Gallbladder and the Extrahepatic Biliary System
BASIC SCIENCE QUESTIONS
1. The common bile duct and pancreatic duct merge to enter the duodenum as a single duct in what percentage of the population?
The union of the common bile duct and the main pancreatic duct follows one of three configurations. In about 70% of people, these ducts unite outside the duodenal wall and traverse the duodenal wall as a single duct. In about 20%, they join within the duodenal wall and have a short or no common duct, but open through the same opening into the duodenum. In about 10%, they exit via separate openings into the duodenum. (See Schwartz 9th ed., p 1138.)
2. How much bile does a healthy adult produce each day?
A. 50-100 ml
B. 200-300 ml
C. 500-1000 ml
D. 1200-1800 ml
The liver produces bile continuously and excretes it into the bile canaliculi. The normal adult consuming an average diet produces within the liver 500 to 1000 mL of bile a day. The secretion of bile is responsive to neurogenic, humoral, and chemical stimuli. Vagal stimulation increases secretion of bile, whereas splanchnic nerve stimulation results in decreased bile flow. Hydrochloric acid, partly digested proteins, and fatty acids in the duodenum stimulate the release of secretin from the duodenum that, in turn, increases bile production and bile flow. Bile flows from the liver through to the hepatic ducts, into the common hepatic duct, through the common bile duct, and finally into the duodenum. With an intact sphincter of Oddi, bile flow is directed into the gallbladder. (See Schwartz 9th ed., p 1138.)
3. Bile is normally a neutral pH or slightly alkaline. Consumption of large amounts of which of the following will decrease the pH of bile?
Bile is mainly composed of water, electrolytes, bile salts, proteins, lipids, and bile pigments. Sodium, potassium, calcium, and chlorine have the same concentration in bile as in plasma or extracellular fluid. The pH of hepatic bile is usually neutral or slightly alkaline, but varies with diet; an increase in protein shifts the bile to a more acidic pH. (See Schwartz 9th ed., p 1138.)
4. The cystic artery most commonly arises from the right hepatic artery (80-90%). The second most anatomic configuration of the cystic artery, which occurs in 10% of people, is
A. Two cystic arteries, both arising from the right hepatic artery
B. Two cystic arteries, one arising from the right hepatic artery and one arising from the left hepatic artery
C. One cystic artery, arising from an aberrant right hepatic artery
D. One cystic artery, arising from the gastroduodenal artery
The second most common anatomic configuration is one cystic artery, arising from an accessory, or aberrant right hepatic artery. (See Schwartz 9th ed., p 1139, and Fig. 32-1.)
FIG. 32-1. Variations in the arterial supply to the gallbladder. A. Cystic artery from right hepatic artery, about 80–90%. B. Cystic artery from right hepatic artery (accessory or replaced) from superior mesenteric artery, about 10%. C. Two cystic arteries, one from the right hepatic, the other from the common hepatic artery, rare. D. Two cystic arteries, one from the right hepatic, the other from the left hepatic artery, rare. E. The cystic artery branching from the right hepatic artery and running anterior to the common hepatic duct, rare. F. Two cystic arteries arising from the right hepatic artery, rare.
5. The gallbladder is able to store only a small fraction of the bile produced by the liver. What is the primary mechanism used to keep the gallbladder from becoming distended (and developing high pressure) by this volume of bile?
A. The bile is continuously secreted into the duodenum once the pressure in the gallbladder increases
B. There is enough contraction of the gallbladder in response to eating to empty the large volume of bile
C. The gallbladder concentrates the large volume of bile
D. The liver decreases bile production when the pressure in the gallbladder increases
In the fasting state, approximately 80% of the bile secreted by the liver is stored in the gallbladder. This storage is made possible because of the remarkable absorptive capacity of the gallbladder, as the gallbladder mucosa has the greatest absorptive power per unit area of any structure in the body. It rapidly absorbs sodium, chloride, and water against significant concentration gradients, concentrating the bile as much as 10-fold and leading to a marked change in bile composition. This rapid absorption is one of the mechanisms that prevent a rise in pressure within the biliary system under normal circumstances. Gradual relaxation as well as emptying of the gallbladder during the fasting period also plays a role in maintaining a relatively low intraluminal pressure in the biliary tree. (See Schwartz 9th ed., p 1139.)
