Biliary System - Clinical Tree

Anatomy and Physiology

As anatomic variations in biliary anatomy are common, occurring in up to 30% of patients, understanding of both normal anatomy and the variations is important for the management of patients with biliary disease.

Bile ducts, either intrahepatic or extrahepatic, lie superior to the corresponding portal vein, which in turn are lateral and inferior to the arterial supply ( Fig. 55.1 ). The left hepatic duct retains a longer transverse extrahepatic portion and travels under the edge of segment IV before diving before joining the bifurcation. It can receive a few subsegmental branches from segment IV in this transverse portion. The left duct drains segments I, II, III, and IV, with the most distal branch draining segment IVA. Further superolateral, the ducts draining segment IVB arise, and yet further up the left duct are the ducts for segments II and III. These ducts can generally be found just posterior and lateral to the umbilical recess. The caudate lobe drains through smaller ducts that enter the right and left hepatic duct systems. The drainage of the right duct system includes segments V, VI, VII, and VIII and is substantially shorter than the left duct, bifurcating almost immediately. The junction of two sectoral ducts, posterior and anterior, creates this short right hepatic duct. The anterior sectoral duct runs in a vertical direction to drain segments V and VIII, whereas the posterior sectoral duct follows a horizontal course to drain segments VI and VII.

Fig. 55.1, Hepatic lobar segmental biliary anatomy.

The gallbladder is a partially intraperitoneal structure that lies attached to the undersurface of the liver on segments IVB and V. It is 7 to 10 cm in length, holds 30 to 60 mL of bile as a reservoir, and is divided into neck, infundibulum with Hartmann pouch, body, and fundus ( Fig. 55.2 ). On the side of the gallbladder that is attached to the liver, there is no peritoneal covering; a fibrous lining known as the cystic plate occupies this space. Bile is drained via a cystic duct to the common bile duct (CBD). The cystic duct can range from 1 to 5 cm in length and drains at an acute angle into the CBD. There are numerous variations in this insertion, including into the right hepatic duct ( Fig. 55.3 ). The valves of Heister, which are folds of mucosa oriented in spiral pattern within the neck of gallbladder, function to retain bile in the gallbladder until contraction in response to enteric stimulation.

Fig. 55.2, Laparoscopic photograph of the gallbladder in situ. The gallbladder is being suspended by the fundus to expose the infundibulum and porta hepatis.

Fig. 55.3, Variability in cystic duct anatomy. Knowledge of these variations is important to try to avoid inadvertent injury to the biliary tree during cholecystectomy.

The CBD is divided into three portions: supraduodenal, retroduodenal, and the pancreatic portion, which is the most inferior portion, encompassed by head of pancreas. The insertion of cystic duct marks the separation of the CBD (below) from the common hepatic duct (above). The CBD ends in the second portion of duodenum at the ampulla of Vater. The pancreatic duct also joins the ampulla, although in variants may have a separate orifice ( Fig. 55.4 ).

Fig. 55.4, Patterns of biliary duct–pancreatic duct junction and insertion into the duodenal wall. (A) Separate common bile duct (CBD) and pancreatic duct (PD) entry. (B) Joining ducts at the ampula. (C) Joining ducts before the ampula. (D) PD entering the CBD.

As mentioned, the cystic duct divides the bile duct to common hepatic duct and CBD. The common hepatic duct drains the left and right hepatic ducts and their confluence at the hilar plate, which is an extension of Glisson’s capsule. There are generally no vascular structures overlying bile ducts at this location, allowing exposure of the bifurcation by incision at the base of segment IV and lifting the liver off these structures. This technique, called lowering hilar plate, is used to expose the proximal extrahepatic biliary tree.

Vascular Anatomy

As described by Couinaud, the hepatic parenchyma is divided into lobes, each of which is divided into lobar segments ( Fig. 55.5 ) to define the basic hepatic anatomic resections.

Fig. 55.5, Couinaud segmental anatomy. Segment I is the caudate lobe. Segments II and III are supplied by the lateral branch of the left portal vein, with segment II lying above the passage of the portal vein and segment III below it. Segment IV is supplied by the medial branch of the left portal vein and is further subdivided into IVA above and IVB below the segmental portal vein. Segment V is supplied by the inferior distribution of the anterior branch of the right portal vein, and segment VIII receives flow from the superior distribution of this branch. Similarly, with respect to the posterior branch of the right portal vein, segment VI lies inferior to the portal vein, whereas segment VII lies superior.

The blood supply to the entire biliary tree is solely arterial as contrasted with the hepatic parenchyma, where dual perfusion comes as well from the portal vein, which makes the biliary tree susceptible to ischemic injury.

The cystic artery normally arises from the right hepatic artery, and similar to the variability of the cystic duct, it may arise from the right hepatic, left hepatic, proper hepatic, common hepatic, gastroduodenal, or superior mesenteric artery. The cystic artery can pass posterior or anterior to the CBD to supply the gallbladder. Although variable, the cystic artery generally lies superior to the cystic duct and is usually associated with a lymph node, known as Calot node ( Fig. 55.6 ). This node can be enlarged in the setting of gallbladder disease, whether inflammatory or neoplastic, due to the fact that it provides the lymphatic drainage of the gallbladder.

Fig. 55.6, Operative photograph of Calot node. This node (arrow) is useful for identification of the common location of the cystic artery.

