- Email: [email protected]
RADIOLOGICALLY UNDETECTABLE PULMONARY COLLAPSE IN THE SUPINE POSITION
399
factor,
as
currently defined,
to
promote the absorption of
the vitamin. REFERENCES Documenta
Geigy (1962) Scientific Tables, p. 464. Ellenbogen, L. (1962) Vitamin B12 and Intrinsic Factor; p. 450. Stuttgart Gazet, J. C., McColl, I. (1967) Br. J. Surg. 54, 128. Glass, G. B. J. (1963) Physiol. Rev. 43, 529. Grasbeck, R. (1958) Acta chem. scand. 12, 142. (1959a) Acta physiol. scand. 45, 88. (1959b) ibid. p. 116. Heathcote, J. G., Mooney, F. S. (1958a) Lancet, i, 982. (1958b) J. Pharm. Pharmac. 10, 593. McColl, I., Andrews, D., Gazet, J.-C., Raven, J. L., Streek, S. (1967 Lancet, i, 544. Mooney, F. S., Heathcote, J. G. (1966) Br. med. J. i, 1149. —
—
—
—
RADIOLOGICALLY UNDETECTABLE PULMONARY COLLAPSE IN THE SUPINE POSITION M.B.
FORMERLY RESEARCH FELLOW
Fig. 2-Experiment B : release of assayable vitamin Bi, and aminoacid nitrogen during digestion.
vitamin B12 is in direct contrast to the view that the vitamin has to be attached to a protein molecule (intrinsic factor) before absorption can take place. There is no evidence that " binding " to protein occurs at any stage of the experiments, but rather that a continuous process of release from protein takes place slowly at first, under the influence of gastric proteases, and then more rapidly during intestinal digestion. This pattern is what might be expected, bearing in mind the two stages of normal protein digestion. Thus the first stage, of breakdown to large polypeptides, is achieved by the endopeptidases in the upper part of the gastrointestinal tract. After endopeptidase digestion, the intermediate products are still relatively large and little release either of free aminoacids or cobalamin would, therefore, be expected at this stage. The second and final stage of digestion is then achieved by the various exopeptidases of the small intestine which act upon terminal peptide linkages and hence bring about a release of both aminoacids and free cobalamin in much larger amounts. Thus during the first 72 hours of simulated intestinal action, large quantities of both a-amino groups and free vitamin appear. This rate of release then diminishes slowly and ceases finally after incubation for approximately 100 hours. The in-vitro evidence which we have presented here suggests that both the release of vitamin B12 from bound protein and the digestion of the protein itself to smaller
simultaneously and progressively in a logical manner, as is to be expected in the alimentary canal. Our findings give no support to the view that the vitamin binds itself to any large molecule during the normal stages of digestion; rather they support our previously expressed concept that the primary cause of pernicious anaemia is simply a lack of proteolytic digestion (Heathcote and Mooney 1958a). Concerning the alleged role of intrinsic factor in the absorption of vitamin B12 by the small intestine of the healthy individual, a team of workers at Guy’s Hospital has shown that it has apparently no appreciable influence on this (Gazet and McColl 1967, McColl et al. 1967).
components
occur
Their results accord with the considerable amount of clinical evidence (Mooney and Heathcote 1966) which has demonstrated the absence of any need for an intrinsic
C. PRYS-ROBERTS Lond., F.F.A. R.C.S., D.A.
J. F. NUNN M.B., Ph.D. Birm., F.F.A. R.C.S. PROFESSOR OF ANAESTHESIA
R. H. DOBSON Birm., F.F.A. R.C.S., D.A.
M. B. SENIOR
M.B.
REGISTRAR, LEEDS
GENERAL INFIRMARY
R. H. ROBINSON Lond., D.T.M. & H., F.F.A. R.C.S., D.A.
FORMERLY SENIOR
M.B.
REGISTRAR,
LEEDS GENERAL INFIRMARY
R. GREENBAUM Manc., F.F.A. R.C.S., D.A.
FORMERLY LEVERHULME RESEARCH FELLOW
M.B.
