Structural relationship between liver and gallbladder

Gallbladder | anatomy |

structural relationship between liver and gallbladder

Liver, Gallbladder, Pancreas, and Related Organs position; duct system; exocrine secretions; endocrine secretions; "diabetes mellitus" relationships Each cellular plate is two cells thick and between the two cells are small bile. The human biliary system consists of the gallbladder, the cystic duct, dynamic viscosity of gallbladder bile is higher than that of hepatic bile and The relation between the cystic duct geometry and cholelithiasis has been investigated in vivo . . In a second study, the structural and mechanical changes were quantified in . The digestive function of the liver is to produce bile, which is then delivered to the Hepatic sinusoids are spaces that lie between groups of layers, while.

This article has been cited by other articles in PMC. Abstract This review discusses anatomical facts that are of relevance to the performance of a safe cholecystectomy. Misinterpretation of normal anatomy and anatomical variations contribute to the occurrence of major postoperative complications like biliary injuries following a cholecystectomy, the incidence being higher with laparoscopic cholecystectomy. A look at the basic anatomy is therefore important for biliary and minimally invasive surgeons.

This includes normal anatomy and variations of the biliary apparatus as well as the arterial supply to the gallbladder. Specific anatomical distortions due to the laparoscopic technique, their contribution in producing injury and a preventive strategy based on this understanding are discussed. Investigative modalities that may help in assessing anatomy are considered.

Newer insights into the role of anatomic illusions as well as the role of a system-based approach to preventing injuries is also discussed. Specifically, in the context of a cholecystectomy, it has been recognized since long that misinterpretation of normal anatomy as well as the presence of anatomical variations contribute to the occurrence of major postoperative complications especially biliary injuries.

They are also one of the commonest causes of litigation against abdominal surgeons in the developed world. There is now a fair amount of data to suggest that the acceptance of laparoscopic cholecystectomy LC as the standard procedure, has led to an increase in bile duct injuries.

Hence, it is important for biliary and minimally invasive surgeons to appreciate basic anatomical facts as they apply to the performance of cholecystectomy as well as understand from literature how anatomical distortions or variations can contribute to complications. This review attempts to address these issues. It is not an exhaustive description of biliary anatomy but discusses anatomical facts that are of relevance to the performance of a safe cholecystectomy.

It is variable in shape and volume. Normally present at the junction of segments 4 and 5 and at the lower limit of the principal plane or Cantlie's line its position in relation to the liver may vary.

This may create difficulties in dissection and may increase the chance of intraoperative injury to the liver. Although the main right pedicle is fairly deep in the liver parenchyma, large portal, and hepatic venous branches traverse the liver at a depth of around one cm from the gallbladder. Thus, a deep liver tear during the dissection of the gallbladder off its fossa can occasionally bleed profusely. Also, during the dissection it may be important to err on the side of the gallbladder rather than the liver parenchyma.

The gallbladder is divided into a fundus, a body and a neck or infundibulum. The motility of the sphincter of Oddi, like the rest of the gastrointestinal tract, is influenced by fasting and digestive periods.

The Liver and Gallbladder

During the fasting period the sphincter pressures are influenced by all four phases of the migrating motor complex [ 38 ]. The phase 3 of the migrating motor complex generates high amplitude and more frequent contractions that occur simultaneously with the duodenal component.

The simultaneous occurrence of the phase 3 in both structures prevents reflux of duodenal contents enzymes and bacteria into the common bile duct. During the intestinal phase of the digestive period fats and proteins release CCK from the duodenal mucosa inducing simultaneous contraction of the gallbladder and relaxation of the sphincter of Oddi and duodenum [ 26 ].

The coordinated gallbladder contraction and sphincter of Oddi and duodenal relaxation allow bile stored in the gallbladder to flow through the common bile duct and to the duodenum with minimal sphincter of Oddi and duodenal resistance.

These effects of CCK are enhanced by the simultaneous actions of the vagus nerve that contracts the gallbladder and relaxes the sphincter of Oddi. They both relax the sphincter of Oddi by stimulating postganglionic nonadrenergic noncholinergic inhibitory neurons that release VIP and nitric oxide as their main neurotransmitters [ 1239 ]. CCK stimulates CCK-1 receptors present in nonadrenergic noncholinergic neurons, since its inhibitory effect is blocked only by tetrodotoxin and by CCK-1 receptor antagonists [ 28 ].

However, in the absence of these neurons or after treatment with tetrodotoxin CCK contracts the sphincter of Oddi by stimulating CCK-1 excitatory receptors present in its smooth muscle. In summary, the motor functions of the biliary tract are integrated with the rest of the gastrointestinal tract in the fasting and digestive periods through complex neurohormonal mechanisms that include the vagus and splanchnic nerves and the hormone CCK as the major actors.

During the fasting state the steady hepatic secretion of bile is mostly diverted toward the cystic duct and gallbladder where is stored and concentrated because of the sphincter of Oddi resistance. In this period a small fraction of bile leaks into the duodenum during the diastolic phase of the sphincter of Oddi phasic contractions and during the phase II of the migrating motor complex when there is slight gallbladder contraction.

During the digestive period the gallbladder contracts emptying most of its contents, and bile is transported to the duodenum through the cystic and common bile ducts flowing through a relaxed sphincter of Oddi and duodenum. In the duodenum and jejunum bile salts participate in the digestion and absorption of fats triglycerides, Ch and phospholipids, and liposolubles vitamins. Then bile salts are transported to the terminal ileum where are mostly recycled as part of the enterohepatic circulation by an active transport mechanism present in the epithelial cells of the terminal ileum.

Chronic and Acute Cholecystitis 3. Pathogenesis The most common cited hypothesis in the pathogenesis of chronic and acute cholecystitis is that caused by obstruction of the cystic duct from small and medium sized gallstones that migrate from the gallbladder or in the case of large gallstones that they intermittently obstruct the neck of the gallbladder.

However, this hypothesis is not supported by clinical and histological human studies or by experimental obstruction of the cystic duct in normal animals. Although occasionally gallstones are found in the cystic duct it is unclear whether these stones are actually obstructing the bile flow.

A carefully conducted study in patients with acute cholecystitis in which the gallbladder was subjected to minimal manipulation, gallstones were found in the cystic duct in only The failure to visualize the gallbladder in patients with acute cholecystitis has been interpreted as due to obstruction cystic duct.

However, other explanations for this failure are more likely that a obstruction of the cystic duct could be due to the extension of the acute inflammation and edema from the gallbladder, or b an atonic gallbladder impedes the entry of the bulk of the isotope-labeled agent because it is filled with inflammatory secretions. Moreover, the acutely inflamed gallbladder may not be able to distend passively because of edema or actively because of a defective relaxation that have been shown to be present in gallbladders with lithogenic bile with high Ch concentrations [ 42 ].

The hypothesis of cystic duct obstruction is further challenged by the presence of cholecystitis associated only with lithogenic bile acalculous gallbladder or with a single large stone several times bigger than the typical diameter of the lumen of the cystic duct. It is unlikely that such large stones would cause recurrent episodes of obstruction by blocking the gallbladder neck.

Moreover the occurrence of acute inflammation superimposed on a chronically inflamed or atrophic fibrotic gallbladder has been difficult to explain because it would imply recurrent episodes of cystic duct obstruction.

It is more likely that the development of acute inflammation that is due to the progression from a chronic process had been in place long before. Such gallbladders frequently show mucosal thickening, hypertrophic muscle layers, and macrophage infiltration of the lamina propria. Chronic cholecystitis also is frequently seen histopathologically in the absence of gallstones. They occur in morbidly obese patients who have lithogenic bile without gallstones.

These gallbladders have mucosal abnormalities consistent with chronic cholecystitis compared to the normal mucosa in nonobese subjects [ 4344 ]. Moreover the hypothesis of cystic duct obstruction has not been able to propose potential factors that could induce the inflammatory process. It has been suggested that gallbladder distension due to increasing amount of fluid in the lumen could lead to ischemia.

However, these fluids are due to secretions from an already inflamed gallbladder. Some of the proposed proinflammatory agents that have been suggested are cellular mediators of inflammation such as lysolecythin and platelet activating factors secreted by epithelial cells already subjected to oxidative stress [ 45 ]. There is absence of histological and functional abnormalities in gallbladders with black pigment stones [ 46 ]. The mucosa of gallbladders containing pigment stones shows no evidence of chronic cholecystitis and no adenomatous hyperplasia or Rokitansky-Aschoff sinuses.

These histological features are commonly found in gallbladders containing Ch stones. In contrast to the impaired contraction of gallbladders with Ch stones the contraction of muscle cells from gallbladders with pigment stones is not different from that observed in muscle preparations from normal gallbladders [ 47 ]. Although it has been reported a slight reduction of postprandial emptying in some patients with gallbladders with black pigment stones this functional impairment was likely due to a concurrent delayed gastric emptying that occurs in patients with thalassemia.

Most of the patients included in this study suffered with this hematological disease [ 48 ]. Animal experiments do not support cystic duct obstruction as the initial event in the development of acute cholecystitis. Cystic duct ligation in prairie dogs does not cause cholecystitis unless concentrated bile is injected in the obstructed gallbladders [ 49 ]. Daily infusions of sterile fresh bile have to be introduced into ligated gallbladders of dogs for these animals to develop acute cholecystitis [ 3 ].

In contrast, animals fed lithogenic bile reproduce the epithelial and muscle abnormalities that are present in patients with chronic cholecystitis Figure 1. These high concentrations of bile Ch inflict damage to gallbladder epithelial and muscle cells [ 50 ].

The increase in proliferative activity preceding the formation of gallstones is another indication that these abnormalities are unrelated. Figure 1 These data, therefore, suggest that both gallstones and abnormalities of the gallbladder mucosa and muscle are caused by lithogenic bile with excessive Ch concentrations.

They develop independently of each other, even though they may be detected simultaneously in symptomatic patients.

Ch diffuses through the gallbladder wall and is taken up by epithelial cells, macrophages in the lamina propria cholesterolosis and incorporated in the plasma membrane of muscle cells [ 53 ]. The rates of Ch diffusion through the mucosa appear to depend on its gallbladder bile concentrations [ 50 ]. Epithelial cells exposed to lithogenic bile with excess Ch increase PGE2 levels that stimulate water and mucus secretion before gallstones are formed [ 5455 ].

PGE2 stimulates mucin secretion by activating camp creating a thick mucus layer that frequently covers the mucosa of gallbladders with chronic cholecystitis [ 56 ]. The increased levels of this prostaglandin also are likely to be responsible for the mucosal hyperplasia, Rokitansky-Ashoff sinuses, and gastric and intestinal metaplasia [ 5257 ].

These abnormalities are frequently present in gallbladders with chronic inflammation [ 50 ]. Moreover these gallbladders also show macrophages in the lamina propia even in the absence of gallstones. Animal experiments show the effects of feeding lithogenic bile with excess Ch on gallbladder muscle cells.

The muscle contraction induced by CCK-8 is impaired in prairie dogs fed a lithogenic diet compared to muscle cells from animals fed a regular chow [ 5859 ]. This impaired contraction is due to higher uptake of Ch by muscle cells. Similar abnormalities are present in the plasma membranes of muscle cells of human gallbladders with Ch stones.

They also have higher levels of Ch than muscle cells from gallbladders with pigment stones.

structural relationship between liver and gallbladder

Most of the Ch in the plasma membrane is found in caveolae [ 60 ]. Under normal and pathological conditions cellular influx and efflux of Ch take place through these caveolae [ 61 ]. These domains are rich in Ch bound to caveolin proteins. In addition to transporting Ch across membranes, caveolin proteins bind and help to internalize receptor-G protein complexes into the cytosol.

Agonist activation of receptors leads to their coupling to specific G proteins and then transferred to caveolae domains where they bind to caveolin proteins. These receptor-G protein complexes then phosphorylate caveolin proteins utilizing specific tyrosine kinases [ 62 ].

The phosphorylation of caveolin proteins makes possible the transfer of caveolin protein-receptor-G protein complexes to endosomes, organelles designed to recycle receptors back to the plasma membrane, so they can become available for further agonist activation. However, high Ch levels in the caveolae inhibit tyrosine kinases phosphorylation of caveolin proteins thereby blocking the internalization of these receptors and their recycling to the plasma membrane [ 62 ].

This inhibition leads to sequestration of receptors and caveolin proteins in the caveolae resulting in fewer receptors returning to the plasma membrane. The lower receptor binding and weaker muscle response are not unique to CCK-1 receptors, since others are equally affected including cholinergic receptors that are internalized through these domains.

Anatomy relevant to cholecystectomy

In contrast, receptors internalized through clathrin-coated pit pathways like delta-opiate and erythromycin receptors express normal muscle responses. The finding that the clathrin pathway has low levels of Ch explains why erythromycin causes a normal contraction and emptying in gallbladders with Ch stones [ 62 ].

These pathological effects of high levels of Ch in the plasma membrane were experimentally demonstrated in isolated gallbladder muscle cells from humans and guinea pigs treated with Ch rich or Ch free liposomes. Liposomes are phospholipids aggregates that can carry Ch that is easily exchanged with cellular phospholipid membranes.

The exchange is passive, and its direction is dependent on the Ch gradient between liposomes and plasma membranes. Ch free liposomes remove Ch from membranes of muscle cells from gallbladders with Ch stones that have high Ch levels [ 42 ]. In contrast, Ch diffuses from Ch rich liposomes to muscle cells from gallbladders with pigment stones that have normal levels of Ch. This Ch exchange correlates with the magnitude of muscle contraction induced by CCK There is a significant increase in the magnitude of contraction of muscle cells from gallbladders with Ch stones after incubation with Ch free liposomes, which removed the excess Ch from the plasma membranes.

The opposite occurs when normally contracting gallbladder muscle cells from human or guinea pigs are incubated with Ch rich liposomes. These cells acquire abnormal concentrations of Ch and develop a weaker contraction in response to CCK High Ch levels only affect membrane receptors since the pathways that mediate the contraction of gallbladder muscle cells distal to them are normal. Moreover, high levels of membrane Ch equally affect the muscle relaxation. The relaxation of muscle strips from gallbladders with Ch stones induced by receptor dependent agonists such as isoproterenol or VIP was lower than that induced in muscle strips from gallbladders with black pigment stones.

However, there was no difference in the magnitude of relaxation between these two types of muscle strips induced by nitric oxide or 8-bromo-cAMP that bypasses membrane receptors [ 65 ]. Thus the effects of high levels of membrane Ch that impair muscle contraction and relaxation are confined to the plasma membrane receptors. The effects of high concentrations of Ch in the plasma membrane of gallbladder muscle cells also affect calcium without involving potassium channels.

High levels of Ch also affect small intestinal muscle cells that in turn contribute to the development of cholecystitis.

Structure and Function of the liver, gallbladder, pancreas, and related organs

Lithogenic diets fed to C57L mice impair the contractility of muscle cells of the small bowel resulting in slower intestinal transit.

The slow transit generates in the distal small intestine the secondary bile acid deoxycholic acid [ 69 ] and greater Ch absorption. They both increase the number of inflammatory cells in the lamina propria and muscle hypertrophy of the gallbladder. These abnormalities take place four weeks after they are fed a lithogenic diet and before gallstones are formed [ 70 ]. These abnormalities do not occur when these mice are pretreated with maximal doses of ezetimibe that blocks the intestinal absorption of Ch.

Normal gallbladders tolerate physiological concentrations of hydrophobic bile salts. However, in the presence of lithogenic bile with high concentrations of Ch or after obstruction of the common bile duct these bile salts can damage the epithelial and muscle cells by increasing the levels of oxidative stress H2O2 and lipid peroxidation [ 5171 ] Figure 2.

Guinea pigs develop an acute inflammatory reaction following ligation of the common bile duct within 3 days [ 72 ].

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Pretreatment of these animals for 2 weeks with the hydrophilic bile acid URSO prior to the ligation of the common bile duct prevents the development of acute cholecystitis. In contrast, acute cholecystitis was far more severe when they were pretreated with a hydrophobic bile acid chenodeoxycholic acid for two weeks prior to the common bile ligation compared to guinea pigs that received no treatment during this period of time.

Figure 2 The mechanism whereby URSO exerts this therapeutic effect was examined in epithelial and muscle cells. The lipid peroxidation in the epithelial cells and mucosal secretion of mucin and water secretion induced by treatment with hydrophobic bile salts alone were prevented by pretreatment with URSO [ 73 ].

Pretreatment with URSO also prevented the impaired muscle contraction induced in isolated muscle cells treated with hydrophobic bile salts [ 74 ].

Hydrophobic bile salts inhibit smooth muscle contraction by acting on G-protein coupled BAR1 receptors, activating KATP channels [ 74 ] and high detergency properties. They increase oxidative stress in muscle cells in vitro and in vivo.

URSO reduced the levels of free radicals and cytoprotection response in gallbladder muscle cells compared to muscle cells incubated with chenodeoxycholate alone [ 75 ]. Other mucosal tissues can be similarly affected by prolonged exposure to hydrophobic bile salts leading to esophagitis and gastritis.

The therapeutic effect of URSO treatment was demonstrated in patients with symptomatic gallbladders with Ch gallstones. URSO treatment for one month prior to surgery increased gallbladder muscle contractility and reduced the levels of membrane Ch and indices of oxidative stress [ 76 ].

This short-term study is supported by a larger study performed in patients with symptomatic gallbladder stones. An year-old study demonstrated that URSO treatment reduced the incidence of biliary pain and rates of cholecystectomy compared to untreated patients [ 77 ].

The positive effect of URSO occurred despite the persistence of gallbladder stones. The mechanism of URSO protection from the effects of hydrophobic salts in vivo is not completely known.

Hydrophobic bile salts increase oxidative stress levels in gallbladder muscle cells in vitro causing impaired contraction. URSO prevents these deleterious effects on gallbladder epithelial and muscle cells by blocking the actions of hydrophobic bile salts at the cellular level [ 75 ] and by inhibiting the intestinal absorption of Ch [ 78 ]. The high levels of plasma membrane Ch also affect PGE2 receptors involved in cytoprotective functions. PGE2 is an autacoid released by cells but acting on their plasma membrane receptors that stimulate the activation of catalase.

This enzyme inactivates free radicals e. However, the effects of exogenous PGE2 or of oxidative stress H2O2 on catalase activity and degree of free radical inactivation are reduced in muscle cells from gallbladders with Ch gallstones compared to muscle cells from gallbladder with pigment stones [ 80 ].

These findings suggest that high levels of plasma membrane Ch impair cytoprotective responses to exogenous and endogenous PGE2 because, as with CCK receptors, fewer PGE2 receptors are available for stimulation.