The blood supply of the common hepatic duct and CBD comes from the right hepatic and cystic artery. Typically, the right hepatic artery passes posterior to the common hepatic duct to supply the right lobe of the liver. It passes through the triangle of Calot (bordered by the cystic duct, common hepatic duct, and edge of the liver), after crossing the duct. The cystic artery takes off from the right hepatic artery in this triangle, which is at risk for injury during cholecystectomy. It is important to remember that in 20% of the population, there is an accessory or replaced right hepatic artery passing through the portacaval space and ascending to the right lobe along the lateral aspect of the CBD. A pulsatile structure palpated on the most lateral aspect of the porta during a Pringle maneuver identifies this anomaly. In addition, it can be noted on computed tomography (CT) as a vessel passing transversely between the portal vein and inferior vena cava behind the head of the pancreas.

The perfusion to the inferior bile duct, below the duodenal bulb, comes from tributaries of the posterosuperior pancreaticoduodenal and gastroduodenal arteries. The small branches coalesce to form the two vessels that run along the CBD at the 3- and 9-o’clock positions. These vessels can be damaged and leave the bile duct at risk for ischemic injury with close dissection of the areolar tissue surrounding the bile duct.

Physiology

The smallest functional unit of liver is the hepatic lobule. It is created by four to six portal triads and identified by its central terminal hepatic venule. Each hepatocyte is encircled by bile canaliculi, which coalesce to form small bile ducts, entering portal triad. Bile salts, such as cholic acid and deoxycholic acid, are originally created from cholesterol and secreted into bile canaliculi as cholic acid and its metabolite, deoxycholic acid. The liver actually makes only a small amount of the total bile salt pool used on a daily basis because most bile salts are recycled after use in the intestinal lumen, known as the enterohepatic circulation ( Fig. 55.7 ). Bile is secreted into canaliculi directly from hepatocytes. Once the bile components are secreted into the bile canaliculi, the tight junctions in the biliary tree keep these components within the bile secretory pathway. The secretion of bile components into the biliary tree is a major stimulus to bile flow, and the volume of bile flow is an osmotic process. Because bile salts combine to form spherical pockets, known as micelles, the salts themselves provide no osmotic activity. Instead, the cations that are secreted into the biliary tree along with the bile salt anion provide the osmotic load to draw water into the duct and to increase flow to keep bile electrochemically neutral. For this reason, bile maintains an osmolality approximately comparable to that of plasma.

After passage into the intestinal tract and reabsorption by the terminal ileum, bile acids are transported back to the liver for recycling bound to albumin. On the opposite side from the canalicular surface of the hepatocyte lies the sinusoidal surface, which contacts the space of Disse. In this contact area, the hepatocyte absorbs the circulating components of bile, an important step in the enterohepatic circulation. The passage of reabsorbed bile salts bound to albumin through the space of Disse allows uptake into the hepatocyte in an efficient process that involves sodium cotransport and sodium-independent pathways. In the less specific sodium-independent pathway, a number of organic anions are transported, including unconjugated and indirect bilirubin. The transport of bile salts across the canalicular membrane remains the rate-limiting step in bile salt excretion. Given the vast differences in concentration of bile salts, the transport of bile up an extreme concentration gradient is adenosine triphosphate dependent. Less than 5% of bile salts are lost each day in the stool. When sufficient quantities of bile salts reach the colonic lumen, the powerful detergent activity of the bile salts can cause inflammation and diarrhea. This can sometimes be seen after a cholecystectomy when the speed of the enterohepatic circulation of bile increases and may overwhelm the ability of the terminal ileum to absorb bile salts.

In addition to bile salts, bile contains proteins, lipids, and pigments. The major lipid components of bile are phospholipids and cholesterol. These lipids not only dispose of cholesterol from low- and high-density lipoproteins but also serve to protect hepatocytes and cholangiocytes from the toxic nature of bile. The sources of most biliary cholesterol are circulating lipoproteins and hepatic synthesis. Therefore, the biliary secretion of cholesterol actually serves to excrete cholesterol from the body.

Aside from absorption of nutrients from the intestinal tract, bile secretion from the liver serves an opposing function, namely, excretion of toxins and metabolites from the liver. Bile pigments such as bilirubin are breakdown products of hemoglobin and myoglobin. These products are transported in the blood, bound to albumin, to hepatocytes. Inside hepatocytes, they will be transferred into the endoplasmic reticulum and conjugated to form bilirubin glucuronides, known as conjugated or “direct” bilirubin. Bile pigment gives the color of bile and, when converted to urobilinogen by bacterial enzymes, gives stool its characteristic color.

Much of the bile flow is dependent on neural, humoral, and chemical stimuli. Vagal activity induces bile secretion as does the gastrointestinal hormone secretin. Cholecystokinin (CCK), secreted by the intestinal mucosa, serves to induce biliary tree secretion and gallbladder wall contraction, thereby augmenting excretion of bile into the intestines. Secreted bile will pass through the biliary tree into the intestine and be reabsorbed. The gallbladder serves as an extrahepatic storage site of bile, absorbing water and concentrating bile in an osmotic process performed through the active sodium transport. With the absorption of sodium and water across the gallbladder epithelium, the chemical composition of bile changes in the gallbladder lumen. Increases in cholesterol and calcium concentration calcium lead to decreased stability of phospholipid cholesterol vesicles. The reduced vesicle stability predisposes to nucleation of this stagnant pool of cholesterol and, thus, to cholesterol stone formation. The gallbladder neck and cystic duct also secrete glycoproteins to help protect the gallbladder from the detergent activity of bile. These glycoproteins also promote cholesterol crystallization.

