The flow of bile in the human cystic duct

Clinical studies suggest that the flow of bile in the biliary system may be a contributing factor in the pathogenesis of cholelithiasis, but little is known about its transport mechanism. This paper reports a numerical study of steady flow in human cystic duct models. In order to obtain parametric data on the effects of various anatomical features in the cystic duct, idealised models were constructed, first with staggered baffles in a channel to represent the valves of Heister and lumen. The qualitative consistency of these findings are validated by modelling two of the real cystic ducts obtained from operative cholangiograms. Three-dimensional (3D) models were also constructed to further verify the two-dimensional (2D) results. It was found that the most significant geometric parameter affecting resistance is the baffle clearance (lumen size), followed by the number of baffles (number of folds in the valves of Heister), whilst the least significant ones are the curvature of the cystic duct and the angle between the neck and the gallbladder. The study presented here forms part of a larger project to understand the functions of the human cystic duct, especially the influence of its various anatomical structures on the resistance to bile flow, so that it may aid the assessment of the risk of stone formation in the gallbladder.     

Migration of gall stones.

The factors influencing the migration of gall stones are ill understood. Altogether 331 patients undergoing cholecystectomy were studied prospectively. The diameters of the cystic and common bile ducts and of stones in the gall bladder and bile ducts were measured. Increasing pressure was applied to the freshly excised gall bladder in an attempt to evacuate stones through the cystic duct. Stones passed in 33 (60.0%) of patients with choledocholithiasis, 45 (67.2%) of patients with pancreatitis, and 7 (3.2%) of patients without either pancreatitis or choledocholithiasis. Stones migrated in 6 (3.0%) who had a normal cystic duct diameter (less than or equal to 4 mm) and in 46 (32.5%) with a duct over 4 mm diameter. Common bile duct stones were often larger than the diameter of the cystic duct and when reintroduced into the gall bladder would not migrate. The passage of debris (less than or equal to 1 mm) through the cystic duct bore no relation to the presence or absence of choledocholithiasis or a dilated cystic duct. Small stones (1-4 mm diameter) must migrate to initiate and facilitate further migration; some must increase in size in the common bile duct. Increased biliary pressure consequently dilates the duct system retrogradely, allowing larger stones to follow. Patients at risk of stone migration and thereby pancreatitis and jaundice have large ducts that can be detected by ultrasound assessment.     

A new method for cannulation of the common bile duct in an experiment]

The proposed method of common biliary duct cannulation is simple, easily performed and permits studying bile hydrodynamics biligenesis for a necessary time. Tightness of the system is completely preserved after removal a choledochostomical tube. Walls of the invaginated stump of the cystic duct are swiftly abated as a result of hydrostatic pressure and cover its gap. The presence of purse string kapron suture in a stump orifice creates an obstacle to deinvagination. Good reparation properties of serous and subserous membranes, covering the biliary duct, promote rapid closing of stoma. Effectiveness of the proposed method of common biliary duct cannulation by means of the invaginated stump of the cystic duct is confirmed by the smooth postoperative course and absence of a biliary fistula after the tube removal.     

Telocytes and interstitial cells of Cajal in the biliary system

A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal‐like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles in physiological and pathophysiological processes.     

Manometric changes during retrograde biliary infusion in mice

The manometric, ultrastructural, radiographic, and physiological consequences of retrograde biliary infusion were determined in normostatic and cholestatic mice. Intraluminal biliary pressure changed as a function of infusion volume, rate, and viscosity. Higher rates of constant infusion resulted in higher peak intraluminal biliary pressures. The pattern of pressure changes observed was consistent with biliary ductular and/or canalicular filling followed by leakage at a threshold pressure. Retrograde infusion with significant elevations in pressure led to paracellular leakage of lanthanum chloride, radiopaque dye, and [(14)C]sucrose with rapid systemic redistribution via sinusoidal and subsequent hepatic venous drainage. Chronic extrahepatic bile duct obstruction resulted in significantly smaller peak intrabiliary pressures and lower levels of paracellular leakage. These findings indicate that under both normostatic and cholestatic conditions elevated intrabiliary volumes/pressures result in an acute pressure-dependent physical opening of tight junctions, permitting the movement of infusate from the intrabiliary space into the subepithelial tissue compartment. Control of intraluminal pressure may potentially permit the selective delivery of macromolecules >18-20 A in diameter to specific histological compartments.     

