cholecystokinin and Cholestasis

The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic nervous system, intestinal failure and gut microbiota has been investigated in the development of hepatic, intestinal and extra-intestinal disease.. The autonomic nervous system can be stimulated via enteral fat leading to cholecystokinin release, stimulating receptors in the gut and in the brain. This promotes bowel integrity, dampening the inflammatory response to food antigens. Consensus exists that intravenously administered long-chain fatty acids can cause liver damage but randomized-controlled trials are lacking. Disruption of the enterohepatic circulation of bile salts can give rise to cholestasis and nonalcoholic fatty liver disease, which may progress to fibrosis and cirrhosis. Reduced intestinal availability of bile salts reduces stimulation of the farnesoid X receptor. This may induce hepatic bile salt overload and associated hepatotoxicity through reduced action of intestinal fibroblast growth factor 19. Evidence is put forward to suggest that the intestinal microbiota is associated with liver abnormalities.. Enteral lipids reduce inflammation and liver damage during stress or systemic inflammation, whereas parenteral lipid is associated with liver damage. Maintaining the enterohepatic circulation of bile salts limits hepatic cholestasis through an farnesoid X receptor feedback pathway. Changes in gut microbiota composition may induce liver disease.

Topics: Administration, Intravenous; Bile Acids and Salts; Cholecystokinin; Cholestasis; Chronic Disease; Fatty Acids; Fatty Acids, Omega-3; Fatty Liver; Gastrointestinal Tract; Humans; Intestinal Diseases; Liver; Metabolic Syndrome; Microbiota; Non-alcoholic Fatty Liver Disease

The use of cholescintigraphy to diagnose acute cholecystitis, biliary obstruction, and biliary leakage dates back to the late 1970s. Today, despite the many advances in imaging instrumentation, radiopharmaceuticals, and methodology over these years, cholescintigraphy still plays an important role in confirming or excluding these diagnoses in acutely ill patients. Acute calculous and acalculous cholecystitis, gallbladder perforation, biliary obstruction, and biliary leakage often present as acute abdominal pain, and must be differentiated from other surgical and nonsurgical etiologies with similar symptoms and presentation. Understanding the pathophysiology of acute hepatobiliary diseases is vital for deciding on the most advantageous imaging work-up and for interpretation of the studies. To optimize the value of cholescintigraphy, up-to-date methology, proper use of appropriate pharmacologic interventions, and recognition of characteristic image findings are critical.

Topics: Abdominal Pain; Acute Disease; Biliary Fistula; Biliary Tract; Cholecystectomy; Cholecystitis, Acute; Cholecystokinin; Cholestasis; Diagnosis, Differential; False Positive Reactions; Humans; Morphine; Practice Patterns, Physicians'; Radionuclide Imaging; Sensitivity and Specificity

Total parenteral nutrition-associated cholestasis (TPN-AC) may be a fatal disease. The only known effective treatment is to discontinue TPN and institute full enteral feedings. However, this is not possible for many patients with severe gastrointestinal failure. Current research supports two theories regarding the etiology of TPN-AC. One proposes that the enteral fast disrupts the enterohepatic circulation. Cholestasis, in this hypothesis, results from a combination of altered gut hormone production and endotoxins produced by bacterial translocation. The second theory implicates the direct toxicity of TPN solution. Amino acid solutions and plant sterols in intralipid have generated much interest. Ursodeoxycholic acid and S-adenosyl-L-methionine are promising treatments for TPN-AC. They have been proven to be effective in animals and adult liver diseases. Cholecystokinin also has been investigated as a possible prophylactic agent. However, results from these experiments do not conclusively show a beneficial effect.

Topics: Animals; Cholecystokinin; Cholestasis; Humans; Methionine; Parenteral Nutrition, Total; Phytosterols; S-Adenosylmethionine; Ursodeoxycholic Acid

Parenteral nutrition-associated cholestasis is a persistent problem that has been a major cause of morbidity and mortality in young neonates. This review discusses some of the more recently associated risk factors, potential etiologies, including some potential genetic causes, and discusses potential forms of therapy, including the use of ursodeoxycholic acid and cholecystokinin.