An increase in the activity of the sphincter of Oddi in the fasting state ( Fig. 55.8 ), whose musculature is independent from the duodenal intestinal wall, increases pressure in the CBD, filling the gallbladder, which is capable of storing up to 300 mL of daily bile production, through a retrograde mechanism. This muscular sphincter normally maintains high tonic and phasic activity, which is inhibited by CCK. The passage of fat, protein, and acid into the duodenum induces CCK secretion from duodenal epithelial cells. CCK, as its name suggests, then causes gallbladder contraction, with intraluminal pressures up to 300 mm Hg. Vagal activity also induces gallbladder emptying but is a less powerful stimulus to gallbladder contraction than CCK. At the same time, CCK induces relaxation of the sphincter, causing bile flow more readily from the biliary tree. Coordinated with gallbladder contraction, the relaxation of this sphincter allows evacuation of up to 70% of the gallbladder contents within 2 hours of CCK secretion. During the fasting state, the oblique passage of the bile duct through the duodenal wall and the tonic activity of the sphincter prevent duodenal contents from refluxing into the biliary tree.

Fig. 55.8, Sphincter of Oddi. Because the sphincter is responsible for control of most bile flow, this sphincter maintains a high tonic contraction but is inhibited by cholecystokinin.

Biliary Tree Pathophysiology

Laboratory Tests

A hepatic panel tests a number of metabolic and functional aspects of the liver and biliary system.

For example, increase in levels of bilirubin and alkaline phosphatase will be determinative in a cholestatic process, but serum transaminase level is suggestive of hepatocyte physiology.

Hyperbilirubinemia could be secondary to conjugated bilirubin, possibly due to obstruction, or to unconjugated hyperbilirubinemia caused by increased synthesis, impaired hepatocyte uptake of unconjugated bilirubin, and decreased intracellular conjugation. Although this is an oversimplification of a complex process, derangements up to and including conjugation will be manifested as elevated unconjugated bilirubin levels. Elevation in serum bilirubin caused by obstruction of the biliary system will be identifiable in the frenulum of the tongue, sclera, or skin. It is important to check the frenulum first, as the level of bilirubin must reach to 2.5 mg/dL to be seen in sclera and above 5 mg/dL to be manifested in skin.

Imaging Studies

Plain Films

As the simplest radiographic study, plain radiographs are of limited use in the overall evaluation of biliary tree disease. Gallstones are not regularly seen by plain films, and even when they are seen, it rarely changes therapy. Therefore, the role of plain radiographs in the evaluation of possible biliary disease is limited to exclusion of other diagnoses, such as a duodenal ulcer with free air, small bowel obstruction, or right lower lobe pneumonia causing right upper quadrant pain.

Ultrasound

Transabdominal ultrasound is a sensitive, inexpensive, reliable, and reproducible test to evaluate most of the biliary tree, being able to separate patients with medical jaundice, in which the source of hyperbilirubinemia is from hemoglobin breakdown through the process of conjugation, from those with surgical jaundice, in which the hyperbilirubinemia occurs from a blockage of excretion. Therefore, this modality is seen as the study of choice for the initial evaluation of jaundice or symptoms of biliary disease. The finding of a dilated CBD in the setting of jaundice suggests an obstruction of the duct from stones, usually associated with pain, or from a tumor, which is commonly painless ( Fig. 55.9 ). Gallbladder diseases are regularly diagnosed by ultrasound because the superficial location of the gallbladder with no overlying bowel gas enables its evaluation by sound waves. Ultrasound has a high specificity and sensitivity for cholelithiasis, or gallstones. The density of gallstones allows crisp reverberation of the sound wave, showing an echogenic focus with a characteristic shadowing behind the stone ( Fig. 55.10 ). Most gallstones, unless impacted, will move with positional changes in the patient. This feature allows their differentiation from gallbladder polyps, which are fixed, and from sludge, which will move more slowly and does not have the sharp echogenic pattern of gallstones. Pathologic changes seen in many gallbladder diseases can be identified by ultrasound. For example, the gallbladder wall thickening and pericholecystic fluid seen in cholecystitis are visible by ultrasound ( Fig. 55.11 ). Porcelain gallbladder, with its calcified wall, will appear as a curvilinear echogenic focus along the entire gallbladder wall, with posterior shadowing ( Fig. 55.12 ). In addition to the division of medical versus surgical jaundice, ultrasound can sometimes identify the cause of obstructive jaundice, showing CBD stones or even cholangiocarcinoma.

Fig. 55.10, Ultrasound image of a gallstone in the gallbladder neck. The sharp echogenic wall of the gallstone (arrow) , with the characteristic posterior shadowing stripe under the stone, helps differentiate it from other intraluminal findings.

Fig. 55.11, Ultrasound image with acute cholecystitis and thickened gallbladder wall (arrows) .

Fig. 55.12, Ultrasound image of porcelain gallbladder. The curvilinear sharp echogenic focus (arrow) combined with substantial posterior shadowing helps confirm this diagnosis.

