- Email: [email protected]
7. The graver side of gravity
Br.
J. Dis.
Chest
(1983)
77,
105
Does the Lung Work?
7. THE GRAVER SIDE OF GRAVITY D. M. DENISON Lung
Function
Unit,
Brompton
Hospital,
London
A Curious Observation A few years ago Sundstrom (1975) took a group of five healthy young men (about 25 years old) and found, as many others before, that their lungs absorbed carbon monoxide more rapidly when they lay supine than when they sat upright. However, when he repeated the study on five healthy men about 60 years old, the reverse was true. The study was careful, rich in supporting data and limited to non-smokers, so there is every reason to accept the findings. Why do they occur? The Findings
in Younger
People
In an earlier article, Davies (1982) p ointed out that whole-lung carbon monoxide transfer (TLCO) is mainly a measure of the volume of accessible haemoglobin in the lung. The observation that it diminishes in healthy young men when they sit up implies that some previously accessible blood becomes inaccessible or leaves the lung altogether. There is abundant evidence that this is true. The displacements of blood in and out of the thorax with posture are visible on conventional chest radiographs and have been appreciated for a long time. In normal people the apical vessels are obvious radiographically when they lie supine but on sitting up they can no longer be seen. The basal vessels remain much the same size as before. Compressing the leg vessels externally or by exercise makes the apical vessels reappear. Raising intrathoracic pressure causes them to disappear again. The heart and great veins are seen to get bigger or smaller at the same time. These changes are largely complete within a few seconds. The dimensions of the thoracic cavity at total lung capacity and residual volume are little affected by posture because the respiratory muscles are stronger than the gravitational forces involved. Nevertheless the volumes of gas in the lung at these extremes increase by 200-500 ml on sitting up (Fig. 1). These volume changes reflect the alterations in intrathoracic blood volume. They are exaggerated by applying suction to the legs alone, are prevented by cuffing the limbs, and are reversed by compressing the legs with an antigravity suit or immersing them in water, or by tilting the body head down. They are accompanied by corresponding changes in TLCO, that arise from alterations in the pulmonary capillary volume Vc rather than the membrane component Dm. They can also be mimicked by Valsalva and Mueller manoeuvres and by altering the breathing pressure in the chest.
106
Does the Lung
Work ?
The shifts in pulmonary capillary volume as judged from TLC0 are too small (So-100 ml) to account for all of the alterations in lung gas volume but the changes in central blood volume or total thoracic blood volume as measured by dye dilution or scintigraphy, which include the blood in the heart and great vessels, are of the right order to do so (300-500 ml). The displacements seem to occur in three stages - first, a mechanical shift, over a few seconds, attributable almost entirely to the distensibilities and relative positions of the pulmonary and systemic venous beds; second, a slower shift in the same direction due to filtration of fluid out of the vacated and into the invaded tissues; and third, a reflex correction in the opposite sense, initiated by signals from the intravascular stretch receptors in the thorax that measure and control central blood volume.
On sitting
up: OBSERVATIONS TLC rises by 500 ml VC rises by 300 ml RV rises by 200 ml FRC rises by 750 ml Apical vessels disappear from CXR DLCO falls in young men, but rises men
/ /I\-. :
t-4 c.
.*-----N-d--
Fig. 1. A summary
of some of the functional
changes in the lung, that occur on sitting
in older
up
These processes have been under study for a long time. Hartshorne anticipated the existence of intrathoracic stretch receptors as long ago as 1847, and as early as 1887 Or-the argued that the pressure in the pulmonary artery was too low for blood to reach to the very top of the lung in upright man. His ideas did not really come to fruit until 1950 when Rothstein et al. found that if people lay on their side the oxygen uptake of the upper lung fell. A few years later, Martin et al. (1953) and Mattson and Carlens (1955) sh owed that a more severe fall in oxygen uptake occurred at the apex when subjects sat up. A few years later again, Riley calculated that this change was roughly equivalent to losing the use of one-seventh of the lung. Soon after, West and Dollery began the studies of isolated lung which culminated in West’s three-zone model of the effects of gravity on lung perfusion (West 1977). Essentially, he saw the lung as a mass of alveoli of identical characteristics, inflated to the same pressure, and perfused by a vertical array of vessels originating from the hilum. These were fed by a common supply pressure to which was added or subtracted the change in hydrostatic head as blood travelled towards the apex or the base of the lung. The model could be thought of in three horizontal slices. In the upper slice, pulmonary arterial pressure was less than alveolar
The Graver Side of Gravity
107