Topics: Bacterial Translocation; Cholagogues and Choleretics; Cholecystokinin; Cholestasis; Humans; Infant, Newborn; Parenteral Nutrition, Total; Ursodeoxycholic Acid

Topics: Bile; Biliary Dyskinesia; Biliary Tract; Cholecystokinin; Cholelithiasis; Cholestasis; Humans; Middle Aged; Muscle Contraction

Total parenteral nutrition (TPN) is not free of complications. One of the most serious is cholestasis; the cause of this complication is unclear but it may be due to a lack of an enteral stimulus for cholecystokinin (CCK) production. CCK is essential for contraction of the gallbladder and also stimulates intrahepatic bile flow. Its absence may contribute to cholestasis. After any hepatic aggression, the Kupffer cells respond and release proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-alpha), which increase the hepatic damage. The objective of this experimental study has been to observe the effect that the exogenous administration of CCK could have on hepatic damage in experimental short bowel with and without TPN, determined using the serum levels of IL-1 and TNF-alpha.. A resection of 80% of the small bowel was performed on 53 Wistar rats and a continuous infusion of saline or TPN was initiated. The rats were divided into the following groups: SHAM (N = 14): normal saline infusion and free access to food and water. TPN (N = 15): Standard TPN. SHAM-CCK (N = 14): same as the SHAM group but with a daily dose of CCK. TPN-CCK (N = 10): same as the TPN group but with a daily dose of CCK. At the end of the experiment, the animals were sacrificed and blood samples were obtained to determine the IL-1 and TNF-alpha values by ELISA.. The IL-1 and TNF-alpha levels were higher in the TPN group (7.537 and 5.899 pg/mL, respectively) than in the SHAM group (6.509 and 4.989 pg/mL, respectively) (p > 0.05). The TNF-alpha values were higher in the SHAM group (4.989 pg/mL) than in the SHAM-CCK group (4.583 pg/mL) (p < 0.001). The IL-1 and TNF-alpha levels were higher in the TPN group than in the TPN-CCK group (6.709 and 4.794 pg/mL, respectively) (p < 0.001 for TNF-alpha).. 1. There is a rise in the serum levels of the pro-inflammatory cytokines IL-1 and TNF-alpha in animals with short bowel on TPN or enteral nutrition. 2. The administration of CCK causes a fall in the IL-1 and TNF-alpha levels, and could be used such as a further measure to prevent TPN-associated cholestasis.

Topics: Animals; Cholecystokinin; Cholestasis; Interleukin-1; Parenteral Nutrition, Total; Rats; Rats, Wistar; Short Bowel Syndrome; Tumor Necrosis Factor-alpha

Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein.. In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated.. Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction.. Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.

Topics: Amylases; Animals; Ceruletide; Cholecystokinin; Cholestasis; Constriction, Pathologic; Disease Models, Animal; Disease Progression; Hemorrhage; In Vitro Techniques; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsin

The aim of this study was to examine the effect of the most potent CCK receptor antagonist, L364,718, on two major factors involved in pancreatitis development: enzyme load and cytosolic calcium (Ca2+) levels in acinar cells. L364,718 (0.1 mg/kg/12 hr) was administered from 30 min before inducing acute pancreatitis (AP) by pancreatic duct obstruction (PDO) for 48 hr. The results obtained at different AP stages in PDO rats treated and not treated with the CCK antagonist were compared. Similar increases in the intracellular enzyme content were found at earlier stages of pancreatitis in all PDO rats treated or not treated with L364,718. The CCK antagonist increased cytosolic Ca2+ levels up to 6 hr after administration, inducing a higher cytosolic Ca2+ overload at the earliest stages of pancreatitis in L364,718-treated PDO rats than in those not treated. This event might justify the higher increases in ascites volume and haematocrit found in PDO rats treated with L364,718 and the exacerbation in pancreatic morphological alterations induced by PDO. The CCK receptor antagonist L364,718 produces alterations in the acinar calcium homeostasis that prevent to reduction in the severity of pancreatitis induced by obstruction.

Topics: Acute Disease; Amylases; Animals; Calcium; Cholecystokinin; Cholestasis; Devazepide; Hormone Antagonists; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsinogen

Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage.. Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage.. Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively).. Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.

Topics: Adult; Aged; Aged, 80 and over; Amylases; Analysis of Variance; Anorexia; Bile Acids and Salts; Bilirubin; Case-Control Studies; Cholecystokinin; Cholestasis; Drainage; Endotoxins; Energy Intake; Female; Humans; Linear Models; Male; Middle Aged; Nutritional Requirements; Prospective Studies; Secretin; Time Factors; Transaminases; Tumor Necrosis Factor-alpha

Deterioration in the respiratory function of a newborn infant with a repaired diaphragmatic hernia and respiratory insufficiency followed administration of cholecystokinin for cholestatic jaundice. The possible mode of action is discussed and a vasoactive/bronchoactive effect is proposed.