Hepatic Iminodiacetic Acid Scan

Although incapable of providing any precise anatomic delineation, biliary scintigraphy, also known as a hepatic iminodiacetic acid (HIDA) scan, can be used to evaluate the physiologic secretion of bile. The injection of an iminodiacetic acid, which is processed in the liver and secreted with bile, allows identification of bile flow. Therefore, the failure to fill the gallbladder 2 hours after injection demonstrates obstruction of the cystic duct, as seen in acute cholecystitis ( Figs. 55.13 and 55.14 ). In addition, the scan will identify obstruction of the biliary tree and bile leaks, which may be useful in the postoperative setting. HIDA scans can also be used to determine gallbladder function because the injection of CCK during a scan will document physiologic ejection of the gallbladder. This may be useful in patients with biliary tract pain but without stones because some patients have pain from impaired emptying, known as biliary dyskinesia. As a nuclear medicine test, the test demonstrates physiologic flow but does not provide fine anatomic detail, nor can it identify gallstones.

Fig. 55.14, Hepatic iminodiacetic acid (HIDA) scan showing nonfilling of the gallbladder. With no filling of the gallbladder (arrows) even on delayed images, HIDA confirms occlusion of the cystic duct, the characteristic feature of acute cholecystitis.

Computed Tomography

Although ultrasound is clearly the first test of choice for delineation of biliary disease, CT provides superior anatomic information and therefore is indicated when more anatomic delineation is required. Because most gallstones are radiographically isodense to bile, many will be indistinguishable from bile. However, because ultrasound is operator dependent and provides no anatomic reconstruction of the biliary tree, CT can be used to identify the cause and site of biliary obstruction ( Fig. 55.15 ). When it is performed for the evaluation of hepatic or pancreatic parenchyma or possible neoplastic processes, CT is invaluable in preoperative planning, and the use of arterial phase, portal venous phase, and delayed phase imaging, known as a triple-phase CT, has essentially replaced diagnostic angiography of the liver.

Magnetic Resonance Imaging and Magnetic Resonance Cholangiopancreatography

Magnetic resonance imaging (MRI) uses the water in bile to delineate the biliary tree and thus provides superior anatomic definition of the intrahepatic and extrahepatic biliary tree and pancreas. Although management of most patients with biliary disease does not require the fine detail of anatomic evaluation shown by cross-sectional imaging, MRI is noninvasive, requires no radiation exposure, and can prove extremely useful in planning resection of biliary or pancreatic neoplasms or management of complex biliary disease. By use of the water content of bile, a cholangiopancreatogram can be created ( Fig. 55.16 ), which makes it an excellent modality for cross-sectional imaging of the biliary tree.

Fig. 55.16, Normal magnetic resonance cholangiopancreatography image. Note the normal common bile duct (CBD) and pancreatic duct (PD) .

Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive test using endoscopy and fluoroscopy to inject contrast material through the ampulla to image the biliary tree ( Fig. 55.17 ). Although it does carry a complication rate of up to 10%, its usefulness lies in its ability to diagnose and to treat many diseases of the biliary tree. For patients with malignant obstruction, ERCP can be used to provide tissue samples for diagnosis while also decompressing an obstruction, but it does not stage disease accurately. Many benign diseases, such as choledocholithiasis, can be easily treated by endoscopic means. ERCP has also proven extremely useful in the diagnosis and treatment of complications of biliary surgery.

Percutaneous Transhepatic Cholangiography

Interventional radiologic techniques can be used in the evaluation of biliary anatomy. Similar to ERCP, percutaneous transhepatic cholangiography (PTC) is an invasive procedure used to evaluate the biliary tree. A needle is passed directly into the liver to access one of the biliary radicals, and the tract is then used for contrast imaging and can serve to allow insertion of transhepatic catheters for drainage and sometimes biopsy. It can be useful for patients with intrahepatic biliary disease or in whom ERCP is not technically feasible; PTC can decompress biliary obstruction and stent obstructions nonoperatively and can provide anatomic information for biliary reconstruction ( Fig. 55.18 ).

Intraoperative Cholangiography

Another imaging tool for the diagnosis of biliary tract abnormalities is intraoperative cholangiography. With the injection catheter inserted through the cystic duct during a cholecystectomy or through another point in the biliary tree, intraoperative cholangiography can help delineate anomalous biliary anatomy, identify choledocholithiasis, or guide biliary reconstruction. Some surgeons advocate routine cholangiography during cholecystectomy. Advocates for routine cholangiography note that common duct injuries can be identified and managed immediately when cholangiography is used routinely. However, because it adds operative time and fluoroscopic exposure to the operation, many surgeons use intraoperative cholangiography selectively during the performance of a cholecystectomy. Although debated, the routine use of intraoperative cholangiography does not reduce significantly the incidence of injury to the biliary tree during laparoscopic cholecystectomy. Indications for the selective use of cholangiography include pain on the day of operation, abnormal hepatic function panel, anomalous or confusing biliary anatomy, and alteration in anatomy that precludes the ability to perform ERCP after cholecystectomy, such as Roux-en-Y gastric bypass, dilated biliary tree, or any preoperative suspicion of choledocholithiasis ( Box 55.1 ).

Box 55.1

Indications for selective cholangiography.