6. The primary mediator of gallbladder contraction is
A. Vasoactive intestinal polypeptide
One of the main stimuli to gallbladder emptying is the hormone cholecystokinin (CCK). CCK is released endogenously from the duodenal mucosa in response to a meal. When stimulated by eating, the gallbladder empties 50 to 70% of its contents within 30 to 40 minutes. Over the following 60 to 90 minutes, the gallbladder gradually refills. This is correlated with a reduced CCK level.
Vasoactive intestinal polypeptide inhibits contraction and causes gallbladder relaxation. Somatostatin and its analogues are potent inhibitors of gallbladder contraction. Patients treated with somatostatin analogues and those with somatostatinoma have a high incidence of gallstones, presumably due to the inhibition of gallbladder contraction and emptying. Other hormones such as substance P and enkephalin affect gallbladder motility, but the physiologic role is unclear. (See Schwartz 9th ed., p 1139.)
7. The half-life of CCK is
A. 2-3 minutes
B. 20-30 minutes
C. 2-3 hours
D. 20-30 hours
CCK is a peptide that comes from epithelial cells of the upper GI tract and is found in the highest concentrations in the duodenum. CCK is released into the bloodstream by acid, fat, and amino acids in the duodenum. CCK has a plasma half-life of 2 to 3 minutes and is metabolized by both the liver and the kidneys. CCK acts directly on smooth muscle receptors of the gallbladder and stimulates gallbladder contraction. It also relaxes the terminal bile duct, the sphincter of Oddi, and the duodenum. CCK stimulation of the gallbladder and the biliary tree also is mediated by cholinergic vagal neurons. In patients who have had a vagotomy, the response to CCK stimulation is diminished and the size and the volume of the gallbladder are increased. (See Schwartz 9th ed., p 1139.)
1. The sensitivity of ultrasound in detecting gallstones is
An ultrasound is the initial investigation of any patient suspected of disease of the biliary tree. It is noninvasive, painless, does not submit the patient to radiation, and can be performed on critically ill patients. It is dependent upon the skills and the experience of the operator, and it is dynamic (i.e., static images do not give the same information as those obtained during the ultrasound investigation itself). Ultrasound will show stones in the gallbladder with sensitivity and specificity of >90%. Stones are acoustically dense and reflect the ultrasound waves back to the ultrasonic transducer. Because stones block the passage of sound waves to the region behind them, they also produce an acoustic shadow (Fig. 32-2). Stones move with changes in position. Polyps may be calcified and reflect shadows, but do not move with change in posture. Some stones form a layer in the gallbladder; others a sediment or sludge. (See Schwartz 9th ed., p 1140.)
FIG. 32-2. An ultrasonography of the gallbladder. Arrows indicate the acoustic shadows from stones in the gallbladder.
2. Which of the following is associated with an increased risk for cholelithiasis?
A. Ulcerative colitis
B. Crohn’s disease
C. Jejunal resection
D. Carcinoma of the colon
Certain conditions predispose to the development of gallstones. Obesity, pregnancy, dietary factors, Crohn’s disease, terminal ileal resection, gastric surgery, hereditary spherocytosis, sickle cell disease, and thalassemia are all associated with an increased risk of developing gallstones. Women are three times more likely to develop gallstones than men, and first-degree relatives of patients with gallstones have a twofold greater prevalence. (See Schwartz 9th ed., p 1142.)
3. A 35-year-old woman has an incidental finding of cholelithiasis on a plain radiograph obtained following a minor car accident. Her risk of developing symptoms from these gallstones in the next 20 years is
Gallstones in patients without biliary symptoms are commonly diagnosed incidentally on ultrasonography, CT scans, or abdominal radiography or at laparotomy. Several studies have examined the likelihood of developing biliary colic or developing significant complications of gallstone disease. Approximately 3% of asymptomatic individuals become symptomatic per year (i.e., develop biliary colic). Once symptomatic, patients tend to have recurring bouts of biliary colic. Complicated gallstone disease develops in 3 to 5% of symptomatic patients per year. Over a 20-year period, about two thirds of asymptomatic patients with gallstones remain symptom free. (See Schwartz 9th ed., p 1143.)
