Biliary Tract Anatomy and Embryology

• Cholelithiasis affects 10% to 15% of the adult population in developed and developing societies, which equates to 20 to 25 million Americans.
• Laparoscopic cholecystectomy is a common surgery in the United States with a low complication rate
• Knowledge of biliary tract anatomy, embryology, and anomalies is important for biliary surgeons in decision-making.
• Biliary tract anatomy and embryology are linked to the liver and pancreas.

Anatomy and Embryology

• In the fourth week of human embryo development, a projection appears in the ventral wall of the primitive midgut at the primitive duodenum level
• At the 3-mm stage, three buds are recognizable.
• The cranial bud develops into two liver lobes.
• The caudal bud becomes the gallbladder and extrahepatic biliary tree.
• Part of the caudal bud becomes the cystic diverticulum by day 26, that forms the cystic duct (CD) and gallbladder by week four.
• The ventral pancreas, which becomes the pancreatic head and uncinate process, also develops from the caudal bud.
• The third primitive bud develops from the midgut's dorsal surface and becomes the anlage of the pancreatic head, neck, body, and tail.
• At the 5-mm stage, the primitive gallbladder and common bile duct (CBD) have appeared.
• At the 7-mm stage, the liver and hepatic ducts have formed, along with the gallbladder, CD, and ventral pancreas.
• At this stage, the stomach has begun to form, and the ventral pancreas has developed from the dorsal mesogastrium.
• By the 12-mm stage, the ventral pancreatic bud has rotated 180 degrees clockwise around the duodenum
• This rotation causes the fusion of the ventral and dorsal buds to form the complete pancreas by the sixth or seventh week.
• Annular pancreas, a ringlike formation around the duodenum's second portion, happens when rotation occurs in different directions.
• When the ventral and dorsal buds fuse correctly, their ductal systems interconnect.
• The duct from the dorsal bud degenerates usually, leaving the ventral pancreatic duct to be the main pancreatic duct.
• In another week, a completely open lumen forms in the gallbladder, bile ducts, and pancreatic ducts.
• By the 12th week of fetal life, the liver begins to secrete bile, and the pancreas secretes fluid that flows through the extrahepatic biliary tree and pancreatic ducts, respectively, into the duodenum.

Intrahepatic Ducts

• The anatomy of the intrahepatic ducts is closely related to the liver's anatomy.
• The liver's lobar and segmental anatomy is determined by the branching of the portal vein, hepatic artery, and biliary tree as they enter the parenchyma at the hilum.
• All three structures run parallel and bifurcate before entering the liver.
• This bifurcation divides the liver into left and right lobes.
• According to the Couinaud classification:
  • The caudate lobe is segment I
  • Segments II to IV are on the left
  • Segments V to VIII are on the right
• The right and left hepatic ducts receive biliary drainage from the right and left liver, respectively.
• The left hepatic duct forms within the umbilical fissure from the union of three segmental ducts draining the liver's left side (segments II through IV).
• The left hepatic duct crosses the base of segment IV (medial segment of the left lobe) horizontally to join the right hepatic duct and form the common hepatic duct (CHD).
• The right hepatic duct drains segments V through VIII
• The right hepatic duct is formed from the union of the right posterior and right anterior segmental ducts.
  • The right posterior segmental duct forms from the confluence of ducts draining segments VI and VII.
  • The right anterior segmental duct is formed by the union of the ducts draining segments V and VIII
• In 15% to 20% of cases, the right posterior duct drains into the left hepatic duct.
• The posterior right duct usually passes superior to the right anterior portal vein (80%).
• The ducts from segments II and III join to the left of the intrahepatic left portal vein, and the segment IV duct joins to the right of the umbilical fissure, forming the main left duct.
• The main left (horizontal) and right hepatic ducts (vertical) join at the hilum to form the CHD in 56% of cases.
• The biliary drainage of the caudate lobe (segment I) is variable.
  • In approximately 80% of individuals, the caudate lobe drains into both the right and left hepatic ducts.
  • In 15% of cases, the caudate lobe drains only into the left hepatic duct
  • In the remaining 5% of cases, the caudate is drained exclusively by the right hepatic duct.