Pain at time of operation
Abnormal hepatic function panel
Anomalous or confusing biliary anatomy
Inability to perform postoperative endoscopic retrograde cholangiopancreatography
Dilated biliary tree
Any suspicion of choledocholithiasis

Endoscopic Ultrasound

Although of limited use in the evaluation of gallbladder disease or intrahepatic disease of the biliary tree, endoscopic ultrasound is valuable in the assessment of distal CBD and ampulla. With the close apposition of the distal CBD and pancreas to the duodenum, sound waves generated by endoscopic ultrasound provide detailed evaluation of the bile duct and ampulla; this has proved most useful in assessing tumors for invasion into vascular structures. Echoendoscopes are subdivided into those that scan perpendicular to the long axis of the endoscope, known as radial echoendoscopes, and those that scan parallel, known as linear echoendoscopes. Radial echoendoscopes are most useful for providing a tomographic evaluation, whereas linear echoendoscopes can guide interventions such as needle biopsies under real-time ultrasound guidance ( Fig. 55.19 ).

Fluorodeoxyglucose Positron Emission Tomography

Fluorodeoxyglucose positron emission tomography (FDG PET) exploits the metabolic difference between a highly metabolically active tissue, such as a neoplasm, and normal tissue. With the injection of a radiolabeled glucose molecule, FDG PET scans can differentiate benign and malignant lesions, detect recurrence, and identify metastatic disease. Unfortunately, FDG PET is incapable of demonstrating carcinomatosis and, given the high metabolism of the immune system, is of limited value in the setting of infection or inflammation.

Bacteriology

The biliary tree inserts into the duodenum and therefore cannot be considered truly sterile. Through a low bacterial load and with the flow of bile, infection in the absence of obstruction is rare. However, with the presence of stones or obstruction, the likelihood of bacterial infection increases. The most common types of bacteria found in biliary infections are Enterobacteriaceae, such as Escherichia coli , Klebsiella , and Enterobacter , followed by Enterococcus spp.

Prophylactic antibiotics should be used in most patients undergoing interventions in the biliary tree, such as ERCP or PTC. To cover the most common bacterial species, a first- or second-generation cephalosporin or fluoroquinolone should suffice. For those undergoing elective laparoscopic cholecystectomy for biliary colic, no antibiotic prophylaxis is necessary. However, antibiotics should be used for any patient with suspected or documented infection of the biliary tree, such as acute cholecystitis or ascending cholangitis, and should be chosen to cover gram-negative bacteria and anaerobes.

Benign Biliary Disease

Calculous Biliary Disease

Cholelithiasis is the most common disease of gallbladder and biliary tree, affecting 10% to 15% of the population. Gallstones are generally classified into two major subtypes, cholesterol and pigment stones, depending on the principal solute that precipitates into a stone. More than 70% of gallstones in the United States are formed by precipitation of cholesterol and calcium, and pure cholesterol stones account for less than 10%. Pigment stones can be divided into black stones, as seen in hemolytic conditions and cirrhosis, and brown stones, which tend to be found in the bile ducts and are thought to be secondary to infection. The difference in color arises from incorporation of cholesterol into the brown stones. Because black pigment stones occur in hemolytic states from concentration of bilirubin, they are found almost exclusively in the gallbladder. Alternatively, brown stones can occur within the biliary tree and suggest a disorder of biliary motility and associated bacterial infection.

Four major factors explain most gallstone formation: supersaturation of secreted bile, concentration of bile in the gallbladder, crystal nucleation, and gallbladder dysmotility. High concentrations of cholesterol and lipid in bile secretion from the liver constitute one predisposing condition to cholesterol stone formation, whereas increased hemoglobin processing is seen in most patients with pigment stones. Once in the gallbladder, bile is concentrated further through the absorption of water and sodium, increasing the concentrations of the bile solutes and calcium. Bile salts act to solubilize cholesterol. With respect to cholesterol stones ( Fig. 55.20 ), cholesterol precipitates out into crystals when the concentration in the gallbladder vesicles exceeds the solubility of cholesterol ( Fig. 55.21 ). Crystal formation is further accelerated by pronucleating agents, including glycoproteins and immunoglobulins. Finally, abnormal gallbladder motility can increase stasis in the gallbladder, allowing more time for solutes to precipitate in the gallbladder. Therefore, increased stone formation can be seen in conditions associated with impaired gallbladder emptying, such as in prolonged fasting states, with use of total parenteral nutrition, after vagotomy, and with use of somatostatin analogues.

Fig. 55.20, Gallbladder with characteristic yellow cholesterol stones.

Fig. 55.21, Triangle of solubility. With the three major components of bile that determine cholesterol solubility and stability, each can be quantified by molar percentage to show a relative ratio to the other two. Cholesterol is completely soluble in only the small area in the left lower corner, where a clear micellar solution exists, below the closed circles. Just above this, in the area between the open and closed circles , cholesterol is supersaturated but stable and thus crystallized only with stasis. In the remainder of the triangle, cholesterol is significantly supersaturated and unstable. In this region, crystals form immediately.

