The digestive tract is one of the largest systems in the human body. In addition to the primary segments extending from mouth to anus, there are numerous accessory digestive organs that facilitate the generation and absorption of micronutrients from ingested macromolecules. One such organ is the gallbladder.
This article will review the anatomy of the gallbladder as well as the associated biliary apparatus. Special attention will also be paid to the relevant embryology, histology and adjacent anatomical structures.
- Gallbladder function
- Embryology of the gallbladder and biliary tree
- Anatomy of the gallbladder
- Intrahepatic biliary system
- Extrahepatic biliary system
- Histology of the gallbladder and biliary apparatus
- Triangle of Calot
- Neurovascular supply and lymphatic drainage of the gallbladder
- Clinical aspects
This pear-shaped sac primarily functions as a reservoir for bile that was synthesized at the level of the hepatocytes. While ingesting a meal, the presence of fats and proteins in the intestines stimulate the release of cholecystokinin; which acts at the level of the body and neck of the gallbladder, and cystic and extrahepatic ducts. This peptide hormone causes simultaneous contraction of the body of the gallbladder and relaxation of the neck of the gallbladder.
Once the pressure within the biliary tree reaches 10 mm H2O of bile, there is relaxation of the sphincter of Oddi. Therefore, bile can be released from both the gallbladder and directly from the liver via the biliary tree. However, during fasting states, the absence of cholecystokinin results in contraction of the sphincter of Oddi. Increased pressure in the biliary tree results in diversion of bile into the gallbladder where it is stored and concentrated.The endothelial membrane of the gallbladder is equipped with numerous ion channels that actively absorb sodium, chloride and bicarbonate ions. The water molecules subsequently follow the osmotic gradient generated by the ion shift, resulting in concentration of bile. Finally, the gallbladder also produces about 15 – 20 mL of mucus throughout the course of each day.
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Embryology of the gallbladder and biliary tree
During week four of development, differentiation of embryonic endoderm gives rise to an outpouching of the distal region of the foregut. This structure, known as the hepatic diverticulum, gives rise to the gallbladder and associated biliary duct; as well as the liver. Recall that around this time there is extensive cardiac origami and as such, it is necessary that cells of the developing heart and digestive system be separated. Therefore, an organized layer of splanchnic mesoderm known as the septum transversum grows between the heart and the midgut.
As the hepatic diverticulum grows, it divides unequally. The larger cranial bud, commits to becoming the liver primordium and the extrahepatic biliary tree. The extrahepatic biliary system (discussed below) is identifiable by the 5th week of gestation. The extrahepatic bile ducts extend into the mesenchyme of the septum transversum and gives rise to the characteristic fibrous appearance of the liver.
Within the liver, the endometrial cells that overlap each other to form the hepatocytes also give rise to the intrahepatic biliary system. Communication with the extrahepatic bile ducts marks the completion of the intrahepatic biliary system, which occurs around the 10th gestational week.
The smaller caudal bud of the hepatic diverticulum further subdivides into superior and inferior buds. The superior bud and its associated stalk will become the gallbladder and cystic duct (respectively), while the inferior bud becomes the ventral component of the pancreas. Both the liver and gallbladder will grow into the ventral mesogastrium (formed from the septum transversum).
The gallbladder, cystic duct, and extrahepatic bile ducts are initially occluded with cells. As the bile duct continues to grow, the centrally located cells undergo apoptosis; thus converting the solid tube into a luminal structure. Initially, this process starts within the common bile duct and continues distally at the end of the 5th gestational week. Recanalization is a slow process that overlaps with an anatomical change in the position of the common bile duct and ventral pancreas; such that the common bile duct is situated on the dorsomedial surface of the duodenum. The bile duct only becomes patent between the end of the second and beginning of the 8th gestational weeks as it continues into the duodenum. Proximally, in the 7th gestational week, recanalization progresses into the cystic duct and extends into the gallbladder by the 12th gestational week. Neonates have a small peritoneal surface and as a result, the fundus lies within the liver margin. After the second year of life, gall bladder assumes the relative size.
The common hepatic duct and pancreatic ducts unite to form the hepatopancreatic duct. It extends into the duodenal wall at the level of the submucosa as the ampulla of Vater (major duodenal papilla). Concentric mesenchymal rings surround the ampulla and give rise to the sphincter of Oddi. The sphincter of Oddi further differentiates around the 10th gestational week into the sphincter choledochus superior and inferior; both of which surround the bile duct. Although final development of the ampulla continues to the 28th gestational week, the extrahepatic is ready to transport bile from the liver to the duodenum by week 12 of gestation (i.e. 6 weeks after the onset of hematopoiesis).