Extrahepatic Ducts

• In most patients, the right and left hepatic ducts join to form the CHD at a bifurcation
• The junction may occur as a wide or acute angle, or the two hepatic ducts may run parallel before joining.
• In some patients, three hepatic ducts join to form the CHD.
• Usually, the hepatic ducts meet just outside the liver parenchyma, with the CD entering 2 to 3 cm distally.
• Occasionally, the two hepatic ducts do not unite until after the CD has joined the right hepatic duct.
• The CHD extends for a variable length from the junction of the right and left hepatic ducts to the entrance of the CD into the gallbladder.
• The CBD is formed by the union of the cystic and common hepatic ducts.
• The CBD is approximately 8 cm in length, but it varies in length according to the union point of the CD and the CHD.
• The normal diameter of the CBD ranges from 4 to 9 mm and is considered enlarged if the duct diameter exceeds 10 mm.
• The upper third (supraduodenal portion) of the CBD courses downward in the free edge of the lesser omentum, anterior to the portal vein and to the right of the proper hepatic artery.
• The middle third (retroduodenal portion) of the CBD passes behind the first duodenum portion, lateral to the portal vein and anterior to the inferior vena cava.
• The lower third (intrapancreatic portion) of the CBD traverses the posterior aspect of the pancreas through a tunnel or groove to enter the duodenum's second portion, where it is usually joined by the pancreatic duct.
• The intramural or intraduodenal portion of the CBD passes obliquely through the duodenal wall to enter the duodenum at the papilla of Vater.
• The relationship between the lower CBD and pancreatic duct is variable:
  • Rarely, the two unite outside the duodenal wall forming a long common channel.
  • Usually, they join within the duodenal wall to form a short common channel.
  • Rarely, enter the duodenum independently through separate orifices.
• The lower portion of the CBD and the terminal portion of the pancreatic duct are enveloped and regulated by the sphincter of Oddi.
• In 5% to 10% of patients with pancreas divisum, the dorsal pancreatic duct enters the duodenum through an accessory sphincter, and the ventral pancreatic duct joins the CBD at the sphincter of Oddi.
• The extrahepatic bile ducts contain a columnar mucosa surrounded by a connective tissue layer.
• The surface is relatively flat, with basal nuclei and an absent or small nucleolus.
• The lamina propria consists of collagen, elastic fibers, and vessels.
• Occasional lymphocytes are found, and pancreatic acini and ducts may be seen in the wall of the intrapancreatic portion of the distal CBD.
• Muscle fibers in the bile duct are sparse and discontinuous, usually longitudinal, but circular fibers are occasionally observed.
• The distal CBD develops a more substantial muscle layer in the intrapancreatic portion, which becomes prominent at the sphincter of Oddi, where distinct bundles of longitudinal and circular fibers are identified.