R. S. HARRIS Birm., Ph.D. Brist., D.M.R.D. LECTURER IN RADIOLOGY
From the
Departments of Anaesthesia and Radiology, University of Leeds
Pulmonary collapse was induced in four supine volunteers by maximal reduction of lung volume during oxygen breathing. The consequent pronounced reduction in arterial Po2 was consistent with the development of substantial pulmonary arterial/venous shunts. In contrast to previous observations in upright subjects, there was no radiographic evidence of collapse in any instance. The fall in arterial Po2 is a much more sensitive index of shunting through areas of lung which have undergone absorption collapse with the subject in the supine position. Summary
Introduction
EXTENSIVE pulmonary collapse may be produced in the upright, healthy subject by maximal voluntary reduction of lung volume while breathing oxygen. In their study of this change Nunn, Coleman, Sachithanandan, Bergman, and Laws (1965) based their diagnosis of collapse on the following criteria: (1) radiographic evidence of collapse in the basal lung fields; (2) radiographic evidence of reduced lung volume; (3) reduction of arterial oxygen saturation or tension; (4) characteristic tearing sensation within the chest, particularly on attempting re-expansion. These workers considered that the collapse resulted from absorption of oxygen from alveoli beyond obstructed airways, and it seemed possible that therein lay a mechanism for development of the pulmonary collapse, which is postulated by some as the cause of the increased alveolar/arterial
400
Po2 difference which is almost
a
normal feature of general
anaesthesia. A difficulty in this hypothesis is that large alveolar/ arterial Po2 differences have often been found in anoesthetised patients who have no abnormalities of their chest radiographs (Bendixen et al. 1963, Hamilton et al. 1964, Nunn 1964). Since the pulmonary collapse was very easily detected by chest radiography in the volunteers studied by Nunn et al. (1965), we considered possible causes for the disparity. In the first place, it remains that the increased unproven alveolar/arterial P02 difference found in uncomplicated anaesthesia is mainly due to pulmonary collapse, although this assumption is often made as though it were self-evident. In fact there is now evidence that, at least during anaesthesia with passive hyperventilation, a major factor is the desaturation of venous blood due to reduction of cardiac output (Kelman, Nunn, Prys-Roberts, and Greenbaum 1967). Secondly, the difference in posture between the two situations seemed of considerable importance, since pulmonary collapse produced in the supine position might be expected to have a different distribution and to be less easily detected by
chest radiography. We have therefore attempted to produce pulmonary collapse by reduction of lung volume while breathing oxygen in the supine position, and have made strenuous attempts to detect any radiological changes both during and immediately after this procedure. Collateral evidence of interference with oxygenation of arterial blood was obtained by monitoring the arterial Po2. Method
subjects for this study were four healthy male physicians, aged 31-40, one of whom was the subject whose chest radiographs were presented in the earlier study in the upright position (Nunn et al, 1965). Control chest radiographs, taken before the investigation, consisting of anteroposterior, left lateral and right and left posterior oblique views at full inspiratory capacity and at functional residual capacity (F.R.C.). In two subjects, the brachial artery was cannulated under local analgesia using a ’Teflon ’ needle-cannula. In these subjects, control arterial-blood samples were obtained during air-breathing, and after breathing 100% oxygen at normal lung volumes for at least 15 minutes. All the subjects lay in a supine position on a level X-ray table during the study. While continuing to breathe 100% oxygen, each subject made a maximal expiration and maintained his end-expiratory lung volume as close to residual volume as possible over a period of 10-12 minutes. No attempt was made to control the rate of breathing or the end-expiratory PC02 as in the previous study by Nunn et al. (1965). The subject’s chest was intermittently screened during this period for evidence of developing pulmonary collapse. Arterial samples were taken at 5 and 10 The
VALUES FOR
Pao2/PAo2 Pao2,
BREATHING OF
100%
AND
PACJZ
IN TWO
SUBJECTS DURING
OXYGEN AT REDUCED LUNG VOLUME
measured by the interpolation method (Kelman, Coleman, and Nunn 1966). A Beckman macrocathode polarographic electrode was used to determine the Po,. Corrections were applied to the Po2 value to allow for the difference in the response of the electrode to oxygen in the gas and blood at the same P02. A factor determined from a series of tonometer studies was used for this purpose and raised the measured Po2 by 4%. Corrections were also applied to pH, PC02, and P02 for elapsed time, and temperature differences between the subject and the measuring electrode (Kelman and Nunn 1966). Alveolar oxygen tension (PAo) during oxygen breathing was determined from the expression: PAo2=PIo2-PHzo-Paco2, where PI02=inspired O2 tension, PH2o=S.V.P. of water, Pac02=arterial CO2 tension. Results
