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Gallbladder
Gallbladder
Gallbladder
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Gallbladder
Diagram of human gallbladder
The gallbladder sits beneath the liver
Details
PrecursorForegut
SystemDigestive system
ArteryCystic artery
VeinCystic vein
NerveCeliac ganglia, vagus nerve[1]
Identifiers
Latinvesica biliaris, vesica fellea
MeSHD005704
TA98A05.8.02.001
TA23081
FMA7202
Anatomical terminology

In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although the structure and position of the gallbladder can vary significantly among animal species. It receives bile, produced by the liver, via the common hepatic duct, and stores it. The bile is then released via the common bile duct into the duodenum, where the bile helps in the digestion of fats.

The gallbladder can be affected by gallstones, formed by material that cannot be dissolved – usually cholesterol or bilirubin, a product of hemoglobin breakdown. These may cause significant pain, particularly in the upper-right corner of the abdomen, and are often treated with removal of the gallbladder (called a cholecystectomy). Inflammation of the gallbladder (called cholecystitis) has a wide range of causes, including the result of gallstone impaction, infection, and autoimmune disease.

Structure

[edit]

The human gallbladder is a hollow grey-blue organ that sits in a shallow depression below the right lobe of the liver.[2] In adults, the gallbladder measures approximately 7 to 10 centimetres (2.8 to 3.9 inches) in length and 4 centimetres (1.6 in) in diameter when fully distended.[3] The gallbladder has a capacity of about 50 millilitres (1.8 imperial fluid ounces).[2]

The gallbladder is shaped like a pear, with its tip opening into the cystic duct.[4] The gallbladder is divided into three sections: the fundus, body, and neck. The fundus is the rounded base, angled so that it faces the abdominal wall. The body lies in a depression in the surface of the lower liver. The neck tapers and is continuous with the cystic duct, part of the biliary tree.[2] The gallbladder fossa, against which the fundus and body of the gallbladder lie, is found beneath the junction of hepatic segments IVB and V.[5] The cystic duct unites with the common hepatic duct to become the common bile duct. At the junction of the neck of the gallbladder and the cystic duct, there is an out-pouching of the gallbladder wall forming a mucosal fold known as "Hartmann's pouch".[2]

Lymphatic drainage of the gallbladder follows the cystic node, which is located between the cystic duct and the common hepatic duct. Lymphatics from the lower part of the organ drain into lower hepatic lymph nodes. All the lymph finally drains into celiac lymph nodes.

Microanatomy

[edit]
Micrograph of a normal gallbladder wall (H&E stain)

The gallbladder wall is composed of a number of layers. The innermost surface of the gallbladder wall is lined by a single layer of columnar cells with a brush border of microvilli, very similar to intestinal absorptive cells.[2] Underneath the epithelium is an underlying lamina propria, a muscular layer, an outer perimuscular layer and serosa. Unlike elsewhere in the intestinal tract, the gallbladder does not have a muscularis mucosae, and the muscular fibres are not arranged in distinct layers.[6]

The inner portion of the gallbladder wall (the mucosa) consists of a lining of a single layer of columnar cells which possess small hair-like attachments called microvilli.[2] This sits on a thin layer of connective tissue, the lamina propria.[6] The mucosa is curved and collected into tiny outpouchings called rugae.[2]

A muscular layer sits beneath the mucosa. This is formed by smooth muscle, with fibres that lie in longitudinal, oblique and transverse directions, and are not arranged in separate layers. The muscle fibres here contract to expel bile from the gallbladder.[6] A distinctive feature of the gallbladder is the presence of Rokitansky–Aschoff sinuses, deep outpouchings of the mucosa that can extend through the muscular layer, and which indicate adenomyomatosis.[7] The muscular layer is surrounded by a layer of connective and fat tissue.[2]

The outer layer of the fundus of gallbladder, and the surfaces not in contact with the liver, are covered by a thick serosa, which is exposed to the peritoneum.[2] The serosa contains blood vessels and lymphatics.[6] The surfaces in contact with the liver are covered in connective tissue.[2]

Variation

[edit]
Abdominal ultrasonography showing gallbladder and common bile duct

The gallbladder varies in size, shape, and position among different people.[2] Rarely, two or even three gallbladders may coexist, either as separate bladders draining into the cystic duct, or sharing a common branch that drains into the cystic duct. Additionally, the gallbladder may fail to form at all. Gallbladders with two lobes separated by a septum may also exist. These abnormalities are not likely to affect function and are generally asymptomatic.[8]