Healthy gallbladder cells, therefore, protect themselves from aggressive actions of hydrophobic bile salts by utilizing cytoprotective mechanisms that include the actions of PGE2 and motility mechanisms that empty the gallbladder bile regularly [ 79 ]. Both protective mechanisms are affected by supersaturated levels of Ch rendering the mucosa and muscle layers vulnerable to hydrophobic bile salts. In the initial stages of the inflammatory process these bile salts damage unprotected receptors, such that they are stimulated by exogenous agonists.

CCK-1 receptors of the smooth muscle are initially damaged impairing muscle contraction. Some receptors remain unaffected because they are protected by the release of autacoids such as the case of PGE2 receptors protected by the cellular release of PGE2. However, high levels of membrane Ch affect even these receptors. These effects were clearly demonstrated in isolated gallbladder muscle cells treated with Ch rich or Ch free liposomes [ 80 ].

There is a normal response to the actions of PGE2 on muscle cells from gallbladders with pigment stones or muscle cells from gallbladders with Ch stones treated with Ch free liposomes. In contrast, the effects of PGE2 are impaired in normal muscle cells incubated with Ch rich liposomes. The prevalence of lithogenic bile and gallbladder disease is higher in females than in males suggesting that sex hormones may be involved in the pathogenesis of cholecystitis.

Progesterone impairs the contraction induced by CCK-8 in normal gallbladder muscle cells, but it does not affect muscle cells from gallbladders that contain Ch stones or normal muscle cells treated with Ch rich liposomes. Like Ch progesterone is transported across the plasma membrane by caveolin proteins. Experimentally, treatment with Ch rich liposomes blocks the entry of 3H-progesterone into the plasma membrane of normal muscle cells compared to cells treated with Ch free liposomes [ 82 ].

Ch inhibits entry of this hormone into the plasma membrane possibly because of stronger hydrophobic interactions of Ch with the hydrophobic binding sites of caveolae proteins. Estrogens are likely to play a more important role in the pathogenesis of gallbladder disease because they increase biliary secretion of Ch.

Estrogen receptor alpha, but not beta, plays a major role in beta-estradiol-induced murine Ch gallstones [ 83 ]. Increases in estrogen and progesterone levels during pregnancy explain the gallbladder hypomotility, stasis, and Ch supersaturated bile. Other hormones may also increase the incidence of gallbladder disease. Octreotride is one hormone that causes gallbladder hypomotility. Patients treated with octreotride for long periods of time have an increased incidence of cholelithiasis.

It is likely that this hormone causes gallbladder disease by increasing bile saturation with Ch. It causes hyperabsorption of Ch from both dietary and biliary sources by inducing hypomotility of the small intestine [ 84 ]. This slow intestinal transit also leads to the formation of more secondary and therefore more hydrophobic bile salts such as deoxycholate conjugate.

Gallbladder hypomotility and bile stasis tend to promote the formation of macroscopic gallstones from Ch crystals in bile because bile is retained for longer periods of time in the interdigestive and postprandial states. However, unless the bile is supersaturated with Ch there is no evidence that impaired motility per se leads to gallbladder inflammation [ 85 ].

The factors that contribute to the progression from chronic to acute cholecystitis are not known. Most cases of acute cholecystitis develop in patients whose gallbladders already have evidence of chronic cholecystitis as determined by presence of Ch gallstones and histology consistent with chronic inflammation. These chronic changes are characterized by mucosal and muscle hypertrophy and thickened serosal layer. The widely accepted assumption that acute cholecystitis is triggered by gallstone obstruction of the cystic duct is not supported by human and animal studies see the section on the pathogenesis of chronic cholecystitis associated with lithogenic bile with excess Ch.

However, there are risk factors known to increase the incidence of this progression. Organ transplantation and chemotherapy are also known to increase this progression. There is a higher incidence of acute cholecystitis with or without gallstones in conditions that are known to affect the immune response such as leukemia, chemotherapy and following major surgery and other debilitating conditions.