4. Which of the following is an indication for cholecystectomy in an asymptomatic patient with an incidental finding of gallstones?
A. Any history of abdominal pain
B. Family history of complications of cholelithiasis
C. Porcelain gallbladder
D. Frequent travel out of the country
Because few patients develop complications without previous biliary symptoms, prophylactic cholecystectomy in asymptomatic persons with gallstones is rarely indicated. For elderly patients with diabetes, for individuals who will be isolated from medical care for extended periods of time, and in populations with increased risk of gallbladder cancer, a prophylactic cholecystectomy may be advisable. Porcelain gallbladder, a rare premalignant condition in which the wall of the gallbladder becomes calcified, is an absolute indication for cholecystectomy. (See Schwartz 9th ed., p 1143.)
5. Which of the following is one of the components of gallstones?
D. Short chain fatty acids
Lecithin is a phospholipid that is one of the three major components of gallstones (see Fig. 32-3). Gallstones form as a result of solids settling out of solution. The major organic solutes in bile are bilirubin, bile salts, phospholipids, and cholesterol. Gallstones are classified by their cholesterol content as either cholesterol stones or pigment stones. Pigment stones can be further classified as either black or brown. In Western countries about 80% of gallstones are cholesterol stones and about 15 to 20% are black pigment stones. Brown pigment stones account for only a small percentage. Both types of pigment stones are more common in Asia. (See Schwartz 9th ed., p 1143.)
FIG. 32-3. The three major components of bile plotted on triangular coordinates. A given point represents the relative molar ratios of bile salts, lecithin, and cholesterol. The area labeled “micellar liquid” shows the range of concentrations found consistent with a clear micellar solution (single phase), where cholesterol is fully solubilized. The shaded area directly above this region corresponds to a metastable zone, supersaturated with cholesterol. Bile with a composition that falls above the shaded area has exceeded the solubilization capacity of cholesterol and precipitation of cholesterol crystals occurs. (Reproduced with permission from Holzbach RT: Pathogenesis and medical treatment of gallstones, in Slesinger MH, Fordtran JS, eds: Gastrointestinal Diseases. Philadelphia: WB Saunders, 1989, p 1672.)
6. Which of the following is the most common location for pain during an attack of biliary colic?
A. Left periumbilical
B. Right shoulder
The most common location for pain during an episode of biliary colic is the epigastrium (64%) followed by the right upper quadrant (50%).
Atypical presentation of gallstone disease is common. Association with meals is present in only about 50% of patients. Some patients report milder attacks of pain, but relate it to meals. The pain may be located primarily in the back or the left upper or lower right quadrant. Bloating and belching may be present and associated with the attacks of pain. In patients with atypical presentation, other conditions with upper abdominal pain should be sought out, even in the presence of gallstones. These include peptic ulcer disease, gastroesophageal reflux disease, abdominal wall hernias, irritable bowel disease, diverticular disease, liver diseases, renal calculi, pleuritic pain, and myocardial pain. Many patients with other conditions have gallstones. (See Schwartz 9th ed., p 1146, and Fig. 32-4.)
FIG. 32-4. A. Sites of the most severe pain during an episode of biliary pain in 107 patients with gallstones (% values add up to >100% because of multiple responses). The subxiphoid and right subcostal areas were the most common sites; note that the left subcostal area was not an unusual site of pain. B. Sites of pain radiation (%) during an episode of biliary pain in the same group of patients. (Reproduced with permission from Gunn A, Keddie N: Some clinical observations on patients with gallstones. The Lancet 300(7771):239–241, Copyright © 1972, with permission from Elsevier.)
7. Which of the following is the appropriate treatment for adenomyomatosis of the gallbladder?
A. Observation only
C. Serial exams with EGD and ultrasound every 12 months
Adenomyomatosis or cholecystitis glandularis proliferans is characterized on microscopy by hypertrophic smooth muscle bundles and by the ingrowths of mucosal glands into the muscle layer (epithelial sinus formation). Granulomatous polyps develop in the lumen at the fundus, and the gallbladder wall is thickened and septae or strictures may be seen in the gallbladder. In symptomatic patients, cholecystectomy is the treatment of choice. (See Schwartz 9th ed., p 1146.)
