Ch. 54 – Biliary System

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1556 Section X Abdomen Box 54-1 Common Bacterium Species Found in Biliary Tract Infections* Enterobacteriaceae (68% incidence) Escherichia coli Klebsiella species Enterobacter species Enterococcus species (14% incidence) Anaerobes (10% incidence) Bacteroides species Clostridium species (7% incidence) Streptococcus species (rare) Pseudomonas species (rare) Candida species (rare) *Cholecystitis, cholangitis, biliary sepsis, or common duct obstruction. From Thompson JE Jr, Pitt HA, Doty JE, et al: Broad spectrum penicillin as an adequate therapy for acute cholangitis. Surg Gynecol Obstet 1990;171:275-282. cholecystitis than chronic cholecystitis (46% versus 22%) and increases further in the presence of common bile duct stones. Positive bile cultures are signifi cantly more common in elderly (>60 years) patients with symptomatic gallstones than in younger patients (45% versus 16%). 5,6 Gram-negative aerobes are the organisms most frequently isolated from bile in patients with symptomatic gallstones, acute cholecystitis, or cholangitis (Box 54-1). Escherichia coli and Klebsiella species are the most common gram-negative bacteria isolated. However, Pseudomonas and Enterobacter species are being seen with increased frequency, particularly in patients with malignant biliary obstruction. 5 Other common isolates include the gram-positive aerobes, Enterococcus species, and Streptococcus viridans. Anaerobic bacteria, such as Bacteroides and Clostridium species, are infrequent but remain signifi cant pathogens in biliary infections. Candida species are also being increasingly recognized as a signifi cant biliary pathogen particularly in critically ill patients. The source of bacteria in patients with biliary tract infections is controversial. Most theories favor an ascending route through the duodenum as the main source of biliary bacteria. The bacterial fl ora in the small intestine is similar to that detected in the biliary tract. Antibiotic Selection Antibiotics should be used prophylactically in most patients undergoing elective biliary tract surgery or other biliary tract manipulations such as ERCP or PTC. In lowrisk patients undergoing laparoscopic cholecystectomy for biliary colic or chronic cholecystitis, there is no benefi t of prophylactic antibiotics. In high-risk patients, such as elderly patients, patients with recent acute cholecystitis, and those with high risk for conversion to open cholecystectomy, a single dose of the fi rst-generation cephalosporin, cefazolin, provides good coverage against the gram-negative aerobes commonly isolated from bile and skin fl ora. Box 54-2 Risk Factors for Gallstones Obesity* Rapid weight loss Childbearing Multiparity Female sex First-degree relatives Drugs: ceftriaxone, postmenopausal estrogens, total parenteral nutrition Ethnicity: Native American (Pima Indian), Scandinavian Ileal disease, resection or bypass Increasing age *Obesity is defi ned as body mass index greater than 30 kg/m2 . Adapted from Bellows CF, Berger DH, Crass RA: Management of gallstones. Am Fam Physician 72:637-642, 2005. Therapeutic antibiotics should be used in patients with acute cholecystitis and cholangitis and should cover gram-negative aerobes, gram-positive coverage, and anaerobes. BENIGN PATHOPHYSIOLOGIC CONDITIONS Calculous Biliary Disease Epidemiology Gallstones are among the most common gastrointestinal illness requiring hospitalization and frequently occur in young, otherwise healthy people with a prevalence of 11% to 36% in autopsy reports. Female sex, obesity, pregnancy, fatty foods, Crohn’s disease, terminal ileal resection, gastric surgery, hereditary spherocytosis, sickle cell disease, and thalassemia are all associated with an increased risk for developing gallstones 7 (Box 54-2). Only fi rst-degree relatives of patients with gallstones and obesity (defi ned as body mass index >30 kg/m 2 ) have been identifi ed as strong risk factors for development of symptomatic gallstone disease. 8 Gallstone Pathogenesis Gallstones represent an inability to maintain certain biliary solutes, primarily cholesterol and calcium salts, in a solubilized state. Gallstones are classifi ed by their cholesterol content as either cholesterol or pigment stones. Pigment stones are further classifi ed as either black or brown. Pure cholesterol gallstones are uncommon (10%), with most cholesterol stones containing calcium salts in their center, or nidus. In the United States, 70% to 80% of gallstones are cholesterol, and black pigment stones account for most of the remaining 20% to 30%. Biliary sludge refers to a mixture of cholesterol crystals, calcium bilirubinate granules, and a mucin gel matrix. It is most commonly found in prolonged fasting states or with the use of parental nutrition. The fi nding of macromolecular complexes of mucin and bilirubin suggests that sludge may serve as the nidus for gallstone pathogenesis.