Gallbladder and Cystic Duct

• The gallbladder is a pear-shaped organ that lies on the inferior surface of the liver between Couinaud segments IV and V
• The gallbladder ranges from 7 to 10 cm in length and 2.5 to 3.5 cm in width.
• Its volume varies considerably, being large during fasting and small after eating.
• A moderately distended gallbladder has a capacity of 50 to 60 mL of bile but may become much larger in certain pathologic states, containing up to 300 mL.
• The gallbladder has four areas: the fundus, body, infundibulum, and neck.
  • The fundus is commonly located at the level of the ninth costal cartilage and the external border of the right rectus muscle and is covered by peritoneum because it projects beyond the liver's inferior border.
  • The body occupies the gallbladder fossa of the liver and has intimate contact with the duodenum's first and second portions.
  • The infundibulum is the portion of the body between the neck and the entrance point of the cystic artery, and when this portion is dilated, it becomes the Hartmann pouch.
  • The neck curves forming an S-shaped structure that becomes the CD where the cystic artery is usually found, coursing parallel within the connective tissue attaching the gallbladder neck to the liver.
• The gallbladder wall consists of five layers: the epithelium, lamina propria, smooth muscle, perimuscular subserosal connective tissue, and serosa.
• The gallbladder has no muscularis mucosae or submucosa.
• Most cells in the mucosa are columnar cells that are capable of absorption and active secretion.
  • These cells align in a single row with slightly eosinophilic cytoplasm, apical vacuoles, and basal or central nuclei.
• The lamina propria contains nerve fibers, vessels, lymphatics, elastic fibers, loose connective tissue, mast cells, and macrophages.
• The muscle layer is a loose arrangement of circular, longitudinal, and oblique fibers without well-developed layers.
• Ganglia are found between smooth muscle bundles, and the subserosa is composed of a loose arrangement of fibroblasts, elastic and collagen fibers, vessels, nerves, lymphatics, and adipocytes.
• Rokitansky-Aschoff sinuses are invaginations of epithelium into the lamina propria, muscle, and subserosal connective tissue.
  • Present in approximately 40% of normal gallbladders and in abundance in almost all inflamed gallbladders.
• The ducts of Luschka are tiny bile ducts found around the muscle layer on the gallbladder's hepatic side.
  • Found in approximately 10% of normal gallbladders and have no relation to Rokitansky-Aschoff sinuses or cholecystitis.
• The CD arises from the gallbladder and joins the CHD to form the CBD.
• The length of the CD is variable, averaging between 2 and 4 cm.
• The CD usually courses downward in the hepatoduodenal ligament to join the lateral aspect of the supraduodenal CHD at an acute angle.
• Occasionally, the CD may join the right hepatic duct or extend downward to join the retroduodenal duct.
• The CD may join the CHD:
  • At a right angle
  • Run parallel to the CHD
  • Enter the CHD dorsally
  • On its left side
  • Behind the duodenum
  • Directly enter the duodenum (rarely)
• The CD contains a variable number of mucosal folds, similar to those found in the gallbladder neck, called valves of Heister, but these spiral folds do not have a valvular function.
• Variations in the length and course of the CD and its union point with the CHD are common.

Calot Triangle

• Calot described a triangular anatomic region in 1891 that is formed by the CHD medially, the CD laterally, and the cystic artery superiorly.
• Calot triangle comprises the triangular area with an upper boundary that is formed by the inferior margin of the right liver lobe.
• Appreciation of Calot triangle anatomy is essential during a cholecystectomy because important structures pass through this area.
• The cystic artery usually arises as a branch of the right hepatic artery within the hepatocystic triangle.
• A replaced or aberrant right hepatic artery arising from the superior mesenteric artery usually courses through the triangle's medial aspect, posterior to the CD.
• Aberrant or accessory hepatic ducts also may pass through Calot triangle before joining the CD or CHD.
• Clear visualization of the hepatocystic triangle is essential during a cholecystectomy with accurate identification of all structures within this triangle.

Sphincter of Oddi

• The sphincteric system of the distal bile duct and pancreatic duct is the sphincter of Oddi.
• It regulates bile and pancreatic juice flow toward the duodenum, preventing duodenal content regurgitation into the biliary tree and diverting bile into the gallbladder, leading to its distention.
• The sphincter is subdivided into sections and contains circular and longitudinal fibers.
• The sphincter mechanism functions independently from the surrounding duodenal musculature and has separate sphincters for the distal bile duct, the pancreatic duct, and the ampulla.
• In >90% of the population, the common channel, where the biliary and pancreatic ducts join, is <1.0 cm long and lies within the ampulla.
• A common channel longer than 1.0 cm, or biliary and pancreatic ducts that open separately into the duodenum, may cause biliary or pancreatic problems.
• The sphincter mechanism has four sphincters containing circular and longitudinal smooth muscle fibers: the superior and inferior sphincter choledochus, the sphincter pancreaticus, and the sphincter of the ampulla.