Anatomy of the gallbladder
The gallbladder is essentially a pear-shaped cul-de-sac that communicates with the common hepatic ducts via the cystic duct. In vivo, the sac is actually grey-blue in appearance (and not green as depicted in the texts). The 7.5 – 12 cm long organ is found on the inferior aspect of the anatomical right lobe of the liver, near the hepatic scissura, deep to the hepatic part of the peritoneum.
There are instances where the gallbladder may be completely buried within the liver parenchyma; here it is said to have an intraparenchymal pattern. In other cases, the gallbladder may have its own mesentery arising from the visceral and parietal peritoneum; in which case it is described as having a mesenteric pattern. These are two extremes of a spectrum on which the gallbladder may appear. The sac can accommodate 25 – 30 mL of bile under normal circumstances; but can expand up to 50 mL.
There are three anatomical parts of the gallbladder. From lateral to medial, these are the fundus, body and neck (infundibulum). The fundus is the most lateral part of the gallbladder. It typically protrudes beyond the lower border of the liver and may touch the anterior abdominal wall. A clinical landmark for the fundus of the gallbladder is at the level of the 9th costal, at the intersection of the lateral border of the right rectus abdominis and the costal margin. An enlarged gallbladder can be appreciated clinically at this point.
Medial to the fundus is the body of the gallbladder. This is the portion of the sac that is either embedded in, or in contact with the gallbladder fossa of the liver. The pars descendens (second part) of the duodenum, as well as the hepatic flexure and proximal transverse colon, are posteriorly related to the gallbladder.
The body of the gallbladder tapers off medially into the neck or infundibulum. It is proximal to the porta hepatis and is generally associated with a short mesentery that also contains the cystic artery. As the neck narrows into the cystic duct, it contains slanted grooves that progresses into the spiral valve of the cystic duct. There is a relatively inconsistent, albeit common, pathological variation at the neck of the gallbladder known as Hartmann’s pouch. It is an outpouching of the wall of the neck as a result of stones in the gallbladder or dilatation of the sac. There size of the pouch may vary among patients, and can be associated with numerous complications.
Intrahepatic biliary system
The intrahepatic biliary tract is a unique system designed to transport bile from the hepatocytes to the extrahepatic biliary tree. It commences at the level of the bile canaliculi (s. canaliculus), which is a dilated space between adjacent hepatocytes. Recall that the polyhedral hepatocytes are arranged such that their apical ends project into the hepatic sinusoids (which eventually coalesce into the hepatic veins). The bases of these cells face the bile canaliculi and secrete bile into these channels. The walls of the canaliculi are believed to be modified regions of the walls of the contributing hepatocytes. As these channels are formed, they follow a similar pathway to the hepatic sinusoids. However, their contents flow in the opposite direction.
The canaliculi within each hepatic segment coalesce to form the segmental ducts. Therefore, there are eight segmental ducts corresponding to each functional segment of the liver: The segmental ducts arising from segments II and III of the liver give rise to the right hepatic duct. They are usually also joined by the segment IV duct; however this may vary among patients. Segments V to VIII will eventually contribute to the left hepatic duct. However, segments V and VIII give rise to the right anterior (medial) sectoral duct, while segments VI and VII give rise to the right posterior (lateral) sectoral ducts.
The right posterior sectoral duct is longer than its counterpart, and can be seen coursing medially, behind the right anterior sectoral duct (forming Hjortsjo’s crook) before piercing the right anterior sectoral duct on the medial surface to form the left hepatic duct. It should be noted that hepatic segment I (i.e. the caudate lobe) drains to both the left hepatic duct, as well as the right posterior sectoral duct.
Another set of intrahepatic ducts have been encountered with relative frequency. These structures develop from autonomic growth of the distal biliary ducts that arise from the pars hepatica of the septum transversum. In areas that where hepatic parenchyma is expected to regress, these ducts may fail to degenerate; hence, they give rise to subvesical ducts (also known as the ducts of Luschka). These small channels often arise as lobular collections of ductules of varying dimensions. They often originate from the right lobe and may either drain to intrahepatic ducts, extrahepatic ducts, or the gallbladder. Several subtypes of subvesical ducts have been described. These include:
- Accessory subvesical ducts are the most common variants of subvesical ducts. They arise from either of the right sectoral arteries and drain into the principal bile ducts after traversing the gallbladder fossa. These ducts are usually present in excess of the typical biliary tree.
