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1 VARIATIONS IN ALVEOLAR CARBON DIOXIDE PRESSURE IN RELATION TO MEALS1. By (From the Bland-Sutton Institute qf Pathology, Middlesex Hospital.) THE investigation described below arose in the following manner. More than a year ago a gas analysis apparatus for the estimation of oxygen and carbon dioxide was being tested; atmospheric air was, of course, used as a source of oxygen, and it was thought that the alveolar air of one person would provide an approximately constant concentration of carbon dioxide. However, ten analyses on samples taken at different times of the day showed a range of about 8 mm. in carbon dioxide pressure. As such differences could not be attributed to error in tlhe analyses, it seemed that the pressure of alveolar carbon dioxide was less constant than one had been accustomed to think. On considering the factors which could theoretically produce such variations the taking of food seemed to be the most probable; on putting this to the test, a rise in CO2 pressure after a meal, and a fall later, were found to occur. The matter was not pursued further until quite recently, when the above observations were mentioned to Dr Haldane; he had noticed sucb variations and thought the matter would repay thorough investigation. The experiments described below were therefore carried out. Methods. All the samples were collected by the Haldane-Priestley method, and all analyses were carried out on the Haldane apparatus. Each point on the following curves is the mean of four analyses, namely, of two inspiratory and two expiratory samples; one pair of samples was analysed in a large and one in a small Haldane apparatus; these had been thoroughly calibrated and compared. Observations were made on twelve normal persons and on one who had undergone the operation of gastrectomy. The first subjects were three healthy men, of ages between 20 and 40. (1) In A. N. K. (Fig. 1 and Table I) the alveolar CO2 was determined by A report to the MIedical Research Council.

2 ALVEOLAR CARBON DIOXIDE. 343 the above method half-an-hour before his lunch, taken between and a.m., and at half-hourly intervals afterwards until the C02 presure had regained its original level, which occurred at 2.30 p.m. The figure shows that the C02 pressure rose nearly 5 mm. during the hour following the meal; it then fell to nearly the same extent below the original level, and had reached this level again about three hours after the meal. This series of changes might, of course, be a diurnal variation inde-, pendent of the taking of food. Accordingly, observations were made A Fig. 1. Observations on A. N. K. Series A, meal from to Series B, meal from 3.15 to Arrows indicate time of meal over the same portion of the day, but lunch was deferred until 3.15 p.m. It will be seen that the pressures remained within a range of only 1 mm. during the whole four hours from 11 to 3, while the meal at 3.15 was followed by a rise and fall of the same type as that observed after the customary lunch hour. (2) A confirmatory result was obtained in an experiment of exactly the same type on another subject E. L. K. (Table I), though the full series of changes following the later meal was not followed. (3) Four series of observations were made on E. C. D. In three of these the usual lunch was taken, and the alveolar CO2

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4 ALVEOLAR CARBON DIOXIDE. 345 pressure rose 5*5, 1*8, and 2*0 mm. respectively on the three occasions; on the fourth no food was taken throughout the period of observation, and the CO pressure remained within a range of 0-8 mm. (Fig. 2 and Table I). It seemed clear then that these changes were associated with the ingestion of food. Observations were then made on a further series of healthy persons, of ages ranging from 15 to 50, before and after their usual mid-day meal. All the data obtained are given in Table II, and as manv as can be drawn without confusion are shown in Fig. 3 together with one of the series (B2) from E. C. D. mentioned above. It will be seen that in CO. H 1 Fig. 2. -;F lcn I 3 4 Continuous lines. Observations on E. C. D. (normal). Series A and B with meal. Series C without meal Broken lines. Observations on G. A. (gastrectomy case). Series D and E with meal. Before meal Hours i H J. D G M. 37*6 J T Mr A. N. 37*2 McK TABLE II. Alveolar carbon dioxide presmsres of healthy pereonw before and after the mid-day meal i After meal * * j 42*

