjects reported that they could breathe only through their mouths: The work of breathing through the nose was too great. This is one reason for replacing nitrogen with helium for deep dives. Helium is only about one seventh as dense as nitrogen.

Control of Breathing

The respiratory system’s sensitivity to carbon dioxide is decreased at great depths because of increased gas densities and work of breathing, because high arterial

Other Hazards at Depth

Other hazards that may be encountered in diving to great depths include barotrauma, decompression illness, nitrogen narcosis, oxygen toxicity, and high-pressure nervous syndrome.

Barotrauma

Barotrauma occurs when ambient pressure increases or decreases but the pressure in a closed unventilated area of the body that cannot equilibrate with ambient pressure does not. The barotrauma of descent is called “squeeze.” It can affect the middle ear, if the eustachian tube is clogged or edematous, so that a person cannot equilibrate pressure in the middle ear; the sinuses; the lungs, resulting in pulmonary congestion, edema, or hemorrhage; and even cavities in the teeth. The barotrauma of ascent can occur if gases are trapped in areas of the body and begin to expand as the diver ascends. If a diver does not exhale while ascending, expanding pulmonary gas may overdistend and rupture the lung (“burst lung”). This may result in hemorrhage, pneumothorax, or air embolism. Gases trapped in the gastrointestinal tract may cause abdominal discomfort and eructation or flatus as they expand. Barotrauma of the ears, sinuses, and teeth may also occur on rapid ascent from great depths.

Decompression Illness

Decompression illness occurs when gas bubbles form in the blood and body tissues as the ambient pressure decreases. The term “decompression illness” encompasses 2 different problems, both of which involve gas bubbles. Arterial gas embolism is gas bubbles in the arterial blood. Because bubbles do not seem to form in the arterial blood itself, arterial gas embolism usually occurs when airway obstruction prevents expanding gas from being exhaled. As expanding alveoli rupture, gas bubbles may enter pulmonary capillaries and be carried into the arterial blood. Arterial gas embolism is a likely consequence of an ascending diver neglecting to exhale upon rapid ascent. Bubbles resulting from arterial gas embolism may be carried to cerebral blood vessels. The second component of decompression illness, decompression sickness, occurs when bubbles form in tissues of the body. During a dive, the increasing ambient pressure causes an elevation of the partial pressure of nitrogen in the body. The high partial pressure of nitrogen causes this normally poorly soluble gas to dissolve in the body tissues and fluids according to Henry’s law. This is especially the case in body fat, which has a relatively high nitrogen solubility. At great depths, body tissues become supersaturated with nitrogen.

During a fast ascent, ambient pressure falls rapidly and nitrogen comes out of solution, forming bubbles in body tissues and fluids. The effect is the same as opening a bottle of a carbonated beverage. During the production of a carbonated beverage it is exposed to higher than atmospheric pressures of gases, mainly carbon dioxide, and then capped. The total pressure in the gas layer above the liquid remains greater than atmospheric pressure. The partial pressures of gases dissolved in the liquid phase are in equilibrium with the partial pressures in the gas phase. Gases dissolve in the liquid phase according to Henry’s law. When the bottle is uncapped, the pressure in the gas phase drops suddenly and the gas dissolved in the liquid phase comes out of solution, forming bubbles.

The bubbles formed in decompression sickness may enter the venous blood or affect the joints of the extremities. Bubbles that enter the venous blood are usually trapped in the pulmonary circulation and rarely cause symptoms. The symptoms that do occasionally occur, which are known as “the chokes” by divers, include substernal chest pain, dyspnea, and cough and may be accompanied by pulmonary hypertension, pulmonary edema, and hypoxemia. These symptoms are obviously an extremely dangerous form of decompression illness. Even more dangerous, of course, are bubbles in the circulation of the central nervous system, which may result in brain damage and paralysis. They may result from alveolar rupture and arterial gas embolism, as discussed previously, or be carried from the venous blood to the arterial side through a patent foramen ovale or an intrapulmonary shunt. Bubbles that form in the joints of the limbs cause pain (“the bends”). Osteonecrosis of joints may also be caused by inadequate decompression.

