One of the important peculiarities of gallstones in Korea is that most of them arise in the common bile duct, whereas in the occident most of the biliary calculi are located in the gallbladder( Hur et al., 1963). This peculiarity plus the reluctance of patients to accept early surgical treatment results in complex clinical symptoms and signs. Subsequently complex and radical surgical procedures are needed, such as frequent exploration of the common bile duct, T-tube insertion, and transduodenal sphincterotomy for the removal of calculi impacted in the terminal portion of the common bile duct. Pancreatic cannulation was indicated in some of the cases in order to prevent postoperative panereatitis due to surgical trauma and bleeding induced by repeated instrumentation or to mucosal edema from the longstanding irritation of gallstones around the orifice of the pancreatic duct.
Of these procedures, both the T-tube insertion into the common bile-´duct and direct pancreati
c duct
cannulation are indispensable for the treatment of patients. In addition, there then is a unique opportunity for the experimental investigation of human biliary and pancreatic secretion. Hence. a series of studies were made in these patients to clarify several physiological aspects of biliary and pancreatic secretion which can not be satisfactorily investigated in the human by other methods.
I . The composition and concentrating mechanism of human bile.
Bile samples were aspirated anaerobically from the gallbladder and common bile duct in 43 patients who had an abdominal exploration. Twelve were free from biliary tract disease whereas 31 patients had evidence of biliary tract pathology. The samples were analyzed for pH, osmotic pressure, concentrations of HCOs-, Cl-, Na+, K+, cholate and bilirubin.
Normal human gallbladder bile was lower in its concentrations of HCO3 and Cl- and in pH, but was higher in concentrations of Na+. K+, cholate and bilirubin compared with those of bile obtained from normal common bile duct. No gross change of the osmotic pressure was demonstrated between the two.
Bile in the diseased gallbladder contained higher concentrations of HCO3 and Cl- and pH whereas the concentrations of Na+.K+, cholate and bilirubin were lower than those found in normal gallbladder. These data clearly indicate that there is marked disturbance in the normal mechanism of concentration and acidification in the diseased gallbladder.
Bile obtained from diseased common bile ducts contained higher concentrations of HCO3- and Cl-. The concentrations of cholate and bilirubm were lower than those of normal common duct bile. This inadequate concentration of bile in the pathologic common bile dud is probably caused by disturbance in the concentrating mechanism of the gallbladder if it is present or of the common bile duct itself.
II. Bromsulfalein (BSP) excretion of the human liver.
The bromsulfalein test is used widely for the clinical determination of liver function. However, there is no available data as to how these dyes are excreted through the human liver and kidney. Studies were made on patients who had biliary surgery and a T-tube insertion into the common bile duct. A dingle does of BSP(5mg/Kg body weight) was given intravenously at zero time following which urine and bile samples were obtained every 10 minutes and blood every 20 minutes for 3 hours. The output and concentration of dye in the bile reached its peak after 50 minutes while the concentration of-: dye in the plasma reached its peak in the 10 minutes sample after which it dropped rapidly.
As the second step, 80 mg/Kg of Diodrast was given while the BSP was being given by a continuous drip in order that the plasma level of BSP would remain constant. When Diodrast was administered intravenously, the excretions of BSP in both urine and bile were significantly reduced. When the corresponding clearance values and the urine/plasma or bile/plasma concentration ratios were calculated for the dye, it was found that these values were generally lowered by Diodrast administrations.
On the basis of these results, it is postulated that the human kidney and liver also excrete BSP through a common active transport system as has been shown in other animals.
III. The mechanism of the human pancreatic electrolyte secretion and the effects of acetazolamide.
Pancreatic juice was obtained through a direct pancreatic cannulation from the patients having biliary surgery. The cannulations were done by the method of Doubilet and Mulholland(1951) as modified by Hur (1962). While the gastric juice was aspirated continuously, secretions were collected every 10 to 20 minutes for one hour. Secretin(1.0 unit/Kg body weight) was given intravenously after one hour control period and collections of pancreatic juice and urine were continued every 10 to 20 minutes for an hour. Acetazolamide was injected intravenously and was followed by the intravenous injection of secretin immediately or 30 minutes later. The specimens were collected again every 10 to 20 minutes for 80 minutes.
During the control period when acid was completely excluded from the stomach, flow of pancreatic juice was small and varied between 0.1 to 0.5 ml/min. Concentrations of bicarbonate and chloride were 46 and 93 mEq/L on the average, the sodium and potassium, 141 and 5.4 mEq/L, respectively.
The administration of secretin resulted in an increse in the flow and the concentration of bicarbonate and a reduction in the concentration of chloride of the pancreatic juice. However, when the flow was increased above 3.0 ml/min., there were no further changes in the electrolyte composition. The sum of the main anions, bicarbonate and chloride remained constant, i.e., 1350.7mEq/L. The concentration of the principal cations of the secretion, Na+, and K+, and osmotic pressure were constant and similar to the levels found in serum. The administration of acetazolamide resulted in a reduction in the flow and concentration of bicarbonate and in an increase in the concentration of chloride, within the normal flow-concentration relationship of the control period.
At present, there are a limited number of rather rudimentary postulates regarding the mechanism for the electrolyte secretion of the pancreas. These are in three main catagories. (1) Admixture concept(Lim et al., 1936) (2) Exchange concept (Dreiling and Janowitz, 1959) and (3) Admixture and exchange concept (Pak et al., 1966). The major difference between the concept of Dreiling and Janowitz and Pak et al. is based on a difference in the findings of the effects of acetazolamide. Janowitz and Dreiling reported that acetazolamide decreased the flow rate but remained bicarbonate concentration still high. Pak
et al. also reported that acetazolamide reduced the flow of juice but, on the contrary, the bicarbonate concentration was lower than expected if the usual relationship to volume held.
In contrast to the above two reports, the present study revealed that the administation of acetazolamide did not disrupt the normal bicarbonate flow relationship. This suggests that the bicarbonate-chloride exchange process probably is not involved in the electrolyte secretion of the human pancreas, and if it is involved, it is not affected by the carbonic anhydrase system. Accordingly, it is suggested that perhaps there are two isotonic pancreatic secretions: one high in chloride and containing bicarbonate dependent on plasma bicarbonate; and the other high in bicarbonate dependent on carbonic anhydrase and low in chloride. Acetazolmide inhibits the latter secretion and reduces the rate of flow and bicarbonate concentration proportional to the normal characteristic relationship between them. According to this new concept, a hyperbola was obtained mathematically and this line is very similar to that obtained in this study.
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