Enteric nervous system. II. Physiology and pathophysiology of the gallbladder.
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Animals↗
Biomedical subjects
J Svanvik
Publications and source records attributed to J Svanvik.
Vasoactive intestinal peptide in the normal and inflamed feline gallbladder.
Intravenous infusion of vasoactive intestinal peptide (VIP) causes gallbladder mucosal fluid secretion by an action on epithelial cell receptors in the cat. Gallbladder fluid secretion is observed also in experimental cholecystitis and this secretion is abolished when the intramural gallbladder nerves are blocked. In the present study, immunoreactive VIP was detected in the gallbladder contents (29 +/- 5 (S.E.M.) pM) in the obstructed lumen of the gallbladder in cats with experimental cholecystitis and gallbladder mucosal fluid secretion, but not in the normal feline gallbladder. During luminal perfusion of the gallbladder in vivo, the calculated secretion of VIP into the gallbladder lumen in animals with experimental cholecystitis was significantly higher (0.31 +/- 0.08 (S.E.M.), pmol/h) than in controls (0.11 +/- 0.02 (S.E.M.), pmol/h) while plasma levels of VIP were similar. Recovery of exogenously administered VIP was similar in normal and inflamed gallbladders. The present results support the hypothesis that intramural VIP-releasing nerve fibers may be activated in cholecystitis.
Animals↗
Naloxone-reversible inhibition of gall-bladder mucosal fluid secretion in experimental cholecystitis in the cat by acetorphan, an enkephalinase inhibitor.
1. Enkephalin immunoreactive nerve fibres have been demonstrated in the gall bladder of various mammals including man. In various tissues, enkephalins are partly degraded by a membrane metallo-endopeptidase, enkephalinase (EC 3.4.24.11). 2. Using 3H-labelled [D-Ala2,Leu5]enkephalin as a substrate, enkephalinase activity, immunoprecipitated by a monoclonal antibody directed against the rabbit kidney enzyme, was demonstrated in the feline gall bladder. Using the same antibody in 125I-labelled form, the peptidase was immunolocalized by autoradiography, mainly in the epithelium. 3. In experimental cholecystitis, elicited by implantation of human gall-stones into the cat gall bladder, the continuous fluid secretion into the lumen was inhibited by exogenous enkephalins. 4. Acetorphan, an enkephalinase inhibitor, was found to block fluid secretion by the inflamed gall bladder via a naloxone-sensitive mechanism, but not to affect fluid transport in the normal gall bladder. The drug also transiently contracted the gall bladder and increased bile outflow from the liver. 5. It is suggested that acetorphan, by reducing the degradation of endogenous enkephalins in the inflamed gall bladder, decreases fluid secretion by the epithelium and that enkephalinase inhibitors may find clinical applications in acute cholecystitis.
Animals↗
Prostaglandin precursor fatty acids in serum and bile as influenced by oophorectomy, contraceptive steroids and pregnancy. An experimental study in the cat.
Variations in the occurrence of prostaglandin precursor fatty acids might be of importance for the pathogenesis of gallstones. Pregnancy and use of contraceptive steroids increase the risk of gallstones. The present study reports the relative fatty acid composition in serum and biliary phospholipids studied by gas-liquid chromatography in four groups of female cats, which were on a standard diet: 1) oophorectomized animals, 2) animals on contraceptive steroids, 3) pregnant animals and 4) control animals. It was consistently found that the portions of palmitic and linoleic acid were higher and stearic and arachidonic acid were lower in biliary than in serum lecithin. In biliary lysolecithin, sphingomyelin and cephaline there were only small portions of linoleic and negligible amounts of arachidonic acid. Oophorectomy, contraceptive steroids or pregnancy did not induce any gross changes in the fatty acid pattern of lecithin in serum or bile. In animals treated with contraceptive steroids a reduced portion of linoleic acid was seen in the bile lecithin, and in pregnant animals there was a reduction of omega 3 and omega 6 fatty acids in biliary lecithin.
Animals↗
Flow resistance in the feline choledocho-duodenal sphincter as studied by constant-pressure and constant-perfusion techniques.
During interdigestive periods, there is a resistance to flow in the biliary tract exerted by the sphincter of Oddi, resulting in a pressure gradient between the common bile duct and the duodenum. In this experimental study, this flow resistance was studied with both a constant-flow and a constant-perfusion technique in fasted, anaesthetized cats. The flow resistance exerted by the sphincter is higher when it is perfused by a constant flow compared to when the common bile duct pressure is kept constant and the flow varies in response to its muscular activity. It was demonstrated with each method that the flow resistance in the choledocho-duodenal junction is reduced in response to distension of the biliary tree and gallbladder and also by distension of the duodenum. Cholecystokinin was shown to reduce the flow resistance in the choledocho-duodenal junction as estimated with either method.
Ampulla of Vater↗
Gastric and gallbladder emptying in relation to the secretion of cholecystokinin after a meal in late pregnancy.