The Prevention of Residual Biliary Calculi

Residual calculi following cholecystectomy may be expected in approximately seven percent of cases. The vast majority of these are overlooked during operation; truly re-formed stones are rare.Calculi are missed during cholecystectomy because of failure to explore the common bile duct. This is due to (1) the presence of silent choledochal stones, and (2) reliance on negative cystic duct cholangiograms in the presence of indications for common duct exploration.Overlooking of silent stones during cholecystectomy may be prevented by routine operative cholangiography. Ideally, false-negative cystic duct cholangiograms should be eliminated by the use of fluoroscopic cholangiography.Retained calculi following duct exploration may be prevented by (a) routine biliary endoscopy and (b) completion fluoroscopic cholangiography.Re-formation of ductal calculi can probably be prevented by appropriate biliary drainage procedures performed during the initial choledochotomy. Selection of patients for primary biliary decompression remains an experimental problem.     

The effect of secretin and cholecystokinin-pancreozymin on the secretion of bile in the anaesthetized rabbit.

Effects of secretin and Cholecystokinin-Pancreozymin (CCK-PZ) on the secretion of bile in anaesthetized rabbits have been studied. Single injections of secretin (5.0 u.kg(-1) significantly increased the flow of bile irrespectively of whether the cystic duct was free or had been tied. A sustained increase in bile flow could be obtained by the continuous infusion of secretin. Cholecystokinin-Pancreozymin was effective in increasing the bile flow in doses of 1.0 u.kg(-1). Much of the effect could be attributed to contraction of the gallbladder but a significant increase in flow could still be elicited after ligation of the cystic duct. Our findings strongly suggest that the biliary secretion in rabbits is not as different from the general pattern as has previously been suggested.     

By-passing the sphincter of Oddi does not affect gallbladder emptying in the pig

A study of the relationship between bile secretion and nutrition in the pig requires a complete and continuous collection of the bile and its reinfusion to the animal. In most of the studies performed in different species, bile has been directly reinfused into the duodenum, leading to the exclusion of the sphincter of Oddi from the biliary pathway. It has been postulated that such an exclusion could inhibit gallbladder emptying. The aim of the present work was to study postprandial gallbladder emptying in the pig, depending on the site of bile reinfusion, i.e. the duodenum or the lower bile duct. The gallbladder bile was coloured with indocyanine green (ICG) and marker secretion was recorded after a test-meal. The results showed that after meal intake, the gallbladder emptied over a similar period of time and according to similar kinetics, whatever the site of bile reinfusion.     

Determinants of biliary secretory pressure: the effects of two different bile acids

Biliary secretory pressure represents the force generated to deliver bile through the biliary system. Bile acid-induced toxicity may decrease canalicular bile formation and (or) induce back diffusion causing cholestasis. To determine if biliary secretory pressure is a sensitive indicator of bile toxicity, taurocholate was compared with a less cytotoxic bile acid, tauroursodeoxycholate. In fasted male Sprague-Dawley rats, the common bile duct was cannulated and the endogenous bile salt pool was removed by enteroclysis. Taurocholate (n = 35) or tauroursodeoxycholate (n = 35) in saline was infused for 1 h. Maximal biliary secretory pressure was then measured by attaching the biliary cannula to a column monometer and recording the maximum height to which bile rose. With taurocholate administration, bile flow and bile salt secretion linearly rose to a maximum infusion of 0.5 mumol/(min.g liver), above which hemolysis and death occurred. In contrast, tauroursodeoxycholate could be infused at higher rates with bile salt secretion plateauing at 1.25 mumol/(min.g liver] Both had similar choleretic potencies. Mean biliary secretory pressure at low (less than 0.15 mumol/(min.g liver] infusions was lower with taurocholate (22.5 cm bile) than tauroursodeoxycholate (25.2 cm). Further, increasing the taurocholate infusion decreased the biliary secretory pressure; yet for taurousodeoxycholate, pressure remained unchanged even at higher infusions. Thus, taurocholate but not tauroursodeoxycholate decreases biliary secretory pressure at high infusion rates, likely a reflection of its toxicity to the hepatobiliary epithelium.     

Studies on the microvascularization of the digestive tract by scanning electron microscopy of vascular corrosion casts. 2. Bile duct in guinea pigs.

The microvascularization of the bile duct was studied in 20 adult guinea pigs (Cavia porcellus) using microvascular corrosion casts in the scanning electron microscope. The main supplying and draining vessels are located in the adventitial layer; from there they form the subepithelial capillary network. The microangioarchitecture of the common bile duct is reminiscent of that of the cystic and hepatic ducts. The diameter of these ducts is 1,000 microns on average. The microvascular arrangement in the bile duct suggests a probable involvement of the capillaries in the absorption of bile hormones.     

