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Extremes of barometric pressure
PHYSIOLOGY
Extremes of barometric pressure
Learning objectives After reading this article you should be able to: C understand the physical effects of changes in ambient pressure and the physiological consequences on the cardiovascular respiratory and neurological systems C gain an awareness that exposure to reduced ambient pressure produces both acute and more chronic effects, with differing signs, symptoms and time to onset at various altitudes C develop an awareness of the toxic effects of ‘inert’ gases at increased ambient pressures and the pathogenesis and management of decompression illness
Jane E Risdall David P Gradwell
Abstract Ascent to elevated altitude, commonly achieved through flight, by climbing or by residence in highland regions, exposes the individual to reduced ambient pressure. Although there are physical manifestations of this exposure as a consequence of Boyle’s law, the primary physiological challenge is of hypobaric hypoxia. The acute physiological and longer-term adaptive responses of the cardiovascular, respiratory, haematological and neurological systems to altitude are described, together with an outline of the presentation and management of acute mountain sickness, high-altitude pulmonary oedema and high-altitude cerebral oedema. Whilst many millions experience modest exposure to altitude as a result of flight in pressurized aircraft, fewer individuals are exposed to increased ambient pressure. The pressure changes during diving and hyperbaric exposures result in greater changes in gas load and gas toxicity. Physiological effects include the consequences of increased work of breathing and redistribution of circulating volume. Neurological manifestations may be the direct result of pressure or a consequence of gas toxicity at depth. Increased tissue gas loads may result in decompression illness on return to surface or subsequent ascent in flight.
oxygen in air remains constant at 20.9%, the partial pressure of oxygen in inspired air falls progressively. This causes a reduction in the pressure gradient for oxygen from the inspired gas to the tissues and hence into mixed venous blood (Figure 1). Therefore ascent to altitude is a specific, hypobaric, cause of hypoxic hypoxia. Flight within the normal pressurized cabin of a commercial aircraft is equivalent to ascending to 2500 m (8000 ft) and associated with a reduction in barometric pressure of 25%. Ascent to 4000e5000 m (15,000e16,500 ft) will induce hypoxia of such a degree as to stimulate hyperventilation, slow mental processes, impair learning and memory and reduce coordination. However, impairment of night vision has been reported at altitudes as low as 1500 m. Ascent to altitudes greater than 5000 m will result in progressively more rapid loss of consciousness. Studies have shown that individuals exposed to an altitude of 7600 m (25,000 ft) for 4e5 minutes will cease to be able to act in a rational manner to correct their predicament. This interval is described as the time of useful consciousness. The time of useful consciousness will be reduced at 9000 m (30,000 ft) to 2.5 minutes and to just 1 minute at 10,500 m (35,000 ft).
Keywords Acclimatization; acute mountain sickness; decompression illness; hyperbaric exposure; hypobaric hypoxia; inert gas toxicity Royal College of Anaesthetists CPD matrix: 1A01
Most of the world’s population lives close to sea-level. Meteorological changes in ambient pressure have little effect on respiratory physiology. Although adaptation to high altitude is seen in those living for prolonged periods at 3000 m or more above sea-level, millions of people are exposed acutely to changes in ambient pressure as a result of flight in aircraft. A few are exposed to more substantial changes in pressure by undertaking extreme ascents or by diving to depth.
Respiratory system Oxygen uptake: normal oxygenation is dependent on adequate alveolar ventilation. When alveolar PO2 is normal there is rapid diffusion of oxygen molecules through the alveolarecapillary membrane into the red blood cells (RBCs) and then into combination with haemoglobin. At rest, the time course for the transit of an RBC through a pulmonary capillary is of the order of 0.75 seconds. At sea-level, breathing air, within 0.25 seconds the oxygen tension in the blood within the capillary approaches that found within the alveoli. However, at altitude the alveolar PO2 is reduced so the rate of rise of oxygen tension within capillary blood is slower than at sea-level. At rest the capillary transit time is still sufficient to allow the oxygen tension to approach that within the alveoli, but when the transit time is reduced by exercise there will be a marked worsening of any hypobaric hypoxia (Figure 2).
High altitude e low pressure Barometric pressure declines exponentially on ascent. As pressure declines, gas volumes increase and so a fixed volume of gas contains fewer molecules. Thus, although the percentage of
Jane E Risdall is a Consultant Anaesthetist in the Royal Navy and a Senior Lecturer in Military Anaesthesia and Critical Care. Conflicts of interest: none declared. David P Gradwell is the Senior Consultant in Aviation Medicine in the Royal Air Force, working at the Centre of Aviation Medicine, Henlow. He is the Royal College of Physicians (London) Whittingham Professor of Aviation Medicine and is a Visiting Professor at King’s College, London. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:2
Ventilatory response to hypoxia: in most individuals hypoxia induces an increase in ventilation. Although this increases the respiratory work oxygen demand there is an overall fall in
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PHYSIOLOGY
Figure 2
the respiratory alkalosis is corrected by increased excretion of bicarbonate, restoring pH towards normal. There is also an increase in the sensitivity of the respiratory centre to PaCO2, so that despite lowered carbon dioxide tensions in the blood, higher ventilation is maintained. There is also a secondary polycythaemia so that more oxygen is carried by the blood.
