2.1 Chronic Calculous Cholecystitis 

Chronic inflammation of the gallbladder is the most common pathologic process in this organ. Some degree of chronic inflammation inevitably accompanies gallstones, but the stones will have developed first. Even transient obstruction of the cystic duct can produce biliary colic. Yet there is little correlation between the severity and frequency of such biliary episodes and the pathology found in the gallbladder. There may be only modest round cell infiltration with marked symptoms. Conversely, symptoms may be minimal while gallbladder scarring is marked. Prolonged obstruction can lead to acute cholecystitis (Figure 2). Chronic inflammation may follow acute cholecystitis or evolve insidiously. The inflammatory process is chemical in origin.

The clinical features are those of either biliary colic or a previous episode of acute cholecystitis that has resolved, leaving the gallbladder chronically inflamed. The pain characteristically is a constant dull ache in the right hypochondrium and epigastrium, and sometimes also in the right shoulder or back. Nausea is frequent. There may be local tenderness in the right upper quadrant of the abdomen. Flatulence, fatty food intolerance and dyspepsia occur, but are equally frequent in patients without gallstone disease. Fever or leukocytosis suggests acute cholecystitis or another entity.

Diagnosis largely depends upon detecting gallstones by plain film of the abdomen (10-15% are calcified), ultrasound or oral cholecystogram. The latter two are more than 95% accurate. If the gallbladder is fibrotic and shrunken, visualization may be difficult. This is considered a positive finding, given the accuracy of these tests. Merely identifying calculi in the gallbladder confirms biliary tract disease but does not necessarily mean that gallstones were responsible for the symptoms. Nuclear medicine scanning helps. Cholescintigraphy normally demonstrates filling of a healthy gallbladder. Nonvisualization (with radioactivity present in the common duct and duodenum) in suspected cases of acute cholecystitis is diagnostic. The test is much less sensitive for chronic cholecystitis, in which the gallbladder commonly fills. If no filling occurs, then biliary tract disease is likely. Failure of the gallbladder to fill can occur with use of narcotics or after a prolonged fast.

Once symptoms begin, they are likely to recur. Medical management depends upon gallstone size, gallbladder function and any co-morbid conditions (e.g., age, obesity, diabetes). Cholecystectomy provides definitive treatment, removing the stones and the gallbladder.

Here the gallbladder becomes acutely inflamed. In most, a stone obstructs the cystic duct, resulting in a vicious cycle of increased secretion of fluid, causing distention, mucosal damage and the release of chemical mediators of the inflammatory process. Inflammatory damage results from agents such as lysolecithin, derived from the hydrolysis of lecithin by phospholipase, and prostaglandins whose synthesis increases. Any role that bile salts and regurgitated pancreatic enzymes may have is unclear. Bacterial infection is a late complication.

Obstruction of the cystic duct results in the gallbladder becoming distended with bile, an inflammatory exudate or even pus. The gallbladder wall can go on to necrosis and perforation. If resolution occurs, the mucosal surface heals and the wall becomes scarred, but the gallbladder may not function (i.e., fill with contrast agent) on oral cholecystography.

Acute cholecystitis onsets like biliary colic (Table 4). The abdominal pain rises to a plateau and remains constant. Its location is usually the right upper quadrant or epigastrium, sometimes radiating to the back or the right shoulder. There may be a previous history of biliary pain. Pain in acute cholecystitis, unlike biliary colic, persists for more than 6 to 12 hours. As the gallbladder becomes inflamed, the visceral pain is replaced by parietal pain that is aggravated by movement. Anorexia and vomiting are common. Fever is usually low-grade. If rigors occur, suspect bacterial invasion.

Abdominal examination characteristically shows tenderness in the right upper quadrant. During palpation of the right upper quadrant, a deep breath during the inspiratory effort worsens the pain; inspiration suddenly ceases (Murphy's sign). Severe cases exhibit peritoneal signs: guarding and local rebound tenderness. A reflex paralytic ileus may be present. Patients appear unwell and are reluctant to move with such parietal pain. An enlarged gallbladder is sometimes palpable, particularly with the first attack.