Effects of growth and maturation on biliary structures of guinea pigs

The biliary system and major duodenal papilla of male guinea pigs were examined in vivo using intravital microscopy. Study of the photomicrographs and videotape recordings indicated that biliary organs changed with age and growth of the guinea pigs. Physiological data including the frequency of sphincteric contractions were recorded and efforts were made to correlate these data with changes in structure thought to be due to maturation. The volume of smooth muscle in the bile duct sphincter (measured using histological sections) increased with age as did surface area of the mucosa. The bile duct was separate from the pancreatic duct in each of 28 guinea pigs. Study of the guinea pig extrahepatic biliary system (EBS) allowed the isolated examination of effects of maturation on bile duct capacity. The anatomical reason for this is that the ampulla of the bile duct emptied into the duodenum (independently of the pancreatic duct) at the major duodenal papilla. The duct of the pancreas entered the duodenum distally (caudally) to the major duodenal papilla on the minor duodenal papilla. The separation of biliary and pancreatic ducts simplified the making of casts of the EBS. It is important to consider this feature in selection of a model for studies of bile duct function in living animals. Three anatomical techniques were selected to focus from differing perspectives on growth-related changes that occurred among the EBS of neonatal, juvenile and adult animals. These techniques were: The capacity (volume) of bile contained within the EBS was determined using plastic casts of the system.(ABSTRACT TRUNCATED AT 250 WORDS)     

胆道微生态的研究进展

人体微生态是微生物与宿主在长期相互作用过程中形成的特殊生态系统,在人体的健康与疾病中起着重要作用。目前对消化系统微生态的研究主要集中在肠道,而胆道系统可能存在独特的微生态体系,它们与胆道系统的健康和疾病之间的关系尚不明确,研究人员探讨了胆道的微生物群与胆囊结石、胆总管结石、Oddi括约肌受损、胆总管结石复发、原发性硬化性胆管炎和胆道肿瘤等肝胆疾病的发生发展、诊断和治疗的关系。本文从健康人群、肝移植供肝者的胆道及以上疾病着手,对胆道微生态的相关研究和进展作一综述。

     

多镜联合治疗胆总管结石合并胆囊结石的技术优势

目的探讨十二指肠镜、胆道镜、腹腔镜等多镜联合治疗胆总管结石合并胆囊结石的技术优势。方法采用腹腔镜胆总管探查术+腹腔镜胆囊切除术(LCBDE+LC)和内窥镜逆行胰胆管造影术+内窥镜下括约肌切开取石术+腹腔镜胆囊切除术(ERCP+EST+LC)两种术式治疗胆总管结石合并胆囊结石患者。结果有两组病例,其中LCBDE+LC组36例,本组术后胆道残余结石2例,后经T管窦道行胆道镜取石治愈。ERCP+EST+LC组54例,本组术后并发一过性高淀粉酶血症3例,发生急性轻型胰腺炎2例。结论多镜联合治疗胆总管结石合并胆囊结石具有创伤小、效果好、并发症少、恢复快的优点,多镜联合发挥出其独特技术优势,避免了因接受传统开腹手术而造成较大创伤的不合理治疗模式。     

Oblique Bile Duct Predisposes to the Recurrence of Bile Duct Stones

Background and Study Aims

Bile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation.

Patients and Methods

1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD) and the horizontal plane was measured (angle α). Oblique common bile duct (OCBD) was defined as a CBD with angle α<45°.

Results

103 patients (7.9%) were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i) significantly older (72±13 vs. 67±13, p<0.00001); (ii) more frequently underwent a cholecystectomy (p = 0.02) and biliary surgery (p = 0.003) prior to the diagnosis and (iii) more often developed chronic pancreatitis (p = 0.04) as well as biliary fistulae (p = 0.03). Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003). OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005) as well as more ERCPs later on due to recurrent stone formation (p<0.05).

Conclusion

OCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones.     

