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Transport functions of the gallbladder.

The absorptive functions of the gallbladder are responsible for concentrating the Na+ salts of bile acids during interprandial periods. This can be attributed entirely to its ability to absorb NaCl (and NaHCO3) and water in isotonic proportions, thus reducing the volume of hepatic bile by 80%--90%. The results of studies employing gallbladders of several species are consistent with the presence of neutral NaCl (and NaHCO3) absorption that is due to the presence of a coupled (one-for-one) NaCl entry process at the mucosal membrane. Active Na+ extrusion from cell to serosal solution appears to provide the energy for cellular Cl- accumulation, and thus for transepithelial Cl- transport. The mechanism of Cl- exit from the cell to serosal solution is uncertain andrequires further study. Rabbit gallbladder provided an ideal preparation for the characterization of NaCl cotransport and continues to be the tissue of choice for further study of this mechanism. Electrophysiological studies support the concept of nonconductive NaCl cotransport and also suggest that departures from the process of strictly neutral salt absorption may be related to the presence of additional (diffusional) pathways for Na+ and/or Cl- movement across the mucosal membrane so that the mechanistic constraint of neutral copuling between the absorptive movements of these ions is removed. Under these conditions, a significant serosa-positive transepithelial PD is observed and a fraction of Cl- absorption may be electrically coupled to that of Na+. Water is absorbed passively by virtue of osmotic coupling to electrolyte transport. A region of hypertonicity generated within the epithelium, at the level of the lateral intercellular space, provides the driving force for osmotic water flow. In view of the high osmotic water permeability of the gallbladder, the degree of hypertonicity required to account for the rate of water absorption is probably smaller than originally anticipated and is likely to be difficult to detect experimentally. Recent studies of the effects of humoral and pharmacological agents on electrolyte and water transport suggest that the rate of fluid absorption may be subject to physiological regulation. For example, secretin, which stimulates a HCO3--rich biliary secretion, also inhibits the reabsorption of this HCO3--rich fluid by the gallbladder, and in this manner may expedite the neutralization of the duodenal lumen. Inquires aimed at defining the physiological control of the absorptive functions of the gallbladder should provide an exciting avenue for future studies.

Absorption↗

[Na+ and Cl- ion concentration gradients between the external medium and tissues of the rabbit gallbladder wall].

It was shown in experiments on isolated gallbladders of rabbits that after 2 hours of incubation in Krebs solution, the concentration of Na+ and Cl- in mucous solutions decreased by 9.6 +/- 3.1 mM and 14.8 +/- 4.3 mM, respectively. Stereomicroscopy showed, under scraping of the epithelial layer of the gallbladder, a lucid intercellular fluid that could be collected in an amount of 2--4 mkl. The concentration of Na+ in this liquid was equal to 220.8 mM and that of Cl- amounted to 218.6 mM, the mean rate of the gallbladder fluid absorption being 43 mkl/h per 100 mg of the wet gallbladder wall weight. The concentration of the ions in intercellular fluid was inversly proportional to the volumetric epithelial flow rate. Na+ and Cl- concentration in the intercellular fluid was 20--25 mM higher than in incubation medium, with the absorption rate reaching 60 mkl/h per 100 mg of the wet gallbladder wall weight. The results obtained confirm the Diamond hypothesis of the existence of hyperosmotic area in the gallbladder wall.

Absorption↗

Malignant potential of the gallbladder in patients with anomalous pancreaticobiliary ductal junction. The difference in risk between patients with and without choledochal cyst.

Anomalous pancreaticobiliary ductal junction (APBDJ) is considered to be a factor developing carcinoma of the biliary tract. However, the difference in clinical significance of APBDJ between patients associated with choledochal cyst and those without cyst with special reference to the malignant potential of the gallbladder has been little studied. Of 1,325 patients examined with direct cholangiography, 29 patients were found to have APBDJ of whom 21 patients were associated with choledochal cyst while eight were not. Their associated hepatobiliary diseases were clinicopathologically examined and compared. The frequencies of carcinoma of the gallbladder in patients without choledochal cyst and in those with cyst were 50% and 5%, respectively, the difference being significant (p < 0.05). This frequency did not depend upon the type of APBDJ. None of the patients with gallbladder carcinoma had gallstones. The overall frequencies of carcinoma of the biliary tract (gallbladder and bile duct) were 14% in patients with cyst and 50% in those without cyst. All were gallbladder carcinoma in the latter group. We conclude that the gallbladder is under the condition with significantly greater malignant potential in patients with APBDJ especially in cases not associated with choledochal cyst. Prophylactic cholecystectomy and excision of cyst if associated should be indicated for patients with APBDJ.

Adult↗

[Gallbladder contractility in early stages of lithogenesis in the lithogenic fed guinea pig].

