The influence of bile on canine gastric secretion

JOURNAL

OF SURGICAL

16, 6-12 (1974)

RESEARCH

The

Influence G.

of Bile

WICKBOM, E.

R.

WOODWARD,

M.D.,

on Canine F.

ELLO,

M.D.,

M. H.

FAITH, LANDOR,

M.D., M.D.

METHOD Eighteen mongrel dogs were prepared with denervated (Heidenhain) pouches fashioned from the body of the stomach. The dogs were fed a standard diet of 210 grams horsemeat mixed with 310 g Purina Dog Chow, with 1 tablespoon of table salt added to each day’s feeding. Twenty-fourhour collections of gastric juice from the pouches were begun after a postoperative recovery period of IO or more days, Acidity was determined by titrating with 0.1 N NaOH using phenol red as an indicator, and the HCl content of each 24-hr sample was calculated and expressed in milliequivalents. At the completion of a collection period the mean 24-hr secretion of HCl was calculated. Liver function was evaluated by means of bromsulphalein tests which were done by injecting 10 mg/kg of BSP dye intravenously and determining the retention of the dye by analyzing a blood sample collected 15 min after injection. Upper limits of normal in this laboratory were found to be 10% + 3. When a minimum of 30 daily collections of gastric juice had been made, the dogs were assigned to the following groups: 6

@ 1974 by .4oademic Press. Ine. of reproduction in any form reserved.

J.

Secretion

ported to follow internal diversion of bile must be due to causes other than the absence of bile from the proximal intestine. In an attempt to delineate further the possible effects of biliary diversion on gastric secretion it was decided to study several different types of diversion in groups of dogs with Heidenhain pouches maintained under identical conditions.

From the Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida. This work has been supported by NIH grant AM-2372. Submitted for publication June 20, 1973.

Copyright All rights

M.D.,

AND

THE POSSIBLE INFLUENCE OF BILE on gastric function has been the subject of many investigations since Kapsinow [7] reported in 1926 that diversion of bile into the urinary tract was followed by the appearance of duodenal ulcers in a high proportion of animals. External diversion of bile was found by Berg, Johnston, and Jobling [2] to lead to duodenal ulceration in dogs, and ligation of the common bile duct was reported by Bollman and Mann [3] to bring about peptic ulceration. More recently, Menguy [lo] reported that diversion of bile to the distal gut by means of a Roux-en-Y segment of ileum led to a gradual increase in Heidenhain pouch secretion in dogs. This was confirmed by von Heimburg and Hallenbeck [6], who found, in addition, that this operation brought about a heightened gastric secretory response to intraportal injections of histamine. It seemed likely from these experiments that absence of bile from the upper small bowel caused liver damage, and that the ensuing gastric hypersecretion resulted from impaired hepatic degradation of one or more gastric secretagogues. Landor, Behringer, and Wild 191, however, found that external diversion of bile did not bring about augmentation of Heidenhain pouch secretion and concluded that the gastric hypersecretion which is re-

Gastric

WICKBOM

Group A. External (Six Dogs)

ET

AL.:

BILE

AND

CANINE

GASTRIC

SECRETION

Bile Diversion

In each of these dogs the common bile duct was ligated and divided close to its termination. A stainless-steel cannula was placed in the gallbladder and brought to the exterior through a stab wound (Fig. 1). Bile was collected in a rubber bag attached securely to the cannula in the gallbladder and this bag was emptied daily; 24-hr collections of Heidenhain pouch secretions continued as before. Group B. Cholecystoileostomy Dogs)

(Five Fig.

1. Complete

external

bile

diversion.

Group

A.

In these dogs the common bile duct was ligated and divided close to the duodenum. The dome of the gallbladder was anastomosed to the side of the ileum 13-15 cm from the ileocolic junction (Fig. 2). One of the dogs used for this procedure had previous external bile drainage (Group A) ; in this dog the cannula was removed, and the gallbladder was anastomosed to the ileum as in the other four dogs. Group C. Cholecystoileostomy, and Ileocecostomy (Six Dogs)

Roux-en-Y,

In three dogs of this group the bile duct was ligated and divided as before. The distal ileum was transected 13-15 cm from the ileocolic junction and the dome of the gallbladder was anastomosed to the distal cut end. The proximal end of the divided ileum was anastomosed to the side of the cecum (Fig. 3). In an additional three dogs, previously in Group B, the distal ileum was transected just proximal to the cholecystoileostomy; the distal end was closed; and the proximal end was anastomosed to the cecum.