Natural History

Gallstones become symptomatic when they obstruct a visceral structure such as a cystic duct. However, gallstones often remain asymptomatic, only found incidentally on imaging. Biliary colic, caused by temporary blockage of the cystic duct, tends to occur after a meal in which the secretion of CCK leads to gallbladder contraction. Stones that do not obstruct the cystic duct or pass through the entire biliary tree into the intestines without impaction do not cause symptoms. Only 20% to 30% of patients with asymptomatic stones will develop symptoms within 20 years, and because approximately 1% of patients with asymptomatic stones develop complications of their stones before onset of symptoms, prophylactic cholecystectomy is not warranted in asymptomatic patients.

Certain subsets of patients, however, constitute a higher risk pool, so prophylactic cholecystectomy should be considered. Among these are patients with hemolytic anemias, such as sickle cell anemia. These patients have an extremely high rate of pigment stone formation, and cholecystitis can precipitate a crisis. Patients with a calcified gallbladder wall (known as porcelain gallbladder), those with large (>2.5 cm) gallstones, and those with a long common channel of bile and pancreatic ducts all have a higher risk of gallbladder cancer and should consider cholecystectomy. In addition, patients with asymptomatic gallstones undergoing bariatric surgery may also benefit from cholecystectomy; however, it is still controversial. Not only does rapid weight loss favor stone formation, but also, after gastric bypass, ERCP to remove CBD stones in ascending cholangitis is extremely challenging and usually unsuccessful. Also, in diabetic patients with gallstones, one should have lower threshold for cholecystectomy, considering higher rate of gangrene.

Nonoperative Treatment of Cholelithiasis

Medical treatment of gallstones is generally unsuccessful and includes oral bile salt therapy, contact dissolution that requires cannulation of the gallbladder and infusion of organic solvent, and extracorporeal shock wave lithotripsy. With the dissolution strategies, unacceptable recurrence rates of up to 50% limit their application to the most select group of patients. Extracorporeal shock wave lithotripsy has a lower recurrence rate, approximately 20%, and can be used in patients with single stones 0.5 to 2 cm in size. The widespread use, safety, and efficacy of laparoscopic cholecystectomy have relegated nonoperative therapy to patients for whom general anesthesia presents a prohibitively high risk.

Chronic Cholecystitis

Recurrent attacks of biliary colic, with only temporary occlusion of the cystic duct, can cause inflammation and scarring of the neck of the gallbladder and cystic duct. This process causes fibrosis as histologic evidence of repeated self-limited episodes of inflammation and is called chronic cholecystitis. The diagnosis of chronic cholecystitis lies along a continuum with biliary colic because it results from recurrent attacks. Therefore, the presentation is that of symptomatic cholelithiasis, or biliary colic. Pain occurring after ingestion of a fatty meal, with the attendant increase in CCK secretion in response to duodenal intraluminal fat, is classic for biliary colic, although only 50% of patients will report an association with food. Pain from stones tends to locate in the epigastrium or right upper quadrant and may radiate around to the scapula. Biliary colic is a misnomer as the pain is typically constant rather than colicky. These attacks of pain generally last a few hours. Pain lasting longer than 24 hours or associated with fever suggests acute cholecystitis. The pain of biliary colic, even in the absence of cholecystitis, may also cause other gastrointestinal symptoms, such as bloating, nausea, or even vomiting.

Symptomatic stones constitute a risk profile different from that of asymptomatic stones, with a higher likelihood of complications. Therefore, symptomatic cholelithiasis is an indication for cholecystectomy. Documented stones and symptoms are the most common indications to perform a cholecystectomy.

Diagnosis

The diagnosis of chronic cholecystitis relies on a history consistent with biliary tract disease. Transabdominal ultrasonography reliably documents the presence of cholelithiasis. Ultrasound can provide other important information, such as CBD dilation, gallbladder polyps, porcelain gallbladder, or evidence of hepatic parenchymal processes. Cholesterolosis, or the accumulation of cholesterol found in gallbladder mucosal macrophages, can also be seen ( Fig. 55.22 ). Even in the absence of frank stones, so-called sludge found in the gallbladder on ultrasonography, with appropriate symptoms, is consistent with biliary colic.

Fig. 55.22, Ultrasound image of cholesterolosis.

Treatment

Patients with sufficient symptoms from gallstones should undergo elective cholecystectomy. Cholecystectomy carries a low-risk profile but is not without complications, so an analysis of risks and benefits is important. Because patients with mild symptoms have a low rate of complications from gallstones (1%–3%/year), observation and dietary and lifestyle changes are appropriate in this population. Patients with more severe or recurrent symptoms have a higher rate of complications of the disease (7%/year), so elective laparoscopic cholecystectomy is warranted. In more than 90% of patients, cholecystectomy is curative, leaving them symptom free.

Acute Calculous Cholecystitis

Acute cholecystitis is the result of a blockage of the cystic duct and is called acute calculous cholecystitis when the blockage is by a stone. In chronic cholecystitis or biliary colic, the blockage is temporary and repetitive, while in acute cholecystitis, the blockage does not resolve, leading to inflammation with edema and subserosal hemorrhage. Obstruction is followed by infection of the stagnant pool of bile. Without resolution of the obstruction, the gallbladder will progress to ischemia and necrosis. Eventually, acute cholecystitis becomes acute gangrenous cholecystitis and, when complicated by infection with a gas-forming organism, acute emphysematous cholecystitis ( Fig. 55.23 ).

