s. J. RUNE, M.D., AND F. W. HENRIKSEN, M.D.

Transcription

1 GASTROENTEROLOGY Copyright 1969 by The Williams & Wilkins Co. Vol. 56, No.4 Printed in U.S.A. CARBON DOXDE TENSONS N TlE PROXMAL PART OF THE CANNE GASTRONTESTNAL TRACT s. J. RUNE, M.D., AND F. W. HENRKSEN, M.D. nstitute of Experimental Research in Surgery and Medical Department P, Division of Gastroenterology, Rigshospitalet, Copenhagen, Denmark The PC02 was measured in situ in 4 dogs by means of PC02 electrodes inserted through cannulas in the stomach; the first, second, and third part of the duodenum; and in the proximal 25 cm of the jejunum. High carbon dioxide tensions were found in all three parts of the duodenum especially in the second part where fasting values were around 300 mm Hg, increasing after feeding to more than 500 mm Hg. The PC02 in the proximal part of the jejunum was in ::tl cases lower than the tension found in the duodenum. The gastric PC02 varied around 85 mm Hg in the fasting state; here also a rise was observed after feeding, up to 175 mm Hg. The origin of the carbon dioxide as well as some possible physiological implications of the duodenal PC02 are discussed. t is pointed out that the ph endpoint for the intraduodenal titration of gastric acid by pancreatic bicarbonate approximates 4.0. The occurrence of gas in the gastrointestinal tract presented itself as a problem long before it became possible to study this phenomenon more deeply. The origin of the gas has been ascribed to: (1) ingested air, (2) intestinal fermentation, (3) diffusion from the blood, and (4) formation of carbon dioxide as a result of neutralization of the gastric juice by bicarbonate of pancreatic and intestinal secretions. The contribution of carbon dioxide to human flatus has been measured by Danhof et al. 1 who found values between 8 and 30%. Furthermore, they showed this percentage to increase considerably after stimulation of the gastric acid secretion by histamine, thus indicating neutralization of gastric juice as an origin of the intestinal CO2 Studies of the PC02 in aspirated jejunal juice showed values between 60 and 200 mm Hg/ but since no increase was seen after inrtilla- Received August 19, Accepted October 25,1968. Address requests for reprints to: Dr. S. J. Rune, Medical Department P, Division of Gastroenterology, Rigshospitalet, Copenhagen, Denmark. 758 tion of 0.1 N hydrochloric acid, it was concluded that the gastric acid secretion played no role for the jejunal CO2 tension. There can, however, be no doubt th&t carbon dioxide is produced when hyclrochloric acid is neutralized by bicarbonate, and therefore that C02 must be produced in the duodenum where such a neutralization takes place. f carbondioxide of this origin contributes significantly to the PC02 even in more distal parts of the intestinal tract, then quite high tensions are to be expected in the duodenum. Since, to our knowledge, no report exists on the duodenal PC02, the present study was undertaken. Material and Methods Four mongrel dogs (weighing 17.0 to 26.5 kg) were used. Two of the dogs were each equipped with three modified Thomas cannulas, while the other two dogs had only two cannulas. The cannulas were placed in the stomach; the first, second, and third parts of the duodenum; and in the proximal part of the jejunum.