Vascular

• The hepatic artery provides 25% of the liver's blood supply
• The rest is provided by the portal vein.
• The hepatic artery is derived from the celiac trunk in 55% of cases.
• The common hepatic and the right or left hepatic arteries may arise from vessels other than the celiac trunk.
• The cystic artery and the right and left hepatic arteries supply blood to the right and left hepatic ducts and the CHD's upper portion.
• The supraduodenal bile duct is supplied by arterial branches from the right hepatic, cystic, posterior superior pancreaticoduodenal, and retroduodenal arteries.
• The axial blood supply of the supraduodenal bile duct has important arteries running parallel to the duct at the 3 and 9 o’clock positions.
• Approximately 60% of the blood supply to the supraduodenal bile duct originates inferiorly from the pancreaticoduodenal and retroduodenal arteries.
• 38% of the blood supply originates superiorly from the right hepatic artery and CD artery.
• Injury to this axial blood supply may result in ischemic ductal stricture.
• If more than 50% of the CBD's diameter is transected, it will lead to stricture if primarily closed, requiring jejunal limb reconstruction.
• Only 2% of the arterial blood supply to the supraduodenal bile duct is segmental (nonaxial).
• These small segmental arterial branches arise directly from the proper hepatic artery as it ascends in the hepatoduodenal ligament, adjacent to the CBD.
• The retroduodenal and pancreaticoduodenal arteries supply blood to the retroduodenal and intrapancreatic bile duct.
• The cystic artery usually arises as a single branch from the right hepatic artery within Calot triangle.
• The cystic artery may arise from the left hepatic, common hepatic, gastroduodenal, or superior mesenteric artery.
• When the cystic artery arises from the right hepatic artery, it usually courses parallel, adjacent, and medial to the CD.
• As it crosses Calot triangle, the cystic artery supplies the CD with one or more small arterial branches.
• Near the gallbladder, the cystic artery usually divides into a superficial branch and a deep branch.
  • The superficial branch courses along the anterior gallbladder surface.
  • The deep branch passes between the gallbladder and liver within the cystic fossa.
• The right hepatic artery passes posterior to the CHD as it ascends to the liver in 85% of individuals, and anterior to the CHD in the remaining 15%.
• In approximately 15% of individuals, a replaced or aberrant right hepatic artery originates from the superior mesenteric artery and courses through the medial aspect of Calot triangle, posterior to the CD.
• The hepatic ducts and the gallbladder's hepatic surface drain through small vessels that empty into branches of the hepatic veins within the liver.
• A small venous trunk ascending parallel to the portal vein receives veins that drain the gallbladder and bile duct before entering the liver, separate from the portal vein.
• The lower bile duct portion's venous drainage is directly into the portal vein.

Lymphatic Drainage

• Lymphatic vessels from the hepatic ducts and upper CBD drain into the hepatic lymph nodes, a chain of lymph nodes that follows the hepatic artery's course to drain into the celiac lymph nodes.
• Lymph from the lower bile duct drains into the lower hepatic nodes and the upper pancreatic lymph nodes.
• Lymphatic vessels from the gallbladder and CD drain primarily into the hepatic nodes.
• Two main trunks descending along the gallbladder's lateral borders join together by an oblique trunk, forming a large “N” on the surface.
• The trunks to the gallbladder's left drain into the cystic node, a constant lymph node at the CD and CHD junction.
• The right trunks do not enter the node but continue down, joining the bile duct lymphatics.
• Lymphatic vessels from the gallbladder's hepatic surface may also communicate with lymphatic vessels within the liver.

Neural Innervation

• The gallbladder and biliary tree are innervated by sympathetic and parasympathetic nerve fibers derived from the celiac plexus and courses along the hepatic artery.
• The left (anterior) vagal trunk branches into hepatic and gastric components.
  • The hepatic branch supplies fibers to the gallbladder, bile duct, and liver.
• Sympathetic fibers from the fifth to ninth thoracic segments pass through the greater splanchnic nerves to the celiac ganglion.
• Postganglionic sympathetic fibers travel along the hepatic artery to innervate the gallbladder, bile duct, and liver.
• Visceral afferent nerve fibers from the liver, gallbladder, and bile duct travel with sympathetic afferent fibers through the greater splanchnic nerves to enter the dorsal roots of the fifth through ninth thoracic segments.
• Sensory fibers from the right phrenic nerve also innervate the gallbladder through communications between the phrenic and celiac plexuses, explaining referred shoulder pain in patients with gallbladder disease.
• Three nerve plexuses are within the gallbladder wall: mucosal, muscular, and subserous.
• The number of ganglion cells decreases from the subserous to mucosal plexus.
• The subserous plexus ganglia are larger and spaced farther apart, unlike the myenteric plexus of the gut.

Anomalies - Biliary Ducts

• The anatomy of the extrahepatic biliary tree is highly variable.
• Knowledge of this variable anatomy is important because unrecognized anatomic variations may result in ductal injury.
• Anomalies of the extrahepatic biliary tree may involve the hepatic ducts, CBD, or CD.