The treatment for decompression illness is immediate recompression in a hyperbaric chamber, followed by slow decompression. Decompression illness may be prevented by slow ascents from great depths (according to empirically derived decompression tables) and by substituting helium for nitrogen in inspired gas mixtures. Helium is only about half as soluble as nitrogen in body tissues.

Gas bubbles, although they are sterile, are perceived by the body as foreign. They elicit inflammatory and other responses, including platelet activation, blood clotting, the release of cytokines and other mediators, leukocyte aggregation, free radical production, and endothelial damage. These responses are not reversed by recompression and may continue unless additional treatment is initiated.

Divers who ascend from submersion with no immediate effects of decompression may subsequently suffer decompression illness if they ride in an airplane within a few hours of the dive. Commercial airplanes normally maintain cabin pressures well below 760 mm Hg, with cabin pressures similar to those at altitudes 5000 to 8000 ft above sea level.

Nitrogen Narcosis

Very high partial pressures of nitrogen directly affect the central nervous system, causing euphoria, loss of memory, clumsiness, and irrational behavior. This “rapture of the deep” occurs at depths of 100 ft or more and at greater depths may result in numbness of the limbs, disorientation, motor impairment, and ultimately unconsciousness. The mechanism of nitrogen narcosis is unknown.

Oxygen Toxicity

Inhalation of 100% oxygen at 760 mm Hg or of lower oxygen concentrations at higher ambient pressures can cause central nervous system, visual system, and alveolar damage, although pulmonary manifestations are rare among divers. The mechanism of oxygen toxicity is controversial but probably involves the formation of superoxide anions or other free radicals.

High-Pressure Nervous Syndrome

Exposure to very high ambient pressures, such as those encountered at very great depths (greater than 250 ft), is associated with tremors, decreased mental ability, nausea, vomiting, dizziness, and decreased manual dexterity. This high-pressure nervous syndrome (HPNS) usually occurs when nitrogen has been replaced by helium to decrease gas density, prevent nitrogen narcosis, and help avoid decompression sickness. Small amounts of nitrogen added to the inspired gas mixture help counteract the problem. One hypothesis explaining HPNS is that the syndrome may result from alterations in cerebral neurotransmission.

Mechanics of Breathing

Significant changes in the mechanics and control of breathing occur during normal sleep. Altered body position causes major changes in the mechanics of breathing before the onset of sleep. As discussed in Chapter 2, changing from the upright to the supine position decreases the outward recoil of the chest wall because of the decreased effect of gravity pulling downward on the abdomen and diaphragm. This decreases the volume at which the outward recoil of the chest wall is equal and opposite to the inward recoil of the lungs and therefore decreases the functional residual capacity (Figures 2–14 and 2–15). The alveolar

Control of Breathing

The control of breathing is altered during non rapid eye movement (NREM) sleep by removal of the “wakefulness” component of respiratory drive discussed in Chapter 9 (Figure 9–5). Minute volume decreases by about 16% (about 0.5–1.5 L/min in a 70-kg person) and the arterial

The tone of the pharyngeal muscles is decreased and the pharyngeal dilator reflex is depressed. That may be a major factor in the development of obstructive sleep apnea, as discussed in Chapter 9. Other protective respiratory reflexes are also depressed. One consequence of the depression of the protective reflexes is an increased likelihood of aspiration of saliva and other contents of the oro- and nasopharynx into the tracheobronchial tree. Depression of respiratory drive and the reflexes protecting the upper airway is exacerbated by ethanol consumption.

Rapid eye movement (REM) sleep decreases the tone of the intercostal and accessory muscles, but it has less effect on the diaphragm. Upper airway resistance may increase during REM sleep. The depression of minute volume and the increase in arterial

As noted in Chapter 9, in OSA the central respiratory controller issues the command to breathe and the inspiratory muscles contract, but the upper airway is obstructed; in central sleep apnea, there is a lack of central respiratory drive and the inspiratory muscles do not contract.