Gastric and gallbladder emptying was studied in response to a mixed liquid meal in 18 pregnant women and 24 controls without a history of gallbladder or liver disease. Gallbladder and gastric volumes were measured with ultrasound and calculated by the 'sum-of-cylinders' method. The gastric emptying of protein was estimated by nasogastric aspiration in separate groups of controls and pregnant women. In a subgroup of 9 pregnant women and 8 controls, the secretion of cholecystokinin (CCK) was also measured. Neither gastric volume reduction and emptying nor contraction of the gallbladder and CCK secretion after a liquid mixed meal differed significantly between pregnant women and controls. The gallbladder fasting volume and the residual volume after contraction, however, were significantly increased in pregnant women.
Adult↗
Screening and rescreening for colorectal cancer. A controlled trial of fecal occult blood testing in 27,700 subjects.
All inhabitants of the city of Göteborg who in 1982 were between 60 and 64 years of age (27,700) were randomly divided into a test and a control group. The 13,759 subjects in the test group were invited to perform Hemoccult II (Smith Kline Diagnostic, Sunnyvale, CA) fecal occult blood testing over 3 days and to repeat the testing after 16 to 22 months. At the first screening 9,040 (66%) completed the test, and 7,770 (58%) completed the test at the second screening. In the first screening the test group was divided into two subgroups in which the tests were rehydrated and unhydrated before development. All tests were rehydrated in the second screening; 1.9% and 5.8% of the tests were positive in the unhydrated and rehydrated subgroups, respectively. The number of diagnosed neoplasms in the first screening was significantly larger (P less than 0.01) in the rehydrated group compared to the unhydrated group, 50 and 24 neoplasms, respectively. Sixteen of 61 carcinomas in the test group were found in the interval between the two screenings, 19 of the carcinomas at the second screening, and ten among the nonresponders. Rehydration of the Hemoccult II test is a necessity. Significantly more carcinomas (61) were found in the test group compared to the control group (20). There was a trend toward favorable tumor staging in the test group compared to the control group.
Clinical Trials as Topic↗
Effects of intraluminal prostaglandin E2 in vivo on secretory behavior and ultrastructural changes in mouse gallbladder epithelium.
It has been suggested that glycoproteins play an important role as a nucleating agent in the pathogenesis of gallstone formation. Arachidonic acid, by an indomethacin-sensitive mechanism, is known to enhance gallbladder mucus release, suggesting that prostaglandins may regulate gallbladder epithelial release of mucus. In this study, the glycoprotein granules of the principal cells of the mouse gallbladder epithelium were morphometrically analyzed using electron microscopy. It was shown that 5 micrograms of prostaglandin E2, injected into the gallbladder lumen of the anesthetized mouse, reduced the relative volume of glycoprotein granules from 3.0% to 0.7% of the cytoplasmic volume within 20 min, whereas injection of the same amount of the solvent for prostaglandin E2 had no such effect.
Animals↗
Naloxone increases mucosal fluid secretion in the inflamed and distended feline gall bladder: evidence for a possible protective mechanism by endogenous opioids.
1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory action in the small intestine, is also contained in nerves in the gall-bladder wall. 2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin. 3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall-bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high. 4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall.
Animals↗
Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat.
Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non-cholinergic intramural nerve cells.
Animals↗
Enterohepatic bile-acid circulation in the pregnant cat.
Pregnancy increases the risk of gallstones. The physiological changes responsible for this are not clearly demonstrated. Adjustments in the enterohepatic circulation of bile acids have earlier been studied in pregnancy by methods involving dilution of labelled bile acids. In the present study the bile-acid circulation was measured with direct drainage methods in pregnant animals and controls. It was found that the total bile-acid-pool size was reduced to 65% in the pregnant cat (P less than 0.01) and there was a reduced accumulation of bile acids in the gallbladder after fasting 24 h (P less than 0.01). Bile-acid synthesis by the liver was not reduced and the relation between water and bile-acid secretion by the liver was unchanged. It is concluded that, in the pregnant cat, the bile-acid-pool size is reduced due to a decreased accumulation of bile acids in the gallbladder and an increased interdigestive recycling rate of the bile-acid pool (P less than 0.05). One possible explanation for the reduced accumulation of bile acids in the gallbladder is delayed emptying of the stomach, inducing a late refilling of the gallbladder after a meal.
Animals↗
Hepatic clearance of polyethylene glycol 900 and mannitol in the pig.
Fluid phase markers like erythritol and mannitol have been used to study canalicular bile secretion in the liver. It has recently been suggested that these molecules cross the ductular epithelium and thereby their biliary clearance may underestimate the canalicular bile flow. In the present study, the hepatic clearance of polyethylene glycol 900 (PEG 900), a fluid phase marker that has been used in studies of the kidney, was compared to the clearance of mannitol in the pig. We found that the hepatic clearance of PEG 900 exceeded that of mannitol by a factor of 55. After intravenous bolus injections, both mannitol and PEG 900 appeared within 1 min in bile while significant proportions of inulin were seen only after 7 min. The hepatic clearances of both mannitol and PEG 900 positively correlated to the bile acid secretion rate and were not affected by secretin infusion. The high hepatic clearance of PEG 900 compared to mannitol may be explained by a higher fluid flux into the canaliculi than previously estimated and a continuous ductular reabsorption of fluid and mannitol. Another possibility is an active transcellular vesicular transport of this molecule--an explanation that is not supported by the immediate appearance of PEG 900 in bile following an intravenous bolus injection nor by the finding that hepatic clearance of labeled PEG was not affected by a load of unlabeled marker.