Fig. 5’. Cholecystoileostomy. is drained into the distal

Group

B.

The

bile

ileum.

Group D. Blind Ileal Segment, Roux-en-Y, Ileocecostomy (Five Dogs) Five dogs with Heidenhain pouches were prepared by transecting the distal ileum 15 cm from the ileocecal junction, closing the distal end, and anastomosing the proximal

Fig. 3. Cholecystoileostomy. is drained through a loop is excluded from the thyme.

Group of distal

C. Here bile ileum which

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1974

to check the macroscopic appearance of the liver and verify the unimpeded bile flow through the various types of anastomoses. The average secretion of HCl in milliequivalents was determined for each dog and the standard error of the mean (SEM) was calculated. The secretory results for each group before and after operation were compared and significance of differences was determined by using Student’s t test for paired observations [ 151.

8

v

RESULTS Fig. 4. Roux-en-Y to create a control

arrangement group. Group

of

distal

ileum

D.

end to the cecum, thus creating a Rouxen-Y diversion of the distal ileum as in Group C, but not diverting bile from the proximal gut (Fig. 4). During the observation periods the 24-hr Heidenhain pouch secretions were collected and evaluated as before and liver-function tests were continued at weekly intervals. At the end of each observation period the abdominal cavities were explored surgically

Group A. The dogs with external bile diversion tolerated the procedure well, maintained good appetites, and did not lose weight. Liver-function tests remained normal. All dogs in this group showed a decrease in Heidenhain pouch secretion and the decrease was statistically significant (P < 0.01) (Fig. 5). Bile drainage averaged 100-400 cc daily. Group B. Four of the five dogs with simple cholecystoileostomy appeared healthy, maintained their weights, and had good appetites. BSP retention tests showed slight to moderate elevations, but Heidenhain pouch

BO-

70-

60-

503 I zr 40-

U

CONTROL

PERIOD

EXTERNAL ;y- BSP

BILIARY

DIVERSION

IN%

z E z

30-

El m 20-

IO-

I RED 128

0 J 37

Fig. 5. Average 24-hr acid output in meq -c- SEM from total external biliary diversion. The secretion is significantly biliary diversion.

IBW24

Heidenhain increased

IBW 176

IY 144 DOG#

pouches before and after (P < 0.01) after external

WICKBOM

ET

AL.:

BILE

cl

AND

CONTROL

BILE 60

CANINE

GASTRIC

9

SECRETION

PERIOD

DIVERSION

TO

DISTAL

ILEUM

lsl c

.

I SW

116

I WHITE

151

I WHlrE

12

IWHITE

155

II DOG#

Fig. 6. Average HCl secretion in meq 2 SEM from Heidenhain diversion of bile to the ileum. No significant change is seen.

secretion was unchanged (Fig. 6). On exploration, bile ducts were normal, ileointestinal anastomoses were patent, and livers appeared normal. The fifth dog (1 red white 11) had clay-colored feces, was visibily jaundiced, and developed BSP retention of approximately 30%. Despite this, appetite was good and there was no weight loss. The Heidenhain pouch secretion in this dog increased significantly. At laparotomy at the end of the period of observation the liver was enlarged and the bile ducts were markedly distended, although the cholecystointestinal anastomosis appeared patent. Group C. These dogs with Roux-en-Y diversion appeared healthy, had good appetites, and lost no more than l-2 lb each. The three dogs which were entered into this group from Group B had reversion of BSP retention tests to normal. The other three dogs in this group maintained normal BSP tests throughout the trial period. Heidenhain pouch secretion was increased in all dogs compared to the control periods, and the increase was statistically significant at the 95% probability level (Fig. 7). Exploration at the end of the collection periods showed normal biliary systems and normal-appearing livers.

IRW

pouches before and after

Group D. These five dogs also had a normal, healthy appearance and good appetite. They maintained their preoperative weight and had no impairment of liver function. The Heidenhain pouch secretion showed no significant change (Fig. 8). DISCUSSION These results confirmed the previous finding [9] that external diversion of bile does not bring about gastric hypersecretion in dogs with Heidenhain pouches. When distal internal diversion of bile was carried out by a Roux-en-Y loop, hypersecretion ensued as in the experiments of Menguy [lo] and von Heimburg and Hallenbeck [6]. When, on the other hand, simple internal diversion to the distal ileum was carried out, increase in gastric secretion was not observed except in the one instance in which biliary tract obstruction developed, the latter observation undoubtedly reprcsenting an example of the phenomenon dcscribed by Silen [14] wherein bile duct obstruction brings about increased secretion from Heidenhain pouches. An explanation for these findings is not readily apparent. In the past, effects of bile on gastric secretion have been postulated

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80 -

cl

70 -

CONTROL

BILE 60-

PERIOD

DRAINAGE

SECRETION

B # 50 -

T O DISTAL

WHEN

IN GROUP

ILEUM

(ISOLATED

LOOP)

B

BSP IN%

0

BSP IN % WHEN

IN GROUPB

; I 2 z

40-

f5

30-

s ; m

20-

IO-

I

+ITE

155

IWHITE

12

IRWII

IGW69

IGW 152

I BLACK

WH I IO

DOG#

Fig. 7. Average HCl secretion in meq IL SEM before and after diversion of bile to a Roux-en-Y segment of ileum. Note that in the three dogs that previously were in Group B, BSP has normalized and acid secretion has significantly increased (P < 0.05).

cl 60

CONTROL

PERIOD

ISOLATED

ILEAL

LOOP,NO

BILE

DIVERSION

t l

IRG

81

BLUE

BSP

IN %

248

BLUE

21

IYW27

IYWll4 DOG #

Fig. 8. Average HCl secretion in meq 2 SEM before and after creation of a blind Roux-en-Y ileal segment. No significant change is seen.

to be due to the gastric inhibitory effect of bile salts or to liver damage secondary to distal diversion of bile. Still and Carlson [16] reported that iv injection of bile diminished gastric secretion. Menguy and Peisner [ 111 found that bile salts, both in

vivo and in vitro, inhibited the secretion of HCI, and Albo et al. [l] produced inhibition of gastric secretion by intraduodenal instillation of bile. Indirect evidence for this phenomenon comes from Nicoloff’s finding [ 131 that administration

WICKBOM

ET

AL.:

BILE

AND

of exchange resins which bind and prevent absorption of bile salts leads to an increase in Heidenhain pouch secretion. Our finding that total external diversion of bile does not bring about increased gastric secretion suggests that bile salt,s, absorbed into the bloodstream under physiologically normal conditions, do not exert an important depressive effect on gastric secretion, Instead, the diminution in Heidenhain pouch secretion observed in our experiments aftc>r cxternal diversion of bile flow is in concert with the finding by Nahrwold and Grossman [12] of a diminished gastric secretory response to food when bile was excluded from the intestine. We did not find any correlation between gastric hypersecretion and impairment of liver function except in the one instance in which biliary tract obstruction occurred. Animals with simple cholecystoileostomy developed some increase in BSP retention but failed to show gastric hypersecretion. On the other hand, dogs with distal biliary diversion via a Roux-en-Y ileal loop maintained normal levels of BSP retention but showed significant increase in gastric secretion. Thus, while we were able to confirm the findings of Menguy [lo] and von Heimburg and Hallenbeck [6], insofar as gastric hypersecretion occurred after distal Roux-en-Y biliary diversion, we did not find evidence of impairment of liver function consequent to this procedure. That distal diversion of bile through a Roux-en-Y limb of ileum causes gastric hypersecretion, while simple diversion of bile to the ileum does not, seems enigmatic and without ready explanation. The hypersecretion cannot be related simply to the presence of the Roux-en-Y segment since creation of such a segment alone, without biliary diversion, had no effect on gast,r;c secretion. There is, however, other evidence that drainage of bile through isolated segments may alter gastric secretion. Breen, Molina, and Ritchie [4] found that a choledochojejunostomy Roux-en-Y caused an increased in secretion from Heidcnhain

CANIXE

GrlSTRIC

SECRETION

11

pouches, and Kehne and Campbell [8] reported that a similar procedure not only increased the incidence of histamine-induced ulceration but also induced peptic ulcer formation in dogs not receiving histamine. Finch et al. [5] recently reported that, in dogs on an atherogenic regimen, diversion of bile to an isolated segment of ileum caused perforated peptic ulcers in seven of eight animals while simple divesion of bile to the ileum was not ulcerogenic. Thus, there appears to be a real difference in gastric secretory effect between simple internal diversion of bile and internal diversion to an isolated segment of intestine. Whether this difference is reIated to an effect of bile on small bowel mucosa (perhaps bringing about the release of a substance which influences gastric secretion) or whether it is due to the absorption of components of bile not normally absorbed, or absorbed in abnormal ratio, remains to be defined. SUMMARY The effect of various types of biliary diversion on the daily secretion of Heidenhain pouches in dogs was studied. Total external diversion of bile brought about a decrease in gastric secretion while simple internal diversion of bile to the distal gut via Roux-en-Y segment caused significant increase in Heidenhain pouch secretion; the observed increases in secretion could not be accounted for on the basis of impairment of liver function as measured by serial BSP determinations. REFERENCES Albo, R. J., Silcn, W., Ruby, L., Heim, M., and Harper, H. Studies on the mechanism of action of secretin on gastric secretion. Gastroentei-ologg 48:784, 1965. Berg, B., Johnston, A., and Jobling, J. W. Duodenal and gastric ulcers in dogs with bilinry fistulas. Proc. Sot. Exp. Biol. Med. 25:334, 1927. Bollman. J. L., and Mann, F. C. Peptic ulcer in experimental obstructive jaundice. Arch. hug. 24:126, 1932. 4. Breen, J. J., Molina, E., and Ritchie, W. P.

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5.

6.

7.

8.

9.

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RESEARCH,

Effect of common bile duct transplantation on gastric acid secretion in the dog. Br. J. Surg. 55:282, 1968. Finch, W. T., Morgan, C. V., Jr., Lanier, V., Younger, R. K., Ackermann, J., and Scott, H. W. Ulcerogenic effects of bile diversion to the bypassed distal ileum in dogs on atherogenie regimen. Surg. Forum 21:324, 1970. von Heimburg, R. L., and Hallenbeck, G. A. The effect of diversion of bile to the ileum on inactivation of histamine by the liver (dog). Fed. Proc. 23:214, 1964. Kapsinow, R. The experimental production of duodenal ulcers by exclusion of bile from the intestine. Ann. Surg. 83:614, 1926. Kehne, J., and Campbell, R. Choledochojejunostomy en Roux Y. Arch. Surg. 73:12, 1956. Landor, J., Behringer, B., and Wild, R. The effect of enterectomy on gastric secretion in dogs with biliary fistulas. Am. J. Dig. Dis. 15633, 1970.

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10. Menguy, R. Effect of biliary diversion from the small intestine on gastric secretory activity in dogs. Gastroenterology 41:568, 1961. 11. Menguy, R., and Peisner, L. In vivo and in vitro effects of bile salt compounds on gastric secretory activity. Am. J. Dig. Dis. 5:669, 1960. 12. Nahrwold, D., and Grossman, M. Effect of exclusion of bile from the intestine on gastric: acid secretion. Gastroenterolog~ 52:667, 1967. 13. Nicoloff, D. Relationship of bile and gastric secretion. Surg. Forum 17:329, 1966. 14. Silen, W., Skillman, J. J., Hein, M. F., and Harper, H. A. The effect of biliary obstruction upon canine gastric secretory activity. J. Surg. Res. 2:197, 1962. 15. Snedecor, G. W., and Cochran, W. G. Statistic Methods, 6th ed., Iowa State University Press, p. 128, 1967. 16. Still, K. S., and Carlson, A. J. The motor and secretory activity of the stomach during acute and chronic obstructive jaundice in dogs. Am. J. Physiol. 89:34, 1929.