The values for blood-gas tensions and alveolar-arterial Po2 difference in the two subjects are shown in the accompanying table. In both subjects, breathing oxygen at normal lung volume raised the Pao2 to over 500 mm Hg, and indicated an alveolar-arterial P02 difference of 153 mm. Hg and 164 mm. Hg respectively. In both subjects the period of breathing at reduced lung volume was followed by a pronounced reduction in the arterial Po2 together with a small increase in Paco2’ The maximal increase in PAo2-Pao2 in the two subjects was 155 mm. Hg and 279 mm. Hg respectively. After maximal inspiration the Pao2 was restored to control levels in both subjects, denoting a complete resolution of the changes in alveolar-arterial P02 difference caused by the experimental procedure. On attempting full re-expansion of their lungs after the of breathing at reduced lung volume, all four subperiod minutes. noted the characteristic tearing sensation in the chest, jects The subjects then reverted to breathing 100% oxygen at the effects being transient in three subjects but longernormal resting lung volumes, care being taken to avoid deep in the fourth. inspiration. Chest radiographs (anteroposterior, left lateral, lasting At no time could changes in the radiographic appearance and two posterior oblique views) were taken then at F.R.c., and simultaneously an arterial-blood sample was obtained. The of the lung fields be detected during screening in any of subjects then attempted to inspire to maximal capacity for the subjects, nor could any evidence of collapse be detected in any of the views at either F.R.c. or full inspiratory several breaths, and the sequence of chest radiographs was repeated at maximal inspiratory capacity. Arterial-blood capacity positions. Lung volumes were not compared samples were obtained in one subject when this procedure was radiographically before and after collapse since identical performed during oxygen breathing and subsequently during anteroposterior views at the same phase of movement of air breathing; while in the other subject the blood sample the chest walls were not obtained. Radiological estimation was obtained only during air breathing at normal lung of total lung capacity (T.L.C.) by Barnhard’s (1960) method volume. may give values from -18 to + 13 % of the spirometric The arterial-blood samples were analysed within 5 minutes for pH, Paco2, Pao2, and hxmoglobin concentration. pH was T.L.C., and this degree of change could cause greater measured with a capillary micro-electrode, and PC02 was changes of Po2 than were measured in this study.
401 Discussion
There is no doubt of the ability of chest radiography to reveal collapse in a segmental or lobar distribution, such as occurs when gas is absorbed distally to an obstructed bronchus. Radiological evidence shows that such collapse is rare during routine anaesthesia or in the early postoperative stage. Nevertheless such changes may develop in the first few days after operation. There is less certainty of the ability of radiography to display the " miliary collapse " which has been postulated as the cause of the increased alveolar/arterial P02 gradient during anaesthesia. It was therefore unexpected that such obviously visible pulmonary collapse was produced in the upright subject by inhalation of oxygen at low lung volume-a procedure which reduces the arterial P02 to levels which are typical of those during routine anxsthesia with a high concentration of oxygen in the inspired gas. The present study seems to suggest that an apparently equal degree of collapse produced in the supine position by the same respiratory manoeuvres cannot be detected by conventional radiographic techniques. We believe that this difference is due to the fact that, in the upright position, the dependent parts of the lungs are concentrated in the costophrenic angles and in the neighbourhood of the diaphragm where collapse can be easily detected. In contrast, in the supine position the dependent part of the lung is spread out over a comparatively large area lateral to the thoracic vertebrae, spreading over a distance of about seven rib spaces. It might be expected that collapse would occur in a plane parallel to the skin of the back and that this would be specially difficult to see on an anteroposterior film. This was anticipated by taking lateral and oblique films, but here again no changes were visible. In the absence of radiological findings, it is reasonable to ask whether collapse had actually occurred in this study. We believe that collapse had occurred for the following reasons:
1. The
arterial P02 difference is a much more reliable index of the degree of shunting through collapsed areas of lung. The results of this study provide no positive evidence of the cause of the increased alveolar/arterial P02 difference during anxsthesia. However, it seems to provide negative evidence implying that collapse as a cause of increased PAo—Pao cannot be excluded by failure to demonstrate collapse radiologically either during or after anaesthesia. This is not to say that collapse is the sole, or even the most important, cause of increased PAo2-Pao2, and independent evidence of this is still required. This work was supported by a grant from the Medical Research Council.
Requests for reprints should be addressed to J. F. N., University Department of Anaesthesia, 24 Hyde Terrace, Leeds 2. REFERENCES
Barnhard, H. J., Pierce, J. A., Joyce, J. W., Bates, J. H. (1960) Am. J. Med. 28, 51. Bendixen, H. H., Hedley-Whyte, J., Laver, M. B. (1963) New Engl. J. Med. 269, 991. Hamilton, W. K., McDonald, J. S., Fischer, H. W., Bethards, R. (1964) Anesthesiology, 25, 607. Kaneko, K., Milic-Emili, J., Dolovich, M. B., Dawson, A., Bates, D. V. (1966) J. Appl. Physiol. 21, 767. Kelman, G. R., Coleman, A. J., Nunn, J. F. (1966) ibid. p. 1103. Nunn, J. F. (1966) ibid. 1484. Prys-Roberts, C., Greenbaum, R. (1967) Brit. J. Anaesth. 39, 450. Milic-Emili, J., Henderson, J. A. M., Dolovich, M. B., Trop, D., Kaneko, K. (1966) J. appl. Physiol. 21, 749. Nunn, J. F. (1964) Brit. J. Anaesth. 36, 327. Coleman, A. J., Sachithanandan, T., Bergman, N. A., Laws, J. W. (1965) ibid. 37, 3. —
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BILATERAL RENAL CALCULI AND AMINOACIDURIA AFTER EXCESSIVE INTAKE OF WORCESTERSHIRE SAUCE KEVIN J. MURPHY Queensland, M.R.A.C.P.
M.B. MEDICAL
the same as in the in which overt collapse
respiratory previous study in the upright position was seen in the radiographs. 2. The reduction of arterial P02 must be due to a very substantial increase in pulmonary venous admixture, for which alveolar collapse seems to be the only explanation. 3. The changes in arterial P02 were completely reversed by a series of maximal inspirations. manoeuvres
were
In upright subjects Milic-Emili et al. (1966) showed minimal changes in volume of basal segments when the total lung volume was increased between residual volume and 10% of T.L.c. above residual volume. This implies airway obstruction in the basal segments, and we employed lung-volume changes within this range. In a subsequent study (Kaneko et al 1966) posture was varied, and qualitatively similar changes were found in the dependent lung zones whatever the body position. In the supine position the failure of ventilation of dependent zones at low lung volumes was somewhat less distinct, probably owing to the diminished height of the lungs. Nevertheless, the gross changes in arterial P02 in our study suggest that collapse occurred to approximately the extent found in the previous study in the upright position. The present study suggests that dispersed absorption collapse, occurring in the supine position, is radiologically undetectable. In fact, the situation in clinical practice would be made worse by the use of portable radiographic equipment, and further difficulties arise with unconscious patients who cannot maintain an inspiration during exposure of the plate. We further conclude that the alveolar/
SUPERVISOR, PRINCESS ALEXANDRA HOSPITAL, BRISBANE, QUEENSLAND, AUSTRALIA
Summary
Two
patients with bilateral renal calculi
have aminoaciduria and a and excessive intake of Worcestershire sauce. No other cause of kidney stones was found. As Worcestershire sauce contains a number of potentially nephrotoxic ingredients it is suggested that these agents have caused the aminoaciduria and the kidney
history
of
were
found
to
long-continued
stones.
Introduction
IN the course of investigation of over a hundred patients with bilateral and recurrent urinary calculi, two patients only were noted to have an abnormal excretion of aminoacids in urine on routine chromatography. These two patients were also in the habit of taking excessive quantities of Worcestershire sauce and both had no other cause for recurrent renal calculi. They are, therefore, the subject of this report.