Hepatic Ducts Anomalies

• In 57% to 68% of patients, the right anterior and right posterior intrahepatic ducts join, and the right hepatic duct unites with the left hepatic duct to form the CHD.
• Three other variations are recognized:
  • In 12% to 18% of patients, the right anterior, right posterior, and left hepatic ducts unite to form the CHD.
  • In 8% to 20% of patients, the right posterior and left hepatic ducts join to form the CHD, and the right anterior duct joins below the union.
  • In 4% to 7% of patients, the right posterior duct joins the CHD below the union of the right anterior and the left hepatic ducts.
• In 1.5% to 3% of patients, the CD joins at the union of all the ducts or with one of the right hepatic ducts.
• Accessory hepatic ducts may emerge from the liver to join the right hepatic duct, CHD, CD, CBD, or gallbladder.
  • These ducts are present in approximately 10% of individuals
  • They often approach the size of a normal CD but are often delicate, thin structures that may easily be overlooked.
  • Accessory hepatic ducts often course through Calot triangle and may be injured during dissection in this area.
• Cholecystohepatic ducts are small biliary ducts that emerge from the liver to enter the gallbladder's hepatic surface directly.
  • If a cholecystohepatic duct is discovered during dissection of the gallbladder from the cystic fossa, it should be ligated to avoid a postoperative bile leak.

Common Bile Duct Anomalies

• Malpositions or duplications of the CBD are rare anomalies.
• Recognition of their presence is extremely important to prevent serious injury to the CBD during biliary tract or stomach operations.
• Several variations of CBD malposition and duplication exist:
  • A single duct opening into the pylorus or antrum
  • A single duct opening into the gastric fundus
  • A single duct entering the duodenum independently of the pancreatic duct
  • Two separate ducts entering the duodenum
  • A bifurcating duct, with one branch entering the duodenum and the other branch entering the stomach.
  • A bifurcating duct with both branches entering the duodenum
  • A septate CBD, with two openings of the single duct into the duodenum
• These anomalies do not produce symptoms, and their importance relies on their recognition and avoiding injury during an operation.

Cystic Duct Anomalies

• In 1976, Benson and Page described five ductal anomalies of clinical significance to the surgeon during a cholecystectomy:
  • Abnormalities in the CD's length, course, or insertion into the CHD.
  • The CD may run parallel to the CHD for a variable distance.
  • The CD may spiral anterior/posterior to the CHD to form a left-sided union.
• Parallel CDs occur in 15% of individuals, and spiral CDs are found in approximately 8%.
  • The parallel or spiral CD may be normal in length or course downward in the hepatoduodenal ligament for a considerable distance before forming a low union with the CHD.
• In both situations, the CD is usually closely adhered to the CHD by a connective tissue sheath.
• The CD may join the right hepatic duct or a right segmental duct.
• The CD, right hepatic duct, and left hepatic duct may join at the same level to form a trifurcation
  • Mistaking the right hepatic duct for the CD is easy, leading to inadvertent ligation and division.
• The gallbladder may join the CHD with a short or nonexistent CD.
  • Care must be taken not to compromise the CBD's lumen during ligation of a short CD.

Anomalies - Gallbladder

• Some gallbladder anomalies are acquired, but most result from arrested/abnormal development during embryonic growth.
• Anomalies vary in clinical significance:
  • Some are medical curiosities with no need for correction
  • Others require surgical intervention
• Gallbladder anomalies are divided into three groups based on formation, number, and position.

Phrygian Cap Formation

• Most common gallbladder anomaly, occurring in individuals all ages, and more commonly in women.
• Boyden found that oral cholecystography confirmed this anomaly in 18% of patients with a functioning gallbladder.
• The phrygian cap deformity is created by an infolding of a septum between the body and the fundus.
• The gallbladder functions normally, and this anomaly is not an indication for cholecystectomy.

Bilobed Gallbladder Formation

• This rare anomaly consists of a completely divided gallbladder drained by a common CD.
• Bilobed gallbladder occurs in two forms:
  • A type that has the outward appearance of a single gallbladder but is divided internally by a longitudinal fibrous septum
  • A type that has the outward appearance of two separate gallbladders that are fused at the neck
• A bilobed gallbladder has no clinical significance and does not require excision unless symptomatic.

Hourglass Gallbladder Formation

• Alterations in the gallbladder's contour may result in a dumbbell or hourglass form.
• These anomalies are not rare and can be congenital or acquired.
  • Congenital version does not require removal in children
  • Acquired version usually results from chronic cholecystitis and should be removed in patients with appropriate biliary symptoms

Diverticulum of the Gallbladder Formation

• Congenital diverticula are rare
• Found in only 25 of 29,701 surgically removed gallbladders at the Mayo Clinic
• Diverticula may occur in any gallbladder part and vary greatly in size from 0.5 to 9 cm in diameter.
• They are insignificant unless they become the disease site, in which they may contain stones, become inflamed, or perforate.
• Hartmann pouch is an acquired diverticulum of the gallbladder's infundibulum or neck.
• This pouch projects from the gallbladder neck's convexity and may adhere to the CBD.
• Hartmann pouch is associated with pathological conditions of the gallbladder, especially those involving prolonged obstruction to gallbladder emptying.

Rudimentary Gallbladder Formation

• This condition consists of a small nubbin at the end of the CD.
• When found in infants and children, it is believed to be caused by congenital hypoplasia and requires no treatment.
• In older adults, it may result from fibrosis from cholecystitis and require removal if causing biliary symptoms.

Absence of the Gallbladder (Agenesis) Number

• More than 200 cases have been reported
• Most cases are associated with other biliary abnormalities,
• Most of the patients died before 6 months
• One publication reviewed 185 cases finding:
  • 70 (38%) were completely absent
  • 60 (32%) were rudimentary
  • 55 (30%) were a fibrous structure
• The absence of the gallbladder must not be confused with an intrahepatic gallbladder or a left-sided gallbladder.
• A history of gallbladder disease with subsequent cholecystectomy is insufficient to establish the organ's absence.
• There have been cases where two gallbladders were present in a single patient, but only one was removed.

Duplication Number

• Blasius first described a double gallbladder found at autopsy in 1674, and Sherren recorded the first observation from a living patient in 1911.
• Anomaly occurs in approximately 1 in 4000 persons.
• A true duplicated gallbladder has two separate cavities, each drained by its own CD and sometimes supplied by its own cystic artery.
• Duplication occurs as one of two varieties:
  • The more common ductular type- Each gallbladder has its own CD, which empties independently into the same or different parts of the extrahepatic biliary tree
  • A type in which the two ducts gradually merge into a common CD before emptying into the CBD
• The gallbladder itself may be seen as two distinct organs at variable distances apart or may outwardly have the appearance of a single organ.
• Each cavity may function normally or become diseased independently of the other.
• Duplication is clinically unimportant and requires no treatment.

Floating Gallbladder Position

• Recognized anomaly that has been reported to occur in approximately 5% of persons.
• The gallbladder is completely surrounded by peritoneum and attached to the cystic fossa's undersurface by the peritoneal reflection from the liver.
• Attachment may extend the gallbladder's entire length or only include the CD, leaving the gallbladder unsupported and ptosed.
• The condition usually occurs in women older than 60 years and is subject to the same pathological changes as a normally placed gallbladder, but may undergo torsion around its pedicle.
• This type of gallbladder requires no treatment unless symptomatic.

Torsion of Gallbladder

• The torsion usually occurs in people 60 to 80 years old
• Has been reported in young children as well.
• Torsion causes of sudden onset of:
  • Acute right upper quadrant abdominal pain
  • Nausea
  • Vomiting
• Torsion requires operative detorsion and gallbladder removal which may be infarcted due to blood vessel occlusion. Torsion is one of a variety of rare positions

Intrahepatic Gallbladder Position

• Normal in the embryologic period
• Defined when it is partially/completely embedded within the liver substance
• The condition is suspected if the cholecystogram or ultrasound reveals a gallbladder in an unusually high location.
• Approximately 60% of the time it is associated with gallstones.
• Most are only partially embedded within the hepatic parenchyma and can usually be easily identified at cholecystectomy.
• Identifying the CD where it joins the CHD and following the CD back to the gallbladder allows for better exposure and surgical approach.

Left-Sided Gallbladder Position

• Two types:
  • Left-sided gallbladder associated with situs inversus, in which the heart and abdominal viscera are transposed from their usual position
  • Gallbladder alone is transposed
• Rare type found on the left lobe of the liver's undersurface, where the CD joins the CHD in the usual location, but may occasionally join the left hepatic duct.
• Usually no malfunction is associated with this anomaly.
• Ultrasonography should be able to detect this anomaly, requiring radiologist awareness.

Transverse Gallbladder Position

• Anomalous alignment, in which the gallbladder is positioned horizontally in the liver's transverse fissure.
• Deeply embedded within the liver parenchyma.
• These position anomalies, require no position, unless symptomatic.

Vascular Anomalies

• Variations in the arterial supply of the of the extrahepatic biliary tree are more common than variations in the ductal anatomy.
• Anatomic variations of the hepatic and cystic arteries are present in approximately 50% of individuals.
• Benson and Page described three surgically important variations in the arterial anatomy based on their anatomic dissections:
  • An accessory/double, cystic artery occurs in approximately 15% to 20% of individuals
    • These arteries usually arise from the right hepatic artery within Calot triangle. Triple CAs are unusual and occur in <1% of individuals
    • Care should be taken to exclude the presence of an accessory CA during the dissection of Calot triangle.
  • In other occurrences the right hepatic artery courses through Calot triangle:
    • Close to the CD (5% to 15% of individuals) before turning upward to enter the liver's hilum, where the cystic artery arises from the hepatic artery's angled portion
    • Mistaking the CA for the "caterpillar hump" right hepatic artery may lead to inadvertent ligation during a cholecystectomy
    • The CA that arises from the caterpillar hump is typically short and may easily be avulsed from the hepatic artery if excessive traction is applied to the gallbladder
• The cystic artery may occasionally pass anterior to the CBD/CHD. When the CA rather than the CD is usually encountered in dissection
  • Rather than the CD, these arteries usually require ligation and division early in cholecystectomy dissection to provide adequate CD exposure.

Physiology - Bile Production

• Bile formation by the hepatocyte serves two purposes:
  • Represents the route of excretion for certain organic solutes, such as bilirubin and cholesterol.
  • Facilitates intestinal absorption of lipids and fat-soluble vitamins.
• Bile secretion results from the active transport of solutes into the canaliculus, followed by the passive flow of water.
• Water constitutes 85% of the bile volume. Phospholipids, bile salts, and cholesterol constitute approximately 90% of the solids in bile, the remainder consists of bilirubin, fatty acids, and inorganic salts.
• Bilirubin, the breakdown product of spent red blood cells, is conjugated with glucuronic acid by the hepatic enzyme glucuronyl transferase and is excreted actively into the adjacent canaliculus.
• Normally, a large reserve exists to handle excess bilirubin production in hemolytic states.
• Approximately 250 to 300 mg of bilirubin is excreted each day in the bile
  • 75% from the breakdown of red cells in the reticuloendothelial system
  • 25% from turnover of hepatic heme and hemoproteins
• Bile salts are steroid molecules synthesized by the hepatocyte.
• The primary bile salts in humans cholic and chenodeoxycholic acid account for >80% of those produced.
• The primary bile salts are then conjugated with either taurine or glycine and can undergo bacterial alteration in the intestine to form the secondary bile salts, deoxycholate, and lithocholate.
• The purpose of bile salts is to solubilize lipids and facilitate their absorption.
• Phospholipids are synthesized in the liver with bile salt synthesis; lecithin is the primary phospholipid in human bile, constituting >95% of its total.
• Cholesterol, also produced primarily by the liver with little dietary contribution, is the final major solute of bile.
• The normal amount of bile secreted daily by the liver is 750 to 1000 mL. Three main factors contribute to bile flow: hepatic secretion, gallbladder contraction, and sphincteric resistance.
• In the fasting state, the pressure in the CBD is 5 to 10 cm H2O, and the produced bile is diverted to the gallbladder, storing up to 50 to 60 mL.
• After a meal, the gallbladder contracts, and the sphincter relaxes in response to vagal and cholecystokinin stimulus.
• As a result, the bile is forced to the duodenum as ductal pressure exceeds sphincteric resistance.
• The pressure within the gallbladder can reach 25 cm H2O, and the CBD pressure may reach 20 cm H2O, favoring a gradient toward the duodenum.
• Bile is usually concentrated 5- to 10-fold by the absorption of water and electrolytes, leading to a marked change in bile composition.
• Active sodium chloride transport by the gallbladder epithelium is the driving force for bile concentration, where water is passively absorbed in response to the osmotic force generated by solute absorption.