Figure 1
arterial PCO2 and a rise in arterial PO2. This hypoxia-induced ventilatory response is mediated through the aortic and carotid bodies. The associated fall in PaCO2 and the consequent respiratory alkalosis, acts centrally as a respiratory depressant, setting up a conflict in response, the outcome reflecting the balance between the two influences. Respiratory control commonly is more sensitive to changes in PaCO2 and an acute reduction in PaO2 does not induce a respiratory response until the oxygen tension falls to 6e6.7 kPa (45e50 mmHg). Below this level hypoxia induces a brisk increase in ventilation, exerting a stronger effect than the fall in PaCO2 or hydrogen ion concentration. The response to acute exposure to altitude is altered in those who acclimatize. The time course of acclimatization varies but the most important changes are in the cardio-respiratory systems and in the composition of the blood. Over a few days at altitude
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Oxyhaemoglobin: when breathing air at sea-level, approximately 98.5% of the oxygen carried in blood is combined with haemoglobin. The shape of the dissociation curve means that moderate variations in PaO2 have relatively little effect on haemoglobin saturation and hence the oxygen content of the blood. When oxygen tension falls significantly, at altitudes above 3000 m (10,000 ft), oxygen is more readily dissociated from haemoglobin and delivery of oxygen to the tissues is compromised. The presence of a significant proportion of reduced haemoglobin in arterial blood gives rise to cyanosis at altitude. At altitude, the low PaCO2 moves the oxyhaemoglobin dissociation curve to the left. However, an increase in
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PHYSIOLOGY
2,3-diphosphoglycerate, moves it to the right, but the effect of the alkalosis predominates.
effects of acute exposure to altitude. Individuals with anaemic hypoxia will be particularly vulnerable to the added effects of hypobaric hypoxia and consideration should be given limiting the degree of anaemia suffered before transporting a patient by air. After a more prolonged exposure to moderate altitude, a reduction in plasma volume increases packed cell volume and haemoglobin concentration, but there is also greater erythropoietin production leading to a rise in red cell mass. After several weeks plasma volume will increase to produce a partial correction of the haemoglobin concentration. Myoglobin, containing just one haem group, is valuable in the transfer of oxygen into mitochondria within cells. At altitude myoglobin production is increased, and mitochondrial volume density also increases. These effects improve the utilization of oxygen after a period of acclimatization to moderate altitudes.
Cardiovascular responses Heart rate: heart rate is increased on acute exposure to altitudes above 2000e2500 m (6000e8000 ft). At 4500 m (15,000 ft) the rate is about 10e15% above the resting level at sea-level and approximately doubled at rest at 7500 m (25,000 ft). Stroke volume: stroke volume remains unchanged initially, but with acclimatization to altitude stroke volume is reduced. Blood pressure: mean arterial pressure remains unchanged on exposure to altitude. Systolic pressure is usually raised and there is an overall reduction in peripheral resistance, with a resulting increase in pulse pressure.
Acute mountain sickness (AMS): this condition ranges from relatively benign effects such as headache, lassitude, insomnia, fatigue and irritability to the severe, life-threatening conditions of high-altitude pulmonary oedema (HAPE) or high-altitude cerebral oedema (HACE). The mechanisms of AMS are unknown, but rapid ascent and duration of exposure are critical. It requires an exposure of some hours to develop AMS, but it has been reported at altitudes as low as 2500 m (8000 ft) and with exposures as short as 12 hours. The development of ultra-long haul flights may increase the incidence of AMS as a flight-related condition. Slow ascent allows acclimatization to take place and reduces the risk of AMS. Sleeping at an altitude below that reached during the day and no greater than 300 m (1000 ft) above the altitude of the previous night’s sleep will reduce the risk of AMS. HAPE is associated with tachycardia, tachypnoea and crackles in the lung bases with a dry cough. HACE is a severe form of AMS with progression to ataxia, hallucinations, coma and eventually, death. If symptoms suggestive of HAPE or HACE are encountered the individual should be given oxygen and immediately descend. Dexamethasone and diuretics may be of value, but the only definitive treatment is descent.