Topics: Cholecystokinin; Cholestasis; Fatal Outcome; Hernia, Diaphragmatic; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung; Parenteral Nutrition; Respiratory Insufficiency

Topics: Acid-Base Equilibrium; Bicarbonates; Carbon Dioxide; Cholecystokinin; Cholestasis; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Partial Pressure

Neonatal infants who require total parenteral nutrition (TPN) after major operations are susceptible to total parenteral nutrition-associated cholestasis (TPNAC). A therapeutic dilemma ensues if cholestasis does not resolve after the institution of full enteral nutrition. The authors report the reversal of TPN-associated cholestasis by intravenous cholecystokinin in eight infants who had undergone major surgery during the neonatal period. The indications for surgery were necrotizing enterocolitis in three patients, midgut volvulus in one, gastroschisis in one, diaphragmatic hernia in one, necrosis of the stomach in one, and cardiac anomaly in one. Four of the infants were premature. Median duration of TPN was 25 days (range, 20 to 150 days). Seven patients were weaned from TPN before treatment with cholecystokinin was instituted Mean duration of pretreatment full enteral nutrition in these seven patients was 35 days (range, 20 to 55 days). One girl with short gut syndrome tolerated only 10% of her caloric needs via the enteral route. All patients had alcoholic stools, conjugated hyperbilirubinemia, no excretion of Technetium-labeled HIDA to the biliary tree or duodenum (six patients), and significantly elevated liver enzyme values. In three patients, echography showed biliary sludge or stones in the gall bladder. Porcine cholecystokinin (2 IDU/kg) was administered intravenously for 3 to 5 days. If the stool color did not normalize, cholecystokinin injections were repeated using a larger dose (4 IDU/kg). In seven patients, including the girl with short gut syndrome, the clinical jaundice and conjugated hyperbilirubinemia completely resolved within 1 to six weeks. No biliary sludge or stones were seen in the posttreatment echography in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cholecystokinin; Cholestasis; Female; Humans; Infant, Newborn; Infusions, Intravenous; Parenteral Nutrition, Total; Postoperative Complications; Prospective Studies

The influences of (a) intraluminal bile deficiency due to common bile duct obstruction and (b) intraduodenal administration of pooled own bile and bovine trypsin on the plasma cholecystokinin (CCK) response to oral fat (Lipomul) ingestion were investigated in seven patients with periampullary tumors and 10 healthy volunteers. Basal and fat-stimulated plasma CCK levels in the patients were significantly higher than in the normal controls. Intraduodenal administration of pooled own bile at a rate of 100 ml/h significantly suppressed both basal and fat-stimulated CCK secretion. Simultaneous administration of pooled own bile (100 ml/hr) and bovine trypsin (600 mg/hr) caused further significant suppression of fat-stimulated CCK secretion compared with that under bile infusion alone. These results indicate that both intraluminal bile and trypsin exert a negative feedback effect on the release of CCK in humans.

Topics: Aged; Bile; Bile Duct Neoplasms; Carcinoma; Cholecystokinin; Cholestasis; Dietary Fats; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Trypsin

Patients on total parenteral nutrition (TPN) commonly have hepatobiliary dysfunction. Interruption of the enterohepatic circulation (EHC) and gallbladder stasis are part of the pathogenesis. Cholecystokinin-octapeptide (CCK-OP), by emptying the gallbladder, stimulates the EHC. This study was performed to determine whether daily CCK-OP infusions can ameliorate the hepatobiliary dysfunction caused by TPN.. Rabbits maintained on a standard TPN for 12 days were divided into two groups. One group (n = 6) received daily intravenous doses of CCK-OP, and the other (n = 13) received TPN only. A lab-chow-fed (LCF) group (n = 8) served as controls. The authors studied bile flow and bile acid secretion rates, sulfobromophthalein (BSP) secretion, gallbladder emptying in response to CCK-OP, and liver histology.. The LCF group had a bile flow of 82.3 microL/kg/min; that for the TPN-only group was 45.7 microL/kg/min (P < .001). The daily CCK-OP group did not improve more than the TPN-only group, with a bile flow of 45.8 microL/kg/min (P = NS). Bile acid secretion was 0.64 mumol/kg/min for the LCF group, 0.46 for the TPN-only group (P = NS), and 0.46 for the daily CCK-OP group (P = NS). TPN impaired the ability of the gallbladder to empty, and this was restored with daily CCK-OP. In the LCF group, the mean BSP secretion was 81.7% of a 5-mg/kg bolus within 60 minutes, compared with 72.5% in the daily CCK-OP group (P = NS) and 63.5% in the TPN-only group (P < .01). Histological examination of the liver showed that daily CCK-OP produced less periportal inflammation and fibrosis, although all TPN groups had hepatocyte damage in the centrilobular area.. Stimulation of the EHC with daily CCK-OP infusions during TPN decreased periportal inflammation and fibrosis, maintained gallbladder emptying capacity, and improved organic anion (BSP) secretion, although bile flow and bile acid secretion were not improved, and hepatocyte damage persisted.

