인체췌장의 외분비에 관한 연구

Abstract

[한글]

Experimental Observations on Human Pancreatic Secretion

By Kyung Bal Hur, M.D.

Department of Pharmacology and Toicology, Department of Surgery,

Yonsei University, School of Medicine, Seoul, Korea.

Since Bayliss and Starling demonstrated the presence of humoral regulation of the

external secretion of pancreas in 1902, a large body of knowledge of the external

secretion of pancreas in avaliable in the literature. Recently, in conscious dogs

equipped with a pancreatic fistula and a Thiry-Vella loop of the duodenum, Magee

and Hong found that HCI, milk, or methionine solution when introduced into the loop

increased both the volume and the enzyme content of the pancreatic juice.

Furthermore they found that the intravenous injection of hexamethonium either

decreased or abolished the responses to milk or methionine.

Inaccessibility of human pancreatic duct by the ordinary measures, however, made

direct experimental investigation on the secretion of human pancreas difficult, and

the greater part of the information regarding the external secretion of the

pancreas has been driven either from experiments conducted on lower animals or by

indirect experiments on human being. An opportunity of experimental investigation

of the human pancreatic secretion by direct cannulation of main pancreatic duct

(Duct of Wirsung) is obtained following operative treatment of Korean gall-stone

patients. Patients in whom pancreatic cannulation was performed permit the

collection and analysis of pancreatic juice under various experimental conditions.

Rationale of clinical indications of the pancreatic cannulation and the effects of

hexamethonium and some dietary factors ell human pancreatic secretion consitute the

following reports.

A statistical review of biliary surgery done at the Severance Hospital for the

past 5 years period showed 74 gall-stone patients among total 122 cases of all kind

of biliary tract diaeases including malignant tumors. Further analysis of the 74

cases,according to location of the gall-stones found during the operative

intervention disclosed 171at only 12cases had gall-stones in gall-71a4der, 41 cased

had no stones in the gall-bladder 7ut in the common bile duct, and 18 cases had

them in both gall-bladder and common bile duct. Three others were intra-hepatic

calculi. Preference of patients for medical treatment and reluctancy of early

surgical treatment, in spite of the far advanced picture of biliary symptoms were

present, are well illustrated by high incidence of acute suppurative cholangitis(9

cases in the series). Subsequently it developed into unusual and complex pathology

associated with the gall-stone impacted in the terminal portion of the common bile

duct. Trans-duodenal sphincterotomy was done 29 times for effetive removal of the

stones, and pancreatic cannulation was indicted in 9 patients in order to overcome

complicated pathological changes due to either surgical trauma and bleeding induced

by repeated instrumentation from the initial choledochal approch or mucosal edcma

from tee longstanding irritation of gall-stones around the orifice of tee

pancreatic duct and the ampullary region.

Of the 9 cases studied, 7 pancreatic cannulations were done by the method

described by Doubilet and Mulholland and 2 cannulations were done by author's

modification. During the experiments the pancreatic juice was collected for

consecutive 20 min. Period. The volume was recorded and the total quantities of

lipase and amylase activity in pancreatic juice were estimated in each sample. The

Nelson's method was used to determine amylase, and the method of Cherry and

Crandall was used for lipase. The experimental procedures consisted of the

administration of whole milk or of a 1% solution of dl-Methionine in water. Both of

these were given orally in 200 ml. both before and after intramuscular injection of

hexamethonium chloride. In patients not receiving hexamethonium, "Starch Chyme",

20% 91UC7Be Solution,water and beer containing 5% ethyl alcohol were administered

orally as before in a volume of 200ml. Ten units of Secretin (Vitrum, Sweden) and

Pancreozymin (Boots , England) were diluted into 10 ml. of normal saline solution

respectively, and slowly administered by intravenous injection.

1) Total volume of daily 7ut-put of the pancreatic juice i9 minimum in fasting

stake but sharply increased after oral fe7ding. This is clearly shown in subject 2,

in whom gastric contents were aspirated for the first 3 days fellowed by oral

feeding. The volume secrete(I per day for the first 3 days was 15ml, next day it

was 30 ml. and after the oral feeding it was 650, 800 and 1000 ml. in order. and

Iropped to 450 ml. and fairly maintained at this level. In Subject 5, when

naso-gastric suction was discontinued but still fasting the volume slightly

increased, and then sharp increase was noted with the patient's diet becoming

regular.