pressure, so the capillaries were empty and unperfused. In the middle slice, pulmonary artery pressure exceeded alveolar pressure but pulmonary venous pressure did not. Thus the veins were collapsed and no siphoning of blood could occur. In this zone blood flow increased linearly down the lung due to the rise in the effective delivery pressure. In the lower slice pulmonary venous pressure was greater than alveolar, so the veins were open and transmitted an equal hydrostatic head opposing arterial pressure. In this zone the increase in flow with descent down the lung was less marked because it was due to vessel distension alone. This model of the behaviour of blood flowing in floppy tubes running through an isotropic foam turned out to be inaccurate in two minor respects. First, it was found that blood reached higher up the lung than anticipated because of the alveolar surface traction, and then it was noted that in vivo blood flow reduced with descent in the lowermost regions of the upright lung. Nevertheless the model is still central to our understanding of the perfusion of the lung. When it is combined with present knowledge of the shapes and distensibilities of the systemic vascular tree the shifts of blood between body and lungs with changes in posture can be modelled with surprising precision (Shimizu et al. 1979) and appear easily to explain almost all of the physiological and radiological observations cited so far. However they do not give reasons why blood flow diminishes at the very bottom of the lung, nor do they account for Sundstrom’s observations on the five older men. The Findings
in Older Subjects
These phenomena are determined by the effects of gravity on the alveoli rather than the vessels of the lung. When the isolated lung is supported from the hilum it does behave as an almost isotropic foam in the sense that all the alveoli have much the same mechanical properties, are exposed to a common transmural pressure and are thus much the same size. However inside the chest the external pressure varies from point to point so the diameters of the alveoli are no longer the same throughout the lung. The causes and extent of these variations in external pressure are still not completely understood. About 150 years ago, Carson and Donders, working separately, measured the retractile force of the lung and found it to be a few to several centimetres of water dependent on the degree of inflation. Soon after, Ludwig and Luciani independently discovered that the pleural and oesophageal pressures were slightly subatmospheric, and then in 1887 West demonstrated that pressures much greater than a few centimetres of water were needed to separate two pieces of wood covered with moist gastric mucosa. From then on it was supposed that the lungs were attached to the chest wall by surface tension alone. However, there were two faults in West’s elegant experiment. First, there are normally no air/water edges in the pleural cavity. These would magnify the binding pressures to an extent that is inversely related to the edges’ radii of curvature. Second, the pleurae, like the gastric mucosa, are permeable to gas and water, so, in vivo, there is a constant tendency for the visceral and parietal pleura to separate as the retractile forces suck gas and blood in.
108
Does the Lung Work ?
In the 1920s Rist and Strohl proposed that any gas diffusing into the pleural space would be absorbed because the total gas pressures in blood and tissue fluid were always subatmospheric; and Neergaard suggested that any fluid filtering into the pleural cavity would be resorbed by plasma colloid osmotic pressure. These two mechanisms did indeed explain why the pleural space is normally so slight. Since then it has become clear that pleural fluid is secreted by the parietal layer which is perfused by the high-pressure systemic circulation, and it is resorbed by the visceral lining, which gets its blood supply from the low pressure pulmonary circuit. For this reason the pressures in the visceral bilayers of the mterlobar fissures and possibly the mediastinum are more negative than those on the outer surfaces of the lung. Recently, Miserocchi et al. (1981) have found that there is also a gradient of about 0.7 cmHzO per cm inward travel, drawing pleural fluid along the interlobar fissures towards the mediastinum. This flow, which is increased by hyperventilation and tachycardia, may be due to augmented drainage by lymphatics. These mechanisms by themselves would create a film of fluid moving centripetally over the surface of the lung in which it would be reasonable to find a vertical hydrostatic pressure gradient of about 1 cmH,O per cm ‘descent, down the lung. In fact, it is extremely difficult to measure pleural pressures correctly because the thickness of the fluid layer (5-10 pm) is less than the heights of the microscopic corrugations on the pleural surface and the diameters of some of the cells within. The pleurae are rather like a couple of waffles pressed together, with the syrup between representing pleural fluid. With this image it is easy to see there will be at least two pressures of importance - the fluid pressure exerted on the cavities, and the surface pressures between the bars. Obviously the liquid pressure can be more negative than the surface pressure, but not vice versa. Largely due to the work of Agostoni and his colleagues (summarized in two reviews; Agostoni 1972, 1977) we know now that the vertical pressure gradient in the liquid is not 1 cm of water per cm descent but roughly a quarter of that amount - and it shows several discontinuities especially over the apex and other highly curved surfaces. Although this gradient is very similar to the density of the lung and rises linearly with applied head-to-toe accelerations, it is not due to the fluid pressure of the lung acting on the visceral pleura but to the weight of the chest wall pressing from the parietal side, on lakes of pleural fluid that are not necessarily in contact with each other. It is possible to imitate this situation in the laboratory by surrounding the isolated lung with an egg-white foam or a bed of fluidized plastic beads. In these circumstances, as in the upright lung in vivo, the uppermost alveoli and small airways are exposed to the most negative surface pressures and are most expanded whilst the basal alveoli are the most compressed but have a greater potential for expansion. As a result in the upright posture at FRC, a slow tidal inspiration is preferentially distributed to the bases with their greater capacity for expansion but a rapid tidal breath is largely directed to the apices where airway resistance is least. As the lung ages, and its elastin fibres become floppier, the tendency for airways to close off at FRC increases. Once this occurs the subtended alveoli are