Cardiac output: since heart rate increases and stroke volume is unchanged, cardiac output increases on acute exposure to altitude in proportion to the increase in rate. With a subsequent reduction in stroke volume the cardiac output declines. Wellacclimatized individuals demonstrate a normal relationship between cardiac output and work load, but on initial exposure to altitude an exaggerated response to exercise is observed. The development of a degree of polycythaemia may be the means by which more normal oxygen delivery to the tissues is restored with acclimatization. Regional cardiovascular effects: hypoxia increases blood flow through the coronary and cerebral circulations, at the expense of renal, splanchnic and cutaneous blood flow. Flow through skeletal muscle may increase by 30e100%. Coronary blood flow increases in parallel with heart rate, matching the metabolic requirements of the myocardium. This prevents the emergence of electrocardiographic signs of hypoxia, even up to the point at which consciousness can be lost but in severe hypoxia myocardial depression will influence the ECG results with T depression and reduced height of the T-wave observed. The response of the cerebral circulation is determined by the relationship between oxygen and carbon dioxide. At oxygen tensions above 6e6.7 kPa (45e50 mmHg) flow is determined predominantly by PaCO2. With more severe hypoxia the falling oxygen tension predominates and at PaO2 of 4.7e5.3 kPa (35e40 mmHg) there is a 50e100% increase in cerebral blood flow. The blood flow in the pulmonary circulation is responsive to oxyhaemoglobin saturation of the blood. A 20% fall in saturation will cause rapid, reversible pulmonary vasoconstriction such that local perfusion is matched to local ventilation. Acute ascent to altitude sufficient to induce such a fall in saturation will cause the entire pulmonary vascular bed to constrict, increasing pulmonary arterial pressure. Long-term exposure to altitude has been associated with pulmonary hypertension and right ventricular hypertrophy in acclimatized lowlanders and high-altitude natives.
Depth e increased pressure Exposure to increased ambient pressure can occur in various circumstances: recreationally, commercially and clinically. SCUBA (self-contained underwater breathing apparatus) diving is a popular activity. Commercial raised-pressure work encompasses professional diving (including saturation diving where individuals remain at a raised ambient pressure for prolonged periods) and caisson workers who use pressurized chambers in underground tunnel construction. Clinically, patients (and, if ventilated, their accompanying anaesthetist) will encounter elevated pressures in the course of the administration of hyperbaric oxygen therapy, for conditions as diverse as decompression illness and carbon monoxide poisoning. Conventionally, exposures to increased ambient pressure are described in terms of a ‘dive’ to an equivalent depth of seawater in metres (msw), even if the exposure occurs in a dry, static hyperbaric chamber on the surface. The physiological challenges of raised ambient pressure are posed by the physical effects of pressure and the effect of pressure on gas solubility.
Haematology: hypoxia induces an increase in the oxygen carrying capacity of the blood. However these effects take time to be expressed and therefore are less relevant when considering the
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:2
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Ó 2014 Elsevier Ltd. All rights reserved.
PHYSIOLOGY
Physical effects of pressure
forces about 500 ml of blood centrally, raising right atrial pressure, cardiac output and improving ventilationeperfusion relationships. The pressure receptors in the cardiovascular system detect this apparent increase in circulating volume and promote a diuresis, mediated via a decrease in antidiuretic hormone and an increase in atrial natriuretic peptide release. Immersion of the face in cold water induces the ‘diving reflex’. Here the heart rate falls, sometimes quite profoundly and peripheral vasoconstriction occurs.
Under water, pressure increases by 1 atmosphere absolute (ata) for every 10 msw; so at a depth of 30 msw a diver is exposed to 4 ata. Although the body is composed largely of incompressible solids and water, gas is present in the lungs, gastrointestinal tract, sinuses and middle ear. Using Boyle’s law and a constant temperature: volume f 1=pressure at 10 msw, the ambient pressure will be 2 ata and the volume of a fixed mass of gas will halve. Where the volume of a gas-filled space is fixed, as in the sinuses or middle ear, this gas will have to equilibrate with the increased pressure during descent, via the sinus ostia or Eustachian tube. If equilibration is not achieved, sinus or otic barotrauma will occur, with possible capillary or tympanic membrane rupture. In the gut, provided the mass of gas remains constant, the volume will shrink on descent and re-expand to its former volume on ascent.
Neurological effects of pressure Although the tissues are relatively incompressible compared with gas-filled spaces, lipids are more compressible than water. As lipids are a major constituent of cell membranes, increased ambient pressure can have a direct effect on cell function, including neuromuscular transmission. The result is termed high-pressure neurological syndrome. Symptoms include tremor, decreased manual dexterity, attention loss and nausea. It is seen at depths over 200 msw and is worse when the rate of descent is rapid. The symptoms may be lessened by adding nitrogen to the helium/oxygen mixtures normally breathed at these depths.
Respiratory system Work of breathing: during a dive the work of breathing is increased because the water pressure compresses the chest. To expand the lungs against this restriction, the work of the inspiratory muscles has to increase. The greatest pressure the respiratory muscles can generate is about 90 cmH2O. When water pressure exceeds this (at a depth of 1.2 m) inspiration of gas at surface pressure is impossible. In practice, divers breathe from a pressurized source via a demand valve, from a surface-supply regulated to equal the pressure at which they are working or from the gas at the ambient increased pressure within a hyperbaric chamber. In these circumstances, transthoracic pressure (i.e. the difference between intra-alveolar and ambient pressure at depth) is normal. With increasing ambient pressure, gas density also rises, which contributes to the increased work of breathing. Airflow may become turbulent compounding this effect. The increased gas density also slows intra-alveolar diffusion and may impair gas exchange.
Gas toxicity Gases considered benign or inert at sea-level may become toxic at depth. Nitrogen narcosis: at increased partial pressures, nitrogen behaves as a narcotic agent. It produces symptoms resembling alcohol intoxication, including euphoria, irrational behaviour, reduced manual dexterity and impaired mental function. The cause is thought to be an effect on cell membranes, similar to that seen with volatile anaesthetic agents. Symptoms can occur when breathing compressed air at 30 msw and become more marked as depth increases. Below 90 msw, divers breathing air risk unconsciousness. Oxygen toxicity: this is manifest in two forms; pulmonary and central nervous system (CNS). Pulmonary oxygen toxicity is time/dose related and although there is considerable individual variation, it is generally accepted that the threshold is a prolonged (12e24 hours) exposure to oxygen above 50 kPa. At greater partial pressures, there is more rapid development of symptoms and signs, including tracheal irritation, dry cough, reduced vital capacity and occasionally pulmonary oedema requiring positive-pressure ventilation. The underlying pathology is thought to be due to the disruption of endothelial and epithelial cells and the process can be modified by intermittent breathing of gas mixtures with a PiO2 less than 50 kPa. CNS toxicity occurs over a threshold exposure of 150 kPa oxygen. Exercise, elevated PaCO2 and nitrogen narcosis are all predisposing factors, but, at rest, in a dry environment, patients undergoing hyperbaric oxygen therapy can tolerate up to 280 kPa oxygen, if given intermittently. Although prodromal symptoms have been reported, the classical presentation is that of a sudden epileptiform convulsion. To overcome the limitations imposed by nitrogen narcosis, oxygen toxicity and the increased work of breathing due to changes in gas density, helium is the most commonly used inert
Pulmonary barotrauma: since the lungs will be in free communication with gas at the increased ambient pressure during a dive it is important that the diver breathes normally on ascent. Gas in the lungs will expand (Boyle’s law) and if exhalation does not occur alveolar rupture and pulmonary barotrauma may occur. Breath-hold diving: in a breath-holding dive from the surface, the lung volumes are compressed with the increasing pressure, then re-expand to their original volume on ascent. Breath-hold dives deeper than those predicted from the simple application of Boyle’s law, are possible due to redistribution of blood volume into the thoracic cavity, but such exposures are not without considerable risk of hypoxia and lung damage due to congestion, oedema and haemorrhage.
Cardiovascular system On the surface there is a hydrostatic pressure gradient in the upright individual with fluid pooling in the lower half of the body. However, when submerged in water, the surrounding pressure
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PHYSIOLOGY
diluent gas in breathing mixtures for use below 50 msw. It is less soluble and less narcotic than nitrogen and being less dense, reduces the work of breathing.
DCI is a combination of recompression, to reduce bubble size and hyperbaric oxygen therapy to maximize the gradient for the elimination of inert gas. The risk of DCI is minimized by ensuring a slow, controlled ascent, the precise rate of which will depend on the depth and duration of the dive, in accordance with published tables. Saturation divers, who remain under pressure for several weeks and become fully equilibrated with gases at the increased ambient pressure may take several days to decompress and their decompression obligation may be undertaken in a hyperbaric chamber. The risk of DCI is increased if, within 24 hours of a dive or hyperbaric exposure, the individual then goes to altitude or flies, even in a commercially pressurized cabin, since reequilibration of all tissue compartments to sea-level pressure may not be complete. A
Decompression illness According to Henry’s law, at a constant temperature the amount of gas which dissolves in a liquid is proportional to the pressure of that gas or its partial pressure, if it is part of a mixture of gases. Breathing gases at increased ambient pressure will increase the amount of each gas dissolved in the fluid phases of body tissues. On ascent this excess gas has to be given up. If the ascent is controlled at a sufficiently slow rate, elimination will be via the respiratory system. If the ascent is too fast, excess gas may come out of solution and form free bubbles in the tissues or circulation. Bubbles may contain any of the gases in the breathing mixture, but it is the presence of inert gas bubbles (nitrogen or helium) that are thought most likely to give rise to problems, since the elimination of excess oxygen is achieved by metabolism as well as ventilation. These bubbles may act as venous emboli or may trigger inflammatory tissue responses giving rise to symptoms of decompression illness (DCI). Signs and symptoms of DCI may appear up to 48 hours after exposure to increased ambient pressure and include joint pains, motor and sensory deficits, dyspnoea, cough and skin rashes. Treatment of
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FURTHER READING Brubakk AO, Neuman TS, eds. Bennett and Elliott’s physiology and medicine of diving. 5th edn. London: Saunders, 2003. Rainford DJ, Gradwell DP, eds. Ernsting’s aviation medicine. 4th edn. London: Hodder Headline, 2006. West JB, Schoene RB, Luks AM, Milledge JS. High altitude medicine and physiology. 5th edn. London: Hodder Headline, 2012.
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Ó 2014 Elsevier Ltd. All rights reserved.