- The sectoral/segmental subvesical duct is relatively common. It represents ducts that have an uncharacteristic course that is superficial in the gallbladder fossa. It originates from the right posterior segmental or sectoral ducts and drains separately into the main right hepatic duct.
- Hepatocholecystic subvesical ducts drain directly into the gallbladder from the liver and typically arises from the right lobe.
- Aberrant subvesical ducts are found within the capsule of the gallbladder fossa. They have peri-hepatic communication with intrahepatic ducts, but terminate distally as cul-de-sacs.
Extrahepatic biliary system
As described above, the segmental and sectoral ducts give rise to the left and right hepatic ducts. The left hepatic duct is slightly longer than the right hepatic duct, and it takes a more horizontal pathway than the right duct, as it courses along the base of segment IV of the liver. The right hepatic duct usually has a vertical course and is more susceptible to anatomical variations than the left hepatic duct. While majority of patients will have normal anatomy of these structures, there are other variations described by Blumgart that should be familiar to surgeons involved in the hepatobiliary field.
Both ducts merge on the lateral side of the porta hepatis to form the common hepatic duct. This portion of the biliary tree is about 2.5 to 3 cm long and is often found lateral to the hepatic artery, with the portal vein behind it. All three structures can be found in the free border of the lesser omentum (as it forms the gastroepiploic foramen of Winslow).
The neck of the gallbladder funnels off medially into the cystic duct. This tubular structure is usually 3 – 4 cm long and about 1 – 3 mm wide. The cystic duct mucosa is spirally folded and forms the valves of Heister; which some anatomists believe help to maintain the patency of the duct. It also has an associated sphincter – the sphincter of Lütkens – that help to regulate the flow of bile from the gallbladder. The cystic duct then takes a posterior course, along with (and adherent to) the common hepatic duct, prior to their union. In most patients, the cystic and common hepatic ducts unite above the duodenum near the porta hepatis.
The union of the cystic and common hepatic ducts give rise to the 6 – 8 cm long common bile duct. On average, the adult common bile duct is about 6 mm wide; however, there have been reports of it increasing with age. This structure can be anatomically divided into four portions:
- The supraduodenal portion accounts for 2.5 cm of the total length of the structure. It travels inferiorly in the right part of the free edge of the lesser omentum, anterior to the gastroepiploic foramen of Winslow. Of note, the hepatic artery is medially related to this part of the common bile duct, and the portal vein is posteromedial to it as well.
- The retroduodenal portion travels behind the pars superioris (first part) of the duodenum along with the gastroduodenal artery also medially related to the duct at this level.
- The infraduodenal portion travels in a groove on the superolateral aspect of the posterior surface of the head of the pancreas. The inferior vena cava is posterior to the duct here. The duct usually lies within 2 cm of the pars descendens of the duodenum.
- The intraduodenal portion pierces the medial wall of the pars descendens (second part) of the duodenum along with the pancreatic duct.
The common bile duct and pancreatic duct often fuse after piercing the duodenum to form the hepatopancreatic duct. The duct emerges on the luminal surface of the second part of the duodenum as the hepatopancreatic ampulla of Vater. Recall that there are two circular muscular structures around the hepatopancreatic ampulla – superior and inferior sphincter choledochus. The superior sphincter choledochus is located around the distal portion of the common bile duct. There is also a similar sphincter around the distal aspect of the main pancreatic duct. Therefore, release of contents from the biliary tract and pancreatic duct can be regulated independently. The inferior sphincter choledochus becomes the hepatopancreatic sphincter of Oddi.
Histology of the gallbladder and biliary apparatus
Mucosa and submucosa
Like most of the intra-abdominal viscus, the gallbladder has three distinct layers within its wall. Most of these layers are also continuous throughout the extrahepatic biliary system. The sac and ducts are equipped with a mucous membrane, muscular layer and surrounding serosa. The yellow-brown mucosa is formed from simple columnar epithelium that sits on the lamina propria. These cells possess microvilli at the apical surface and are these cells rich in mitochondria. They also have numerous sodium – adenosine triphosphate (Na+ -ATP) pumps on the basolateral surface of the cells that allows the cells to actively transport sodium ions from the lumen of the gallbladder. Subsequently, water will diffuse along the osmotic gradient generated by the ionic shift. As a result, bile can be concentrated as it is stored in the gallbladder.
The luminal surface of the gallbladder – much like that of the small intestines – is highly folded into rugae, and has a honeycomb appearance. However, unlike the small intestines, the rugae are temporary structures that go away once the gallbladder becomes distended. There are also diverticula within the mucosa that extend to the muscular layer known as the crypts of Luschka. The relatively loose submucosa beneath the mucosa layer is rich in elastic fibers , blood vessels and lymphatics.