Although research studies are needed in this area it is possible to speculate that reductions in local or systemic immunity may facilitate this progression. In conclusion, the data obtained from the above-mentioned human and animal studies strongly suggest that cholecystitis develops in the presence of lithogenic bile with high Ch concentrations that creates a permissive environment allowing hydrophobic bile salts to increase the levels of oxidative stress and initiate the inflammatory process.

This inflammatory process requires the continuous entry of hydrophobic bile salts into the diseased gallbladder. Clinical Symptoms Patients with chronic cholecystitis may be asymptomatic or complain of recurrent episodes of epigastric and right upper quadrant pain that frequently radiates around the waist and toward the scapula. The pain is of moderate-to-severe intensity and is not postprandial but frequently nocturnal. It does not occur daily and tends to occur every two to three weeks.

Usually the diagnosis is made by ultrasonography. This test can detect the presence of gallstones and thickening of the gallbladder wall. Laboratory studies are normal [ 88 ]. Although gallstones are frequently asymptomatic they are blamed for a variety of upper gastrointestinal symptoms because they are easily detected in gallbladders by imaging studies.

Gallstones are commonly believed to be responsible for nonspecific gastrointestinal symptoms due to chronic dyspepsia, gastroparesis, and even irritable bowel syndrome. Patients with these functional conditions usually complain of daily upper gastrointestinal symptoms that are frequently postprandial and brought about by fatty foods or large meals. These patients complain of epigastric distress, nausea, and bloating.

structural relationship between liver and gallbladder

Cholecystectomy does not improve these complaints even though pathological studies may reveal gallstones and histological evidence of chronic cholecystitis. Several studies, including autopsy studies, have shown that gallstones may remain asymptomatic for prolonged periods of time.

In a prospective Italian study most patients with asymptomatic gallstones remained symptom free for the entire 8-year followup period [ 89 ]. Risk Factors The incidence of gallstones and inflammatory gallbladder disease is high in the Western hemisphere particularly in the native Indian population of North and South America. The epidemiology and natural history of this disease in Pima Indians suggest that genetic factors play an important role.

In addition Ch lithogenic genes appear widely spread among Chilean Indians and Hispanics. These genes could determine the early formation of gallstones and explain the high prevalence of gallbladder diseases among some South American populations [ 92 ].

The incidence of gallbladder disease in females is particularly higher in obese and diabetic patients compared to controls.

In contrast there are no differences in the incidence of gallbladder disease in males between diabetics and nondiabetics. Diagnosis A right upper quadrant ultrasound is the diagnostic test of choice in patients with chronic cholecystitis.

This test is performed in patients with biliary pain usually described as epigastric and right upper quadrant pain. Ultrasonography detects gallstones or biliary sludge [ 93 ]. Gallstones are usually but not always the imaging sign of lithogenic bile with excess Ch in the gallbladder. Chronic cholecystitis can be present in the absence of gallstones. It is not unusual to find histological evidence of chronic cholecystitis in acalculous gallbladders from obese patients. Patients with chronic cholecystitis due to lithogenic bile with high Ch concentrations have impaired motility and emptying compared to normal subjects or patients with black pigment stones [ 14 ].

This test cannot distinguish between acalculous chronic cholecystitis and functional gallbladder disease.

The final diagnosis can be reached only after careful histological examination of the gallbladder using specific COX-2 antibodies that can detect the presence of activated macrophages containing up regulation of COX These cells should be absent in patients with functional gallbladder disease. Treatment Laparoscopic cholecystectomy is the treatment of choice for patients with chronic cholecystitis and recurrent episodes of moderate-to-severe biliary pain.

However, patients with occasional mild-to-moderate biliary pain with gallbladder stones may not require immediate treatment, since the pain may not recur.

Similar observations were made in an 8-year prospective study that enroll patients without or mild-to-moderate symptoms with gallbladder stones [ 89 ].