8. A 24-year-old woman in the 20th week of pregnancy experiences a single episode of biliary colic. The most appropriate initial management is
A. Observation with plans to follow her after delivery for recurrent episodes
B. Dietary changes
C. Elective laparoscopic cholecystectomy during 2nd trimester
D. Elective open cholecystectomy during 2nd trimester.
Patients with symptomatic gallstones should be advised to have elective laparoscopic cholecystectomy. While waiting for surgery, or if surgery has to be postponed, the patient should be advised to avoid dietary fats and large meals. Diabetic patients with symptomatic gallstones should have a cholecystectomy promptly, as they are more prone to develop acute cholecystitis that is often severe. Pregnantwomen with symptomatic gallstones who cannot be managed expectantly with diet modifications can safely undergo laparoscopic cholecystectomy during the second trimester. Laparoscopic cholecystectomy is safe and effective in children as well as in the elderly. (See Schwartz 9th ed., p 1146.)
9. A 53-year-old man is admitted with 24 hours of pain from acute cholecystitis. He is made npo, IV antibiotics are started, and analgesia is given. He should undergo cholecystectomy
B. In 1-3 days
C. In 7-10 days
D. In 6-8 weeks
Patients who present with acute cholecystitis will need IV fluids, antibiotics, and analgesia. The antibiotics should cover gram-negative aerobes as well as anaerobes. A third-generation cephalosporin with good anaerobic coverage or a second-generation cephalosporin combined with metronidazole is a typical regimen. For patients with allergies to cephalosporins, an aminoglycoside with metronidazole is appropriate. Although the inflammation in acute cholecystitis may be sterile in some patients, more than one half will have positive cultures from the gallbladder bile. It is difficult to know who is secondarily infected; therefore, antibiotics have become a part of the management in most medical centers. Cholecystectomy is the definitive treatment for acute cholecystitis. In the past, the timing of cholecystectomy has been a matter of debate. Early cholecystectomy performed within 2 to 3 days of the illness is preferred over interval or delayed cholecystectomy that is performed 6 to 10 weeks after initial medical treatment and recuperation. Several studies have shown that unless the patient is unfit for surgery, early cholecystectomy should be recommended, as it offers the patient a definitive solution in one hospital admission, quicker recovery times, and an earlier return to work. Laparoscopic cholecystectomy is the procedure of choice. (See Schwartz 9th ed., p 1148.)
10. Primary choledochal stones are usually
A. Cholesterol stones
B. Black pigment stones
C. Brown pigment stones
D. Mulberry stones
The vast majority of ductal stones in Western countries are formed within the gallbladder and migrate down the cystic duct to the common bile duct. These are classified as secondary common bile duct stones, in contrast to the primary stones that form in the bile ducts. The secondary stones are usually cholesterol stones, whereas the primary stones are usually of the brown pigment type. The primary stones are associated with biliary stasis and infection and are more commonly seen in Asian populations. The causes of biliary stasis that lead to the development of primary stones include biliary stricture, papillary stenosis, tumors, or other (secondary) stones. (See Schwartz 9th ed., p 1148.)
11. A patient presents with biliary colic. On ultrasound there are multiple small gallstones in the gallbladder and the common bile duct measures 9 mm in diameter. No stone is visualized in the common bile duct. Which of the following is the most reasonable next step?
A. Repeat ultrasound in 24-48 hours
B. MRCP with contrast
C. Percutaneous cholangiography
D. Laparosopic Ccholecystectomy and intraopetrative cholangiography
For patients with symptomatic gallstones and suspected common bile duct stones, either preoperative endoscopic cholangiography or an intraoperative cholangiogram will document the bile duct stones. If an endoscopic cholangiogram reveals stones, sphincterotomy and ductal clearance of the stones is appropriate, followed by a laparoscopic cholecystectomy. An intraoperative cholangiogram at the time of cholecystectomy will also document the presence or absence of bile duct stones (Fig. 32-5). Laparoscopic common bile duct exploration via the cystic duct or with formal choledochotomy allows the stones to be retrieved in the same setting. If the expertise and/or the instrumentation for laparoscopic common bile duct exploration are not available, a drain should be left adjacent to the cystic duct and the patient scheduled for endoscopic sphincterotomy the following day. An open common bile duct exploration is an option if the endoscopic method has already been tried or is, for some reason, not feasible. (See Schwartz 9th ed., p 1148.)