2 April 1969 CARBON DOXDE TENSONS 759 Mter a fasting period of approximately 24 hr the experiments (lasting 3 to 6 hr) were performed with the dogs standing in a sling harness. The in situ PCO, was measured with carbon dioxide electrodes (ES Radiometer, Copenhagen) specially designed for measuring in the upright position. No water jacket was applied. At the onset of the experiments the electrodes were inserted airtight into the cannulas in such a way that the tip of the electrodes was planar to the mucous surface without protruding into the intestinal lumen. The electrodes were in shifts connected to an electrometer (PHM 27, Radiometer) and the carbon dioxide tension (millimeters of mercury) was continuously registered on a Beckman potentiometer recorder, on a logarithmic scale. Before each experiment the PCO, electrodes were standardized in water equilibrated with gas mixtures containing 25 and 50% CO,. This standardizing procedure was made at 34 C, which was the temperature of the electrodes during the in situ measurement in the dogs. Mter measuring the PCO, in the gastrointestinal tract in the fasting state for at least 1 hr, the dogs were given 400 to 450 g of lumps of pork heart and 50 to 100 ml of water, and the measurement was continued for another 2 to 4 hr. At the end of the experiment the electrodes were removed and the standardizing procedure repeated; deviations up to 10% were accepted. No systematic change in sensitivity or of zero point was seen following the in situ measurement. From each recording the range of PCO, was read, both in the fasting state and after the meal. The fasting mean value as well as the mean value after feeding was determined visually. Mter this series of measurements was completed, acute experiments were performed in the 2 dogs who had a cannula in the jejunum. While under Nembutal anesthesia the abdomen was opened and a part of the intestine was isolated between two thick ligatures placed 15 cm apart, so that the jejunal cannula was situated in the middle. Two polyethylene catheters were introduced through the intestinal wall orad to the proximal ligature and anal to the distal ligature. The catheters were advanced through the lumen in distal and proximal direction, respectively, so that they opened in each end of the isolated part of the jejunum. The ligatures were then tightened around the catheters. Direct PCO, recordings were then performed continuously while the isolated intestine was rinsed intermittently with saline through the catheters. Results Very high carbon dioxide tensions were a constant finding in the duodenum both after feeding and in the fasting state. Compared with the duodenal PC02, the tensions found in the stomach and in the jejunum were considerably lower. Figures 1 and 2 show direct recordings from two of the five locations studied, and table: 1 PC02 (mmhg) ~_r---- j MEAL! ~~--f_ ~ ~ MN. FG. 1. Continuously recorded in situ measurement of the PCO, in the duodenal bulb.

3 760 RUNE AND HENRKSEN Vol. 56, No.4 PC02 (mmhg) ,~ ,-r---+--rr------~~~ ~ 200~--~~--~ ~~~ ~----~----~----_,------~----~----_r----~----~~ MN. 90 FG. 2. Continuously recorded in situ measurement of the PC02 in the second part of the duodenum, distal to the papilla of Vater. TABLE 1. Carbon dioxide tensions measured in sittl in the proximal gastrointestinal tract in the dog Location ' Fasting After feeding Xumberl ;--- ex;~ri- e ments Range(1 ] Range Q ; ~ i ' mm g 111m Jg Stomach.. 5 tio Duodenum First part Second part Third part Jejunum 1 Proximal part , 1() a Mean of all experiments G summarizes the results from all experiments. n the stomach, fasting values were often only slightly higher than the presumed PC02 of mixed venous blood. However, peak tensions attaining 140 mm Hg were frequently observed. After feeding the mean gastric PC02 increased to around 130 mm, with peaks reaching 175 mm Hg. The duodenal PC02 was measured in the bulb, in the second part, and in the third part. n all three areas the tension varied greatly from 1 min to another, as the figures clearly demonstrate. Even though the fasting values varied around 200 to 300 mm, a clear rise after feeding was usually observed (table 1). The highest tensions were seen in the second part of the duodenum, where the mean PC02 after feeding was 500 mm, reaching 800 mm for shorter periods (fig. 2). Experiments performed in vitro confirmed the occurrence of tensions of this magnitude when the PC02 was measured in hydrochloric acid during addition of bicarbonate. The jejunal PC02 was considerably lower than the tension found in the duodenum and this was the case in the fasting state as well as in the stimulated state. The effect of feeding on the PC02 was also obvious in the jejunum. The PC02 measurements in the isolated part of the jejunum showed that the tension increased to values around 100 mm after repeated rinsing of the lumen with saline. Discussion Each milliequivalent of hydrochloric acid leads to the formation of approximately 22 ml of carbon dioxide when it is