Drug-induced bile duct injury

Drug-induced liver injury includes a spectrum of pathologies, some related to the mode of injury, some to the cell type primarily damaged. Among these, drug-induced bile duct injury is characterized by the destruction of the biliary epithelium following exposure to a drug. Most of the drugs associated with bile duct injury cause immune-mediated lesions to the epithelium of interlobular ducts. These share common histopathological features with primary biliary cholangitis, such as inflammation and necrosis at the expense of cholangiocytes and, if the insult persists, bile duct loss and biliary cirrhosis. Some drugs selectively target larger ducts. Such injury is often dose-dependent and thought to be the result of intrinsic drug toxicity. The histological changes resemble those seen in primary sclerosing cholangitis. This overview focuses on the clinical and pathological features of bile duct injury associated with drug treatment and on the immunological and biochemical effects that drugs exert on the biliary epithelium. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

The homeobox gene Hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis

Hhex is required for early development of the liver. A null mutation of Hhex results in a failure to form the liver bud and embryonic lethality. Therefore, Hhex null mice are not informative as to whether this gene is required during later stages of hepatobiliary morphogenesis. To address this question, we derived Hhex conditional null mice using the Cre-loxP system and two different Cre transgenics (Foxa3-Cre and Alfp-Cre). Deletion of Hhex in the hepatic diverticulum (Foxa3-Cre;Hhex(d2,3/-)) led to embryonic lethality and resulted in a small and cystic liver with loss of Hnf4alpha and Hnf6 expression in early hepatoblasts. In addition, the gall bladder was absent and the extrahepatic bile duct could not be identified. Loss of Hhex in the embryonic liver (Alfp-Cre;Hhex(d2,3/-)) caused irregular development of intrahepatic bile ducts and an absence of Hnf1beta in many (cystic) biliary epithelial cells, which resulted in a slow, progressive form of polycystic liver disease in adult mice. Thus, we have shown that Hhex is required during multiple stages of hepatobiliary development. The altered expression of Hnf4alpha, Hnf6 and Hnf1beta in Hhex conditional null mice suggests that Hhex is an essential component of the genetic networks regulating hepatoblast differentiation and intrahepatic bile duct morphogenesis.     

Cell-mediated Immune Response in Primary Biliary Cirrhosis to a Protein Fraction from Human Bile

Cell-mediated immune responses to a protein fraction of human bile have been demonstrated, using the leucocyte migration test, in eight out of 10 patients with primary biliary cirrhosis but in only three out of nine with active chronic hepatitis. In the latter condition sensitization to a liver-specific hepatocellular antigen was found more frequently (five out of nine patients) than in primary biliary cirrhosis (two out of 10). These results, as well as the granuloma formation observed histologically, suggest that the initial bile duct lesion in primary biliary cirrhosis may be associated with a cell-mediated response to antigens—perhaps derived from bile duct epithelial cells—which may be normal constituents of hepatic bile.     

Gross anatomy of the liver, biliary tree, and pancreas in the black-tailed prairie dog (Cynomys ludovicianus)

The gross anatomy of the liver, extrapetatic biliary tree, sphincter of Oddi, and pancreas in the black-tailed prairie dog (Cynomys ludovicianus), a widely used animal model for investigations into biliary physiology, pathophysiology, and pathology, was studied in 10 animals. The liver consists of 4 lobes, the left lateral, median, right lateral, and caudate. The gallbladder lies on the ventral surface of the right lobule of the median lobe. The cystic and hepatic ducts unite to form the common bile duct which enters the duodenum approximately 5 mm distal to the pylorus. The lower end of the common duct dilates forming an ampulla which is surrounded proximally by a band of circular muscle fibres which constitute the choledochal sphincter. The pancreatic duct opens separately into the duodenum approximately 80 mm from the pylorus. Earlier physiologic studies have demonstrated that the choledochal sphincter has intrinsic motility distinct from the duodenum.     

胆道系统探查中术中超声的应用及临床价值

目的:探讨胆管系统探查中术中超声(intraoperative ultrasound,IOUS)的应用及临床价值。方法:2007年3月至2014年8月应用术中超声对胆道系统进行探查的病例资料58例,对其术前影像学表现、手术过程、术中超声所见以及术中和术后诊断进行分析,研究术中超声对胆道探查的应用价值。结果:(1)58例应用术中超声病人中,肝内外胆管结石35例、肝门部胆管癌及胆总管癌11例,急性胆囊炎8例,胃癌1例,先天性胆总管囊肿1例,胆总管炎性狭窄1例,胰腺癌1例。术中超声确认取净结石或胆总管未见明显异常34例,定位肝内胆管残余结石6例,发现胆总管内尚有结石2例,术中超声确诊胆管癌2例;另发现胆总管先天性解剖异常2例;(2)在发现胆管结石方面,与术前MRCP无显著性差异(P=0.643);与术前CT、B超比较有显著差异(P0.05),诊断率分别为B超74.3%,MRCP 91.4%,CT 77.1%,IOUS 94.3%。结论:术中超声胆道系统的探查可以在广泛的疾病中得到应用,可以对术前影像学检查起到验证和补充的作用,且在术中引导各种介入操作中起到独特作用。