The Graver Side of Gravity
109
ventilated by deeper breaths only. As a result there is hypoxic vasoconstriction of the local pulmonary arterioles leading to the reduction in blood flow to poorly ventilated dependent zones that was not explained by West’s three-zone model of perfusion in the lung. This is especially obvious in older and emphysematous lungs. If the owners of such lungs breathe oxygen, they trick the constricted vessels into believing that they are serving well-ventilated spaces, the vessels relax, and the continuous apex-to-base gradient of perfusion, typical of the isolated lung, is then seen in vivo (Dosman et al. 1981; Engel & Prefaut 1981; Prefaut & Engel 1981). A More General View (Fig. 2) In summary,. the lung behaves as an isotropic foam that is suspended from the vault of the thorax and carries some of the weight of the liver and spleen. The
EXPLANATIONS Blood leaves the chest (TLC, RV, VC t) The diaphragm falls (FRC t by 750 ml) Apical alveoli and airways get much bigger but ventilation is limited and blood supply fails, (hence D LCO 4) Basal alveoli and airways expand slightly In older people, these alveoli are not in use when they lie down, (hence DLCO t)
Fig. 2. A summary
of the causes for the functional
changes described
in Fig. 1
upper alveoli and airways are patent but so stretched that they cannot expand much and are meagrely supplied with blood. The lower alveoli and airways are compressed, and sometimes closed, but are richly perfused and capable of receiving much air. The mechanical stresses within the lung are concentrated in the uppermost and most acutely curved parts and also around areas that are reluctant to expand. Abdominal traction drags down the diaphragm and tends to constrict the lower margin of the chest. On lying supine the lung hangs from the anterior chest wall and rests on the back, the diaphragm rises 4-6 cm and the unstressed costal margins relax outwards. On moving to lie on one side the non-dependent lung hangs from the upper axillary surface and takes some of the weight of the mediastinum, and is minimally compressed by the upper hemidiaphragm. The dependent lung bears some weight from the mediastinum, lies on the lower axillary surface and is significantly squashed by the bulging lower hemidiaphragm. In all of these positions there is a vertical gradient of blood flow, modified by
Does the Lung Work? hypoxic vasoconstriction wherever airway closure causes ventilation to be poor. In older people, functional residual capacity falls below the closing volume of the lung more when they lie down than when they sit up. So Sundstrom’s observations on young men are explained by the effects of gravity on perfusion but his findings in the older men reflect the overshadowing effects of gravity on the alveoli of ageing lungs. Some Measurement
Problems
The surge of interest in aviation and space matters during and after the Second World War led to many studies on the physiology of acceleration and weightlessness. The respiratory events that occur are interesting but not really limiting. Blood retreats further from the apex, more airways close and poor ventilation occurs at the bases, arterial Paz falls somewhat as a result and, if oxygen is being breathed, absorption atelectasis occurs in the over-perfused unventilated most dependent parts of the lung. Lying supine, central blood pressures and cardiac output fall much less and considerably higher g levels can be tolerated, but respiration does then become limited by the increasing weight of the anterior chest wall. By contrast, in the weightless states experienced in space fIights and ballistic trajectories, the lung comes into its own as a uniformly ventilated and perfused foam. Many of these studies could not be realized in aircraft or space vehicles or even in the man-carrying centrifuge, which are all exorbitantly expensive. Consequently a great deal of work has been done with immersion, supine bed rest and lower body positive pressure (usually by anti-g-suit) as models of weightlessness and with lower body negative pressure or simply negative leg pressure as mimics of increased gravitational stress. Much has been learnt from these studies but they do have limitations. Immersion opposes the hydrostatic head of the systemic circulation and displaces blood into intrathoracic beds, but it leaves the lung and its circulation weighted normally. Bed rest shortens the vertical height of the body and the lungs, but introduces a fair amount of immobility and still leaves the horizontal lung under 1 ‘g’. Similarly applying positive or negative pressures to the abdomen and legs leaves the lungs with more, or less, blood than usual but otherwise weighted as before. Some Clinical
Consequences