Case-reports Case 1 A 28-year-old housewife born in Queensland was referred in November, 1964, for investigation of bilateral urinary calculi. There was no family history of kidney stones, other kidney trouble, or of gout. The patient did not like milk, she took no extra vitamins, nor did she take A.P.C. powders or alkali. She had no thirst, no nocturia, and no bowel trouble. She had been previously diagnosed as having pyelitis. She had a craving for
Worcestershire sauce,
especially
when she
was
pregnant.
factor,
as
currently defined,
to
promote the absorption of
the vitamin. REFERENCES Documenta
Geigy (1962) Scientific Tables, p. 464. Ellenbogen, L. (1962) Vitamin B12 and Intrinsic Factor; p. 450. Stuttgart Gazet, J. C., McColl, I. (1967) Br. J. Surg. 54, 128. Glass, G. B. J. (1963) Physiol. Rev. 43, 529. Grasbeck, R. (1958) Acta chem. scand. 12, 142. (1959a) Acta physiol. scand. 45, 88. (1959b) ibid. p. 116. Heathcote, J. G., Mooney, F. S. (1958a) Lancet, i, 982. (1958b) J. Pharm. Pharmac. 10, 593. McColl, I., Andrews, D., Gazet, J.-C., Raven, J. L., Streek, S. (1967 Lancet, i, 544. Mooney, F. S., Heathcote, J. G. (1966) Br. med. J. i, 1149. —
—
—
—
RADIOLOGICALLY UNDETECTABLE PULMONARY COLLAPSE IN THE SUPINE POSITION M.B.
FORMERLY RESEARCH FELLOW
Fig. 2-Experiment B : release of assayable vitamin Bi, and aminoacid nitrogen during digestion.
vitamin B12 is in direct contrast to the view that the vitamin has to be attached to a protein molecule (intrinsic factor) before absorption can take place. There is no evidence that " binding " to protein occurs at any stage of the experiments, but rather that a continuous process of release from protein takes place slowly at first, under the influence of gastric proteases, and then more rapidly during intestinal digestion. This pattern is what might be expected, bearing in mind the two stages of normal protein digestion. Thus the first stage, of breakdown to large polypeptides, is achieved by the endopeptidases in the upper part of the gastrointestinal tract. After endopeptidase digestion, the intermediate products are still relatively large and little release either of free aminoacids or cobalamin would, therefore, be expected at this stage. The second and final stage of digestion is then achieved by the various exopeptidases of the small intestine which act upon terminal peptide linkages and hence bring about a release of both aminoacids and free cobalamin in much larger amounts. Thus during the first 72 hours of simulated intestinal action, large quantities of both a-amino groups and free vitamin appear. This rate of release then diminishes slowly and ceases finally after incubation for approximately 100 hours. The in-vitro evidence which we have presented here suggests that both the release of vitamin B12 from bound protein and the digestion of the protein itself to smaller
simultaneously and progressively in a logical manner, as is to be expected in the alimentary canal. Our findings give no support to the view that the vitamin binds itself to any large molecule during the normal stages of digestion; rather they support our previously expressed concept that the primary cause of pernicious anaemia is simply a lack of proteolytic digestion (Heathcote and Mooney 1958a). Concerning the alleged role of intrinsic factor in the absorption of vitamin B12 by the small intestine of the healthy individual, a team of workers at Guy’s Hospital has shown that it has apparently no appreciable influence on this (Gazet and McColl 1967, McColl et al. 1967).
components
occur
Their results accord with the considerable amount of clinical evidence (Mooney and Heathcote 1966) which has demonstrated the absence of any need for an intrinsic
C. PRYS-ROBERTS Lond., F.F.A. R.C.S., D.A.
J. F. NUNN M.B., Ph.D. Birm., F.F.A. R.C.S. PROFESSOR OF ANAESTHESIA
R. H. DOBSON Birm., F.F.A. R.C.S., D.A.
M. B. SENIOR
M.B.
REGISTRAR, LEEDS
GENERAL INFIRMARY
R. H. ROBINSON Lond., D.T.M. & H., F.F.A. R.C.S., D.A.
FORMERLY SENIOR
M.B.
REGISTRAR,
LEEDS GENERAL INFIRMARY
R. GREENBAUM Manc., F.F.A. R.C.S., D.A.
FORMERLY LEVERHULME RESEARCH FELLOW
M.B.