4 April 1969 CARBON DOXDE TENSONS 761 neutralized with an equivalent amount of bicarbonate. Since the secretory capacity of acid in the stomach of a dog weighing 20 kg is about 40 meq per hr, and this rate is attained after feeding,3 significant amounts of CO2 should be produced in the duodenum when this neutralization takes place. The present study demonstrates that the liberation of CO2 leads to very high duodenal tensions of this gas. Since in the dog the pancreatic duct opens into the second part of the duodenum, the highest tension is to be expected in this area, which is confirmed by these results. The CO2 tension in the first part of the duodenum was also found to be high. This agrees with in situ ph measurements4, 5 showing that neutralization of the gastric content begins in the bulb. The role played by pancreatic bicarbonate for this proximal neutralization as compared with that of bicarbonate contained in the secretion from the duodenal mucosa and bile is not known. The diffusion rate of C02 in tissues is very high in comparison with other gases. 6,7 Thus Mcver et al. B found that when they instilled 20 ml of pure carbon dioxide into a 25-cm loop of the small intestine of the cat, 8 ml of the gas disappeared in the first 3 min. Therefore, the decrease in PC02 observed in more distal parts (the third part of the duodenum and the upper part of the jejunum) may be explained by diffusion along the concentration gradient through the mucosa. There is reason to believe that the jejunal PC02 not only originates from CO2 liberated in the first and second part of the duodenum. Studies by several groups2, 9-12 have all clearly shown that the equilibration concentration of bicarbonate in the proximal jejunum is between 5 and 10 meq per liter, and the ph slightly acid. This low bicarbonate concentration, compared with that of blood, may be explained either by an active absorption of bicarbonate or by a jejunal secretion of hydrogen ions. The latter possibility implies formation of C02 and is therefore supported by the generation of CO2 in isolated jejunal loops, as demonstrated in this study. The quantitative importance of this locally produced CO2 for the in vivo values of jejunal PC02 is not yet known. The PC02 content of gastric juice was also found to be higher than that of venous blood. Salivary bicarbonate (up to 80 meq per liter) and duodenal regurgitation offer likely explanations of this result. Furthermore, there is reason to believe in an alkaline (i.e., bicarbonate) component of gastric secretionl3, 14; this would also imply formation of gastric CO2 Concluding Remarks An obvious consequence of the high luminal PC02 in the duodenum is, that neutrality in the usual physical sense (i.e., a ph of 7.0) will not occur when equivalent amounts of gastric acid and pancreatic bicarbonate are mixed in the duodenum. n this case, the bicarbonate concentration will be zero and the ph will be determined by the concentration of the weak acid H 2C03. Thus a ph value of 4.0 to 4.2 will result at a PC02 of 400 mm Hg and 300 mm Hg, respectively. (According to the equation for ph in weak acids (PH = 1/2 pk - 1/2 log Ca) using the value 6.1 for pk in water (or plasma) at 38 C and the value 0.03 for lx, the absorption coefficient in water or plasma at 38 C. These physical constants vary with temperature and ionic strength of the solution but not to a degree which could affect the point we wish to make.) n vivo titration of gastric acid by pancreatic bicarbonate is thus completed at a ph of 4 and a neutral ph indicates a surplus of bicarbonate and therefore a bicarbonate secretion rate overshooting the amount of acid emptied from the stomach. The ratio will depend upon the hydrogen ion concentration in the gastric contents. REFERENCES 1. Danhof,. E., F. C. Douglas, and M. O. Rouse Mechanisms of intestinal gas formation with reference to carbon dioxide. Southern Med. J. 56: McGee, L. C., and A. B. Hastings The

5 762 RUNE AND HENRKSEN Vol. 56, No.4 carbon dioxide tension and acid-base balance of jejunal secretions in man. J. Bioi. Chem. 142: Rune, S. J., and F. W. Henriksen Secretory rate of gastric acid and pancreatic bicarbonate in the dog after feeding. Gastroenterology 52: Andersson, S., and M. 1. Grossman Profile of ph, pressure, and potential difference at gastroduodenal junction in man. Gastroenterology 49: Rhodes, J., and C. J. Prestwich Acidity at different sites in the proximal duodenum of normal subjects and patients with duodenal ulcer. Gut 7: Krogh, A The rate of diffusion of gases through animal tissues with some remarks on the coefficient of invasion. J. Physiol. (London) 52: Wright, C The diffusion of carbon dioxide in tissues. J. Gen. Physiol. 17: Mcver, M. A., A. C. Redfiels, and E. B. Benedict Gaseous exchange between the blood and the lumen of the stomach and intestines. Amer. J. Physiol. 76: Parsons, D. S The absorption of bicarbonate-saline solutions by the small intestine and colon of the white rat. Quart. J. Exp. Physiol. 41: Wilson, T. H., and L. Kazyak Acid-base changes across the wall of hamster and rat intestine. Biochim. Biophys. Acta 24: Phillips, S. F., and W. H. J. Summerskill Water and electrolyte transport during maintenance of isotonicity in human jejunum and ileum. J. Lab. Clin. Med. 70: Swallow, J. H., and C. F. Code ntestinal transmucosal fluxes of bicarbonate. Amer. J. Physiol. 212: Hollander, F Studies in gastric secretion. V. Variations in the chlorine content of gastric juice and their significance. J. Bio. Chem. 97: Makhlouf, G. M., J. P. A. McManus, and W. 1. Card A quantitative statement of the two-component hypothesis of gastric secretion. Gastroenterology 51: