GastroenterologiaJaponica Copyright 0 1976 by The Japanese Society of Gastroenterology
Vol. 11, No. 4 Printed in Japan
--Original Article--
EFFECT OF ENTEROHEPATIC CIRCULATION ON BILE P R O D U C T I O N IN REGENERATING LIVER Koji Y A M A N A K A , M.D.
The First Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, 606 Japna
Summary In an investigation of the role of portal blood flow in bile production and of changes in the enterohepatic circulation of bile in the regenerating liver, various branches of the portal vein were ligated in dogs, bile was collected from the liver lobes supplied by ligated and by nonligated portal branches, and the composition of the bile was analyzed. 1. Bileflow and bilirubin excretion from the ligated, atrophic liver lobes decreased with a disappearance of glycine-conjugated bile acids, but bilirubin excretion and especially bile flow increased greatly without any changes in bile acids composition in the nonligated, regenerating liver lobes as the portal blood flow to them per liver weight increased. 2. Infusion of gallbladder bile into the terminal ileum stimulated bile secretion in the nonligated lobes in the postoperative period, but not in the ligated lobes except immediately after the ligation of the portal vein branches supplying two-thirds of the liver. These findings indicate that bile secretion by the ligated lobes could be stimulated via the hepatic artery and the nonligated lobes might be via both the portal vein and the hepatic artery after the infusion during early postoperative period.
Key Words: enterohepaticcirculation, portal bloodflow, bile acid, hepatic regeneration. Introduction The process of bile production consists of the circulatory system carrying the ingredients to the liver, the parenchymal cells acting on them, and the excretory system transporting them to the intestinal tract. Furthermore, any substance secreted in the bile which is reabsorbed from the intestine, returns to the liver mainly via the portal vein and appears once again in the bile may be said to move through an enterohepatic circulation l~. After partial hepatectomy, the remaining liver receives the entire portal blood flow and starts the process of regeneration. Roux and Larimore 2~ in 1920 and others 3,4~ more recently have observed that ligation of a branch of the portal vein leads to marked atrophy of the hepatic lobes supplied by the
ligated branch and hypertrophy of the other lobes supplied by the nonligated branches, indistinguishable from the regeneration seen following resection of the liver. This hypertrophy appears to be a compensatory process, and the total weight of the liver remains constant. In their experiments, the enterohepatic circulation of bile through the portal vein was interrupted in the lobes supplied by the ligated branch, and the total amount of portal blood flowed into the other lobes in the same way as it did in the remaining lobes following partiM resection of the liver. In the present experiment, changes of bile secretion and bile composition were studied in the lobes supplied by ligated and by nonligated portal branches in the acute stage and in the atrophic and hypertrophic lobes in
286
Vol. 11, No. 4
K. YAMANAKA
the chronic stage following permanent ligation of various branches of the portal vein in dogs. The role of the portal blood flow in bile production and that of the enterohepatic circulation in hepatic regeneration were also investigated. Materials
and Methods
Thirty-three adult mongrel dogs of both sexes, weighing between seven and seventeen kg were used. Under intravenous anesthesia with pentobarbital sodium of 25 mg per kg body weight, the abdomen was opened through a midline incision. The experimental dogs were divided into four groups according to the branches of the portal vein which were ligated (Fig. 1). Group 1.--In the control group the abdomen was opened, the portal vein was dissected at the hilum but not ligated, and the abdomen was closed. Group 2 . - - O n e branch of the portal vein supplying the caudate and right lateral lobes was ligated. Group 3 . - - T h e branches of the portal vein supplying the right half of the liver, i.e. the caudate, right lateral and right central lobes, were ligated. Group 4 . - - T h e branches of the portal vein supplying the left sided four lobes, i.e. the right central, quadrate, left central and left lateral lobes, were ligated. Immediately after the ligation of the portal
P.v
F~V.
GROUP 2
GROUP 3
P.v. GROUP 4
P.V. : PortalVein. H.A. : HepaticArtery. ' ~ Li~ated lobes
Fig. l.
Experimental models.
branches, or two, four or eight weeks later, individual bile ducts were cannulated and hepatic bile was collected separately from each lobe following removal of the gallbladder. After the collection of the initial hepatic bile, 50ml of 10% autogenous gallbladder bile in water were infused into the terminal ileum as a test of the effect on bile secretion due to changes in the enterohepatic circulation caused by the ligation of portal branches in Group 4. T h e n the liver was removed and the lobes were weighed separately. The volume of collected bile was measured, and the hourly bile flow per 100 g of liver tissue was calculated. Total bilirubin was measured by the method of Evelyn-Malloy, and bile acid composition was analyzed by the thin layer chromatographic method of Hara et al.5). Results
I.
Acute Experiment Immediately after the ligation of the portal vein branches, the hourly bile flow per 100 g of liver tissue from the lobes supplied by ligated vessels was 0.58 i 0.164 ml, 0.63 ~= 0.057 ml and 0.72 =k 0.327 ml in Groups 2, 3 and 4, respectively, but that from the other lobes supplied by nonligated vessels was 1.30 • 0.447 ml, 1.40 ~_ 0.400 ml and 2.06 ~ 0.385 ml in Groups 2, 3 and 4, respectively, and that from the liver in the control group was 1.12 -~ 0.147ml ( T a b l e 1). Therefore, bile flow from the ligated lobes decreased due to deprivation of the portal inflow, but it was nearly constant and not significantly different among the three groups. Bile flow from the nonligated lobes greatly increased in Group 4 (p
Vol. 11, No. 4 Printed in Japan
--Original Article--
EFFECT OF ENTEROHEPATIC CIRCULATION ON BILE P R O D U C T I O N IN REGENERATING LIVER Koji Y A M A N A K A , M.D.
The First Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, 606 Japna
Summary In an investigation of the role of portal blood flow in bile production and of changes in the enterohepatic circulation of bile in the regenerating liver, various branches of the portal vein were ligated in dogs, bile was collected from the liver lobes supplied by ligated and by nonligated portal branches, and the composition of the bile was analyzed. 1. Bileflow and bilirubin excretion from the ligated, atrophic liver lobes decreased with a disappearance of glycine-conjugated bile acids, but bilirubin excretion and especially bile flow increased greatly without any changes in bile acids composition in the nonligated, regenerating liver lobes as the portal blood flow to them per liver weight increased. 2. Infusion of gallbladder bile into the terminal ileum stimulated bile secretion in the nonligated lobes in the postoperative period, but not in the ligated lobes except immediately after the ligation of the portal vein branches supplying two-thirds of the liver. These findings indicate that bile secretion by the ligated lobes could be stimulated via the hepatic artery and the nonligated lobes might be via both the portal vein and the hepatic artery after the infusion during early postoperative period.
Key Words: enterohepaticcirculation, portal bloodflow, bile acid, hepatic regeneration. Introduction The process of bile production consists of the circulatory system carrying the ingredients to the liver, the parenchymal cells acting on them, and the excretory system transporting them to the intestinal tract. Furthermore, any substance secreted in the bile which is reabsorbed from the intestine, returns to the liver mainly via the portal vein and appears once again in the bile may be said to move through an enterohepatic circulation l~. After partial hepatectomy, the remaining liver receives the entire portal blood flow and starts the process of regeneration. Roux and Larimore 2~ in 1920 and others 3,4~ more recently have observed that ligation of a branch of the portal vein leads to marked atrophy of the hepatic lobes supplied by the
ligated branch and hypertrophy of the other lobes supplied by the nonligated branches, indistinguishable from the regeneration seen following resection of the liver. This hypertrophy appears to be a compensatory process, and the total weight of the liver remains constant. In their experiments, the enterohepatic circulation of bile through the portal vein was interrupted in the lobes supplied by the ligated branch, and the total amount of portal blood flowed into the other lobes in the same way as it did in the remaining lobes following partiM resection of the liver. In the present experiment, changes of bile secretion and bile composition were studied in the lobes supplied by ligated and by nonligated portal branches in the acute stage and in the atrophic and hypertrophic lobes in
286
Vol. 11, No. 4
K. YAMANAKA
the chronic stage following permanent ligation of various branches of the portal vein in dogs. The role of the portal blood flow in bile production and that of the enterohepatic circulation in hepatic regeneration were also investigated. Materials
and Methods
Thirty-three adult mongrel dogs of both sexes, weighing between seven and seventeen kg were used. Under intravenous anesthesia with pentobarbital sodium of 25 mg per kg body weight, the abdomen was opened through a midline incision. The experimental dogs were divided into four groups according to the branches of the portal vein which were ligated (Fig. 1). Group 1.--In the control group the abdomen was opened, the portal vein was dissected at the hilum but not ligated, and the abdomen was closed. Group 2 . - - O n e branch of the portal vein supplying the caudate and right lateral lobes was ligated. Group 3 . - - T h e branches of the portal vein supplying the right half of the liver, i.e. the caudate, right lateral and right central lobes, were ligated. Group 4 . - - T h e branches of the portal vein supplying the left sided four lobes, i.e. the right central, quadrate, left central and left lateral lobes, were ligated. Immediately after the ligation of the portal
P.v
F~V.
GROUP 2
GROUP 3
P.v. GROUP 4
P.V. : PortalVein. H.A. : HepaticArtery. ' ~ Li~ated lobes
Fig. l.
Experimental models.
branches, or two, four or eight weeks later, individual bile ducts were cannulated and hepatic bile was collected separately from each lobe following removal of the gallbladder. After the collection of the initial hepatic bile, 50ml of 10% autogenous gallbladder bile in water were infused into the terminal ileum as a test of the effect on bile secretion due to changes in the enterohepatic circulation caused by the ligation of portal branches in Group 4. T h e n the liver was removed and the lobes were weighed separately. The volume of collected bile was measured, and the hourly bile flow per 100 g of liver tissue was calculated. Total bilirubin was measured by the method of Evelyn-Malloy, and bile acid composition was analyzed by the thin layer chromatographic method of Hara et al.5). Results
I.
Acute Experiment Immediately after the ligation of the portal vein branches, the hourly bile flow per 100 g of liver tissue from the lobes supplied by ligated vessels was 0.58 i 0.164 ml, 0.63 ~= 0.057 ml and 0.72 =k 0.327 ml in Groups 2, 3 and 4, respectively, but that from the other lobes supplied by nonligated vessels was 1.30 • 0.447 ml, 1.40 ~_ 0.400 ml and 2.06 ~ 0.385 ml in Groups 2, 3 and 4, respectively, and that from the liver in the control group was 1.12 -~ 0.147ml ( T a b l e 1). Therefore, bile flow from the ligated lobes decreased due to deprivation of the portal inflow, but it was nearly constant and not significantly different among the three groups. Bile flow from the nonligated lobes greatly increased in Group 4 (p