R. S. HARRIS Birm., Ph.D. Brist., D.M.R.D. LECTURER IN RADIOLOGY
From the
Departments of Anaesthesia and Radiology, University of Leeds
Pulmonary collapse was induced in four supine volunteers by maximal reduction of lung volume during oxygen breathing. The consequent pronounced reduction in arterial Po2 was consistent with the development of substantial pulmonary arterial/venous shunts. In contrast to previous observations in upright subjects, there was no radiographic evidence of collapse in any instance. The fall in arterial Po2 is a much more sensitive index of shunting through areas of lung which have undergone absorption collapse with the subject in the supine position. Summary
Introduction
EXTENSIVE pulmonary collapse may be produced in the upright, healthy subject by maximal voluntary reduction of lung volume while breathing oxygen. In their study of this change Nunn, Coleman, Sachithanandan, Bergman, and Laws (1965) based their diagnosis of collapse on the following criteria: (1) radiographic evidence of collapse in the basal lung fields; (2) radiographic evidence of reduced lung volume; (3) reduction of arterial oxygen saturation or tension; (4) characteristic tearing sensation within the chest, particularly on attempting re-expansion. These workers considered that the collapse resulted from absorption of oxygen from alveoli beyond obstructed airways, and it seemed possible that therein lay a mechanism for development of the pulmonary collapse, which is postulated by some as the cause of the increased alveolar/arterial
400
Po2 difference which is almost
a
normal feature of general
anaesthesia. A difficulty in this hypothesis is that large alveolar/ arterial Po2 differences have often been found in anoesthetised patients who have no abnormalities of their chest radiographs (Bendixen et al. 1963, Hamilton et al. 1964, Nunn 1964). Since the pulmonary collapse was very easily detected by chest radiography in the volunteers studied by Nunn et al. (1965), we considered possible causes for the disparity. In the first place, it remains that the increased unproven alveolar/arterial P02 difference found in uncomplicated anaesthesia is mainly due to pulmonary collapse, although this assumption is often made as though it were self-evident. In fact there is now evidence that, at least during anaesthesia with passive hyperventilation, a major factor is the desaturation of venous blood due to reduction of cardiac output (Kelman, Nunn, Prys-Roberts, and Greenbaum 1967). Secondly, the difference in posture between the two situations seemed of considerable importance, since pulmonary collapse produced in the supine position might be expected to have a different distribution and to be less easily detected by
chest radiography. We have therefore attempted to produce pulmonary collapse by reduction of lung volume while breathing oxygen in the supine position, and have made strenuous attempts to detect any radiological changes both during and immediately after this procedure. Collateral evidence of interference with oxygenation of arterial blood was obtained by monitoring the arterial Po2. Method
subjects for this study were four healthy male physicians, aged 31-40, one of whom was the subject whose chest radiographs were presented in the earlier study in the upright position (Nunn et al, 1965). Control chest radiographs, taken before the investigation, consisting of anteroposterior, left lateral and right and left posterior oblique views at full inspiratory capacity and at functional residual capacity (F.R.C.). In two subjects, the brachial artery was cannulated under local analgesia using a ’Teflon ’ needle-cannula. In these subjects, control arterial-blood samples were obtained during air-breathing, and after breathing 100% oxygen at normal lung volumes for at least 15 minutes. All the subjects lay in a supine position on a level X-ray table during the study. While continuing to breathe 100% oxygen, each subject made a maximal expiration and maintained his end-expiratory lung volume as close to residual volume as possible over a period of 10-12 minutes. No attempt was made to control the rate of breathing or the end-expiratory PC02 as in the previous study by Nunn et al. (1965). The subject’s chest was intermittently screened during this period for evidence of developing pulmonary collapse. Arterial samples were taken at 5 and 10 The
VALUES FOR
Pao2/PAo2 Pao2,
BREATHING OF
100%
AND
PACJZ
IN TWO
SUBJECTS DURING
OXYGEN AT REDUCED LUNG VOLUME
measured by the interpolation method (Kelman, Coleman, and Nunn 1966). A Beckman macrocathode polarographic electrode was used to determine the Po,. Corrections were applied to the Po2 value to allow for the difference in the response of the electrode to oxygen in the gas and blood at the same P02. A factor determined from a series of tonometer studies was used for this purpose and raised the measured Po2 by 4%. Corrections were also applied to pH, PC02, and P02 for elapsed time, and temperature differences between the subject and the measuring electrode (Kelman and Nunn 1966). Alveolar oxygen tension (PAo) during oxygen breathing was determined from the expression: PAo2=PIo2-PHzo-Paco2, where PI02=inspired O2 tension, PH2o=S.V.P. of water, Pac02=arterial CO2 tension. Results