Extremes of barometric pressure
Learning objectives After reading this article you should be able to: C understand the physical effects of changes in ambient pressure and the physiological consequences on the cardiovascular respiratory and neurological systems C gain an awareness that exposure to reduced ambient pressure produces both acute and more chronic effects, with differing signs, symptoms and time to onset at various altitudes C develop an awareness of the toxic effects of ‘inert’ gases at increased ambient pressures and the pathogenesis and management of decompression illness
Jane E Risdall David P Gradwell
Abstract Ascent to elevated altitude, commonly achieved through flight, by climbing or by residence in highland regions, exposes the individual to reduced ambient pressure. Although there are physical manifestations of this exposure as a consequence of Boyle’s law, the primary physiological challenge is of hypobaric hypoxia. The acute physiological and longer-term adaptive responses of the cardiovascular, respiratory, haematological and neurological systems to altitude are described, together with an outline of the presentation and management of acute mountain sickness, high-altitude pulmonary oedema and high-altitude cerebral oedema. Whilst many millions experience modest exposure to altitude as a result of flight in pressurized aircraft, fewer individuals are exposed to increased ambient pressure. The pressure changes during diving and hyperbaric exposures result in greater changes in gas load and gas toxicity. Physiological effects include the consequences of increased work of breathing and redistribution of circulating volume. Neurological manifestations may be the direct result of pressure or a consequence of gas toxicity at depth. Increased tissue gas loads may result in decompression illness on return to surface or subsequent ascent in flight.
oxygen in air remains constant at 20.9%, the partial pressure of oxygen in inspired air falls progressively. This causes a reduction in the pressure gradient for oxygen from the inspired gas to the tissues and hence into mixed venous blood (Figure 1). Therefore ascent to altitude is a specific, hypobaric, cause of hypoxic hypoxia. Flight within the normal pressurized cabin of a commercial aircraft is equivalent to ascending to 2500 m (8000 ft) and associated with a reduction in barometric pressure of 25%. Ascent to 4000e5000 m (15,000e16,500 ft) will induce hypoxia of such a degree as to stimulate hyperventilation, slow mental processes, impair learning and memory and reduce coordination. However, impairment of night vision has been reported at altitudes as low as 1500 m. Ascent to altitudes greater than 5000 m will result in progressively more rapid loss of consciousness. Studies have shown that individuals exposed to an altitude of 7600 m (25,000 ft) for 4e5 minutes will cease to be able to act in a rational manner to correct their predicament. This interval is described as the time of useful consciousness. The time of useful consciousness will be reduced at 9000 m (30,000 ft) to 2.5 minutes and to just 1 minute at 10,500 m (35,000 ft).
Keywords Acclimatization; acute mountain sickness; decompression illness; hyperbaric exposure; hypobaric hypoxia; inert gas toxicity Royal College of Anaesthetists CPD matrix: 1A01
Most of the world’s population lives close to sea-level. Meteorological changes in ambient pressure have little effect on respiratory physiology. Although adaptation to high altitude is seen in those living for prolonged periods at 3000 m or more above sea-level, millions of people are exposed acutely to changes in ambient pressure as a result of flight in aircraft. A few are exposed to more substantial changes in pressure by undertaking extreme ascents or by diving to depth.
Respiratory system Oxygen uptake: normal oxygenation is dependent on adequate alveolar ventilation. When alveolar PO2 is normal there is rapid diffusion of oxygen molecules through the alveolarecapillary membrane into the red blood cells (RBCs) and then into combination with haemoglobin. At rest, the time course for the transit of an RBC through a pulmonary capillary is of the order of 0.75 seconds. At sea-level, breathing air, within 0.25 seconds the oxygen tension in the blood within the capillary approaches that found within the alveoli. However, at altitude the alveolar PO2 is reduced so the rate of rise of oxygen tension within capillary blood is slower than at sea-level. At rest the capillary transit time is still sufficient to allow the oxygen tension to approach that within the alveoli, but when the transit time is reduced by exercise there will be a marked worsening of any hypobaric hypoxia (Figure 2).
High altitude e low pressure Barometric pressure declines exponentially on ascent. As pressure declines, gas volumes increase and so a fixed volume of gas contains fewer molecules. Thus, although the percentage of
Jane E Risdall is a Consultant Anaesthetist in the Royal Navy and a Senior Lecturer in Military Anaesthesia and Critical Care. Conflicts of interest: none declared. David P Gradwell is the Senior Consultant in Aviation Medicine in the Royal Air Force, working at the Centre of Aviation Medicine, Henlow. He is the Royal College of Physicians (London) Whittingham Professor of Aviation Medicine and is a Visiting Professor at King’s College, London. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:2
Ventilatory response to hypoxia: in most individuals hypoxia induces an increase in ventilation. Although this increases the respiratory work oxygen demand there is an overall fall in
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Ó 2014 Elsevier Ltd. All rights reserved.