Muscularis propria is a relatively thin layer of smooth muscle fibres arranged haphazardly. These muscle fibres possess CCK receptors, and there responds to cholecystokinin released from enteroendocrine cells of the duodenum in response to the presence of fats and proteins in the intestines. As a result, concentrated bile from the gallbladder is pumped into the cystic duct, and transported to the duodenum via the common bile duct.
The sac is enclosed in a thin sheet of serosa (external adventitia). The serosa is usually confined to the fundus of the gallbladder, and extends circumferentially around the inferior sides of the body and neck of the sac. However, in the mesenteric gallbladder, the serosa continues superiorly, across the entire gallbladder, to blend with the serosa of the mesentery. The intraparenchymal gallbladder would not have an associated serosa. There is usually a collection of adipocytes and loose connective peritoneal tissue forming a subserosa.
The cystic duct and extrahepatic biliary tree also possess similar histological layers. The luminal surface is lined by cholangiocytes. These are simple cuboidal (or low columnar) epithelial cells that resides on the lamina propria. The submucosa is thin and contains tubuloalveolar mucous glands at some areas along the cystic duct. A thin muscular layer with circular, oblique, and longitudinal smooth muscle fibres surrounds the entire biliary system within a fibrous connective tissue sheath. However, it gradually becomes thicker as the duct approaches its terminal point at the ampulla of Vater. The hepatopancreatic duct also has villous folds with smooth myocytes at its core; they function as one way valves to prevent reflux of duodenal contents into the hepatopancreatic duct.
Triangle of Calot
The cystic duct, inferior border of hepatic segment V and common hepatic duct come together to form an almost triangular space known as Calot’s triangle. The space can be visualized as a pyramid with apices in the following areas:
- Between the cystic duct and the gallbladder fundus
- In the porta hepatis
- Two at the junction of the gallbladder and its fossa
The inferior border of hepatic segment V forms the base of the triangle. The space is enveloped by the mesentery of the cystic duct, and contains adipose tissue, lymphatic nodes and vessels, and other neurovascular structures.
Neurovascular supply and lymphatic drainage of the gallbladder
The main arterial supply to the gallbladder is the cystic artery. Trifurcation of the celiac trunk yields the common hepatic artery as one of its branches. The common hepatic bifurcates after a relatively short lateral journey above the superior border of the head of the pancreas and anterior to the hepatic portal veins. The hepatic artery proper bifurcates near the porta hepatis into the left and right hepatic arteries. It is the right hepatic artery that branches to give the cystic artery that supplies the gallbladder.
The cystic artery is one of the main structures that pass through Calot’s triangle. However, its anatomy may vary among individuals. Subsequent arborisation and anastomoses of derivatives of the cystic artery extends the territory of the vessel to the level of lobar and common hepatic ducts, as well as to the proximal common bile ducts. The extrahepatic biliary tree is supplied by branches from the posterior superior pancreaticoduodenal arteries, along with other arteries within the vicinity.
Multiple small, unnamed veins often drain the gallbladder. They may originate from the areolar tissue that separates the liver from the gallbladder. These vessels will pierce the hepatic parenchyma and form tributaries to the segmental portal veins.
The autonomic branches of the hepatic plexus innervate the gallbladder. Small branches of the vagus nerve (CN X) innervate the retroduodenal common bile duct, as well as the hepatopancreatic ampulla of Vater.
Gallbladder lymph channels traverse the subserosal and submucosal layers of the sac to form their respective plexuses. Some drain into intrahepatic lymph vessels, while others will empty to the cystic node, located in Calot’s triangle. These eventually drain into the nodes of the free edge of the lesser omentum, as well as to nodes of the porta hepatis. The caudal part of the biliary tree drains to the superior pancreaticosplenic and inferior hepatic nodes.
The presence of gallstones, which is clinically known as cholelithiasis is best described as hard spherical deposits of excess byproducts that are needed for the formation of bile, that form within the gallbladder. The two main types of stone are those made of cholesterol and those called pigment stones. The latter form due to chronic hemolysis, a biliary infection or a gastrointestinal disease such as Crohn’s.
Cholesterol stones however have a much longer list of causative factors such as:
- old age
- excessive female sex hormones
- insulin resistance
- gallbladder stasis
- dyslipidemia syndromes
Surgery is usually advised in order to avoid a gallbladder infection that could potentially spread, among other risks.