From Raff H, Levitzky MG, eds. Medical Physiology: A Systems Approach. New York: McGraw-Hill; 2011:742.

Physicians on a medical mission in the mountains of South America treat a 65-year-old man who has lived at altitudes above 3600 meters (about 12,000 ft) since he was born. He has a chronic headache, feels dizzy and tired, has trouble remembering things, and does not sleep well. He is cyanotic (see Chapter 7), and has peripheral edema. His jugular veins are distended even though he is sitting upright. An electrocardiogram indicates right axis deviation (a frontal plane mean electrical axis greater than +105°).

The patient has chronic mountain sickness (also known as Monge Disease) with chronic cor pulmonale. Chronic cor pulmonale is right ventricular failure secondary to pulmonary hypertension, in this case exacerbated by polycythemia (increased hematocrit resulting from increased production of red blood cells). His pulmonary hypertension is mainly a result of the effects of chronic hypoxic pulmonary vasoconstriction (HPV), which not only causes constriction of pulmonary arterioles, but also causes structural changes in the affected blood vessels over time. He has polycythemia because of chronic hypoxemia leading to erythropoiesis. The increase in hematocrit resulted in greater blood viscosity. His low arterial

A 65-year-old professor comes to the family physician because his wife is worried about him. Although he says he sleeps through the night (except to get up to urinate), his wife says he snores loudly and often seems to stop breathing and gasp for breath. He is restless and thrashes around in bed. He almost always wakes up with a headache and for the past year he has been having trouble remembering things. He feels tired all the time and often falls asleep when he attends lectures, seminars, or boring meetings. He is 5 ft 7 in. tall and weighs 250 pounds. His heart rate is 80/min, blood pressure is 145/95 mm Hg and his respiratory rate is 15/min. His electrocardiogram, chest radiograph, and echocardiogram strongly suggest pulmonary hypertension.

The physician assumes that the patient has obstructive sleep apnea (OSA) and schedules a polysomnography test at a sleep laboratory to confirm the diagnosis. Physiologic sensors are connected to the patient and data are collected while the patient sleeps overnight. The data may include electroencephalograms and electrooculograms, to monitor the person’s sleep state; electromyograms of muscles involved in breathing; airflow at the nose or mouth, usually determined with a thermistor; end-tidal CO2; chest and abdominal motion, usually determined by impedance plethysmography; electrocardiograms and blood pressure; and pulse oximetry. OSA is usually defined as 15 or more apneas (10 or more seconds without airflow) per hour during sleep, caused by collapse of the upper airway. (Recall from Chapter 2 that 35%–50% of the resistance to airflow normally resides in the upper airway, even when a person is awake.) Unlike central sleep apnea, obstruction occurs in OSA despite central drive to breathe and inspiratory muscle activity.

The most common symptom of OSA, loud snoring, is often reported by the person’s bed partner, especially if the bed partner is aware of the periods of obstructive apnea indicated by no snoring, and the gasping that accompanies arousals. Snoring is almost always a feature of OSA, but not everyone who snores has OSA. Hypersomnolence (also known as excessive daytime sleepiness) is usually a symptom, often accompanied by depressed mentation. Changes in personality may be noted by people close to the person with OSA. People with OSA often have headaches upon waking and nocturia. The signs of OSA include systemic hypertension; polycythemia; right axis deviation on the electrocardiogram, indicating right ventricular hypertrophy secondary to pulmonary hypertension; and signs of cor pulmonale. There is usually no respiratory abnormality while the person with OSA is awake, but the arterial blood gases may show metabolic alkalosis.

OSA occurs because of collapse of the upper airway during inspiration. Negative pressure in the upper airway can cause the tongue or the soft palate to adhere to the wall of the pharynx. As the airway begins to collapse because of negative pressure in the upper airway, the person with OSA makes greater inspiratory efforts, making upper airway pressure even more negative, exacerbating the problem until arousal occurs. Collapse of the upper airway during normal inspiration is normally prevented by contraction of the pharyngeal dilator muscles, as mentioned in Chapter 9 in the section about the pharyngeal dilator reflex. The pharyngeal dilator muscles pull the tongue forward to prevent upper airway obstruction, move the hyoid bone forward to enlarge and stabilize the pharyngeal airway, and pull the palate away from the posterior wall of the pharynx.

Upper airway obstructions during sleep cause alveolar hypoxia and hypercapnia. Hypoxic pulmonary vasoconstriction (HPV-see Chapter 4) occurs in response to the hypoxia and hypercapnia and increases pulmonary vascular resistance. Repeated episodes of pulmonary hypertension may lead to vascular remodeling resulting in chronic pulmonary hypertension. Chronic alveolar hypoxia during the episodes of upper airway obstruction leads to hypoxemia, causing renal release of erythropoietin. Erythropoietin acts on the bone marrow to produce more red blood cells, which may increase the hematocrit and blood viscosity. The increased pulmonary artery pressure and increased blood viscosity chronically increase the afterload of the right ventricle, producing right ventricular hypertrophy, which can be seen as right axis deviation in the electrocardiogram. As the pulmonary hypertension and increased viscosity progress, the hypertrophied right ventricle may not be able to meet the increased work load, leading to cor pulmonale, right ventricular failure secondary to pulmonary hypertension. Repeated increases in sympathetic tone and systemic blood pressure during arousals may cause vascular remodeling and changes in endothelial function, causing systemic hypertension that may persist when the patient is awake with no upper airway obstruction. Except for the effects of hypercapnia, many of these effects are similar to those seen in chronic mountain sickness; one major difference is compensatory retention of bicarbonate in OSA, leading to daytime metabolic alkalosis, with compensatory excretion of bicarbonate at altitude.

Arterial hypoxemia and hypercapnia during episodes of upper airway obstruction cause increased cerebral blood flow, caused by dilatation of cerebral blood vessels. The repeated dilatations of cerebral blood vessels during sleep are the likely cause of the morning headaches commonly experienced by people with OSA. Increased right ventricular end diastolic pressure and volume lead to increased right atrial volume, which increases the secretion of atrial natriuretic peptide from atrial myocytes, increasing sodium excretion. The increased atrial volume also stretches receptors that suppress ADH secretion from the posterior pituitary gland and increases urine volume. The repeated arousals precipitated by upper airway obstruction, which may occur as many as hundreds of times per night, interfere with normal sleep architecture, especially Rapid Eye Movement (REM) sleep. Abnormal sleep architecture leads to daytime somnolence, decreased attentiveness, blunted mentation, depression, and personality changes; hypersomnolence greatly increases the risk of motor vehicle accidents.

Treatment of OSA depends on the cause and severity of the problem in the individual patient and whether or not the patient is compliant with the treatment. Treatments include lifestyle changes, oral appliances, continuous positive airway pressure (CPAP), or surgery. Because the supine position predisposes upper airway obstruction, changing to another body position during sleep may decrease or eliminate obstructions. Sewing a tennis ball into the back of the patient’s pajama top or the use of special pillows, may prevent assuming the supine position during sleep. Weight loss can help patients for whom adipose tissue around the upper airway is a contributing factor to upper airway obstruction during sleep. Decreased consumption of ethanol will help many patients with OSA. Devices designed to be placed in the oral cavity to maintain airway patency may be effective in patients that can tolerate them. CPAP is positive pressure in the airway during both inspiration and expiration administered to a spontaneously breathing patient. Air is usually delivered to a mask covering the nose via a tube from an electrically powered blower. The mask has a one-way valve to prevent exhaled air from being inhaled and to allow air to flow though the mask so all of the air flow does not enter the patient’s airway. CPAP can be very effective in preventing upper airway collapse during sleep, but many patients cannot tolerate it. Surgical treatment of patients with OSA who are unable to alleviate sleep related upper airway obstruction by lifestyle change, oral appliances, or positive airway pressure is aimed at removing anatomic sites of obstruction in the naso-, oro- or hypopharynx. Tracheotomy to completely bypass the upper airway is considered a last resort.

Exercise

Altitude

Diving

Sleep