PHYSIOLOGY
Figure 2
the respiratory alkalosis is corrected by increased excretion of bicarbonate, restoring pH towards normal. There is also an increase in the sensitivity of the respiratory centre to PaCO2, so that despite lowered carbon dioxide tensions in the blood, higher ventilation is maintained. There is also a secondary polycythaemia so that more oxygen is carried by the blood.
Figure 1
arterial PCO2 and a rise in arterial PO2. This hypoxia-induced ventilatory response is mediated through the aortic and carotid bodies. The associated fall in PaCO2 and the consequent respiratory alkalosis, acts centrally as a respiratory depressant, setting up a conflict in response, the outcome reflecting the balance between the two influences. Respiratory control commonly is more sensitive to changes in PaCO2 and an acute reduction in PaO2 does not induce a respiratory response until the oxygen tension falls to 6e6.7 kPa (45e50 mmHg). Below this level hypoxia induces a brisk increase in ventilation, exerting a stronger effect than the fall in PaCO2 or hydrogen ion concentration. The response to acute exposure to altitude is altered in those who acclimatize. The time course of acclimatization varies but the most important changes are in the cardio-respiratory systems and in the composition of the blood. Over a few days at altitude
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:2
Oxyhaemoglobin: when breathing air at sea-level, approximately 98.5% of the oxygen carried in blood is combined with haemoglobin. The shape of the dissociation curve means that moderate variations in PaO2 have relatively little effect on haemoglobin saturation and hence the oxygen content of the blood. When oxygen tension falls significantly, at altitudes above 3000 m (10,000 ft), oxygen is more readily dissociated from haemoglobin and delivery of oxygen to the tissues is compromised. The presence of a significant proportion of reduced haemoglobin in arterial blood gives rise to cyanosis at altitude. At altitude, the low PaCO2 moves the oxyhaemoglobin dissociation curve to the left. However, an increase in
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PHYSIOLOGY
2,3-diphosphoglycerate, moves it to the right, but the effect of the alkalosis predominates.
effects of acute exposure to altitude. Individuals with anaemic hypoxia will be particularly vulnerable to the added effects of hypobaric hypoxia and consideration should be given limiting the degree of anaemia suffered before transporting a patient by air. After a more prolonged exposure to moderate altitude, a reduction in plasma volume increases packed cell volume and haemoglobin concentration, but there is also greater erythropoietin production leading to a rise in red cell mass. After several weeks plasma volume will increase to produce a partial correction of the haemoglobin concentration. Myoglobin, containing just one haem group, is valuable in the transfer of oxygen into mitochondria within cells. At altitude myoglobin production is increased, and mitochondrial volume density also increases. These effects improve the utilization of oxygen after a period of acclimatization to moderate altitudes.
Cardiovascular responses Heart rate: heart rate is increased on acute exposure to altitudes above 2000e2500 m (6000e8000 ft). At 4500 m (15,000 ft) the rate is about 10e15% above the resting level at sea-level and approximately doubled at rest at 7500 m (25,000 ft). Stroke volume: stroke volume remains unchanged initially, but with acclimatization to altitude stroke volume is reduced. Blood pressure: mean arterial pressure remains unchanged on exposure to altitude. Systolic pressure is usually raised and there is an overall reduction in peripheral resistance, with a resulting increase in pulse pressure.
Acute mountain sickness (AMS): this condition ranges from relatively benign effects such as headache, lassitude, insomnia, fatigue and irritability to the severe, life-threatening conditions of high-altitude pulmonary oedema (HAPE) or high-altitude cerebral oedema (HACE). The mechanisms of AMS are unknown, but rapid ascent and duration of exposure are critical. It requires an exposure of some hours to develop AMS, but it has been reported at altitudes as low as 2500 m (8000 ft) and with exposures as short as 12 hours. The development of ultra-long haul flights may increase the incidence of AMS as a flight-related condition. Slow ascent allows acclimatization to take place and reduces the risk of AMS. Sleeping at an altitude below that reached during the day and no greater than 300 m (1000 ft) above the altitude of the previous night’s sleep will reduce the risk of AMS. HAPE is associated with tachycardia, tachypnoea and crackles in the lung bases with a dry cough. HACE is a severe form of AMS with progression to ataxia, hallucinations, coma and eventually, death. If symptoms suggestive of HAPE or HACE are encountered the individual should be given oxygen and immediately descend. Dexamethasone and diuretics may be of value, but the only definitive treatment is descent.