2) Two patients received milk. In both the secretion of pancreatic juice and the

total out-put of amylase and lipase activity increased. The two pancreatic enzymes

increased in a strictly paralell fashion. After the administration of

hexamethonium7he volume 7f pancreatic juice secreted and its enzymes were reduced

to the resting values and milk was no longer effective.

3) The responses to oral methionine were similar t? those t? milk in subject 2,

but in subject 1 in whom the volume of pancreatic juice was already high, no

further increase was noted. This subject had been atropinized 2 hr. prior to the

experiment, but despite this treatment a respone to milk had been observed earthier

on the same day. In both subjects hexamethonium reduced pancreatic secretory volume

and enzyme activity. In neither case did methionine stimulate pancreatic secretion

after the administration hexamethonium.

4) Two patients were subjected for observation of atropine effect on pancreatic

secretion. In subject 5, 1/150 gr. of atropine was given by subcutaneous injection

did not abolish the response of pancreatic juice to the oral feeding of milk. In

subject 9, the total volume of the daily pancreatic secretion was minimum in

fasting and slightly increased with removal of gastric suction but markedly

increased after Oral feeding, in Spite of 1/150 gr. of atropine given twice daily

for 5 days throughout her fasting and feeding stages. A distinct differerence

between the effect of atropine and hexamethonium on pancreatic secretion is noted.

5) The secretin is known to increase the volume of pancreatic juice but not the

enzymes. In subject 9, the volume of pancreatic juice markedly increased after the

secretin injection. Second administration of the secretin again markedly increased

the volume but the enzyme activities were not remarkably increased as to the

proceeding result. When the secretin is given after hexamethonium. the lipase

activity was reduced to resting vague but the increase of volume was persistently

marked.

6) Starch chyme alone markedly increased both the volume and the enzyme out-put

of the pancreas. Twenty per cent glucose solution markedly depressed both 7he

enzymes and the volume out-put of pancreatic juice. Tap water had little effect,

but beer slightly increased the volume and enzymes.

7) Intravenous fluid administration of an electrolyte solution, M/6 sodium

lactate solution. 5% Amigen solution given 3 ml. per miniute grove no conclusive

effects on pancreatic secretion in human.

[영문]

Since Bayliss and Starling demonstrated the presence of humoral regulation of the external secretion of pancreas in 1902, a large body of knowledge of the external secretion of pancreas in avaliable in the literature. Recently, in conscious dogs equipped with a pancreatic fistula and a Thiry-Vella loop of the duodenum, Magee and Hong found that HCI, milk, or methionine solution when introduced into the loop increased both the volume and the enzyme content of the pancreatic juice.

Furthermore they found that the intravenous injection of hexamethonium either decreased or abolished the responses to milk or methionine.

Inaccessibility of human pancreatic duct by the ordinary measures, however, made direct experimental investigation on the secretion of human pancreas difficult, and the greater part of the information regarding the external secretion of the pancreas has been driven either from experiments conducted on lower animals or by indirect experiments on human being. An opportunity of experimental investigation of the human pancreatic secretion by direct cannulation of main pancreatic duct (Duct of Wirsung) is obtained following operative treatment of Korean gall-stone

patients. Patients in whom pancreatic cannulation was performed permit the collection and analysis of pancreatic juice under various experimental conditions.

Rationale of clinical indications of the pancreatic cannulation and the effects of hexamethonium and some dietary factors ell human pancreatic secretion consitute the following reports.

A statistical review of biliary surgery done at the Severance Hospital for the past 5 years period showed 74 gall-stone patients among total 122 cases of all kind of biliary tract diaeases including malignant tumors. Further analysis of the 74

cases,according to location of the gall-stones found during the operative intervention disclosed 171at only 12cases had gall-stones in gall-71a4der, 41 cased had no stones in the gall-bladder 7ut in the common bile duct, and 18 cases had them in both gall-bladder and common bile duct. Three others were intra-hepatic calculi. Preference of patients for medical treatment and reluctancy of early surgical treatment, in spite of the far advanced picture of biliary symptoms were present, are well illustrated by high incidence of acute suppurative cholangitis(9

cases in the series). Subsequently it developed into unusual and complex pathology associated with the gall-stone impacted in the terminal portion of the common bile duct. Trans-duodenal sphincterotomy was done 29 times for effetive removal of the

stones, and pancreatic cannulation was indicted in 9 patients in order to overcome complicated pathological changes due to either surgical trauma and bleeding induced by repeated instrumentation from the initial choledochal approch or mucosal edcma from tee longstanding irritation of gall-stones around the orifice of tee

pancreatic duct and the ampullary region.