The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.

Animals↗

[Ultrasonography and computerized tomography in the diagnosis of gallbladder carcinoma].

The US and CT images of 40 surgical patients with histologically proved gallbladder carcinoma were retrospectively reviewed. The radiologic diagnosis was correct in 22 patients (55%). Gallbladder carcinoma patterns were: an intraluminal mass (type I) (7 patients, 17.5%), focal or diffuse wall thickening (type II) (5 patients, 12.5%) a mass replacing the gallbladder (type III) (10 patients, 25%). In 5 patients with type I or II gallbladder carcinoma, US and CT diagnosis was made easier by the presence of associated findings--i.e., liver infiltration and/or metastases, lymphadenopathy, dilated intrahepatic ducts, ascites. In 7 patients a gallbladder carcinoma was suspected in the presence of a small intraluminal mass (6 cases) or of focal wall thickening (1 case), with no stones and with dilated intrahepatic biliary ducts. In the extant 18 patients (45%) the radiologic diagnosis was: polyps (6 cases), stones with cholecystitis (11 cases) and empyema (1 case). US is the examination of choice in the diagnosis of gallbladder and biliary ducts conditions, but several diagnostic problems may arise in the differentiation from polyps and acute inflammatory disease. CT better demonstrates gastrointestinal tract invasion and lymphadenopathy, which can be a valuable finding for treatment planning.

Aged↗

Endothelin-1 secretion by human gallbladder epithelial cells in primary culture.

BACKGROUND: The three isoforms of endothelin (ET), ET-1, ET-2, and ET-3 are potent contractile agonists for smooth muscle in a wide variety of tissues including the gallbladder. There is increasing evidence that endothelin acts in a paracrine fashion, however, its cell source in the gallbladder is unclear. EXPERIMENTAL DESIGN: To examine the production of ET by gallbladder and bile duct epithelium. RESULTS: We show that human gallbladder epithelial cells in primary culture secrete endothelin. ET release was time-dependent, and intracellular ET was negligible, indicating de novo synthesis. Secretion was increased by physiologic concentrations of cholecystokinin. Epithelial cells lining hepatic cysts in primary culture also released ET, suggesting that the intrahepatic, as well as the extrahepatic biliary epithelium is a source of this cytokine. High performance liquid chromatography separation of the conditioned medium from both cell types showed a single peak corresponding to that of ET-1. In vivo, ET-1 was present in hepatic cyst fluid, but was not detectable in gallbladder or choledochal bile. On tissue sections, both intrahepatic and extrahepatic bile duct epithelial cells were labeled with an anti-"big" ET-1 polyclonal antibody. CONCLUSIONS: These results suggest that ET-1 is locally produced in the biliary tract and by a paracrine route, could play a role in choledochal motility and gallbladder contraction.

Bile Ducts↗

Adenocarcinoma of the gallbladder associated with anomalous pancreaticobiliary ductal junction.

We have previously shown that an anomalous pancreaticobiliary ductal junction (APBDJ) is a risk factor for developing carcinoma of the gallbladder. However, the incidence of APBDJ in patients with primary carcinoma of the gallbladder has been little examined. Of 53 consecutive patients with gallbladder carcinoma, 37 patients had a direct cholangiography to allow satisfactory evaluation of the pancreaticobiliary ductal junction. Eleven per cent of these 37 patients had an associated APBDJ, which was significantly higher than the reported incidence of APBDJ in human (2%). Two of these four patients were associated with choledochal cyst and the other two were not. The main clinical differences in patients with gallbladder carcinoma associated with APBDJ and those without APBDJ were that the mean age of the former group was lower by about 10 years than the latter, and none had gallstones in the former while 54 per cent had gallstones in the latter group. The results show that APBDJ is a risk factor for developing carcinoma of the gallbladder earlier, and factors other than gallstone are more causative in patients with APBDJ. The frequent association with APBDJ should be kept in mind at the time of surgical treatment of the primary gallbladder carcinoma.

Abnormalities, Multiple↗

An experimental method for studying in vivo gallbladder absorption.

A perfusion technique has been developed for the study of net absorption in the gallbaldder of the cat. The lumen of the gallbladder in situ with intact blood vessels and nerves is perfused at a constant rate with bile or a solution of known composition. Differences in volume input and output from the gallbladder are measured with a volume transducer, which in the absence of changes in gallbladder volume reflects net water absorption. By adding polyethylene glycol to the perfusate, net water absorption rate can be calculated from the changes in concentration of this test substance regardless of gallbladder motility. A combined use of these two methods makes possible a concomitant estimation of net water absorption and changes in gallbladder volume. The technique was tested and used for the study of net water absorption from bile, saline and isotonic mannitol solution in the gallbladder lumen.