Animals↗
Gallstones and previous cholecystectomy in 77- to 78-year-old women in an urban population in Sweden.
A randomly selected sample of 120 women, born in 1906-1907 and living in the city of Gothenburg, were invited to an ultrasound examination for gallstone disease. One hundred and nine subjects participated in the study, and among these, 24% gave a history of a previous cholecystectomy, 27% had gallstones, and 49% had no stones in the gallbladder. Among the women with stones in the gallbladder only 35% had associated symptoms. The design of the study enabled a comparison among women with no stones in the gallbladder, with gallstones, and with a previous cholecystectomy. Women with gallstones, previous or present, had a higher body weight, body mass index, skinfold thickness, and serum triglyceride level than subjects without gallstones.
Aged↗
Relationship between gallbladder histopathology and ability to concentrate biliary lipids and bilirubin. A study on gallstone patients with functioning gallbladder.
Biliary lipids and bilirubin were measured in hepatic and gallbladder bile obtained at routine cholecystectomy in 35 gallstone patients. The gallbladders had opacified at cholecystography and the cystic ducts were patent at operation. The histologic changes in the gallbladder wall were evaluated by an independent pathologist. Increasing abnormality of the gallbladder wall was shown to be associated with reduced gallbladder contents/hepatic bile ratio of biliary lipids and of bilirubin. The concentrating function of the human gallbladder thus appears to be impaired in proportion to the severity of histologic lesions in its wall. Taken together with earlier findings in vitro, this relationship suggests impaired absorption of electrolytes and water by the gallbladder mucosa, or diffusion of biliary constituents from the lumen of the inflamed gallbladder.
Bile↗
Cholecystectomy in the cat damages pericholedochal nerves and impairs reflex regulation of the sphincter of Oddi. A mechanism for postcholecystectomy biliary dyskinesia.
A recent study demonstrated the activity of the feline sphincter of Oddi to be regulated by the distending pressure in the biliary tract via inhibitory nerves running along the common bile duct. In the present study this mechanism was investigated in cats previously subjected to cholecystectomy. An increment in the hydrostatic pressure in the biliary tree from 0 to 20 cmH2O did not affect the function of the sphincter of Oddi in cholecystectomized cats, but relaxed the sphincter in controls and in cats with sham operation. Morphologic study of the nerve arrangement in the feline extrahepatic biliary tract revealed that cholecystectomy is likely to damage pericholedochal nerves. These experimental observations may have relevance for the development of biliary dyskinesia following cholecystectomy in some patients, and suggest that when performing biliary-tract surgery it is important to preserve nerve fibers running along the common bile duct.
Ampulla of Vater↗
[Port-A-Cath in prolonged biliary drainage as a practical alternative to a transcutaneous tube].
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Aged↗
Pathophysiology of acute obstructive cholecystitis: implications for non-operative management.
Recent research suggests that disturbances in gallbladder mucosal functions are important in the initiation of acute cholecystitis and its progression. Prostaglandins have pathophysiological significance and prostaglandin synthesis inhibitors such as indomethacin inhibit fluid secretion by gallbladder mucosa, reduce distension and relieve pain. Nerves in the gallbladder wall are involved in disturbed mucosal function, and the benefits of opiates may derive from reduction of active fluid secretion in the inflamed and obstructed gallbladder as well as from central analgesic effects.
Acute Disease↗
Fluid secretion by gallbladder mucosa in experimental cholecystitis is influenced by intramural nerves.
The normal fluid absorption across the gallbladder mucosa is, in experimental cholecystitis, changed to an active net fluid secretion. This fluid secretion, studied in anesthetized cats, is not abolished by extrinsic gallbladder denervation and is unaffected by atropine but is strongly reduced by intraarterial tetrodotoxin or intraluminal administration of lidocaine hydrochloride. Intravenous somatostatin or hexamethonium administration also reduce this secretion. Indomethacin, known to abolish this fluid secretion, did not further reduce it when administered after nerve blocking agents in the present study. These data demonstrate that the prostaglandin-induced gallbladder fluid secretion in experimental cholecystitis is influenced by intramural nerves. It is suggested that gallbladder inflammation is associated with prostaglandin-induced activation of intrinsic nerves which may stimulate the epithelial cells to fluid secretion. In the obstructed gallbladder, this secretion causes gallbladder distension by increasing the intraluminal pressure. This mechanism may have a key role in the pathophysiology of acute cholecystitis.
Animals↗