Cardiac output: since heart rate increases and stroke volume is unchanged, cardiac output increases on acute exposure to altitude in proportion to the increase in rate. With a subsequent reduction in stroke volume the cardiac output declines. Wellacclimatized individuals demonstrate a normal relationship between cardiac output and work load, but on initial exposure to altitude an exaggerated response to exercise is observed. The development of a degree of polycythaemia may be the means by which more normal oxygen delivery to the tissues is restored with acclimatization. Regional cardiovascular effects: hypoxia increases blood flow through the coronary and cerebral circulations, at the expense of renal, splanchnic and cutaneous blood flow. Flow through skeletal muscle may increase by 30e100%. Coronary blood flow increases in parallel with heart rate, matching the metabolic requirements of the myocardium. This prevents the emergence of electrocardiographic signs of hypoxia, even up to the point at which consciousness can be lost but in severe hypoxia myocardial depression will influence the ECG results with T depression and reduced height of the T-wave observed. The response of the cerebral circulation is determined by the relationship between oxygen and carbon dioxide. At oxygen tensions above 6e6.7 kPa (45e50 mmHg) flow is determined predominantly by PaCO2. With more severe hypoxia the falling oxygen tension predominates and at PaO2 of 4.7e5.3 kPa (35e40 mmHg) there is a 50e100% increase in cerebral blood flow. The blood flow in the pulmonary circulation is responsive to oxyhaemoglobin saturation of the blood. A 20% fall in saturation will cause rapid, reversible pulmonary vasoconstriction such that local perfusion is matched to local ventilation. Acute ascent to altitude sufficient to induce such a fall in saturation will cause the entire pulmonary vascular bed to constrict, increasing pulmonary arterial pressure. Long-term exposure to altitude has been associated with pulmonary hypertension and right ventricular hypertrophy in acclimatized lowlanders and high-altitude natives.
Depth e increased pressure Exposure to increased ambient pressure can occur in various circumstances: recreationally, commercially and clinically. SCUBA (self-contained underwater breathing apparatus) diving is a popular activity. Commercial raised-pressure work encompasses professional diving (including saturation diving where individuals remain at a raised ambient pressure for prolonged periods) and caisson workers who use pressurized chambers in underground tunnel construction. Clinically, patients (and, if ventilated, their accompanying anaesthetist) will encounter elevated pressures in the course of the administration of hyperbaric oxygen therapy, for conditions as diverse as decompression illness and carbon monoxide poisoning. Conventionally, exposures to increased ambient pressure are described in terms of a ‘dive’ to an equivalent depth of seawater in metres (msw), even if the exposure occurs in a dry, static hyperbaric chamber on the surface. The physiological challenges of raised ambient pressure are posed by the physical effects of pressure and the effect of pressure on gas solubility.
Haematology: hypoxia induces an increase in the oxygen carrying capacity of the blood. However these effects take time to be expressed and therefore are less relevant when considering the
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:2
76
Ó 2014 Elsevier Ltd. All rights reserved.
PHYSIOLOGY
Physical effects of pressure
forces about 500 ml of blood centrally, raising right atrial pressure, cardiac output and improving ventilationeperfusion relationships. The pressure receptors in the cardiovascular system detect this apparent increase in circulating volume and promote a diuresis, mediated via a decrease in antidiuretic hormone and an increase in atrial natriuretic peptide release. Immersion of the face in cold water induces the ‘diving reflex’. Here the heart rate falls, sometimes quite profoundly and peripheral vasoconstriction occurs.
Under water, pressure increases by 1 atmosphere absolute (ata) for every 10 msw; so at a depth of 30 msw a diver is exposed to 4 ata. Although the body is composed largely of incompressible solids and water, gas is present in the lungs, gastrointestinal tract, sinuses and middle ear. Using Boyle’s law and a constant temperature: volume f 1=pressure at 10 msw, the ambient pressure will be 2 ata and the volume of a fixed mass of gas will halve. Where the volume of a gas-filled space is fixed, as in the sinuses or middle ear, this gas will have to equilibrate with the increased pressure during descent, via the sinus ostia or Eustachian tube. If equilibration is not achieved, sinus or otic barotrauma will occur, with possible capillary or tympanic membrane rupture. In the gut, provided the mass of gas remains constant, the volume will shrink on descent and re-expand to its former volume on ascent.
Neurological effects of pressure Although the tissues are relatively incompressible compared with gas-filled spaces, lipids are more compressible than water. As lipids are a major constituent of cell membranes, increased ambient pressure can have a direct effect on cell function, including neuromuscular transmission. The result is termed high-pressure neurological syndrome. Symptoms include tremor, decreased manual dexterity, attention loss and nausea. It is seen at depths over 200 msw and is worse when the rate of descent is rapid. The symptoms may be lessened by adding nitrogen to the helium/oxygen mixtures normally breathed at these depths.
Respiratory system Work of breathing: during a dive the work of breathing is increased because the water pressure compresses the chest. To expand the lungs against this restriction, the work of the inspiratory muscles has to increase. The greatest pressure the respiratory muscles can generate is about 90 cmH2O. When water pressure exceeds this (at a depth of 1.2 m) inspiration of gas at surface pressure is impossible. In practice, divers breathe from a pressurized source via a demand valve, from a surface-supply regulated to equal the pressure at which they are working or from the gas at the ambient increased pressure within a hyperbaric chamber. In these circumstances, transthoracic pressure (i.e. the difference between intra-alveolar and ambient pressure at depth) is normal. With increasing ambient pressure, gas density also rises, which contributes to the increased work of breathing. Airflow may become turbulent compounding this effect. The increased gas density also slows intra-alveolar diffusion and may impair gas exchange.