Bile Salt Secretion

• Bile is secreted from the hepatocyte into canaliculi that drain their contents into small bile ducts.
• Bile salts are the major osmotic force behind bile flow.
• Bile acids are formed at a rate of 500 to 600 mg per day.
• Most of the bile salt pool is maintained in the gallbladder, followed by the liver, the small intestine, and the extrahepatic bile ducts.
• Bile acids are synthesized from cholesterol via:
  • A classic pathway leading to cholic acid formation
  • An alternate pathway resulting in the synthesis of chenodeoxycholic acid (less common in human bile).
• In plasma, bile acids circulate in a bound state to albumin or lipoproteins.
• Bile salt uptake into hepatocytes is very efficient, mediated by sodium-dependent and sodium-independent mechanisms.
  • The sodium-dependent pathway accounts for 80% of taurocholate uptake but less than 50% of cholate uptake.
• A number of transport proteins have been identified that play a key role, including:
  • Sodium-taurocholate cotransporting polypeptide (NTCP)
  • Organic anion-transporting polypeptides (OATPs)
• Intracellular bile acid transport occurs within seconds through:
  • Transfer of bile acids from the basolateral membrane to the canalicular membrane via bile acid–binding proteins
  • Vesicular transport
• The transport of bile salts across the canalicular membrane of hepatocytes is the rate-limiting step
• Bile salt concentrations are 1000-fold greater within the canaliculi than in the hepatocyte, necessitating an ATP-dependent active transport mechanism.
• This bile salt export pump (BSEP) is closely related to proteins encoded by the multidrug resistance (MDR) gene family of ATP-binding cassette (ABC) transporters.
• The ABC transporters mediate the transport of metabolites, peptides, fatty acids, cholesterol, and lipids in the liver, intestine, pancreas, lungs, kidneys, brain, and macrophages.
• BSEP is the major transporter for monovalent bile salts, and multidrug resistance-associated protein 2 (MRP2) also transports sulfated and glucuronidated bile salts into the canaliculus.
• MRP2 mediates the export of multiple other organic anions, including conjugated bilirubin, leukotrienes, glutathione disulfide, chemotherapeutic agents, uricosurics, antibiotics, toxins, and heavy metals.

Enterohepatic Circulation

• Bile salts functions: binding calcium ions in bile, inducing bile flow, and facilitating lipid transport.
• Bile salts:
  • Synthesized/conjugated in the liver
  • Secreted into bile
  • Stored temporarily in the gallbladder
  • Passed from the gallbladder into the duodenum
  • Absorbed throughout the small intestine but especially in the terminal ileum by an active transport system
  • Returned to the liver via the portal vein
• This recycling of bile acids between the liver and the intestine is the enterohepatic circulation.
• The total bile acids in the enterohepatic circulation is the circulating bile pool.
• 95% of bile salts are reabsorbed.
• Of the total bile salt pool (2 to 4 g) that recycles, only 600 mg of bile salt is actually excreted into the colon.
• Bacterial action in the colon on cholate and chenodeoxycholate results in the formation of deoxycholate and lithocholate
• Some deoxycholate is reabsorbed passively by the colon, the remainder is lost in fecal waste.
• The enterohepatic circulation provides an important negative feedback system on bile salt synthesis
• If the recirculation is interrupted by terminal ileum resection/disease, abnormally large losses of bile salts can occur, increasing bile salt production.
• Similarly, if bile salts are lost via biliary fistula, more bile salt synthesis is needed.
• Bile salt synthesis matches losses except for excessive losses, maintaining a constant bile salt pool size.
• During fasting, 90% of the bile acid pool is sequestered in the gallbladder.

Cholesterol Saturation

• Cholesterol is nonpolar and insoluble in water/bile.
• The key to cholesterol maintenance in solution is micelle formation
• Micelles are a bile salt–phospholipid-cholesterol complex.
• Bile salts