Topics: Analysis of Variance; Animals; Bile; Cholecystokinin; Cholestasis; Enterohepatic Circulation; Female; Gallbladder; Infusions, Intravenous; Liver; Parenteral Nutrition, Total; Rabbits

This study was conducted to investigate the role of humoral factors in pancreatic alterations induced by obstructive jaundice (OJ) in rats. OJ in male Sprague-Dawley rats induced significant increases in pancreatic weight, DNA content, and RNA content of acinar cells. These changes were accompanied by enlargement of eosinophilic granules and compressed nuclei. Protein, amylase, and trypsinogen contents of pancreas were also increased in OJ rats. In addition, plasma levels of bilirubin, cholecystokinin (CCK), and estradiol increased in OJ rats and were correlated positively with each other and with pancreatic weights. Administration of a specific CCK receptor, L-364,718, to OJ rats partly attenuated the changes of the pancreas, indicating that CCK is involved in these changes. These findings suggest that estradiol may be involved in regulating the pancreatic changes induced by OJ in rats.

Topics: Amylases; Animals; Cholecystokinin; Cholestasis; Estradiol; Male; Pancreas; Proteins; Rats; Rats, Sprague-Dawley; Trypsinogen

Bile exclusion from the gut exacerbates pancreatic duct obstruction-induced acute pancreatitis. We hypothesized that obstruction-induced acute pancreatitis involves an increase in circulating cholecystokinin (CCK), as bile and pancreatic juice exclusion from the gut stimulates duodenal CCK release. We studied 54 rats after the following operations: (1) sham operation (n = 18), (2) hepatic bile duct obstruction alone (n = 18), (3) hepatic bile duct and common bile-pancreatic duct obstruction (n = 18). Rats recovered and were killed in subgroups of six rats each at 3, 6, and 18 hr after operation; blood was collected for measurement of plasma CCK and amylase concentrations. Each pancreas was excised, weighed, and processed for histological examination; an acute pancreatitis score was determined. Combined bile and pancreatic duct obstruction induced acute pancreatitis and was associated with a marked increase of circulating CCK concentration. Bile duct obstruction alone did not induce acute pancreatitis but was associated with an increase of circulating CCK of lower magnitude. The time course of circulating CCK increase showed an early peak. These findings support our hypothesis and suggest that CCK plays a role in the pathogenesis of obstruction-induced acute pancreatitis.

Topics: Amylases; Animals; Cholecystokinin; Cholestasis; Constriction, Pathologic; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Pancreatitis; Rats; Rats, Sprague-Dawley

The role of intraduodenal bile in regulation of plasma cholecystokinin (CCK) levels were investigated in patients with obstructive jaundice under external bile diversion and under physiological bile flow into the duodenum by internal bile drainage. Basal plasma CCK levels determined by a specific and sensitive bioassay in patients under external bile drainage (2.2 +/- 0.2 pmol/liter; mean +/- SE) were significantly higher than those in control subjects (1.0 +/- 0.3 pmol/liter). In control subjects, the peak CCK response (6.2 +/- 0.7 pmol/liter) to a test meal was seen at 45 min, whereas that in patients under external bile drainage, it was seen at 20 min after a test meal (17.6 +/- 3.2 pmol/liter; P < 0.01 vs controls). After peak response, plasma CCK levels in controls gradually decreased, but remained significantly elevated during a 3-hr observation period. In patients under bile diversion, the test meal caused a prompt plasma CCK peak, with a transient fall followed by a continuous rise until 180 min postprandially. In six patients, external bile diversion was changed to internal biliary drainage with a stent tube within two weeks to maintain physiological bile flow into the duodenum. Internal bile drainage normalized basal (0.9 +/- 0.2 pmol/liter) as well as meal-stimulated CCK release (peak value: 5.0 +/- 0.8 pmol/liter). These results demonstrate that endogenous bile exerts tonic inhibition on basal and postprandial plasma CCK levels in humans.

Topics: Adenoma, Bile Duct; Adult; Aged; Ampulla of Vater; Bile; Bile Duct Neoplasms; Cholecystokinin; Cholestasis; Common Bile Duct Neoplasms; Drainage; Eating; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Time Factors