The effects of gravity on the lung are important clinically, but are not always easy to interpret. There is, for example, a clear contradiction between the physiologist’s requirement that patients with chest disease should lie with the healthiest lung lowermost to gain maximum benefit from its richer perfusion (Zack et al. 1974) and the pathologist’s wish that the unhealthy lung should not be uppermost since it tends to drop infected material directly into the opposite lung. As Brock (1954) pointed out this explains why most lung abscesses occur in the lateral, i.e. axillary, segments of the upper lobe. Similarly Helm (1951) made a careful study of the spread of tuberculosis from one lung and found much
The Graver Side of Gravity
111
the same distribution with a clear link to the preferred side of sleeping. Recently Helms et al. (1982) had the opportunity to study 11 infants with unilateral lung disease, comparing the distribution of ventilation and perfusion when they were lain on their right or left sides. They found the effects of gravity were the reverse of those found in adults since, in the infants, arterial blood oxygenation was better when the good lung was uppermost. They believe this occurs because the chest wall is much more compliant in infants than adults. As a result, the dependent lung is compressed more and ventilated less. Many people have speculated on the vertical distribution of disease in the upright lung. One of the most eloquent was Dock (1946) who believed that tuberculosis resided in the apices because the mycobacterium has a predilection for a high Po2. He advanced some compelling arguments in favour of that view. John West, per contra, observed that it is most prevalent in the dorsal segments of quadruped lungs and the phrenic segments of bat lungs and supposed it was linked to local stress concentrations. Both views could be true. The stress argument is certainly an appealing explanation for the apical and sharp-edge concentrations of emphysematous bullae. Other aspects, such as the basal distributions of alpharantitrypsin-deficient emphysema and the vascular changes of mitral stenosis have an obvious gravitational basis but unlike the mechanisms underlying Sundstrom’s observations, the causes of these graver effects of gravity on the lung are not yet clear. Suggestions
for Further
Reading
Agostoni, E. (1972) Mechanics of the pleural space. Physiol. Rev. 52, 57-128. Agostoni, E. (1977) Transpulmonary pressure. In: Regional Differences in the Lung, ed. J. B. West, pp. 245-280. New York: Academic Press. Arborelius, M., Granquist, V., Lilja, B. & Zanner, C. W. (1974) Regional lung function and central haemodynamics in the right lateral body position during hypoxia and hyperoxia. Respiration 31, 193-200. Arborelius, M., Lilja, B. & Senyk, J. (1975) Regional and total lung function studies in patients with hemidiaphragmatic paralysis. Respiration 32, 253-264. Brock, R. C. (1954) Bronchial embolism and posture in relation to lung abscess. The Anatomy of the Bronchial Tree, pp. 13-25. London: Oxford University Press. Davies, N. J. H. (1982) Does the lung work? 4. What does the transfer of carbon monoxide mean? Br. J. Dis. Chest 76, 105-123. Dock, W. (1946) Apical localization of pthisis. Its significance in treatment by prolonged rest in bed. Am. Rev. Tuberc. 53, 297. Dosman, J. A., Hodgson, W., Edwardson, C., Graham, B. L., Cotton, D. J. & Stirling, D. (1981) Effects of inspiratory flow rate on the oesophageal pressure gradient in upright humans. Resp. Physiol. 46, 105-112. Engel, L. A. & Prefaut, C. (1981) C ranio-caudal distribution of inspired gas and perfusion in supine man. Resp. Physiol. 45, 43-54. Helm, W. H. (1951) The importance of sleeping posture in the spread of pulmonary tuberculosis. Thorax 6, 417-425. Helms, P., Heaf, D. P., Turner, H. & Gordon, I. (1982) Down with the bad lung. Thorax 37, 790 (abstract). Macklem, P. T. (1981) Normal and abnormal function of the diaphragm. Thorax 36, 161-163. Martin, C. F., Cline, F. & Marshall, H. (1953) Lobar alveolar gas concentrations: effects of body position. J. din. Invest. 32, 617-621.
112
Does the Lung Work ?
Mattson, S. B. & Carlens, E. (1955) Lobar ventilation and oxygen uptake in man’s influence of body position. J. thorac. cardiovasc. Surg. 30, 676. Miserocchi, G., Nakamura, T., Mariani, E. & Negrini, D. (1981) Pleural liquid pressures over the interlobar, mediastinal and diaphragmatic surfaces of the lung. Resp. Physiol. 46, 61-70. Prefaut, C. & Engel, L. A. (1981) Vertical distribution of perfusion and inspired gas in supine man. Resp. Physiol. 43, 209-219. Riley, R. L., Permutt, S., Said, S., Godfrey, M., Cheng, T. O., Howell, J. B. L. & Shephard, R. H. (1959) Effect of posture on pulmonary dead space in man. /. apph PhysioZ. 14, 339-344.
Rothstein, E., Landis, F. B. & Narodick, B. G. (1950) B ronchospirometry in the lateral decubitus position. J. thorac. Surg. 19, 821. Shin&u, M., Ghista, D. & Sandler, H. (1979) Cardiovascular regulatory response to lower body negative pressure following blood volume loss. A&t. Space Environ. Med. 50, 24-32. Sundstrom, G. (1975) Influence of body position on pulmonary diffusing capacity in young and old men. J. appl. Physiol. 38, 418-423. Svanberg, L. (1949) Influence of posture on the lung volumes, ventilation and circulation in normals. Stand. J. lab. clin. Invest. 9, suppl. 25, 195. West, J. B., (1977) Stresses. In: Regional Difference in the Lung, ed. J. B. West, pp. 281-323. New York: Academic Press. Zack, M. B., Pontoppidan, H. & Kaxemi, H. (1974) Th e effect of lateral positions on gas exchange in pulmonary disease. Am. Rev. Dis. 110, 49-55.