Jaundice with mild hyperbilirubinemia and elevated liver enzymes occurs in about 20% of cases, even in the absence of common duct stones. The higher the bilirubin level, the more likely is a common duct stone. High levels of aminotransferase and of amylase or lipase suggest a common duct stone. Leukocytosis is common. If the patient is febrile, blood cultures may be positive. Cholangitis suggests a common duct stone.

Diagnosis is best confirmed by ultrasound, which detects the stone(s) and a thickened gallbladder wall. In doing the procedure, the physician may elicit tenderness ultrasonographically when pressing over the gallbladder (the ultrasonographic Murphy's sign). A plain film may reveal calcification of the stone(s). Cholescintigraphy typically fails to visualize the gallbladder at one hour, a feature highly accurate for acute cholecystitis. Conversely, a normal scan filling the gallbladder virtually eliminates acute cholecystitis, but cannot detect gallstones. Late visualization (after one hour) sometimes occurs in chronic cholecystitis.

Treatment is surgical and is performed in hospital. General measures include rehydration, observation, analgesia and antibiotics. In mild cases of acute cholecystitis that resolve, cholecystectomy can be delayed for up to six weeks. Because of the risk of recurrent cholecystitis, surgery should be performed early, once the patient has been stabilized during the current admission.

Acute cholecystitis normally resolves spontaneously, usually within three days. Inflammation may progress to necrosis, empyema or perforation in about one-third of cases. These complications will be heralded by (1) a continuation of the pain, along with tachycardia, fever, peritoneal signs and leukocytosis; (2) features of a secondary infection, such as empyema or cholangitis; or (3) a suspected perforation. Urgent surgery then becomes mandatory.

Empyema is suppurative cholecystitis with an intraluminal abscess (i.e., an inflamed gallbladder containing pus). It develops from continued obstruction of the cystic duct leading to secondary infection. The abdominal findings of acute cholecystitis are accompanied by systemic features of bacteremia, with a hectic fever and rigors. Treatment consists of antibiotics and surgery.

Perforation of the gallbladder occurs when unresolved inflammation leads to necrosis, often in the fundus, a part of the gallbladder that is relatively avascular. Gallstones also may erode through a gangrenous wall. If localized, the perforation spawns an abscess, clinically evident as a palpable, tender mass in the right upper quadrant. Free perforation with bile peritonitis is uncommon, fortunately, as the mortality reaches 30%. With perforation the gallbladder, if enlarged, suddenly disappears. The pain and temperature may also transiently resolve, only to be replaced by acute peritonitis. Both localized and free perforations demand surgical drainage of the abscess. Rupture into adjacent viscera (e.g., the small intestine) creates an internal biliary fistula. Large stones can produce a mechanical small intestine obstruction (gallstone ileus). Obstruction usually occurs at the terminal ileum, rarely at the duodenal bulb or the duodenojejunal junction. This is a rather common cause of distal small bowel obstruction in the elderly. Radiologic diagnosis comes from finding air in the biliary system, a small bowel obstruction and perhaps a calcified gallstone ectopically located. Urgent surgery with appropriate antibiotic coverage is imperative.

Hydrops of the gallbladder occurs when the inflammation subsides but the cystic duct remains obstructed. The lumen becomes distended with clear mucoid fluid. The hydropic gallbladder is evident as a right upper quadrant mass that is not tender. Treatment is cholecystectomy.

Limy bile occurs when prolonged gallbladder obstruction causes loss of the pigment material from bile and the residual calcium salts precipitate. The hydropic, obstructed gallbladder secretes calcium into the lumen. Calcium can also accumulate in the wall of the gallbladder, producing a porcelain gallbladder. The mural calcifications are easily identified on plain films of the abdomen. Although presumably there has been at least one episode of acute cholecystitis in the past, most patients with a porcelain gallbladder are asymptomatic. One quarter will develop carcinoma of the gallbladder, making prophylactic cholecystectomy necessary.