The location of the gallbladder in relation to the liver may also vary, with documented variants including gallbladders found within,[9] above, on the left side of, behind, and detached or suspended from the liver. Such variants are very rare: from 1886 to 1998, only 110 cases of left-lying liver, or less than one per year, were reported in scientific literature.[10][11][2]

An anatomical variation can occur, known as a Phrygian cap, which is an innocuous fold in the fundus, named after its resemblance to the Phrygian cap.[12]

Development

[edit]

The gallbladder develops from an endodermal outpouching of the embryonic gut tube.[13] Early in development, the human embryo has three germ layers and abuts an embryonic yolk sac. During the second week of embryogenesis, as the embryo grows, it begins to surround and envelop portions of this sac. The enveloped portions form the basis for the adult gastrointestinal tract. Sections of this foregut begin to differentiate into the organs of the gastrointestinal tract, such as the esophagus, stomach, and intestines.[13]

During the fourth week of embryological development, the stomach rotates. The stomach, originally lying in the midline of the embryo, rotates so that its body is on the left. This rotation also affects the part of the gastrointestinal tube immediately below the stomach, which will go on to become the duodenum. By the end of the fourth week, the developing duodenum begins to spout a small outpouching on its right side, the hepatic diverticulum, which will go on to become the biliary tree. Just below this is a second outpouching, known as the cystic diverticulum, that will eventually develop into the gallbladder.[13]

Function

[edit]
1. Bile ducts:
      2. Intrahepatic bile ducts
      3. Left and right hepatic ducts
      4. Common hepatic duct
      5. Cystic duct
      6. Common bile duct
      7. Ampulla of Vater
      8. Major duodenal papilla
9. Gallbladder
10–11. Right and left lobes of liver
12. Spleen
13. Esophagus
14. Stomach
15. Pancreas:
      16. Accessory pancreatic duct
      17. Pancreatic duct
18. Small intestine:
      19. Duodenum
      20. Jejunum
21–22. Right and left kidneys
The front border of the liver has been lifted up (brown arrow).[14]

The main functions of the gallbladder are to store and concentrate bile, also called gall, needed for the digestion of fats in food. Produced by the liver, bile flows through the biliary tree, consisting of small vessels emptying into the larger hepatic ducts and ultimately the cystic duct, into the gallbladder, where it is stored. At any one time, 30 to 60 millilitres (1.0 to 2.0 US fl oz) of bile is stored within the gallbladder.[15]

When food containing fat enters the digestive tract, it stimulates the secretion of cholecystokinin (CCK) from I cells of the duodenum and jejunum. In response to cholecystokinin, the gallbladder rhythmically contracts and releases its contents into the common bile duct, eventually draining into the duodenum. The bile emulsifies fats in partly digested food, thereby assisting their absorption. Bile consists primarily of water and bile salts, and also acts as a means of eliminating bilirubin, a product of hemoglobin metabolism, from the body.[15]

The bile that is secreted by the liver and stored in the gallbladder is not the same as the bile that is secreted by the gallbladder. During gallbladder storage of bile, it is concentrated 3–10 fold[16] by removal of some water and electrolytes. This is through the active transport of sodium and chloride ions[17] across the epithelium of the gallbladder, which creates an osmotic pressure that also causes water and other electrolytes to be reabsorbed.[15]

A function of the gallbladder appears to be protection against carcinogenesis as indicated by observations that removal of the gallbladder (cholecystectomy) increases subsequent cancer risk. For instance, a systematic review and meta analysis of eighteen studies concluded that cholecystectomy has a harmful effect on the risk of right-sided colon cancer.[18] Another recent study reported a significantly increased total cancer risk, including increased risk of several different types of cancer, after cholecystectomy.[19]

Clinical significance

[edit]
Main article: Gallbladder disease

Gallstones

[edit]
Main article: Gallstones

Gallstones form when the bile is saturated, usually with either cholesterol or bilirubin.[20] Most gallstones do not cause symptoms, with stones either remaining in the gallbladder or passed along the biliary system.[21] When symptoms occur, severe "colicky" pain is often experienced in the upper right quadrant of the abdomen.[20] If the stone blocks the gallbladder, inflammation known as cholecystitis may result. If the stone lodges in the biliary system, jaundice may occur; if the stone blocks the pancreatic duct, pancreatitis may occur.[21]