Animals↗

[Torsion of gallbladder in childhood: a case report].

A 9-year-old girl presented with severe intermittent upper abdominal pain and bilious vomiting for 1 day. Abdominal echography demonstrated severe distension of the gallbladder with marked change in its long axis. Torsion of the gallbladder was suspected preoperatively. Counter-clockwise rotation of the gallbladder around its neck for more than 180 degrees with necrosis of the whole gallbladder was found during the emergency laparotomy. Choleystectomy was performed smoothly after detorsion of the gallbladder. The postoperative recovery was uneventful. Although torsion of the gallbladder is rarely reported in children, we should keep this possibility in mind as a differential diagnosis of acute abdomen.

Abdomen, Acute↗

VIP innervation of the gallbladder.

By immunohistochemistry, vasoactive intestinal polypeptide (VIP) was localized to nerve fibres and nerve cell bodies in the gallbladder wall of several mammals, including man. There is thus a morphological basis for accepting the powerful actions of VIP on gallbladder motility as physiological. VIP (vasoactive intestinal polypeptide), first thought of as a gut hormone, has recently been localized to a widely distributed system of nerves in the gut wall 1,2. In addition, nerves displaying VIP immunoreactivity are present in the wall of brain vessels and in the hypothalamus 1,3. Among known effects of VIP are relaxation of the gallbladder and inhibition of CCK-induced gallbladder contraction4,5. These observations prompted a search for VIP in the gallbladder wall. The present report deals with the immunohistochemical demonstration of VIP nerves in the gallbladder of several species, including man.

Animals↗

Epithelial cyst of the gallbladder demonstrated by ultrasonography: case report.

We present a rare case of epithelial cyst of the gallbladder in a 71-year-old man. Abdominal ultrasonography revealed a small cystic structure adjacent to the gallbladder. The cyst wall was thin and smooth, and protruded into the lumen of the gallbladder. Histologically, the cyst had no communication with the lumen of the gallbladder. The cyst wall was composed of fibro-muscular fiber, and lined by a single layer of ciliated columnar epithelium. Epithelial cyst of the gallbladder should be included in the differential diagnosis when radiological studies show a cystic structure in or adjacent to the gallbladder.

Aged↗

Gallbladder contraction induced by intravenous erythromycin administration. Relation to body mass index.

BACKGROUND/AIMS: To study the action of intravenously administered erythromycin lactobionate on human gallbladder volume, as a possible preventive method against gallbladder stone formation, in high risk patients such as those in sepsis, long standing fasting periods or those receiving prolonged total parenteral nutrition or octreotide. MATERIALS AND METHODS: Twenty-two volunteers randomized to receive intravenously either erythromycin lactobionate 7 mg per kg (study group) or normal saline (controls). We measured ultrasonographically the gallbladder volume before and at 5, 15, 35, 55, 90, 120 and 180 min after the infusion. RESULTS: Erythromycin induced a biphasic gallbladder contraction, with maximum contractility at 15 min (10.2%) and between 120 and 180 min (22.6%), compared to normal saline controls. Late contractility was correlated to body mass index (BMI). CONCLUSIONS: Erythromycin activity on gallbladder contraction is proved. Its biphasic action needs further investigation to find the involved mechanism(s). Long term administration is also necessary to test its efficacy in preventing gallbladder dilatation.

Adult↗

Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women.

The prevalence of gallstones and gallbladder disease was studied between October 1973 and June 1976 in Canadian Micmac Indian women aged 15 to 50 years in an inland rural community near Shubenacadie, NS. Of 132 women at risk 98 underwent cholecystography, 6 had a history of cholecystectomy (verified from hospital records) and 3 had cholecystectomy because of cholecystitis during the 3 years of the study. Of the 17 abnormal cholecystograms 10 showed radiolucent gallstones, and repeated studies documented gallstones in 6 of the 7 radiographs on which the gallbladder was not visualized. The prevalence of gallstones was found to be 211/1000, and that of gallbladder disease, 240/1000. The peak prevalence was at 30 to 39 years of age. The women with gallbladder disease were significantly more obese and of greater parity than those without gallbladder disease even when age was controlled. The Micmac Indian women of Nova Scotia appear to be at a much higher risk for the development of cholesterol gallstones and gallbladder disease than Caucasian women in Framingham, Massachusetts.

Adolescent↗

Analysis of c-Ki-ras oncogene and p53 immunocytochemistry in the gallbladder mucosa of an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts.