Fig. 55.23, Computed tomography scan of emphysematous cholecystitis. Significant pericholecystic inflammatory changes and air in the gallbladder wall (arrows) are signs of emphysematous cholecystitis.

Presentation

The inflammatory changes in the gallbladder wall are manifested as fever and right upper quadrant pain. On exam, patients will exhibit tenderness to palpation and guarding in the right upper quadrant. When the gallbladder lumen cannot fully empty because of a stone in the gallbladder neck, visceral pain fibers are activated, causing pain in the epigastrium or right upper quadrant. The same luminal obstruction of biliary colic but associated with sufficient stasis, pressure, and bacterial inoculum creates infection and, thereby, inflammation, therefore progressing to acute cholecystitis. With this infection and inflammation, the right upper quadrant pain of biliary colic will be accompanied by tenderness noted on palpation of the right upper quadrant. Specifically, the voluntary cessation of respiration when the examiner exerts constant pressure under the right costal margin, known as a Murphy sign, suggests inflammation of the visceral and parietal peritoneal surfaces and can be seen in diseases such as acute cholecystitis and hepatitis. Alternatively, biliary colic in the absence of infection and inflammation is not associated with any reproducible physical examination finding or systemic symptom.

There have been multiple grading systems evaluating severity of cholecystitis, most commonly the Tokyo Guidelines ^, and The American Association for the surgery of Trauma (AAST) Emergency General Surgery (EGS) guidelines. AAST EGS categorizes acute cholecystitis into five grades, grade 1 being localized inflammation, to grade 5 with pericholecystic abscess, bilioenteric fistula, and peritonitis. The Tokyo Guidelines also grade the systemic effect of cholecystitis such as organ failure. Both classifications are helpful to categorize the management of these patients and consider treatment options relative to their severity of disease.

Mild elevations of alkaline phosphatase, bilirubin, and transaminase levels and leukocytosis support the diagnosis of acute cholecystitis. However, given that the CBD is not obstructed, profound jaundice in the setting of a picture of acute cholecystitis is rare and should raise the suspicion of cholangitis. Mirizzi syndrome should be suspected, in which inflammation or a stone in the gallbladder neck leads to inflammation of the adjoining biliary system, with obstruction of the common hepatic duct.

Diagnosis

Transabdominal ultrasonography is a sensitive, inexpensive, and reliable tool for the diagnosis of acute cholecystitis, with a sensitivity of 85% and specificity of 95%. In addition to identifying gallstones, ultrasound can demonstrate pericholecystic fluid ( Fig. 55.24 ), gallbladder wall thickening, and even a sonographic Murphy sign, documenting tenderness specifically over the gallbladder. In most cases, an accurate history and physical examination, along with supporting laboratory studies and an ultrasound examination, make the diagnosis of acute cholecystitis. In atypical cases, a HIDA scan may be used to demonstrate obstruction of the cystic duct, which definitively diagnoses acute cholecystitis. Filling of the gallbladder during a HIDA scan essentially eliminates the diagnosis of cholecystitis. CT may show similar findings to ultrasound with pericholecystic fluid, gallbladder wall thickening, and emphysematous changes, but CT is less sensitive than ultrasound for the diagnosis of acute cholecystitis.

Fig. 55.24, Ultrasound image of pericholecystic fluid. The thickened gallbladder wall with pericholecystic fluid (arrow) indicates acute cholecystitis.

Treatment

Treatment of acute cholecystitis largely depends on the severity of disease and the physiologic status of the patient, and treatment can vary from immediate surgical intervention to conservative management. Although the primary pathophysiologic event in acute cholecystitis is the obstruction of the cystic duct and infection is a secondary event that follows stasis and inflammation, most cases of acute cholecystitis are complicated by superinfection of the inflamed gallbladder. Patients are given nothing by mouth, and intravenous (IV) fluids and parenteral antibiotics are started. Given that gram-negative aerobes are the most common organisms found in acute cholecystitis, followed by anaerobes and gram-positive aerobes, broad-spectrum antibiotics are warranted. Parenteral narcotics are usually required to control the pain.

Cholecystectomy, whether open or laparoscopic, is the treatment of choice for acute cholecystitis. The timing of operative intervention in acute cholecystitis has long been a source of debate. In the past, many surgeons advocated for delayed cholecystectomy with patients managed nonoperatively during their initial hospitalization and discharged home with resolution of symptoms. An interval cholecystectomy was then performed at approximately 6 weeks after the initial episode. More recent studies have shown that early in the disease process (within the first week), the operation can be performed laparoscopically with equivalent or improved morbidity, mortality, and length of stay as well as a similar conversion rate to open cholecystectomy. In addition, approximately 20% of patients initially admitted for nonoperative management failed to respond to medical treatment before the planned interval cholecystectomy and required surgical intervention. Initial nonoperative therapy remains a viable option for patients who present in a delayed fashion and should be decided on an individual basis.

Given the inflammatory process occurring in the porta hepatis, early conversion to open cholecystectomy should be considered when delineation of anatomy is not clear or when progress cannot be made laparoscopically. With substantial inflammation, a partial cholecystectomy, transecting the gallbladder at the infundibulum with cauterization of the remaining mucosa, is acceptable to avoid injury to the CBD. Some patients present with acute cholecystitis but have a prohibitively high operative risk. For these patients, a percutaneously placed cholecystostomy tube should be considered. Frequently performed with ultrasound guidance under local anesthesia with some sedation, cholecystostomy can act as a temporizing measure by draining the infected bile. Percutaneous drainage results in improvement in symptoms and physiology, allowing a delayed cholecystectomy 3 to 6 months after medical optimization. In patients with cholecystostomy tubes, when fluoroscopy shows a patent cystic duct, the cholecystostomy tube can be removed and the decision for cholecystectomy determined by the patient’s ability to tolerate surgical intervention.