3D still, showing gallstones

Gallstones are diagnosed using ultrasound.[20] When a symptomatic gallstone occurs, it is often managed by waiting for it to be passed naturally; however, given the likelihood of recurrent gallstones, surgery to remove the gallbladder is often considered.[21] Some medication, such as ursodeoxycholic acid, may be used; lithotripsy, a non-invasive mechanical procedure used to break down the stones, may also be used.[21]

Inflammation

[edit]
Main article: Cholecystitis

Known as cholecystitis, inflammation of the gallbladder is commonly caused by obstruction of the duct with gallstones, which is known as cholelithiasis. Blocked bile accumulates, and pressure on the gallbladder wall may lead to the release of substances that cause inflammation, such as phospholipase. There is also the risk of bacterial infection. An inflamed gallbladder is likely to cause sharp and localised pain, fever, and tenderness in the upper, right corner of the abdomen, and may have a positive Murphy's sign. Cholecystitis is often managed with rest and antibiotics, particularly cephalosporins and, in severe cases, metronidazole. Additionally the gallbladder may need to be removed surgically if inflammation has progressed far enough.[21]

Gallbladder removal

[edit]
Main article: Cholecystectomy

A cholecystectomy is a procedure in which the gallbladder is removed. It may be removed because of recurrent gallstones and is considered an elective procedure. A cholecystectomy may be an open procedure, or a laparoscopic one. In the surgery, the gallbladder is removed from the neck to the fundus,[22] and so bile will drain directly from the liver into the biliary tree. About 30 percent of patients may experience some degree of indigestion following the procedure, although severe complications are much rarer.[21] About 10 percent of surgeries lead to a chronic condition of postcholecystectomy syndrome.[23]

Complications

[edit]
Main articles: Biliary injury and Biloma

Biliary injury (bile duct injury) is the traumatic damage of the bile ducts. It is most commonly an iatrogenic complication of cholecystectomy (surgical removal of the gallbladder) but can also be caused by other operations or by major trauma. There is a higher risk of biliary injury during laparoscopic cholecystectomy than during open cholecystectomy. Biliary injury may lead to several complications and may even cause death if not diagnosed in time and managed properly. Ideally, biliary injury should be managed at a center with facilities and expertise in endoscopy, radiology, and surgery.[24]

Biloma is an accumulation of bile within the abdominal cavity. It happens when there is a bile leak, for example after surgery for removing the gallbladder (cholecystectomy), with an incidence of 0.3–2%. Other causes are biliary surgery, liver biopsy, abdominal trauma, and, rarely, spontaneous perforation.[25]

Cancer

[edit]
Main article: Gallbladder carcinoma

Cancer of the gallbladder is uncommon and mostly occurs in later life. When cancer occurs, it is mostly of the glands lining the surface of the gallbladder (adenocarcinoma).[21] Gallstones are thought to be linked to the formation of cancer. Other risk factors include large (>1 cm) gallbladder polyps and having a highly calcified "porcelain" gallbladder.[21]

Cancer of the gallbladder can cause attacks of biliary pain, yellowing of the skin (jaundice), and weight loss. A large gallbladder may be able to be felt in the abdomen. Liver function tests may be elevated, particularly involving GGT and ALP, with ultrasound and CT scans being considered medical imaging investigations of choice.[21] Cancer of the gallbladder is managed by removing the gallbladder, however, as of 2010, the prognosis remains poor.[21]

Cancer of the gallbladder may also be found incidentally after surgical removal of the gallbladder, with 1‍–‍3% of cancers identified in this way. Gallbladder polyps are mostly benign growths or lesions resembling growths that form in the gallbladder wall;[26] they are only associated with cancer when large in size (>1 cm).[21] Cholesterol polyps, often associated with cholesterolosis ("strawberry gallbladder", a change in the gallbladder wall due to excess cholesterol),[27] often cause no symptoms and are thus often detected in this way.[21]