Anomalous arrangement of the pancreaticobiliary ducts is a congenital condition which predisposes the affected person to biliary tract carcinoma. We developed an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts to investigate the mechanism of carcinogenesis in this condition. We used this model to analyze point mutations in the c-Ki-ras gene, and to assess the expression of mutant p53 protein in the gallbladder mucosa. The histopathological appearance of the gallbladder mucosa was also examined. Glandular structures were seen in four of seven (57%) gallbladders examined 14 months after the surgical creation of an anastomosis between the gallbladder and the pancreatic duct. Goblet cells were seen in two of seven gallbladders (29%). However, dot-blot hybridization and immunohistochemical study did not reveal any mutations in the c-Ki-ras gene, or any over-expression of the p53 protein in the specimens. These results show that the gallbladder mucosa is damaged by refluxing pancreatic juice in this dog model of anomalous arrangement of the pancreaticobiliary ducts, but that severe damage may be necessary to induce mutations in the c-Ki-ras proto-oncogene, or in the p53 gene.

Animals↗

Xanthogranulomatous cholecystitis versus gallbladder cancer: clinical differentiating factors.

Xanthogranulomatous cholecystitis (XC) is occasionally difficult to differentiate from gallbladder cancer and mandates efforts to avoid extensive operations. We studied the clinical factors to differentiate XC from cancer. Subjects were a consecutive series of 10 patients with XC and 10 with carcinoma, all of whom radiologically showed thickened gallbladder walls. As opposed to cancer, XC was typified by invisible gallbladders on cholangiography (1), the presence of cholelithiasis (P = 0.01) (2), and, intraoperatively, an aspirate of pus or nothing (P < 0.01) (3). To diagnose XC against gallbladder cancer, (1) and (2) in combination and (3) demonstrated an accuracy of 82.4% and 85.0 per cent, respectively. Clinically, XC can be distinguished from gallbladder cancer by cholangiography, calculous findings, and a gallbladder aspirate of pus or nothing.

Aged↗

[Study of volume and kinetics of gallbladder emptying in non-pregnant, pregnant, and puerperal women].

Gallbladder stasis apparently plays an important role in the patho-genesis of cholelithiasis during pregnancy. On the other hand, gallstones diagnosed immediately after delivery disappear spontaneously during late puerperium in one third of these patients. Gallbladder emptying was assessed by biliary scintigraphy and ultrasonography in normal, nulliparous volunteers. The two methods had an excellent correlation: thence, we used ultrasonography to determine gallbladder volume and contraction in pregnant and puerperal women. Fasting and postprandial residual volumes were significantly larger during pregnancy, while the kinetics f gallbladder emptying was similar in nulliparous and pregnant women. During puerperium, gallbladder volume returned to the values observed in nulliparae; but the kinetics of emptying was significantly faster, suggesting an increased sensitivity of gallbladder muscle to physiologic stimuli.

Adolescent↗

[The clinical significance of phasic duodenal intubation and ultrasonic monitoring of the gallbladder in healthy subjects].

Overall twelve essentially healthy subjects were evaluated for the tone and contractile function of the gallbladder according to phases of interdigestive motility of duodenum as were for effects on these functions of phase-by-phase administration of 30 ml of 33% solution of magnesium sulphate. The gallbladder in healthy individuals was found out to function according to phases of duodenal interdigestive motility and be ready to evacuate bile during phase II. Prior diagnostic techniques did not take advantage of interdigestive phase of duodenal and gallbladder motility during which phase a standard stimulating agent was routinely employed. This can lead to wrong diagnosis of the functional state of the biliary tract, gallbladder and their sphincters in the interdigestive period: incomplete gallbladder emptying from bile in case the stimulating agent is being introduced during phase I or III; hyperdiagnosis of cholecystitis; heterodirectivity of the same patient's notion about type of dyskinesias of the gallbladder and biliary tract.

Adult↗

Solitary neurofibroma of the gallbladder. A case report and review of the literature.

Benign non-epithelial neoplasms of the gallbladder are rare. A case of incidental neurofibroma of the gallbladder in a 44-year-old man without neurofibromatosis 1 is reported. The intramural tumor, located in the neck of the gallbladder, was associated with lithiasis, chronic cholecystitis and localized fundic adenomyomatosis. Seven cases including the present one are reviewed. The seven patients ranged in age from 44 to 77 years, with an average age of 61.6 years. Four of the seven patients were women. Five tumors appeared as mural nodules, and two showed intraluminal growth. The most common location was the body of the gallbladder. The size of the lesion varied from 0.3 to 5.3 cm, with a mean size of 1.3 cm. Five of the seven cases were incidentally found in a gallbladder resected for cholelithiasis. Using ultrasonography, two cases with no lithiasis were detected preoperatively, presenting as intracavitary growing lesions by ultrasonography. It is possible that neurofibroma of the gallbladder may be more common than the small number of known cases indicates.

Adult↗