Pancreatic exocrine stimulation by cholecystokinin (CCK) has been implicated in the pathogenesis of experimental acute pancreatitis. Bile exclusion from the gut stimulates duodenal CCK release and exacerbates obstruction-induced acute pancreatitis. Pancreatic and bile duct obstruction increases circulating CCK concentration. We hypothesized that acute pancreatitis induced by pancreatic and bile duct obstruction would be ameliorated when bile was returned to the duodenum. As many small pancreatic ducts drain into the bile duct in rats, preservation of bile flow required the use of a bile shunt. We studied acute pancreatitis and the time course of circulating CCK increase in three groups of rats after: (1) sham operation (dissection, no obstruction), (2) bile and pancreatic duct obstruction, and (3) bile and pancreatic duct obstruction with bile shunt. The rats were killed at 3-, 6-, and 18-hr intervals after operation. Their blood was collected for measurement of CCK, amylase, and bilirubin concentrations. The pancreata were excised, weighed, and processed for histological examination. The shunting of bile back to the duodenum ameliorated the acute pancreatitis along with a simultaneous limitation of the rise in CCK concentration. This suggests that bile duct obstruction, another form of bile exclusion, exacerbates pancreatic duct obstruction-induced acute pancreatitis. The elevation in CCK concentration showed an early peak indicating that the potential role of CCK in the pathogenesis of obstruction-induced acute pancreatitis is predominantly in the early phase of its development.

Topics: Acute Disease; Anastomosis, Surgical; Animals; Bile Ducts, Intrahepatic; Bilirubin; Cholecystokinin; Cholestasis; Constriction, Pathologic; Duodenum; Pancreatic Diseases; Pancreatic Ducts; Pancreatitis; Rats; Rats, Sprague-Dawley; Time Factors

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Topics: Animals; Benzodiazepinones; Bilirubin; Body Weight; Cholecystokinin; Cholestasis; Devazepide; Feeding Behavior; Male; Rats; Rats, Inbred Strains

A 3.5-month-old white boy was born with meconium ileus, peritonitis, and jejunal atresia from cystic fibrosis. He subsequently developed unrelenting and severe extrahepatic biliary obstruction as demonstrated by liver biopsy showing periportal inflammation, cholestasis, and fibrosis. Surgical exploration confirmed the diagnosis of extrahepatic biliary obstruction by severely inspissated bile. A cholecystostomy tube was left in place. The cholestasis remained unresponsive to conservative medical therapy. The obstruction was relieved by hydrostatic infusion of 2% N-acetylcysteine into the biliary tree over a 6-day period. The child also received concurrently four i.v. injections of synthetic cholecystokinin. This therapeutic modality was thought to be both safe and effective.

Topics: Acetylcysteine; Cholecystokinin; Cholestasis; Cystic Fibrosis; Humans; Infant; Injections, Intravenous; Liver; Male; Radiography; Therapeutic Irrigation

Topics: Biological Assay; Brain; Cholecystokinin; Cholestasis; Chronic Disease; Diabetes Mellitus; Humans; Intestinal Mucosa; Pancreatitis; Radioimmunoassay; Specimen Handling; Tissue Distribution

The influence of intraduodenal bile deficiency due to chronic bile duct obstruction and acute exogenous administration of bile acids on plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) was investigated. Fourteen patients with tumor-induced bile duct stenosis and five healthy volunteers were given a liquid test meal. Four of the patients had a simultaneous pancreatic duct stenosis. On another day 4 g chenodeoxycholic acid were administered concomitantly with the liquid test meal in six of the patients and all controls. Basal and meal-stimulated plasma CCK did not differ between patients and controls. A pancreatic duct stenosis, which was associated with diminished plasma PP concentrations, had no influence on plasma CCK release. Exogenous bile acids significantly reduced the postprandial CCK response in both groups. Bile-induced inhibition was significantly greater in patients than in controls (75 +/- 7% and 44 +/- 11%, respectively; p less than 0.05). It is concluded that intraduodenal bile is an important modulator of the postprandial secretory activity of the CCK cell. Although chronic intraduodenal bile acid reduction in tumor-induced biliary duct stenosis did not influence plasma CCK levels, a negative feedback control of plasma CCK by acute bile acid administration could be demonstrated.

Topics: Adult; Aged; Bile Acids and Salts; Biliary Tract Neoplasms; Cholecystokinin; Cholestasis; Feedback; Gallbladder Neoplasms; Humans; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide

Obstructive jaundice was produced in rats by ligation and transection of bile duct outside the liver; the control group underwent laparotomy alone. Pancreatic wet weight, amylase, lipase, protein, DNA, RNA, RNA/DNA ratio, and weight/100 micrograms DNA were significantly increased in jaundiced rats when compared to control rats. Histologic evaluation of pancreatic tissue obtained from jaundiced rats revealed the appearance of large or multiple nuclei in pancreatic acinar cells. Basal plasma levels of immunoreactive CCK were significantly increased in jaundiced rats at two weeks and four weeks but, when compared to the levels obtained in laparotomized controls at those time intervals, CCK levels were not significantly different. In jaundiced rats, plasma immunoreactive gastrin was found to be significantly decreased at two and four weeks. Plasma gastrin levels were also found significantly decreased when the jaundiced group was compared with laparotomized control group. The results suggest that obstructive jaundice induced enlargement of the pancreas, probably due to hyperplasia and hypertrophy of pancreatic cells. Whether or not this phenomenon is related to changes in gastrin and CCK is not known.