J. Dis.
Chest
(1983)
77,
105
Does the Lung Work?
7. THE GRAVER SIDE OF GRAVITY D. M. DENISON Lung
Function
Unit,
Brompton
Hospital,
London
A Curious Observation A few years ago Sundstrom (1975) took a group of five healthy young men (about 25 years old) and found, as many others before, that their lungs absorbed carbon monoxide more rapidly when they lay supine than when they sat upright. However, when he repeated the study on five healthy men about 60 years old, the reverse was true. The study was careful, rich in supporting data and limited to non-smokers, so there is every reason to accept the findings. Why do they occur? The Findings
in Younger
People
In an earlier article, Davies (1982) p ointed out that whole-lung carbon monoxide transfer (TLCO) is mainly a measure of the volume of accessible haemoglobin in the lung. The observation that it diminishes in healthy young men when they sit up implies that some previously accessible blood becomes inaccessible or leaves the lung altogether. There is abundant evidence that this is true. The displacements of blood in and out of the thorax with posture are visible on conventional chest radiographs and have been appreciated for a long time. In normal people the apical vessels are obvious radiographically when they lie supine but on sitting up they can no longer be seen. The basal vessels remain much the same size as before. Compressing the leg vessels externally or by exercise makes the apical vessels reappear. Raising intrathoracic pressure causes them to disappear again. The heart and great veins are seen to get bigger or smaller at the same time. These changes are largely complete within a few seconds. The dimensions of the thoracic cavity at total lung capacity and residual volume are little affected by posture because the respiratory muscles are stronger than the gravitational forces involved. Nevertheless the volumes of gas in the lung at these extremes increase by 200-500 ml on sitting up (Fig. 1). These volume changes reflect the alterations in intrathoracic blood volume. They are exaggerated by applying suction to the legs alone, are prevented by cuffing the limbs, and are reversed by compressing the legs with an antigravity suit or immersing them in water, or by tilting the body head down. They are accompanied by corresponding changes in TLCO, that arise from alterations in the pulmonary capillary volume Vc rather than the membrane component Dm. They can also be mimicked by Valsalva and Mueller manoeuvres and by altering the breathing pressure in the chest.
106
Does the Lung
Work ?
The shifts in pulmonary capillary volume as judged from TLC0 are too small (So-100 ml) to account for all of the alterations in lung gas volume but the changes in central blood volume or total thoracic blood volume as measured by dye dilution or scintigraphy, which include the blood in the heart and great vessels, are of the right order to do so (300-500 ml). The displacements seem to occur in three stages - first, a mechanical shift, over a few seconds, attributable almost entirely to the distensibilities and relative positions of the pulmonary and systemic venous beds; second, a slower shift in the same direction due to filtration of fluid out of the vacated and into the invaded tissues; and third, a reflex correction in the opposite sense, initiated by signals from the intravascular stretch receptors in the thorax that measure and control central blood volume.
On sitting
up: OBSERVATIONS TLC rises by 500 ml VC rises by 300 ml RV rises by 200 ml FRC rises by 750 ml Apical vessels disappear from CXR DLCO falls in young men, but rises men
/ /I\-. :
t-4 c.
.*-----N-d--
Fig. 1. A summary
of some of the functional
changes in the lung, that occur on sitting
in older
up
These processes have been under study for a long time. Hartshorne anticipated the existence of intrathoracic stretch receptors as long ago as 1847, and as early as 1887 Or-the argued that the pressure in the pulmonary artery was too low for blood to reach to the very top of the lung in upright man. His ideas did not really come to fruit until 1950 when Rothstein et al. found that if people lay on their side the oxygen uptake of the upper lung fell. A few years later, Martin et al. (1953) and Mattson and Carlens (1955) sh owed that a more severe fall in oxygen uptake occurred at the apex when subjects sat up. A few years later again, Riley calculated that this change was roughly equivalent to losing the use of one-seventh of the lung. Soon after, West and Dollery began the studies of isolated lung which culminated in West’s three-zone model of the effects of gravity on lung perfusion (West 1977). Essentially, he saw the lung as a mass of alveoli of identical characteristics, inflated to the same pressure, and perfused by a vertical array of vessels originating from the hilum. These were fed by a common supply pressure to which was added or subtracted the change in hydrostatic head as blood travelled towards the apex or the base of the lung. The model could be thought of in three horizontal slices. In the upper slice, pulmonary arterial pressure was less than alveolar
The Graver Side of Gravity
107
