accompanying meals. In previous papers the variations in alveolar C02(1)

Transcription

1 VARIATIONS IN THE BLOOD CHLORIDES IN RELATION TO MEALS. Part I. BY E. 0. DODDS1 AND K. SHIRLEY SMITH. (From the Biochemical Department, Bland-Sutton Institute of Pathology, Middlesex Hospital.) THIS paper forms one of a series of investigations into the body changes accompanying meals. In previous papers the variations in alveolar C02(1) tension in relation to meals have been described, and also the accompanying changes in blood CO2 tension(2). It was shown by one of us (E. C. D.) in conjunction with McIntosh that as the alveolar CO2 tension rose during gastric secretion the corpuscular C02 content also increased, but the plasma C02 content remained more or less constant. During the fall in C02 tension in the alkaline period of secretion there was a fall in corpuscular C02 content, the plasma again remaining more or less constant. No change could be detected in plasma alkali reserve or actual hydrogen ion concentration as measured by the hydrogen electrode. It was thought that a study of plasma and corpuscles in relation to meals might yield some information on the mechanism of production of HCI in the gastric juice. That the corpuscles must play some very important part in the production of HOl is shown by their varying composition during gastric secretion as contrasted with the relative constancy of composition of the plasma during this period. The importance of the red blood corpuscles in transferring chlorine to and from blood plasma has been shown by several observers, notably by Haggard and Henderson(3) and by Dautrebande and Davies4) on the ha,matorespiratory functions. The present investigations were made into the chloride content of the blood in relation to meals. The subjects were all healthy students, on whom a fractional gastric analysis had been performed. By this means subjects with achlorhydria were excluded. Two series of experiments were carried out. In the first series the chlorides contained in the whole blood, plasma, and corpuscles were estimated before the mid-day meal and at varying intervals after it. Only two samples of 'Working on behalf of the Medical Research Council.

2 158 E. C. DODDS AND K. S. SMITH. blood were taken from the same individual. In the second series blood chloride estimations were carried out in conjunction with fractional gastric analysis, three samples of blood being taken from each subject. Method. Series I. Between 8 and 10 c.c. of blood were drawn from a vein of a fasting subject, and shaken with a crystal of oxalate to prevent clotting. About two-thirds of the blood was centrifuged at once to minimise possible extra-vascular changes in chloride-partition in the blood. The remaining third was estimated by Wetmore's method(5) for chlorides. Plasma taken after 10 minutes' centrifuging was then estimated. It was attempted also to measure chloride content directly in the corpuscles by a modification of Wetmore's method but it was found that the values obtained did not agree with those calculated from the whole blood and plasma readings taking the corpuscles as constituting 48 p.c. by volume of the whole blood. It also became apparent that certain experimental difficulties tended to make the corpuscle determination inaccurate; these determinations were therefore disregarded, and the calculated values used in their place. The meal was taken as a rule between 1 and 1.30 and the second sample of blood drawn at times varying from 40 to 135 minutes after the beginning of the meal. By such a procedure it was hoped to demonstrate any changes occurring in chloride content and partition as a result of gastric, and possibly of the beginning of pancreatic secretion. As control experiments, four subjects were investigated exactly as described above, except that no meal was taken between the drawing of the first and second sample of blood. One of the control subjects had, in a previous experiment, shown considerable variation in blood chloride as a result of a meal. Method. Series II. The subject came to the laboratory at about 9.30 a.m., having taken no food since the previous evening. He then swallowed the aesophageal tube, resting juice being extracted from the stomach by means of a syringe every quarter of an hour; this juice was estimated for free HCI. With the stomach empty, blood was drawn and estimated as whole blood and plasma, as previously described, the corpuscle values being calculated. The subject then drank a pint of the test-meal recommended by Krohn and Reiss(6) and c.c. of stomach contents were withdrawn at quarter-hour intervals thereafter; each sample was estimated immediately for free HCI and total acidity. When it was found that the height of the gastric HCl secretion was at hand a second sample of blood was taken and estimated as before. Finally, a third quantity of blood was taken about two hours after the