Tests

[edit]
Abdominal ultrasonography showing biliary sludge and gallstones

Investigative tests for gallbladder disease include blood tests and medical imaging. A full blood count may reveal an increase in the number of white blood cells, suggestive of inflammation or infection. Tests such as bilirubin and liver function tests may reveal inflammation linked to the biliary tree or gallbladder, and whether this is associated with inflammation of the liver; an elevated lipase or amylase may indicate pancreatitis. The level of bilirubin may rise when there is obstruction to the flow of bile. A CA 19-9 level may be taken to investigate for cholangiocarcinoma.[21]

An ultrasound scan is often the first medical imaging test performed when gallbladder disease, such as gallstones, is suspected.[21] An abdominal X-ray or CT scan is another form of imaging that may be used to examine the gallbladder and surrounding organs.[21] Other imaging options include MRCP (magnetic resonance cholangiopancreatography), ERCP (endoscopic retrograde cholangiopancreatography), and percutaneous or intraoperative cholangiography.[21] A cholescintigraphy scan is a nuclear imaging procedure used to assess the condition of the gallbladder.[28]

Other animals

[edit]

Most vertebrates have gallbladders, but the form and arrangement of the bile ducts may vary considerably. In many species, for example, there are several separate ducts running to the intestine, rather than the single common bile duct found in humans. Several species of mammals (including horses, deer, giraffes, many rodents, and laminoids),[29][30] several species of birds (such as pigeons and some psittacine species), lampreys and all invertebrates do not have a gallbladder.[31][32]

The bile from several species of bears is used in traditional Chinese medicine; bile bears are kept alive in captivity while their bile is extracted, in an industry characterized by animal cruelty.[33][34]

History

[edit]

Depictions of the gallbladder and biliary tree are found in Babylonian models found from 2000 BCE, and in ancient Etruscan model from 200 BCE, with models associated with divine worship.[35]

Diseases of the gallbladder are known to have existed in humans since antiquity, with gallstones found in the mummy of Princess Amenen of Thebes dating to 1500 BCE.[35][36] Some historians believe the death of Alexander the Great may have been associated with an acute episode of cholecystitis.[35] The existence of the gallbladder has been noted since the 5th century, but it is only relatively recently that the function and the diseases of the gallbladder has been documented,[36] particularly in the last two centuries.[35]

The first descriptions of gallstones appear to have been in the Renaissance, perhaps because of the low incidence of gallstones in earlier times owing to a diet with more cereals and vegetables and less meat.[37] Anthonius Benevinius in 1506 was the first to draw a connection between symptoms and the presence of gallstones.[37] Ludwig Georg Courvoisier, after examining a number of cases in 1890 that gave rise to the eponymous Courvoisier's law, stated that in an enlarged, nontender gallbladder, the cause of jaundice is unlikely to be gallstones.[35]

The first surgical removal of a gallstone (cholecystolithotomy) was in 1676 by physician Joenisius, who removed the stones from a spontaneously occurring biliary fistula.[35] Stough Hobbs in 1867 performed the first recorded cholecystotomy,[37] although such an operation was in fact described earlier by French surgeon Jean Louis Petit in the mid-18th century.[35] German surgeon Carl Langenbuch performed the first cholecystectomy in 1882 for a sufferer of cholelithiasis.[36] Before this, surgery had focused on creating a fistula for drainage of gallstones.[35] Langenbuch reasoned that given several other species of mammal have no gallbladder, humans could survive without one.[35]

The debate whether surgical removal of the gallbladder or simply gallstones was preferred was settled in the 1920s, with the consensus that removal of the gallbladder was preferred.[36] It was only in the mid and late parts of the twentieth century that medical imaging techniques such as use of contrast medium and CT scans were used to view the gallbladder.[35] The first laparoscopic cholecystectomy performed by Erich Mühe of Germany in 1985, although French surgeons Phillipe Mouret and Francois Dubois are often credited for their operations in 1987 and 1988 respectively.[38]

Society and culture

[edit]

To have "gall" is associated with bold, belligerent behaviour, whereas to have "bile" is associated with sourness.[39]

In traditional Chinese medicine, the gallbladder (膽) is associated with the Wuxing element of wood, in excess its emotion is belligerence and in deficiency cowardice and judgement, in the Chinese language it is related to a multitude of idioms, including using terms such as "a body completely [of] gall" (渾身是膽) to describe a forward person, and "single, alone gallbladder hero" (孤膽英雄) to describe a lone hero, or "they have a lot of gall to talk like that".[40]