pressure, so the capillaries were empty and unperfused. In the middle slice, pulmonary artery pressure exceeded alveolar pressure but pulmonary venous pressure did not. Thus the veins were collapsed and no siphoning of blood could occur. In this zone blood flow increased linearly down the lung due to the rise in the effective delivery pressure. In the lower slice pulmonary venous pressure was greater than alveolar, so the veins were open and transmitted an equal hydrostatic head opposing arterial pressure. In this zone the increase in flow with descent down the lung was less marked because it was due to vessel distension alone. This model of the behaviour of blood flowing in floppy tubes running through an isotropic foam turned out to be inaccurate in two minor respects. First, it was found that blood reached higher up the lung than anticipated because of the alveolar surface traction, and then it was noted that in vivo blood flow reduced with descent in the lowermost regions of the upright lung. Nevertheless the model is still central to our understanding of the perfusion of the lung. When it is combined with present knowledge of the shapes and distensibilities of the systemic vascular tree the shifts of blood between body and lungs with changes in posture can be modelled with surprising precision (Shimizu et al. 1979) and appear easily to explain almost all of the physiological and radiological observations cited so far. However they do not give reasons why blood flow diminishes at the very bottom of the lung, nor do they account for Sundstrom’s observations on the five older men. The Findings
in Older Subjects
These phenomena are determined by the effects of gravity on the alveoli rather than the vessels of the lung. When the isolated lung is supported from the hilum it does behave as an almost isotropic foam in the sense that all the alveoli have much the same mechanical properties, are exposed to a common transmural pressure and are thus much the same size. However inside the chest the external pressure varies from point to point so the diameters of the alveoli are no longer the same throughout the lung. The causes and extent of these variations in external pressure are still not completely understood. About 150 years ago, Carson and Donders, working separately, measured the retractile force of the lung and found it to be a few to several centimetres of water dependent on the degree of inflation. Soon after, Ludwig and Luciani independently discovered that the pleural and oesophageal pressures were slightly subatmospheric, and then in 1887 West demonstrated that pressures much greater than a few centimetres of water were needed to separate two pieces of wood covered with moist gastric mucosa. From then on it was supposed that the lungs were attached to the chest wall by surface tension alone. However, there were two faults in West’s elegant experiment. First, there are normally no air/water edges in the pleural cavity. These would magnify the binding pressures to an extent that is inversely related to the edges’ radii of curvature. Second, the pleurae, like the gastric mucosa, are permeable to gas and water, so, in vivo, there is a constant tendency for the visceral and parietal pleura to separate as the retractile forces suck gas and blood in.
108
Does the Lung Work ?
In the 1920s Rist and Strohl proposed that any gas diffusing into the pleural space would be absorbed because the total gas pressures in blood and tissue fluid were always subatmospheric; and Neergaard suggested that any fluid filtering into the pleural cavity would be resorbed by plasma colloid osmotic pressure. These two mechanisms did indeed explain why the pleural space is normally so slight. Since then it has become clear that pleural fluid is secreted by the parietal layer which is perfused by the high-pressure systemic circulation, and it is resorbed by the visceral lining, which gets its blood supply from the low pressure pulmonary circuit. For this reason the pressures in the visceral bilayers of the mterlobar fissures and possibly the mediastinum are more negative than those on the outer surfaces of the lung. Recently, Miserocchi et al. (1981) have found that there is also a gradient of about 0.7 cmHzO per cm inward travel, drawing pleural fluid along the interlobar fissures towards the mediastinum. This flow, which is increased by hyperventilation and tachycardia, may be due to augmented drainage by lymphatics. These mechanisms by themselves would create a film of fluid moving centripetally over the surface of the lung in which it would be reasonable to find a vertical hydrostatic pressure gradient of about 1 cmH,O per cm ‘descent, down the lung. In fact, it is extremely difficult to measure pleural pressures correctly because the thickness of the fluid layer (5-10 pm) is less than the heights of the microscopic corrugations on the pleural surface and the diameters of some of the cells within. The pleurae are rather like a couple of waffles pressed together, with the syrup between representing pleural fluid. With this image it is easy to see there will be at least two pressures of importance - the fluid pressure exerted on the cavities, and the surface pressures between the bars. Obviously the liquid pressure can be more negative than the surface pressure, but not vice versa. Largely due to the work of Agostoni and his colleagues (summarized in two reviews; Agostoni 1972, 1977) we know now that the vertical pressure gradient in the liquid is not 1 cm of water per cm descent but roughly a quarter of that amount - and it shows several discontinuities especially over the apex and other highly curved surfaces. Although this gradient is very similar to the density of the lung and rises linearly with applied head-to-toe accelerations, it is not due to the fluid pressure of the lung acting on the visceral pleura but to the weight of the chest wall pressing from the parietal side, on lakes of pleural fluid that are not necessarily in contact with each other. It is possible to imitate this situation in the laboratory by surrounding the isolated lung with an egg-white foam or a bed of fluidized plastic beads. In these circumstances, as in the upright lung in vivo, the uppermost alveoli and small airways are exposed to the most negative surface pressures and are most expanded whilst the basal alveoli are the most compressed but have a greater potential for expansion. As a result in the upright posture at FRC, a slow tidal inspiration is preferentially distributed to the bases with their greater capacity for expansion but a rapid tidal breath is largely directed to the apices where airway resistance is least. As the lung ages, and its elastin fibres become floppier, the tendency for airways to close off at FRC increases. Once this occurs the subtended alveoli are