Topics: Amylases; Animals; Cholecystokinin; Cholestasis; DNA; Female; Gastrins; Lipase; Male; Organ Size; Pancreas; Rats; RNA

We examined the hypersecretory function of the isolated, blood-perfused pancreas of dogs with experimentally obstructive jaundice. There was no difference in basal pancreatic secretion between control dogs and obstructively jaundiced dogs. Secretin- or pancreozymin-stimulated increase in total values for pancreatic juice flow, bicarbonate, protein and amylase were greater in dogs with obstructive jaundice than in control dogs; however, concentrations of bicarbonate, protein and amylase were unchanged in each group. Acetylcholine-stimulated increase in total values and concentrations of these factors were the same in dogs with obstructive jaundice and controls. These data suggest that hypersensitivity of the pancreas to secretin and pancreozymin may be one of the main mechanisms of pancreatic hypersecretion.

Topics: Acetylcholine; Animals; Bicarbonates; Cholecystokinin; Cholestasis; Dogs; Female; In Vitro Techniques; Male; Pancreas; Pancreatic Juice; Proteins; Regional Blood Flow; Secretin

Unexplained abdominal pain after cholecystectomy has been attributed to sphincter of Oddi dysfunction, but no objective diagnostic criteria exist. Biliary excretion was quantitated by computer-assisted cholescintigraphy in 35 postcholecystectomy controls without symptoms, 9 patients with suspected sphincter of Oddi dysfunction (studied before and after sphincterotomy), and 18 patients with overt cholestasis from other causes (6 with extrahepatic obstruction and 12 with parenchymal liver disease). In patients with sphincter of Oddi dysfunction or with cholestasis, the time to attain maximal activity in the biliary system was significantly (p less than 0.05) longer, the percent of radiotracer excreted at 45, 60, and 90 min was less, and the emptying rate was slower compared with the controls. Cholecystokinin (0.02 U/kg X min) did not abolish biliary output, excluding a paradoxical response of the sphincter. After sphincterotomy, biliary activity peaked earlier and the percent excreted at 45 min increased but did not revert to normal. Relief of symptoms occurred in 8 of 9 patients. The one failure had normal emptying characteristics before sphincterotomy, and did not change after surgery. Another developed recurrent pain and a corresponding deterioration in biliary emptying on serial scans. Thus, functional obstruction at the sphincter of Oddi exists, is not due to any paradoxical response to cholecystokinin, and in the absence of overt cholestasis, can be detected by quantitative cholescintigraphy. Successful sphincterotomy may not completely restore biliary emptying to normal.

Topics: Adult; Aged; Ampulla of Vater; Cholecystectomy; Cholecystokinin; Cholestasis; Common Bile Duct Diseases; Female; Humans; Imino Acids; Male; Middle Aged; Postoperative Complications; Radionuclide Imaging; Sphincter of Oddi; Technetium; Technetium Tc 99m Disofenin

Fourteen patients with a cystic duct syndrome (CDS) underwent cholecystokinin (CCK) cholescintigraphy. All patients presented with persistent postprandial right upper quadrant pain and biliary colic. None of the patients had an abnormal oral cholecystography, gallbladder (GB) ultrasound exam or upper GI series. Each patient (NPO after 12 a.m.) received 5 mCi of technetium-99m disofenin. When the GB maximally filled, 0.02 microgram/kg CCK was administered (3 min) intravenously. Background corrected gallbladder ejection fractions (GBEFs) were determined every 5 min X 4 by rationing the pre-CCK GB counts minus post-CCK GB counts to pre-CCK GB counts. GBEFs were: 12% (3 patients), 17% (2), 0%, 1.3%, 3%, 4%, 6%, 11%, 14%, 18.5%, and 22% (1 each). All patients underwent a surgical exploration and all had macro- or microscopically abnormal cystic ducts (five fibrotic, seven elongated and narrow, two kinked) with (12 patients) or without (2 patients) concomitant chronic cholecystitis. No patient with a partially occluded cystic duct with or without concomitant chronic cholecystitis had an ejection fraction that exceeded 22%. In an appropriate clinical setting, a low EF response to CCK should alert the physician to the presence of either chronic acalculous cholecystitis, CDS, or the combination of both.