Stones in the common duct are classified according to their site of origin: primary stones are formed in the bile ducts; secondary stones originate in the gallbladder and then migrate into the common duct. In North America, virtually all cholesterol stones and most pigment stones are considered secondary when the gallbladder is intact. Thus, more than 85% of patients with common duct stones also have stones in the gallbladder. Conversely, about 10% of patients undergoing cholecystectomy for chronic cholecystitis also have common duct stones. Residual stones are those missed at the time of cholecystectomy; recurrent stones develop in the ductal system more than three years after surgery. The composition of stones also varies with their site of origin. Stones are predominantly (approximately 80%) cholesterol when situated in the gallbladder and in the common duct. After cholecystectomy, the proportion of ductal stones that are pigment rises with time: most recurrent ones (more than three years after surgery) are pigment stones. These brown stones result from stasis (e.g., a postoperative stricture) and infection. Bacteria and inflamed tissues release b-glucuronidase, an enzyme that deconjugates bilirubin. The result is calcium bilirubinate, which polymerizes and precipitates along with calcium soaps. Biofilm, a glycoprotein produced by bacteria as its glycocalyx, then agglomerates this pigment material, leading to brown stones.

Common duct stones may be asymptomatic, but usually cause biliary colic, obstructive jaundice, cholangitis or pancreatitis (Figure 2). Biliary colic results from sudden obstruction of the common duct, which increases biliary pressure. The abdominal pain is steady, located in the right upper quadrant or epigastrium, and often bores through to the back.

Acute cholangitis results when duct obstruction leads to infection. Obstruction and ductal damage permit bacteria to regurgitate across the ductal epithelium into the hepatic venous blood, causing a bacteremia with chills and a spiking fever. The raised intrabiliary pressure also initiates abdominal pain. The classical "Charcot's triad" consists of jaundice, upper abdominal pain and a hectic fever. Jaundice results from the mechanical obstruction of the ducts plus a component of intrahepatic cholestasis due to sepsis (endotoxin, for example, impairs hepatic bile formation). Pain and fever are common, though jaundice is often less apparent on presentation. Most patients are toxic. There is abdominal tenderness and a large, tender liver (often containing liver abscesses). Hypotension, confusion and a septic picture predominate in critical cases.

Leukocytosis and abnormal liver biochemistry are common. Urine may be positive for bilirubin. Blood cultures reveal the causal microorganisms, which are usually enteric (e.g., E. coli or Klebsiella) in origin. Ultrasound will show dilated ducts and, in advanced cases, liver abscesses. Cholangiography (by endoscopy from below or via percutaneous transhepatic catheterization from above) is necessary to locate the site and cause of obstruction.

The presence of cholangitis necessitates urgent decompression of the biliary system. In the past, laparotomy was the only recourse. Now, endoscopic surgery (using the ERCP procedure - endoscopic retrograde cholangiopancreatography) is routinely performed under antibiotic coverage (for enteric gram-negative organisms, enterococci and anaerobes). ERCP also allows sphincterotomy followed by extraction of the stone and, if needed, placement of a stent through a stricture. Large common duct stones may need fragmentation, either by mechanical means using a basket for crushing, or by energy delivered as shock or laser waves. This allows cholecystectomy to be done electively. Another option is open cholecystectomy with common duct exploration, removing the gallbladder and all stones.

Pancreatitis can result from gallstones impacting at the ampulla of Vater. Acute biliary pancreatitis does not differ clinically from other forms of acute pancreatitis. Biliary pancreatitis tends to be more commonly associated with jaundice and higher serum levels of bilirubin, alkaline phosphatase and aminotransferase than alcohol-induced pancreatitis, but there is significant overlap. Ultrasound should detect any gallstones and the inflamed pancreas. In patients unfit for surgery, early ERCP with papillotomy may be done, but its role as the definitive procedure is unproven. Most will come to elective cholecystectomy to prevent recurrent pancreatitis. Unlike alcoholic pancreatitis, gallstone-related disease does not progress to chronic pancreatitis.