Tokyo Guidelines, revised in 2018, predict the severity of gallbladder disorder, prognosis, and rate of conversion or bail-out procedure, can be used as a guideline to plan the management.

Choledocholithiasis

CBD stones, or choledocholithiasis, are generally silent, and are seen in up to 10% of patients undergoing biliary imaging. ^, Primary common duct stones arise de novo in the bile duct, and secondary common duct stones pass from the gallbladder into the bile duct. Primary common duct stones are generally brown pigment stones, a combination of precipitated bile pigments and cholesterol. Brown pigment stones are associated with bacterial infections where free bilirubin is formed by hydrolyzing enzymes released by bacteria and then precipitates. Brown pigment stones are more common in Asian populations. Secondary stones are more common in the United States. Retained stones are secondary stones found in bile duct within 2 years of cholecystectomy and occur in 1% to 2% of patients ( Fig. 55.25 ).

When symptomatic, common duct stones clinical manifestations range from biliary colic to obstructive jaundice, including darkening of the urine, scleral icterus, and lightening of the stools. Jaundice with choledocholithiasis is more likely to be painful because the onset of obstruction is acute, causing rapid distention of the bile duct and activation of pain fibers. Cholangitis, first described by Jean Martin Charcot in 1877, is ascending infection of CBD secondary to obstruction and increased intraluminal pressure. Cholangitis presents with right upper quadrant pain, fever, and jaundice, known as Charcot triad, and may progress to septic shock with mental status changes, and hypotension, known as Reynolds pentad, which is an ominous sign, and mortality approaches 100% without prompt treatment.

Diagnosis

Asymptomatic choledocholithiasis is usually an incidental finding. Biliary type pain, jaundice, an abnormal liver function panel, and a dilated bile duct, usually more than 8 mm, are all highly suggestive of choledocholithiasis. Liver function panel abnormalities on their own are neither sensitive nor specific. Even without symptoms of biliary colic, a dilated bile duct in the presence of gallstones suggests choledocholithiasis.

Magnetic resonance cholangiopancreatography (MRCP), as mentioned earlier, is highly sensitive (>90%) and specific (>99%) in identifying CBD stones ( Fig. 55.26 ). But as a noninvasive test, it will stay at diagnostic level, and a treatment procedure, such as ERCP or CBD exploration, still has to be done after diagnosis. Some surgeons resorted to preoperative MRCP to determine the need for preoperative ERCP.

Fig. 55.26, Magnetic resonance cholangiopancreatography with choledocholithiasis. The dilated common bile duct ends abruptly with a convex intraluminal filling defect (arrow) consistent with choledocholithiasis.

ERCP is also highly sensitive and specific for choledocholithiasis ( Fig. 55.27 ) and often is the therapeutic procedure by clearing the duct in more than 75% of patients during first procedure and in 90% with repeated ERCP. A sphincterotomy with a balloon sweep is done and stones are extracted, with a less than 5% to 8% complication rate. Indications for preoperative ERCP include cholangitis, biliary pancreatitis, and patients with multiple comorbidities. However, some studies have suggested higher risk of surgical site infection in patients who receive preoperative ERCP before cholecystectomy.

Fig. 55.27, Endoscopic retrograde cholangiopancreatography (ERCP) with choledocholithiasis. With retrograde injection of contrast material, a filling defect noted within the lumen of the common bile duct (arrow) identifies choledocholithiasis. ERCP can also be used to remove the stone through sphincterotomy and balloons or baskets.

Finding of choledocholithiasis via intraoperative cholangiogram during cholecystectomy may be managed by either CBD exploration or postoperative ERCP. The experience of the surgeon with open biliary exploration may be a factor determining which route is chosen.

PTC can also be used to treat choledocholithiasis in case of unsuccessful ERCP, or anatomical difficulty for ERCP such as the patients’ post-Roux-en-Y procedures. PTC is as effective as ERCP in patients with dilated biliary system with similar complication rate, but less effective in a nondilated biliary tree patient.

In short, in patients with likelihood of CBD stones, other modalities such as ERCP or MRCP must be considered on top of ultrasound. Choledocholithiasis identified but not removed during cholecystectomy mandates ERCP for stone extraction.

Treatment

Treatment for choledocholithiasis is generally ERCP or CBD exploration, which can be performed via laparoscopic or open technique. Endoscopic sphincterotomy with stone extraction is effective for the treatment of choledocholithiasis. In the preoperative setting, it can clear the duct of stones, and when it is unsuccessful at removal of all stones, it will alter intraoperative decision-making. More than half of patients managed by ERCP without cholecystectomy will have recurrent symptoms of biliary tract disease. Large stones (usually more than 2.5 cm), altered gastric or duodenal anatomy such as Roux-en-Y, impacted stones, intrahepatic stones, or multiple stones, are the most common causes of failure of ERCP.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here