3 CHLORIDES IN BLOOD. meal when the gastrio secretion was drawing to a close and the stomaoh was practically empty. Results. In Table I the experiments have been arranged in order of TABLE L Cl before meal in* Time Cl after meal in* A -& 5 between meal,_a Whole Cor- and taking blood Whole Cor- Subject blood Plasma puscles (mins.) blood Plasma pusoles 1 H. K. E. *48 *605 * *47 *595 *335 2 B. M. R. J. *56 *65 * *47.60 * R. W. D. *485 * *45 * W..5 *785 * '425 *625 *208 S D. P. G. *48 * *605 * H. -42 *575 * *42 *56 *268 7 G. C. P. *44 *58 * *45 *57 *320 8 H. I. D. *475 *57 * *465 *585 *335 9t F * *48.59 * F. 0. W..44 *565 * * *295 * Figures represent chloride as NaCl in gm. per 100 c.c. t Subsequently found to be achlorhydrio. length of time intervening between the meal and the drawing of the second sample of blood. With regard to the chloride content of the whole blood it is seen that as a general rule the meal is followed by a fall which may amount to 16 p.c. of the initial quantity present. The chlorides of the plasma show a more uniform decrease, though in one instance (No. 4) it was rather more than 20 p.c. This subject, however, had an unusually high plasma content before the meal. No. 8 is the only exception, and since he showed a fall in a subsequent experiment with the easophageal tube, it may be concluded that in this case some error has crept in. But it is in the corpuscles that the most striking changes in chloride content are found. In this respect the experiments may be divided into three groups: (1 to 3) with a time interval of less than 45 minutes; (4 to 7) with an interval of minutes; and (8 to 10) with an interval of minutes. In the first of these groups is shown a decided fallin chlorides, in the second a marked increase (approximately 8 p.c.), and in the third group a fall not quite as great as in the first group. In Table II the results of the combined blood and gastric analyses are shown. It can be seen that in the specimen of blood removed at the height of gastric secretion there is a fall in plasma and a rise in corpuscular chloride content. The whole blood chloride content shows a steady fall. At the termination of the curve of gastric secretion, the plasma chloride content shows a partial recovery to its former value, whilst the corpuscular value shows a fall to below the initial value. This is well shown in cases 1 and 2 of Table II. Case 3 is one showing a prolonged gastric secretion. PH. LVIII.. 11

4 160 E. C. DODDS AND K. S. SMITH. The second and third samples of blood were drawn while the curve of secretion was still on the rise. The values obtained, therefore, correspond TABLE I. 1. G. C. P. Meal at a.m. Time Free HC1inc.C. N/ CL as gm. NaCl per 100 a.0. Whole blood Plasma Corpuscles Blood I taken at *46 * Blood II taken at 12.0 *46 *55 *363 Blood III taken at 1.5 *445 *57 * H. I. D. Meal at a.m. Time FeeHCIlinc.C. N/ Cl. as gm. NaCl per 100 c.c. Blood I taken at Blood II taken at Blood III taken at Whole blood.50 *49 * A. M. F. Meal at a.m. Time Free HCl in c.c. N/ Blood I taken at Blood II taken at Blood III taken at 1.57 Whole blood *52 *51 *51 Plasma * *61 Corpuscles *359 * Cl. as gin. NaCl per 100 c.c. Plasma *63 *63 *615 Corpuscles *401 *380 *396 to those of 1, 2, 3 in Table I, and hence show a fall in corpuscle and plasma chloride. The final specimen shows a marked rise in corpuscular chloride content. The readings of the four control experiments are given in Table III. No Subject E. C. D. A. L W. A. N. K. B. M. R. J TABLE IIL Control experiments. Cl in* Cl in (1 hour later) Cl in (2 hours later) A- A_ - Whole Whole Whole blood Plasma Corp. blood Plasma Corp. blood Plasma Corp. *48 *61 *339 *48 *61 *339 *48 *61 *339 '60 *329 *78 *197 *47 *59 *340 *472 * *78 * *78 * *340 *47 *58 *351 * Figures represent chloride as NaCl in gm. per 100 C.C. From them it may be seen that the fluctuations in blood chloride content of whole blood, plasma and corpuscles in the absence of a meal are