5 346 everv case the meal is followed by a rise in the CO2 pressure, and wherever the observations are continued over a sufficiently long period a subsequent fall and return are seen. The highest point appears always to be reached within 30 to 45 minutes after the end of the meal; the greatest increase observed was 6 mm. (in Mr.) and the lowest 1-8 mm. (on one occasion in E. C. D.). The lowest point is reached I to 2 hours after the end of the meal except in one case (M.), in which the fall lasts 2 hours. The range of fall observed is about the same as that of the rise, namelv, 46 Co2 mm. Hr HOURS Fig. 3. v Before MeaL Alveolar C02 of six normal persons before and after the mid-day meal. from 2 to 6 mm. The diphasic type of change was found in all the cases that were observed for a sufficiently long time. Since the rise in CO2 tension occurs during the time when the secretion of gastric juice is taking place, the question arose whether the two changes were associated. Through the kindness of Mr Gordon Taylor, F.R.C.S., it was possible to make two series of observations on a man (G. A.) from whom the greater part of the stomach had been removed eight months before, in Feb. 1920, on account of severe gastric ulceration; he had made an excellent recovery, and was leading an active life I0

6 ALVEOLAR CARBON DIOXIDE. 347 as a salesman. The part removed from the patient consists of at least seven-eighths of the stomach together with the pylorus and the duodenojejunal flexure which bad been anastomosed with the stomach at a previous operation (Fig. 4). Thus the only portion of stomach wall which the patient still possessed was that in the immediate neighbourhood of the cardiac orifice; this was joined to the jejunum, with which the duodenum was also brought into connection. The pancreatic juice and bile could thus enter the intestine. The results given in Table I and Fig. 2 show that the CO2 pressure increased after the meal by 04 mm. on the first occasion and by 0-8 mm. on the second, whereas no normal person showed a rise of less than 1-8 mm. (see E. C. D. Series B); this suggests very strongly that the rise seen in a normal person is associated with the secretion of gastric juice. Possibly Fig. 4. even the small rise of 04 to 0-8 mm. would not have occurred if the stomach had been removed completely at the operation. It is noteworthy that this subject showed the later changes in CO2 pressure, namely, the fall followed by the return to the original level, in just the same way as a normal person; this affords strong evidence that these changes are associated with digestive processes in portions of the alimentary canal below the stomach. In Fig. 2 are included for comparison three series of observations on a normal person (E. C. D., Table I) in two of which (A and B) the ordinary lunch was taken, while in the third (C) no food was taken throughout; in this last series the CO2 pressure remained almost constant (between 36-1 and 36-9 mm.). The application of this method to pathological cases is already under trial in this laboratory, and some interesting results have been obtained. The later changes in alveolar CO2 pressure after a meal may perhaps

7 348 throw light on processes such as those of pancreatic secretion which are less accessible to investigation than those taking place in the stomach. Finally, I have to express the debt that I owe to Dr E. L. Kennaway for valuable advice during the work, and for help in the consideration of the results. SUMMARY. In a series of normal persons the alveolar carbon dioxide pressure was found to show the following changes after a meal: (1) a rise of from 2 to 6 mm. within the first half or three-quarters of an hour; (2) a subsequent fall of aboilt the same amount (2-6 mm.) below the original level; (3) a return to this level. In a man from whom the greater part of the stomach had been removed the rise after a meal was very small in amount (0.4 to 0-8 mm.) while the subsequent changes were similar to those seen in a normal person. It seems probable that the rise is associated with the secretion of gastric juice, and the subsequent fall with the later processes of digestion. Addendum. Whilst this Paper was in the Press my attention was drawn to a paper by Higgins (Amer. Jotrn. Physiol ). He noticed the rise in alveolar C02 tension after the taking of food, but did not describe the subsequent fall and ret-urn. He regards the rise as associated with drowsiness and vaso-dilation, but his discussion of the matter is hard to follow.

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