Gas toxicity Gases considered benign or inert at sea-level may become toxic at depth. Nitrogen narcosis: at increased partial pressures, nitrogen behaves as a narcotic agent. It produces symptoms resembling alcohol intoxication, including euphoria, irrational behaviour, reduced manual dexterity and impaired mental function. The cause is thought to be an effect on cell membranes, similar to that seen with volatile anaesthetic agents. Symptoms can occur when breathing compressed air at 30 msw and become more marked as depth increases. Below 90 msw, divers breathing air risk unconsciousness. Oxygen toxicity: this is manifest in two forms; pulmonary and central nervous system (CNS). Pulmonary oxygen toxicity is time/dose related and although there is considerable individual variation, it is generally accepted that the threshold is a prolonged (12e24 hours) exposure to oxygen above 50 kPa. At greater partial pressures, there is more rapid development of symptoms and signs, including tracheal irritation, dry cough, reduced vital capacity and occasionally pulmonary oedema requiring positive-pressure ventilation. The underlying pathology is thought to be due to the disruption of endothelial and epithelial cells and the process can be modified by intermittent breathing of gas mixtures with a PiO2 less than 50 kPa. CNS toxicity occurs over a threshold exposure of 150 kPa oxygen. Exercise, elevated PaCO2 and nitrogen narcosis are all predisposing factors, but, at rest, in a dry environment, patients undergoing hyperbaric oxygen therapy can tolerate up to 280 kPa oxygen, if given intermittently. Although prodromal symptoms have been reported, the classical presentation is that of a sudden epileptiform convulsion. To overcome the limitations imposed by nitrogen narcosis, oxygen toxicity and the increased work of breathing due to changes in gas density, helium is the most commonly used inert
Pulmonary barotrauma: since the lungs will be in free communication with gas at the increased ambient pressure during a dive it is important that the diver breathes normally on ascent. Gas in the lungs will expand (Boyle’s law) and if exhalation does not occur alveolar rupture and pulmonary barotrauma may occur. Breath-hold diving: in a breath-holding dive from the surface, the lung volumes are compressed with the increasing pressure, then re-expand to their original volume on ascent. Breath-hold dives deeper than those predicted from the simple application of Boyle’s law, are possible due to redistribution of blood volume into the thoracic cavity, but such exposures are not without considerable risk of hypoxia and lung damage due to congestion, oedema and haemorrhage.
Cardiovascular system On the surface there is a hydrostatic pressure gradient in the upright individual with fluid pooling in the lower half of the body. However, when submerged in water, the surrounding pressure
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PHYSIOLOGY
diluent gas in breathing mixtures for use below 50 msw. It is less soluble and less narcotic than nitrogen and being less dense, reduces the work of breathing.
DCI is a combination of recompression, to reduce bubble size and hyperbaric oxygen therapy to maximize the gradient for the elimination of inert gas. The risk of DCI is minimized by ensuring a slow, controlled ascent, the precise rate of which will depend on the depth and duration of the dive, in accordance with published tables. Saturation divers, who remain under pressure for several weeks and become fully equilibrated with gases at the increased ambient pressure may take several days to decompress and their decompression obligation may be undertaken in a hyperbaric chamber. The risk of DCI is increased if, within 24 hours of a dive or hyperbaric exposure, the individual then goes to altitude or flies, even in a commercially pressurized cabin, since reequilibration of all tissue compartments to sea-level pressure may not be complete. A
Decompression illness According to Henry’s law, at a constant temperature the amount of gas which dissolves in a liquid is proportional to the pressure of that gas or its partial pressure, if it is part of a mixture of gases. Breathing gases at increased ambient pressure will increase the amount of each gas dissolved in the fluid phases of body tissues. On ascent this excess gas has to be given up. If the ascent is controlled at a sufficiently slow rate, elimination will be via the respiratory system. If the ascent is too fast, excess gas may come out of solution and form free bubbles in the tissues or circulation. Bubbles may contain any of the gases in the breathing mixture, but it is the presence of inert gas bubbles (nitrogen or helium) that are thought most likely to give rise to problems, since the elimination of excess oxygen is achieved by metabolism as well as ventilation. These bubbles may act as venous emboli or may trigger inflammatory tissue responses giving rise to symptoms of decompression illness (DCI). Signs and symptoms of DCI may appear up to 48 hours after exposure to increased ambient pressure and include joint pains, motor and sensory deficits, dyspnoea, cough and skin rashes. Treatment of
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FURTHER READING Brubakk AO, Neuman TS, eds. Bennett and Elliott’s physiology and medicine of diving. 5th edn. London: Saunders, 2003. Rainford DJ, Gradwell DP, eds. Ernsting’s aviation medicine. 4th edn. London: Hodder Headline, 2006. West JB, Schoene RB, Luks AM, Milledge JS. High altitude medicine and physiology. 5th edn. London: Hodder Headline, 2012.
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