In the Zangfu theory of Chinese medicine it is an extraordinary Fu or yang organ, as it holds bile. The gallbladder not only has a digestive role, but is seen as the seat of decision-making and judgement.[40]

See also

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References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Gallbladder

View on Grokipedia
from Grokipedia
The gallbladder is a small, pear-shaped sac-like organ located in the right upper quadrant of the , positioned on the undersurface of the liver's segments IV and V. It functions primarily as a reservoir for , a digestive fluid produced by the liver, storing approximately 30–50 mL of and concentrating it by absorbing water and electrolytes between meals. Upon ingestion of fatty foods, the gallbladder contracts to release concentrated through the into the , delivering it to the to emulsify and aid in the and absorption of dietary . Anatomically, the gallbladder measures about 7–10 cm in length and 4 cm in width, consisting of four main regions: the rounded fundus, the main body, the tapered infundibulum, and the leading to the , which joins the to form the . Its wall is composed of layers including a that lines the mucosa, a , a smooth muscularis for contraction, and an outer serosa, with no distinct capsule except where it adheres to the liver via Glisson's capsule. The organ features specialized structures such as the spiral valves of Heister in the to regulate flow and Hartmann's pouch near the , a common site for formation. Blood supply is provided mainly by the , a branch of the right hepatic artery, while venous drainage occurs directly into the liver's ; innervation includes sensory fibers from the right , parasympathetic input from the to stimulate contraction, and sympathetic fibers from the to modulate tone. Physiologically, the gallbladder's role in is regulated by hormones and neural signals: cholecystokinin (CCK), released from the in response to fats and proteins, induces gallbladder contraction and relaxation of the to facilitate release, while acids themselves regulate motor function via the TGR5 receptor. within the gallbladder, composed of salts, , phospholipids, , and electrolytes, is concentrated up to tenfold, enhancing its emulsifying efficiency for into micelles that enable absorption in the . The recycles about 95% of salts back to the liver via the after intestinal reabsorption in the distal , minimizing daily synthesis needs to roughly 5%. Although not essential for life— as demonstrated by normal post-cholecystectomy—the gallbladder optimizes fat efficiency and contributes to by excreting excess in .

Anatomy

Gross anatomy

The gallbladder is a pear-shaped, hollow organ located in the right upper quadrant of the , specifically within a shallow depression known as the gallbladder fossa on the visceral surface of the liver's right lobe, between segments IV and . It measures approximately 7 to 10 cm in length and 3 to 4 cm in width, with a storage capacity of 30 to 50 mL when distended. This intraperitoneal structure adheres closely to the liver, receiving partial peritoneal covering on its inferior surface. The organ is divided into three main parts: the fundus, body, and . The fundus forms the rounded, blind distal end, projecting beyond the inferior liver border along the mid-clavicular line and often palpable when distended. The body, the largest portion, lies adjacent to the liver's fossa and tapers medially toward the . The , or infundibulum, narrows to connect with the , sometimes featuring a slight outpouching called Hartmann's pouch. Arterial blood supply to the gallbladder arises primarily from the , a branch of the right hepatic artery that emerges within the (Calot's triangle). Venous drainage occurs via the cystic vein from the neck, emptying into the , while veins from the fundus and body drain directly into the liver's portal venous radicles or hepatic sinusoids. Innervation includes sympathetic fibers from the for vasomotor control and pain sensation, parasympathetic input from the hepatic branch of the right for gallbladder contraction, and sensory fibers from the right . Lymphatic drainage follows subserosal and submucosal vessels to the cystic node in Calot's triangle, then proceeds to hepatic nodes along the and ultimately to celiac nodes. In terms of anatomical relations, the gallbladder is embedded superiorly and anteriorly against the liver, with its inferior surface exposed to the peritoneum. Posteriorly, it contacts the second part of the duodenum and the inferior vena cava, while the transverse colon and hepatic flexure lie inferiorly and posteriorly, respectively. The cystic duct descends along the medial border of the gallbladder before joining the common hepatic duct to form the common bile duct.