The values for blood-gas tensions and alveolar-arterial Po2 difference in the two subjects are shown in the accompanying table. In both subjects, breathing oxygen at normal lung volume raised the Pao2 to over 500 mm Hg, and indicated an alveolar-arterial P02 difference of 153 mm. Hg and 164 mm. Hg respectively. In both subjects the period of breathing at reduced lung volume was followed by a pronounced reduction in the arterial Po2 together with a small increase in Paco2’ The maximal increase in PAo2-Pao2 in the two subjects was 155 mm. Hg and 279 mm. Hg respectively. After maximal inspiration the Pao2 was restored to control levels in both subjects, denoting a complete resolution of the changes in alveolar-arterial P02 difference caused by the experimental procedure. On attempting full re-expansion of their lungs after the of breathing at reduced lung volume, all four subperiod minutes. noted the characteristic tearing sensation in the chest, jects The subjects then reverted to breathing 100% oxygen at the effects being transient in three subjects but longernormal resting lung volumes, care being taken to avoid deep in the fourth. inspiration. Chest radiographs (anteroposterior, left lateral, lasting At no time could changes in the radiographic appearance and two posterior oblique views) were taken then at F.R.c., and simultaneously an arterial-blood sample was obtained. The of the lung fields be detected during screening in any of subjects then attempted to inspire to maximal capacity for the subjects, nor could any evidence of collapse be detected in any of the views at either F.R.c. or full inspiratory several breaths, and the sequence of chest radiographs was repeated at maximal inspiratory capacity. Arterial-blood capacity positions. Lung volumes were not compared samples were obtained in one subject when this procedure was radiographically before and after collapse since identical performed during oxygen breathing and subsequently during anteroposterior views at the same phase of movement of air breathing; while in the other subject the blood sample the chest walls were not obtained. Radiological estimation was obtained only during air breathing at normal lung of total lung capacity (T.L.C.) by Barnhard’s (1960) method volume. may give values from -18 to + 13 % of the spirometric The arterial-blood samples were analysed within 5 minutes for pH, Paco2, Pao2, and hxmoglobin concentration. pH was T.L.C., and this degree of change could cause greater measured with a capillary micro-electrode, and PC02 was changes of Po2 than were measured in this study.
401 Discussion
There is no doubt of the ability of chest radiography to reveal collapse in a segmental or lobar distribution, such as occurs when gas is absorbed distally to an obstructed bronchus. Radiological evidence shows that such collapse is rare during routine anaesthesia or in the early postoperative stage. Nevertheless such changes may develop in the first few days after operation. There is less certainty of the ability of radiography to display the " miliary collapse " which has been postulated as the cause of the increased alveolar/arterial P02 gradient during anaesthesia. It was therefore unexpected that such obviously visible pulmonary collapse was produced in the upright subject by inhalation of oxygen at low lung volume-a procedure which reduces the arterial P02 to levels which are typical of those during routine anxsthesia with a high concentration of oxygen in the inspired gas. The present study seems to suggest that an apparently equal degree of collapse produced in the supine position by the same respiratory manoeuvres cannot be detected by conventional radiographic techniques. We believe that this difference is due to the fact that, in the upright position, the dependent parts of the lungs are concentrated in the costophrenic angles and in the neighbourhood of the diaphragm where collapse can be easily detected. In contrast, in the supine position the dependent part of the lung is spread out over a comparatively large area lateral to the thoracic vertebrae, spreading over a distance of about seven rib spaces. It might be expected that collapse would occur in a plane parallel to the skin of the back and that this would be specially difficult to see on an anteroposterior film. This was anticipated by taking lateral and oblique films, but here again no changes were visible. In the absence of radiological findings, it is reasonable to ask whether collapse had actually occurred in this study. We believe that collapse had occurred for the following reasons:
1. The
arterial P02 difference is a much more reliable index of the degree of shunting through collapsed areas of lung. The results of this study provide no positive evidence of the cause of the increased alveolar/arterial P02 difference during anxsthesia. However, it seems to provide negative evidence implying that collapse as a cause of increased PAo—Pao cannot be excluded by failure to demonstrate collapse radiologically either during or after anaesthesia. This is not to say that collapse is the sole, or even the most important, cause of increased PAo2-Pao2, and independent evidence of this is still required. This work was supported by a grant from the Medical Research Council.