Topics: Adolescent; Adult; Aged; Cholecystokinin; Cholestasis; Cystic Duct; Female; Gallbladder; Humans; Imino Acids; Middle Aged; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Disofenin

Mongrel dogs jaundiced by ligation of the common bile duct for 3-week period were submitted to simultaneous biliary drainage and pancreatico-jejunostomy and sacrificed on day 1, 3, 5, 7, 14 and 30 after operation. The wound healing process of the anastomotic site was evaluated in terms of microvasculature, histopathological findings, pancreatic hydroxyproline content, incidence of anastomotic leakage and bursting strength of the anastomotic site. Pancreatic function were assessed by intravenous glucose tolerance and pancreozymin-secretin test. Acute inflammation at the anastomotic site was severer in the jaundiced pancreas on day 1, 3 and 5, respectively, than in sham operated controls. The group of dogs with serum bilirubin levels ranging 1 to 5mg/dl (mean 3.2) tolerated significantly higher bursting strength (p less than 0.01) with less incidence in anastomotic leakage (p less than 0.01) as compared to the group of dogs with serum bilirubin higher than 5mg/dl (mean 7.6). The data demonstrate that pancreatico-duodenectomy is primarily indicated to the icteric patients after serum bilirubin is decreased lower than 5mg/dl. Exocrine function of the pancreas showed no significant differences between the control and jaundiced dogs, but glucose tolerance in jaundiced dogs was decreased without appreciable changes in serum insulin levels.

Topics: Animals; Cholecystokinin; Cholestasis; Dogs; Glucose Tolerance Test; Humans; Jejunum; Microcirculation; Pancreas; Pancreatectomy; Pancreatic Function Tests; Secretin; Wound Healing

A review of gallbladder scintigraphy in patients with potentially compromised hepatobiliary function revealed two groups in whom cholecystitis might be mistakenly diagnosed. In 200 consecutive hospitalized patients studied with technetium-99m-PIPIDA for acute cholecystitis or cholestasis, there were 41 alcoholics and 17 patients on total parenteral nutrition. In 60% of the alcoholics and 92% of those on parenteral nutrition, absent or delayed visualization of the gallbladder occurred without physical or clinical evidence of cholecystitis. A cholecystagogue, sincalide, did not prevent the false-positive features which presumably are due to altered bile flow kinetics related to alcoholism and parenteral nutrition. Four patients on parenteral nutrition undergoing cholecystectomy for suspected cholecystitis had normal gallbladders filled with jellylike viscous thick bile. A positive (nonvisualized or delayed visualized) gallbladder PIPIDA scintigram in these two populations should not be interpreted as indicating a need for cholecystectomy.

Topics: Alcoholism; Bile; Cholecystitis; Cholecystokinin; Cholestasis; False Positive Reactions; Gallbladder; Humans; Imino Acids; Organotechnetium Compounds; Parenteral Nutrition; Parenteral Nutrition, Total; Peptide Fragments; Radionuclide Imaging; Sincalide; Technetium

Topics: Animals; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholestasis; Cholesterol; Dose-Response Relationship, Drug; Male; Sciuridae

Topics: Bile; Child; Cholecystokinin; Cholestasis; Cyclic AMP; Cystic Fibrosis; Humans; Pancreatic Juice; Secretin

In a 5 year period, eight patients in whom acute acalculous cholecystitis developed during intravenous hyperalimentation are reviewed with emphasis on factors contributing to pathogenesis. Gallbladder distention, biliary stasis, and bile inspissation, thought to be important in the pathogenesis of this disease, are enhanced with the use of hyperalimentation, and this potential complication is being seen with increasing frequency in seriously ill or injured patients who are being fed parenterally. In addition to hyperalimentation, sepsis, hypotension, multiple transfusions (more than 10 units), prolonged fasting, and ventilatory support were frequent common denominators. Typical findings of pain, tenderness, and a mass in the right upper abdominal quadrant are infrequent, and the diagnosis rests on a high index of suspicion and ultrasonography. This syndrome may be preventable by the stimulation of gallbladder emptying with intermittent fat ingestion or parenteral infusion of cholecystokinin.