FIG. 32-5. An endoscopic sphincterotomy. A. The sphincterotome in place. B. Completed sphincterotomy. C. Endoscopic picture of completed sphincterotomy.
12. A 75-year-old man presents with cholangitis, symptomatic cholelithiasis, and choledocholithiasis. The best treatment for him is
A. ERCP followed by cholecystectomy
B. Cholecystectomy, flushing of the common bile duct with subsequent ERCP if necessary
C. Laparoscopic cholecystectomy and common bile duct exploration
D. ERC and endoscopic sphincterotomy
Patients >70 years old presenting with bile duct stones should have their ductal stones cleared endoscopically. Studies comparing surgery to endoscopic treatment have documented less morbidity and mortality for endoscopic treatment in this group of patients. They do not need to be submitted for a cholecystectomy, as only about 15% will become symptomatic from their gallbladder stones, and such patients can be treated as the need arises by a cholecystectomy. (See Schwartz 9th ed., p 1149.)
13. Which of the following is NOT part of Reynolds’ pentad?
A. Hypovolemic shock
C. Mental status changes
The most common presentation [of cholangitis] is fever, epigastric or right upper quadrant pain, and jaundice.
These classic symptoms, well known as Charcot’s triad, are present in about two thirds of patients. The illness may progress rapidly with septicemia and disorientation, known as Reynolds’ pentad(e.g., fever, jaundice, right upper quadrant pain, septic shock, and mental status changes). However, the presentation may be atypical, with little if any fever, jaundice, or pain. This occurs most commonly in the elderly, who may have unremarkable symptoms until they collapse with septicemia. (See Schwartz 9th ed., p 1149.)
14. Cholangiohepatitis is seen most commonly in which of the following groups?
A. Caucasian patients of Northern European descent
B. Jewish patients of Ashkenazi descent
C. Asian patients of Chinese descent
D. Native American patients
Cholangiohepatitis, also known as recurrent pyogenic cholangitis, is endemic to the Orient. It also has been encountered in the Chinese population in the United States, as well as in Europe and Australia. It affects both sexes equally and occurs most frequently in the third and fourth decades of life. Cholangiohepatitis is caused by bacterial contamination (commonly E. coli, Klebsiella species, Bacteroidesspecies, or Enterococcus faecalis) of the biliary tree, and often is associated with biliary parasites such as Clonorchis sinensis, Opisthorchis viverrini, and Ascaris lumbricoides. Bacterial enzymes cause deconjugation of bilirubin, which precipitates as bile sludge. The sludge and dead bacterial cell bodies form brown pigment stones. The nucleus of the stone may contain an adult Clonorchis worm, an ovum, or an ascarid. These stones are formed throughout the biliary tree and cause partial obstruction that contributes to the repeated bouts of cholangitis. Biliary strictures form as a result of recurrent cholangitis and lead to further stone formation, infection, hepatic abscesses, and liver failure (secondary biliary cirrhosis). (See Schwartz 9th ed., p 1151.)
15. The treatment of a type II choledochal cyst is
A. Observation with annual ultrasound
B. ERCP with sphincterotomy
C. Drainage with a Roux-en-Y choledochojejunostomy
D. Resection with a Roux-en-Y hepaticojejunostomy
For types I, II, and IV [choledochal cysts], excision of the extrahepatic biliary tree, including cholecystectomy, with a Roux-en-Y hepaticojejunostomy, are ideal. In type IV, additional segmental resection of the liver may be appropriate, particularly if intrahepatic stones, strictures, or abscesses are present, or if the dilatations are confined to one lobe. The risk of cholangiocarcinoma developing in choledochal cysts is as high as 15% in adults, and supports complete excision when they are diagnosed. For type III, sphincterotomy is recommended. (See Schwartz 9th ed., p 1155; 1158, and Fig. 32-6.)