Cholesterol Gallstones The pathogenesis of cholesterol gallstones involves three stages: 1. Cholesterol supersaturation in bile 2. Crystal nucleation 3. Stone growth Gallbladder mucosal and motor function plays a key role in gallstone formation. The key to maintaining cholesterol in solution is the formation of micelles, a bile salt–phospholipid-cholesterol complex, and cholesterolphospholipid vesicles. In states of excess cholesterol production, these large vesicles may also exceed their capability to transport cholesterol, and crystal precipitation may occur. One third of biliary cholesterol is transported in micelles, but the cholesterol-phospholipid vesicles carry the majority of biliary cholesterol. By plotting the percentages of each component on triangular coordinates, the micellar zone in which cholesterol is completely soluble can be demonstrated (Fig. 54-10). In the area above the curve, bile is supersaturated with cholesterol, and precipitation of cholesterol crystals can occur. Pigment Gallstones Pigment stones contain less than 20% cholesterol and are dark owing to the presence of calcium bilirubinate. Otherwise, black and brown pigment stones have little in common and should be considered as separate entities. Black pigment stones are small and tarry, and are frequently associated with hemolytic conditions such as hereditary spherocytosis and sickle cell disease or cir- 60 40 2 phases Percent cholesterol 20 80 1 phase 100 3 phases 20 Ch crystals Micelles Lamelar 2 phases 40 Percent lecithin 60 1 phase 100 80 60 40 20 Percent Na taurocholate 80 100 Chapter 54 Biliary System 1557 Figure 54-10 Triangular-phase diagram with axes plotted in percent cholesterol, lecithin (phospholipid), and the bile salt sodium taurocholate. Below the solid line, cholesterol is maintained in solution in micelles. Above the solid line, bile is supersaturated with cholesterol and precipitation of cholesterol crystals can occur. Ch, cholesterol. (From Donovan JM, Carey MC: Separation and quantitation of cholesterol “carriers” in bile. Hepatology 12:94S, 1990.) rhosis. In hemolytic states, the bilirubin load and concentration of unconjugated bilirubin increases. Cirrhosis may lead to increased secretion of unconjugated bilirubin. These stones are usually not associated with infected bile and are located almost exclusively in the gallbladder. Black stones account for a high percentage of gallstones in Asian countries such as Japan compared with the Western hemisphere. Brown pigment stones are soft and earthy in texture and are typically found in bile ducts, especially in Asian populations. Brown stones often contain more cholesterol and calcium palmitate and occur as primary common duct stones in Western patients with disorders of biliary motility and associated bacterial infection. Bacteria producing slime such as E. coli secrete β-glucuronidase that causes enzymatic hydrolysis of soluble conjugated bilirubin glucuronide to produce insoluble free bilirubin, which then precipitates with calcium. 9 Natural History Most patients remain asymptomatic from their gallstones. Although the mechanism is unclear, some patients develop symptomatic gallstones, with biliary colic caused by a stone obstructing the cystic duct. Additional complications related to gallstones include acute cholecystitis, choledocholithiasis with or without cholangitis, gallstone pancreatitis, gallstone ileus, and gallbladder carcinoma. Gallstones are commonly found incidentally at laparotomy or on imaging either by ultrasonography or CT scan. Only 1% to 2% of asymptomatic individuals with gallstones develop serious symptoms or complications related to their gallstones per year; therefore, only about 1% require a cholecystectomy. Once symptomatic,
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Ch. 54 – Biliary System

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