Significant technical improvements in laparoscopic surgery and greater surgical experience have markedly reduced the incidence of complications. This type of procedure should be performed when surgeons are able to identify the vascular and biliary duct structures. In the presence of adhesions, however, the common bile and cystic ducts may not be easily recognized. If surgeons are unable to fully identify these structures the procedure should be converted to open cholecystectomy.

These surgical procedures, in patients without significant systemic risks, have a very low incidence of surgical complications arising mostly from unrecognized biliary tract anomalies. Common variants of the main hepatic biliary branching is the so-called triple confluence, which is an anomaly characterized by simultaneous emptying of the right posterior duct, right anterior duct, and left hepatic duct into the common hepatic duct [ 94 ].

In patients with this variant, the right hepatic duct is virtually nonexistent. Other common anatomic variants of the branching of the biliary tree involve the right posterior duct and its fusion with the right anterior or left hepatic duct.

As mentioned earlier, the right posterior duct normally passes posterior to the right anterior duct and joins it from the left to form the right hepatic duct, which then forms a junction with the left hepatic duct to form the common hepatic duct. Drainage of the right posterior duct into the left hepatic duct before its confluence with the right anterior duct is the most common anatomic variant of the biliary system. Moreover, several less common and usually more complicated anatomic variations of the bile ducts have been described and consist of both aberrant and accessory bile ducts.

In a clinical context, familiarity with these entities is important because an aberrant bile duct is the only bile duct draining a particular hepatic segment, whereas an accessory one is an additional bile duct draining the same area of the liver.

Failure to recognize some of these bile duct anomalies can result in bile leaks causing inflammation of the peritoneal membranes bile peritonitis.

These leaks are treated by placing stents through an endoscopic retrograde cholagiopancreatography ERCP. They can stop these leaks that arise from the common bile or cystic ducts. Although surgery is the treatment of choice for patients with chronic cholecystitis, medical treatment with URSODIOL is a potential alternative in elderly patients with high surgical risks and recurrent biliary pain due to chronic cholecystitis.

However, in view of our changing concepts of the pathogenesis of cholecystitis the therapeutic objective should be to treat gallbladders with lithogenic bile with high Ch concentrations with URSO to improve the ability of the gallbladder to tolerate the aggressive actions of hydrophobic bile salts please see the pathogenesis of chronic cholecystitis and by blocking their actions at their cellular level.

However, there are only few candidates that qualified to receive this treatment. Therefore, the size of the gallstones should not be criteria for exclusion. The effectiveness of this treatment was examined by comparing the results of treating patients from 50 to 70 years old with typical biliary pain with URSO or elective cholecystectomy.

Patients were included in this study if they had noncalcified gallstones of less 20 mm in diameter and a functioning gallbladder. This clinical trial found that URSO was clinically advantageous and less expensive than surgical treatment in older patients with surgical risks. This study is supported by an year study that compared URSO treatment with no treatment in a large number of patients with symptomatic gallbladder stones. URSO was significantly more effective than no treatment in controlling biliary pain and preventing the need for cholecystectomy [ 77 ].

Medical treatment, however, may not be effective in patients with more advanced chronic cholecystitis. Clinical Symptoms Chronic cholecystitis is the most common risk factor in acute cholecystitis. Physical examination reveals epigastric, right upper quadrant tenderness, and positive Murphy sign, and in severe cases patients may have rebound tenderness.

However, before this diagnosis can be entertained clinicians need to rule out other acute abdominal conditions that include acute appendicitis particularly with a retrocecal appendix, acute pancreatitis, localized perforated peptic ulcer, intestinal perforation, or ischemia. These clinical entities have similar demographic and risk factors patterns. These patients complain of acute abdominal pain, nausea, and vomiting, and physical examination reveals abdominal tenderness that can be localized or diffuse and marked reduction in bowel sounds.

Diagnosis Laboratory studies in patients with acute cholecystitis have leukocytosis of 10, to 15, per cc.