FIG. 32-6. Classification of choledochal cysts. Type I, fusiform or cystic dilations of the extrahepatic biliary tree, is the most common type, making up >50% of the choledochal cysts. Type II, saccular diverticulum of an extrahepatic bile duct. Rare, 5% of choledochal cysts. Type III, bile duct dilatation within the duodenal wall (choledochoceles), makes up about 5% of choledochal cysts. Type IVa and IVb, multiple cysts, make up 5–10% of choledochal cysts. Type IVa affects both extrahepatic and intrahepatic bile ducts while Type IVb cysts affect the extrahepatic bile ducts only. Type V, intrahepatic biliary cysts, is very rare and makes up 1% of choledochal cysts.
16. Primary sclerosing cholangitis is seen more commonly in patients with
A. Ulcerative Ccolitis
B. Crohn’s disease
C. Rheumatoid arthritis
D. Celiac sprue
[Primary sclerosing cholangitis] is associated with ulcerative colitis in about two thirds of patients. Other diseases associated with sclerosing cholangitis include Riedel’s thyroiditis and retroperitoneal fibrosis. Autoimmune reaction, chronic lowgrade bacterial or viral infection, toxic reaction, and genetic factors have all been suggested to play a role in its pathogenesis. The human leukocyte antigen haplotypes HLA-B8, -DR3, -DQ2, and -DRw52A, commonly found in patients with autoimmune diseases, also are more frequently seen in patients with sclerosing cholangitis than in controls. (See Schwartz 9th ed., p 1156.)
17. In addition to regional lymphadenectomy, appropriate surgical treatment for a T2 carcinoma of the gallbladder is
A. Cholecystectomy only
B. Cholecystectomy with resection of liver segments IVB and V
C. Cholecystectomy with limited right hepatectomy
D. Cholecystectomy with extended right hepatectomy
Tumors limited to the muscular layer of the gallbladder (T1) are usually identified incidentally, after cholecystectomy for gallstone disease. There is near universal agreement that simple cholecystectomy is an adequate treatment for T1 lesions and results in a near 100% overall 5-year survival rate. When the tumor invades the perimuscular connective tissue without extension beyond the serosa or into the liver (T2 tumors), an extended cholecystectomy should be performed. That includes resection of liver segments IVB and V, and lymphadenectomy of the cystic duct, and pericholedochal, portal, right celiac, and posterior pancreatoduodenal lymph nodes. One half of patients with T2 tumors are found to have nodal disease on pathologic examination. Therefore, regional lymphadenectomy is an important part of surgery for T2 cancers. For tumors that grow beyond the serosa or invade the liver or other organs (T3 and T4 tumors), there is a high likelihood of intraperitoneal and distant spread. If no peritoneal or nodal involvement is found, complete tumor excision with an extended right hepatectomy (segments IV, V, VI, VII, and VIII) must be performed for adequate tumor clearance. An aggressive approach in patients who will tolerate surgery has resulted in an increased survival for T3 and T4 lesions. (See Schwartz 9th ed., p 1161.)
18. Cholangiocarcinoma most commonly occurs
A. In the intrahepatic ducts
B. In the common hepatic duct, at the bifurcation
C. At the junction of the hepatic and common bile ducts
D. In the distal common bile duct
Cholangiocarcinoma is a rare tumor arising from the biliary epithelium and may occur anywhere along the biliary tree. About two thirds are located at the hepatic duct bifurcation. Surgical resection offers the only chance for cure; however, many patients have advanced disease at the time of diagnosis. Therefore, palliative procedures aimed to provide biliary drainage to prevent liver failure and cholangitis are often the only therapeutic possibilities. Most patients with unresectable disease die within 1 year of diagnosis.
About two thirds of cholangiocarcinomas are located in the perihilar location. Perihilar cholangiocarcinomas, also referred to as Klatskin tumors, are further classified based on anatomic location by the Bismuth-Corlette classification (Fig. 32-7). Type I tumors are confined to the common hepatic duct, but type II tumors involve the bifurcation without involvement of the secondary intrahepatic ducts. Type IIIa and IIIb tumors extend into the right and left secondary intrahepatic ducts, respectively. Type IV tumors involve both the right and left secondary intrahepatic ducts. (See Schwartz 9th ed., p 1162.)
FIG. 32-7. Bismuth-Corlette classification of bile duct tumors.