The Graver Side of Gravity
109
ventilated by deeper breaths only. As a result there is hypoxic vasoconstriction of the local pulmonary arterioles leading to the reduction in blood flow to poorly ventilated dependent zones that was not explained by West’s three-zone model of perfusion in the lung. This is especially obvious in older and emphysematous lungs. If the owners of such lungs breathe oxygen, they trick the constricted vessels into believing that they are serving well-ventilated spaces, the vessels relax, and the continuous apex-to-base gradient of perfusion, typical of the isolated lung, is then seen in vivo (Dosman et al. 1981; Engel & Prefaut 1981; Prefaut & Engel 1981). A More General View (Fig. 2) In summary,. the lung behaves as an isotropic foam that is suspended from the vault of the thorax and carries some of the weight of the liver and spleen. The
EXPLANATIONS Blood leaves the chest (TLC, RV, VC t) The diaphragm falls (FRC t by 750 ml) Apical alveoli and airways get much bigger but ventilation is limited and blood supply fails, (hence D LCO 4) Basal alveoli and airways expand slightly In older people, these alveoli are not in use when they lie down, (hence DLCO t)
Fig. 2. A summary
of the causes for the functional
changes described
in Fig. 1
upper alveoli and airways are patent but so stretched that they cannot expand much and are meagrely supplied with blood. The lower alveoli and airways are compressed, and sometimes closed, but are richly perfused and capable of receiving much air. The mechanical stresses within the lung are concentrated in the uppermost and most acutely curved parts and also around areas that are reluctant to expand. Abdominal traction drags down the diaphragm and tends to constrict the lower margin of the chest. On lying supine the lung hangs from the anterior chest wall and rests on the back, the diaphragm rises 4-6 cm and the unstressed costal margins relax outwards. On moving to lie on one side the non-dependent lung hangs from the upper axillary surface and takes some of the weight of the mediastinum, and is minimally compressed by the upper hemidiaphragm. The dependent lung bears some weight from the mediastinum, lies on the lower axillary surface and is significantly squashed by the bulging lower hemidiaphragm. In all of these positions there is a vertical gradient of blood flow, modified by
Does the Lung Work? hypoxic vasoconstriction wherever airway closure causes ventilation to be poor. In older people, functional residual capacity falls below the closing volume of the lung more when they lie down than when they sit up. So Sundstrom’s observations on young men are explained by the effects of gravity on perfusion but his findings in the older men reflect the overshadowing effects of gravity on the alveoli of ageing lungs. Some Measurement
Problems
The surge of interest in aviation and space matters during and after the Second World War led to many studies on the physiology of acceleration and weightlessness. The respiratory events that occur are interesting but not really limiting. Blood retreats further from the apex, more airways close and poor ventilation occurs at the bases, arterial Paz falls somewhat as a result and, if oxygen is being breathed, absorption atelectasis occurs in the over-perfused unventilated most dependent parts of the lung. Lying supine, central blood pressures and cardiac output fall much less and considerably higher g levels can be tolerated, but respiration does then become limited by the increasing weight of the anterior chest wall. By contrast, in the weightless states experienced in space fIights and ballistic trajectories, the lung comes into its own as a uniformly ventilated and perfused foam. Many of these studies could not be realized in aircraft or space vehicles or even in the man-carrying centrifuge, which are all exorbitantly expensive. Consequently a great deal of work has been done with immersion, supine bed rest and lower body positive pressure (usually by anti-g-suit) as models of weightlessness and with lower body negative pressure or simply negative leg pressure as mimics of increased gravitational stress. Much has been learnt from these studies but they do have limitations. Immersion opposes the hydrostatic head of the systemic circulation and displaces blood into intrathoracic beds, but it leaves the lung and its circulation weighted normally. Bed rest shortens the vertical height of the body and the lungs, but introduces a fair amount of immobility and still leaves the horizontal lung under 1 ‘g’. Similarly applying positive or negative pressures to the abdomen and legs leaves the lungs with more, or less, blood than usual but otherwise weighted as before. Some Clinical
Consequences