Requests for reprints should be addressed to J. F. N., University Department of Anaesthesia, 24 Hyde Terrace, Leeds 2. REFERENCES
Barnhard, H. J., Pierce, J. A., Joyce, J. W., Bates, J. H. (1960) Am. J. Med. 28, 51. Bendixen, H. H., Hedley-Whyte, J., Laver, M. B. (1963) New Engl. J. Med. 269, 991. Hamilton, W. K., McDonald, J. S., Fischer, H. W., Bethards, R. (1964) Anesthesiology, 25, 607. Kaneko, K., Milic-Emili, J., Dolovich, M. B., Dawson, A., Bates, D. V. (1966) J. Appl. Physiol. 21, 767. Kelman, G. R., Coleman, A. J., Nunn, J. F. (1966) ibid. p. 1103. Nunn, J. F. (1966) ibid. 1484. Prys-Roberts, C., Greenbaum, R. (1967) Brit. J. Anaesth. 39, 450. Milic-Emili, J., Henderson, J. A. M., Dolovich, M. B., Trop, D., Kaneko, K. (1966) J. appl. Physiol. 21, 749. Nunn, J. F. (1964) Brit. J. Anaesth. 36, 327. Coleman, A. J., Sachithanandan, T., Bergman, N. A., Laws, J. W. (1965) ibid. 37, 3. —
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BILATERAL RENAL CALCULI AND AMINOACIDURIA AFTER EXCESSIVE INTAKE OF WORCESTERSHIRE SAUCE KEVIN J. MURPHY Queensland, M.R.A.C.P.
M.B. MEDICAL
the same as in the in which overt collapse
respiratory previous study in the upright position was seen in the radiographs. 2. The reduction of arterial P02 must be due to a very substantial increase in pulmonary venous admixture, for which alveolar collapse seems to be the only explanation. 3. The changes in arterial P02 were completely reversed by a series of maximal inspirations. manoeuvres
were
In upright subjects Milic-Emili et al. (1966) showed minimal changes in volume of basal segments when the total lung volume was increased between residual volume and 10% of T.L.c. above residual volume. This implies airway obstruction in the basal segments, and we employed lung-volume changes within this range. In a subsequent study (Kaneko et al 1966) posture was varied, and qualitatively similar changes were found in the dependent lung zones whatever the body position. In the supine position the failure of ventilation of dependent zones at low lung volumes was somewhat less distinct, probably owing to the diminished height of the lungs. Nevertheless, the gross changes in arterial P02 in our study suggest that collapse occurred to approximately the extent found in the previous study in the upright position. The present study suggests that dispersed absorption collapse, occurring in the supine position, is radiologically undetectable. In fact, the situation in clinical practice would be made worse by the use of portable radiographic equipment, and further difficulties arise with unconscious patients who cannot maintain an inspiration during exposure of the plate. We further conclude that the alveolar/
SUPERVISOR, PRINCESS ALEXANDRA HOSPITAL, BRISBANE, QUEENSLAND, AUSTRALIA
Summary
Two
patients with bilateral renal calculi
have aminoaciduria and a and excessive intake of Worcestershire sauce. No other cause of kidney stones was found. As Worcestershire sauce contains a number of potentially nephrotoxic ingredients it is suggested that these agents have caused the aminoaciduria and the kidney
history
of
were
found
to
long-continued
stones.
Introduction
IN the course of investigation of over a hundred patients with bilateral and recurrent urinary calculi, two patients only were noted to have an abnormal excretion of aminoacids in urine on routine chromatography. These two patients were also in the habit of taking excessive quantities of Worcestershire sauce and both had no other cause for recurrent renal calculi. They are, therefore, the subject of this report.
Case-reports Case 1 A 28-year-old housewife born in Queensland was referred in November, 1964, for investigation of bilateral urinary calculi. There was no family history of kidney stones, other kidney trouble, or of gout. The patient did not like milk, she took no extra vitamins, nor did she take A.P.C. powders or alkali. She had no thirst, no nocturia, and no bowel trouble. She had been previously diagnosed as having pyelitis. She had a craving for
Worcestershire sauce,
especially
when she
was
pregnant.