Of the 9 cases studied, 7 pancreatic cannulations were done by the method described by Doubilet and Mulholland and 2 cannulations were done by author's modification. During the experiments the pancreatic juice was collected for consecutive 20 min. Period. The volume was recorded and the total quantities of

lipase and amylase activity in pancreatic juice were estimated in each sample. The Nelson's method was used to determine amylase, and the method of Cherry and Crandall was used for lipase. The experimental procedures consisted of the administration of whole milk or of a 1% solution of dl-Methionine in water. Both of

these were given orally in 200 ml. both before and after intramuscular injection of hexamethonium chloride. In patients not receiving hexamethonium, "Starch Chyme", 20% 91UC7Be Solution,water and beer containing 5% ethyl alcohol were administered orally as before in a volume of 200ml. Ten units of Secretin (Vitrum, Sweden) and Pancreozymin (Boots , England) were diluted into 10 ml. of normal saline solution respectively, and slowly administered by intravenous injection.

1) Total volume of daily 7ut-put of the pancreatic juice i9 minimum in fasting stake but sharply increased after oral fe7ding. This is clearly shown in subject 2, in whom gastric contents were aspirated for the first 3 days fellowed by oral

feeding. The volume secrete(I per day for the first 3 days was 15ml, next day it was 30 ml. and after the oral feeding it was 650, 800 and 1000 ml. in order. and Iropped to 450 ml. and fairly maintained at this level. In Subject 5, when naso-gastric suction was discontinued but still fasting the volume slightly increased, and then sharp increase was noted with the patient's diet becoming regular.

2) Two patients received milk. In both the secretion of pancreatic juice and the total out-put of amylase and lipase activity increased. The two pancreatic enzymes increased in a strictly paralell fashion. After the administration of hexamethonium7he volume 7f pancreatic juice secreted and its enzymes were reduced to the resting values and milk was no longer effective.

3) The responses to oral methionine were similar t? those t? milk in subject 2, but in subject 1 in whom the volume of pancreatic juice was already high, no further increase was noted. This subject had been atropinized 2 hr. prior to the experiment, but despite this treatment a respone to milk had been observed earthier on the same day. In both subjects hexamethonium reduced pancreatic secretory volume and enzyme activity. In neither case did methionine stimulate pancreatic secretion after the administration hexamethonium.

4) Two patients were subjected for observation of atropine effect on pancreatic secretion. In subject 5, 1/150 gr. of atropine was given by subcutaneous injection did not abolish the response of pancreatic juice to the oral feeding of milk. In

subject 9, the total volume of the daily pancreatic secretion was minimum in fasting and slightly increased with removal of gastric suction but markedly increased after Oral feeding, in Spite of 1/150 gr. of atropine given twice daily for 5 days throughout her fasting and feeding stages. A distinct differerence between the effect of atropine and hexamethonium on pancreatic secretion is noted.

5) The secretin is known to increase the volume of pancreatic juice but not the enzymes. In subject 9, the volume of pancreatic juice markedly increased after the secretin injection. Second administration of the secretin again markedly increased the volume but the enzyme activities were not remarkably increased as to the proceeding result. When the secretin is given after hexamethonium. the lipase activity was reduced to resting vague but the increase of volume was persistently marked.

6) Starch chyme alone markedly increased both the volume and the enzyme out-put of the pancreas. Twenty per cent glucose solution markedly depressed both 7he enzymes and the volume out-put of pancreatic juice. Tap water had little effect, but beer slightly increased the volume and enzymes.

7) Intravenous fluid administration of an electrolyte solution, M/6 sodium lactate solution. 5% Amigen solution given 3 ml. per miniute grove no conclusive effects on pancreatic secretion in human.