The effects of gravity on the lung are important clinically, but are not always easy to interpret. There is, for example, a clear contradiction between the physiologist’s requirement that patients with chest disease should lie with the healthiest lung lowermost to gain maximum benefit from its richer perfusion (Zack et al. 1974) and the pathologist’s wish that the unhealthy lung should not be uppermost since it tends to drop infected material directly into the opposite lung. As Brock (1954) pointed out this explains why most lung abscesses occur in the lateral, i.e. axillary, segments of the upper lobe. Similarly Helm (1951) made a careful study of the spread of tuberculosis from one lung and found much
The Graver Side of Gravity
111
the same distribution with a clear link to the preferred side of sleeping. Recently Helms et al. (1982) had the opportunity to study 11 infants with unilateral lung disease, comparing the distribution of ventilation and perfusion when they were lain on their right or left sides. They found the effects of gravity were the reverse of those found in adults since, in the infants, arterial blood oxygenation was better when the good lung was uppermost. They believe this occurs because the chest wall is much more compliant in infants than adults. As a result, the dependent lung is compressed more and ventilated less. Many people have speculated on the vertical distribution of disease in the upright lung. One of the most eloquent was Dock (1946) who believed that tuberculosis resided in the apices because the mycobacterium has a predilection for a high Po2. He advanced some compelling arguments in favour of that view. John West, per contra, observed that it is most prevalent in the dorsal segments of quadruped lungs and the phrenic segments of bat lungs and supposed it was linked to local stress concentrations. Both views could be true. The stress argument is certainly an appealing explanation for the apical and sharp-edge concentrations of emphysematous bullae. Other aspects, such as the basal distributions of alpharantitrypsin-deficient emphysema and the vascular changes of mitral stenosis have an obvious gravitational basis but unlike the mechanisms underlying Sundstrom’s observations, the causes of these graver effects of gravity on the lung are not yet clear. Suggestions
for Further
Reading
Agostoni, E. (1972) Mechanics of the pleural space. Physiol. Rev. 52, 57-128. Agostoni, E. (1977) Transpulmonary pressure. In: Regional Differences in the Lung, ed. J. B. West, pp. 245-280. New York: Academic Press. Arborelius, M., Granquist, V., Lilja, B. & Zanner, C. W. (1974) Regional lung function and central haemodynamics in the right lateral body position during hypoxia and hyperoxia. Respiration 31, 193-200. Arborelius, M., Lilja, B. & Senyk, J. (1975) Regional and total lung function studies in patients with hemidiaphragmatic paralysis. Respiration 32, 253-264. Brock, R. C. (1954) Bronchial embolism and posture in relation to lung abscess. The Anatomy of the Bronchial Tree, pp. 13-25. London: Oxford University Press. Davies, N. J. H. (1982) Does the lung work? 4. What does the transfer of carbon monoxide mean? Br. J. Dis. Chest 76, 105-123. Dock, W. (1946) Apical localization of pthisis. Its significance in treatment by prolonged rest in bed. Am. Rev. Tuberc. 53, 297. Dosman, J. A., Hodgson, W., Edwardson, C., Graham, B. L., Cotton, D. J. & Stirling, D. (1981) Effects of inspiratory flow rate on the oesophageal pressure gradient in upright humans. Resp. Physiol. 46, 105-112. Engel, L. A. & Prefaut, C. (1981) C ranio-caudal distribution of inspired gas and perfusion in supine man. Resp. Physiol. 45, 43-54. Helm, W. H. (1951) The importance of sleeping posture in the spread of pulmonary tuberculosis. Thorax 6, 417-425. Helms, P., Heaf, D. P., Turner, H. & Gordon, I. (1982) Down with the bad lung. Thorax 37, 790 (abstract). Macklem, P. T. (1981) Normal and abnormal function of the diaphragm. Thorax 36, 161-163. Martin, C. F., Cline, F. & Marshall, H. (1953) Lobar alveolar gas concentrations: effects of body position. J. din. Invest. 32, 617-621.
112
Does the Lung Work ?
Mattson, S. B. & Carlens, E. (1955) Lobar ventilation and oxygen uptake in man’s influence of body position. J. thorac. cardiovasc. Surg. 30, 676. Miserocchi, G., Nakamura, T., Mariani, E. & Negrini, D. (1981) Pleural liquid pressures over the interlobar, mediastinal and diaphragmatic surfaces of the lung. Resp. Physiol. 46, 61-70. Prefaut, C. & Engel, L. A. (1981) Vertical distribution of perfusion and inspired gas in supine man. Resp. Physiol. 43, 209-219. Riley, R. L., Permutt, S., Said, S., Godfrey, M., Cheng, T. O., Howell, J. B. L. & Shephard, R. H. (1959) Effect of posture on pulmonary dead space in man. /. apph PhysioZ. 14, 339-344.
Rothstein, E., Landis, F. B. & Narodick, B. G. (1950) B ronchospirometry in the lateral decubitus position. J. thorac. Surg. 19, 821. Shin&u, M., Ghista, D. & Sandler, H. (1979) Cardiovascular regulatory response to lower body negative pressure following blood volume loss. A&t. Space Environ. Med. 50, 24-32. Sundstrom, G. (1975) Influence of body position on pulmonary diffusing capacity in young and old men. J. appl. Physiol. 38, 418-423. Svanberg, L. (1949) Influence of posture on the lung volumes, ventilation and circulation in normals. Stand. J. lab. clin. Invest. 9, suppl. 25, 195. West, J. B., (1977) Stresses. In: Regional Difference in the Lung, ed. J. B. West, pp. 281-323. New York: Academic Press. Zack, M. B., Pontoppidan, H. & Kaxemi, H. (1974) Th e effect of lateral positions on gas exchange in pulmonary disease. Am. Rev. Dis. 110, 49-55.