Microscopic anatomy

The gallbladder wall consists of four main layers: the mucosa, muscularis, perimuscular , and serosa or . Unlike other parts of the , it lacks a and . The innermost mucosa is composed of a resting on a , forming branching folds known as , particularly prominent in the body and fundus to maximize surface area for absorption. The epithelium features tall columnar cells with basally located nuclei, cytoplasm, apical microvilli (forming a ), and apical vacuoles, specialized for active of water and electrolytes to concentrate up to 10-fold. These cells lack goblet cells in the normal state and produce acidic sulfomucins, primarily MUC5B, while tubuloalveolar mucous glands are confined to the neck region. The is a thin layer of containing blood vessels, lymphatics, scattered immune cells such as lymphocytes and plasma cells, and nerve fibers, but typically no neutrophils or eosinophils. The muscularis, or muscular wall, directly adjoins the lamina propria and consists of loosely arranged smooth muscle bundles in a crisscrossing pattern, without distinct inner circular or outer longitudinal layers, enabling contraction for bile expulsion. The perimuscular connective tissue layer includes collagen, elastic fibers, adipose tissue, vessels, lymphatics, and nerves, sometimes with small lymph nodes. The outermost layer is a serosa of simple mesothelium covered by peritoneum on the free surface, while the hepatic surface features adventitia directly adherent to the liver. A characteristic feature of the gallbladder mucosa are Rokitansky-Aschoff sinuses, which are invaginations or outpouchings of the and that penetrate the muscularis layer, potentially representing acquired herniations; they occur in up to 40% of normal gallbladders and become more prominent in chronic inflammation.

Anatomical variations

Anatomical variations of the gallbladder encompass a range of congenital deviations from the typical pear-shaped structure located in the gallbladder fossa on the visceral surface of the right hepatic lobe. These variations occur in approximately 30-50% of individuals, with implications for preoperative imaging and surgical procedures such as , where unrecognized anomalies can elevate the risk of injury or vascular complications. One of the rarest variations is gallbladder agenesis, the congenital absence of the gallbladder, with a prevalence of 0.04-0.1% in the general . This condition is often and discovered incidentally during or , though it may be associated with biliary symptoms mimicking cholelithiasis in some cases. Duplication of the gallbladder, including bilobed forms, is another uncommon anomaly with an incidence of about 1 in 4,000 live births. In bilobed gallbladders, the organ divides into two lobes sharing a common or possessing separate ducts, potentially complicating laparoscopic procedures due to altered anatomy. The phrygian cap deformity, distinct from true duplication but sometimes radiologically mimicking it, involves a folded or partially divided fundus and affects approximately 4% of the ; it is typically and requires no intervention. Ectopic gallbladders deviate from the standard position and occur in 0.1-0.7% of cases. Intrahepatic location, where the gallbladder is embedded within the liver , is rare and may be overlooked on , necessitating advanced imaging like MRI for confirmation. Left-sided (sinistropositioned) gallbladders, positioned to the left of the without , have a of 0.04-0.3% and pose surgical challenges due to altered vascular relations. Retrodisplaced variants, situated behind the liver, further exemplify ectopic positioning and can increase operative risks. Variations in the cystic duct are frequent, affecting up to 11-15% of individuals and critical for surgical planning. Short cystic ducts (less than 2 cm) occur in about 1-5% of cases, while long ducts (greater than 4 cm) are seen in 3-4%; these length anomalies can lead to misidentification during dissection. A parallel course of the cystic duct alongside the common hepatic duct is noted in 7-8% of patients, heightening the risk of inadvertent injury to the common bile duct. Absent cystic ducts are exceedingly rare, often associated with other biliary malformations. Low or medial insertion of the cystic duct into the common bile duct has prevalences of 9-11%, further contributing to anatomical complexity. Supernumerary cystic arteries, where multiple arteries supply the gallbladder instead of the typical single branch from the right hepatic artery, occur in 15-20% of cases and significantly increase surgical risk during cholecystectomy by complicating hemostasis and raising the potential for hepatic artery injury. Preoperative recognition via CT angiography or MRCP is essential to mitigate these risks in 10-15% of patients with overall aberrant biliary-vascular anatomy.