Topics: Abdominal Injuries; Adult; Aged; Cholecystectomy; Cholecystitis; Cholecystokinin; Cholestasis; Dietary Fats; Female; Humans; Male; Middle Aged; Parenteral Nutrition; Parenteral Nutrition, Total; Ultrasonography

The gallbladder can be visualized by ultrasound (cholecystosonography) and gallstones seen as echo producing densities. Under cholecystosonographic observation the gallbladder can be demonstrated to contract following stimulation by cholecystokinin. This establishes patency of the cystic duct and excludes a diagnosis of acute obstructive cholecystopathy. The gallbladder has been identified in 84 of 86 patients. Stones have been identified sonographically in 64% of 42 patients with proven gallstones (75% of the last 20 cases). The gallbladder contracted following stimulation in 18 of 20 cases with a patent cystic duct. Cholecystosonography is simple, safe and economical. Cholecystonography with cholecystokinin stimulation is the first diagnostic study to be performed when cholecystolithiasis is suspected and the following circumstances exists: a) an acute right upper quadrant (RUQ) syndrome consistant with acute obstructive cholecystopathy. b) cholestasis or hepatic dysfunction. c) a history of allergy to contrast media. Cholecystosonography may detect gallstones in a gallbladder visualized by oral cholangiography when stones are of the same density as the contrast media.

Topics: Cholangiography; Cholecystokinin; Cholelithiasis; Cholestasis; Drug Hypersensitivity; Evaluation Studies as Topic; Humans; Iodized Oil; Transducers; Ultrasonics; Ultrasonography

Topics: Cholecystokinin; Cholestasis; Diagnosis, Differential; Humans; Liver Diseases; Secretin

C-terminal octapeptide of cholecystokinin was administered at six dose levels, 4-128 ng/kg, by 184 intravenous injections to three mongrel dogs under several pressure conditions of the biliary system. Gallbladder contraction was monitored radiographically. A good, dose-dependent contraction response resulted with intraductal pressures of 0 and 10 cm water. At 20 cm water, a markedly reduced and dose-independent response occurred. No contraction response was found with an intraductal pressure of 30 cm water. This animal experimental work suggests that in man, a contraction response of 30% or more may rule out significant common bile duct obstruction.

Topics: Animals; Biliary Tract Diseases; Catheterization; Cholangiography; Cholecystography; Cholecystokinin; Cholestasis; Common Bile Duct; Diagnosis, Differential; Dogs; Gallbladder; Injections, Intravenous; Jaundice; Pressure

The mechanisms of bile excretion are investigated in 27 experiments in 21 mini-pigs. The results confirm the known three fractions of bile flow for mini-pigs, too: a canalicular bile acid dependent, a canalicular bile acid independent and a ductular bile acid independent bile flow. These different fractions of bile flow may be stimulated either by taurocholate, by phenobarbital and ioglycamide or by secretin and pancreozymin. The total bile acid pool amounts 4,4 mMol. Measurements of its distribution over the gallbladder and the enterohepatic circulation after fasting for 18-24 hours emphasize the importance of the gallbladder resp. the fasting as factors that may be responsible for the secretion of lithogenic bile.

Topics: Animals; Bile; Bile Acids and Salts; Cholecystectomy; Cholecystokinin; Cholelithiasis; Cholestasis; Enterohepatic Circulation; Fasting; Gallbladder; Ioglycamic Acid; Phenobarbital; Secretin; Stimulation, Chemical; Swine; Taurocholic Acid

The hormones secretin and cholecystokinin-pancreozymin (CCK) have been shown to release brush-border alkaline phosphatase into the small-intestinal lumen in the human subject. In contrast to the disaccharidases, large amounts of alkaline phosphatase are present in human duodenal juice. The range has been established in normal subjects. Following the intravenous administration of both secretin and CCK-pancreozymin there is a large rise in the output of alkaline phosphatase in human duodenal juice. These rises are also present in patients with complete obstruction of the common bile and pancreatic ducts, and since the pancreatic juice of man contains negligible amounts of alkaline phosphatase, it is clear that both hormones must cause small-intestinal alkaline phosphatase to be released into duodenal juice. The isoenzyme characteristics of bile, small-intestinal, and pancreatic alkaline phosphatase have been established, and isoenzyme studies used to confirm this new action of secretin and CCK-pancreozymin.

Topics: Alkaline Phosphatase; Amylases; Bilirubin; Cholecystokinin; Cholestasis; Electrophoresis, Polyacrylamide Gel; Glucosidases; Humans; Intestinal Mucosa; Intestine, Small; Isoenzymes; Lipase; Neuraminidase; Pancreatic Diseases; Pancreatic Juice; Pancreatitis; Secretin; Secretory Rate; Stimulation, Chemical

Topics: Carcinoma; Cholecystokinin; Cholestasis; Duodenum; Gallstones; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin

Topics: Cholecystokinin; Cholestasis; Humans

Topics: Bile; Cholecystokinin; Cholestasis; Humans; Secretin

Topics: Adult; Aged; Cholecystokinin; Cholestasis; Diabetes Mellitus; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Secretin

Topics: Amylases; Biliary Tract Diseases; Cholecystokinin; Cholestasis; Diagnosis, Differential; Humans; Injections, Intravenous; Pancreatic Neoplasms; Pancreatitis; Secretin