5 CHLORIDES IN BLOOD. 161 extremely small, and well within the limits of experimental error. This fact is still better demonstrated by a comparison of the figures for Subject 4 with his figures in Table I (No. 2) where a meal intervened between the drawing of the samples of blood. Discusiuon. It was found by Giirber(7) that as a result of increase in the CO2 tension in the plasma, the alkalinity of the latter increases. This, he found, was due to a migration of C1 into the blood corpuscles, the kation being left to form bicarbonate with the C02 of the plasma. Further, it has been shown by one of us (E. C. D.) that such a condition of increased blood C02 tension, as evidenced by increased alveolar C02 tension, occurs after a meal during the period of gastric secretion. It would be expected then at this time to find also an increase in the chloride of the corpuscles, and this fact is demonstrated by the figures given in Table I (4 to 7). Within the first 40 minutes following the meal, a sudden demand for Cl is made on the blood, with the result that the chlorides fall universally. As gastric secretion proceeds and the blood C02 tension rises the plasma must not only give up C1 to the gastric glands but also to the corpuscles which become loaded. The loss of Cl from the plasma is possibly made up in part from the chlorides of the tissue spaces and re-absorption from the digestive tract. Between 14 and 24 hours following the meal, gastric secretion is coming to an end, and pancreatic secretion with its concomitant fall in blood C02 tension is setting in. The last group in Table I (8 to 10) shows how the corpuscles unload their excess Cl in response to falling C02 tension in the blood. How far the increase in chloride content of the corpuscles plays a part in the mechanism of formation of the gastric Hal cannot as yet be said. It may be that this redistribution is merely a necessary result of the changes in C02 tension, in combination with the property of permeability possessed by the cell. However, in the light of a great body of work which demonstrates the immense importance of the corpuscles as active agents in the various functions of the blood, it is probable that the chloride changes in the corpuscles should be regarded as a step in the very complicated and as yet unknown mechanism by which HCl is formed and secreted with the gastric juice. 11-2

6 162 E. C. DODDS AND K. S. SMITH. CONCLUSIONS. 1. The chloride contents of whole blood, plasma and corpuscles were investigated at various times after a meal with the following results:- (a) During the first 40 minutes, the whole blood, plasma, and corpuscle chloride content showed a fall. (b) During the period between minutes after a meal, the whole blood chloride content showed a recovery to its normal figure, whilst the corpuscles showed a marked increase above the normal value. The plasma remained about the same as in the former group. (c) From minutes following the meal the whole blood chloride content had again fallen slightly. The plasma and corpuscle values showed a partial return to the initial values. 2. By combining fractional gastric analyses with blood chloride estimations, the first period was shown to correspond with the commencement of gastric secretion, the second with the height of gastric secretion, and the third with termination of gastric and probably the beginning of pancreatic secretion. 3. A series of control experiments was performed in which the meal was omitted. No change in blood chlorides could be demonstrated. 4. In accordance with the increased alveolar C02 tension during the period of gastric secretion, it was found that the corpuscles increased their chloride content, the latter decreasing again with falling alveolar C02 tension. This is in agreement with the so-called " Hamburger effect." REFERENCES. (1) Dodds. This Journ (2) DoddsandMcIntosh. Ibid (3) Haggard and Henderson, Y. Journ. Biol. Chem (4) Dautrebande and Davies. This Journ (5) Wetmore. Journ. Biol. Chem (6) Krohn and Reiss. Amer. Journ. Med. Sci (7) Gurber. Maly's Jahresb