Development and embryology

Embryonic origins

The gallbladder originates from the ventral as an outgrowth known as the hepatic , which emerges during the third to fourth week of . This arises from the caudal portion of the , specifically at the junction with the , and represents the for the liver, extrahepatic biliary system, and ventral . By the end of the fourth week (Carnegie stage 13), the hepatic begins to branch, forming a larger cranial portion (pars hepatica) that develops into the liver and intrahepatic ducts, while a smaller caudal portion (pars cystica or cystic ) buds from the hepatic duct to give rise to the gallbladder and . This budding process establishes the initial separation of the gallbladder lineage from the hepatic tissue, driven by differential proliferation of endodermal cells under the influence of signaling from the surrounding . By the fifth week of , the further separates from the liver bud, becoming a distinct structure while remaining connected via the developing hepatic ducts; at this stage, all major elements of the biliary tree are recognizable, with the undergoing marked elongation and temporary epithelial plugging of its lumen. Recanalization of the ductal lumens begins in the late fifth week for the and progresses proximally into the by the sixth to seventh week, restoring patency through formation and epithelial remodeling, although the gallbladder itself remains solid until around the twelfth week. Key transcription factors such as Hhex and Sox17 play critical roles in the specification of the ventral during these early stages; Hhex regulates the differentiation of hepatopancreatic progenitors that contribute to the and , while Sox17 acts cell-autonomously to direct endodermal cells toward the gallbladder and lineages, preventing their diversion to pancreatic fates. During weeks 6 to 10, the developing gallbladder undergoes and repositioning as part of the broader midgut and liver descent within the enlarging . In the sixth week, the and ventral pancreatic bud rotate 180 degrees clockwise around the , repositioning the and gallbladder attachment to the inferior surface of the liver. This , influenced by the ventral pancreatic bud's proximity and shared developmental origin from the hepatic , ensures proper alignment of the biliary and pancreatic ducts for their eventual fusion into the hepatopancreatic ampulla. As the liver descends caudally between weeks 6 and 10, the gallbladder migrates to its final extrahepatic position, adherent to the visceral aspect of the liver and oriented toward the , completing the organ's topographic integration with surrounding structures.

Developmental anomalies

Developmental anomalies of the gallbladder arise from errors during embryogenesis, primarily involving disruptions in the formation and recanalization of the , which gives rise to the gallbladder and around the fourth to sixth weeks of . Key mechanisms include failure of recanalization of the initially solid of the gallbladder bud, leading to or , or abnormal budding from the , which can result in duplication or septation. These malformations often manifest as obstructions to flow and are associated with broader biliary tree defects. Gallbladder , the complete absence of the gallbladder, results from failure of the pars cystica to develop or vacuolize properly during embryogenesis. It has an estimated incidence of 0.01-0.06% (1 in 1,667-10,000 live births), with a female predominance (3:1 ratio in symptomatic cases), and is often isolated but can associate with other biliary or chromosomal anomalies in 10-30% of cases. Most individuals are asymptomatic, as bile flow is maintained via the extrahepatic ducts, but some present with or dyspepsia mimicking cholelithiasis. is typically incidental during or , confirmed by ultrasonography or showing absence of the gallbladder fossa and normal patency; may be needed to rule out intrahepatic location. Management is conservative unless symptoms arise, in which case for is employed. Atresia or of the represents a rare congenital defect, often occurring alongside , with related prevalence ranging from 0.01% to 0.04% in surgical series for combined absence. This anomaly impedes bile drainage from the gallbladder into the , causing early postnatal , biliary dilation, and potential hydrops of the gallbladder due to obstruction. Diagnosis typically requires imaging such as to confirm the absence or narrowing of the duct. Biliary atresia stands as a severe end-stage malformation characterized by progressive , , and obliteration of both extrahepatic and , including potential involvement of the gallbladder and . It occurs in approximately 1 in 10,000 to 15,000 live births worldwide, with higher rates in Asian populations, and leads to profound , , and if untreated. The condition likely stems from a combination of genetic, infectious, and immune factors disrupting normal biliary recanalization. Duplicated or septated gallbladders result from incomplete separation of the primordial gallbladder bud or the formation of accessory buds, with an incidence of about 1 in 3,800 to 4,000 live births for true duplication and 2.5 to 3.3 per 10,000 for septation. In duplicated forms, two distinct gallbladder structures may share a single (Y- or V-shaped) or have separate ducts, increasing surgical risks during due to misidentification. Septated variants feature internal partitions that divide the lumen, often but prone to stasis-related complications like . These arise from aberrant vacuolization during the third month of development. Certain developmental anomalies are linked to genetic syndromes, notably , caused by mutations in the JAG1 gene in approximately 90% of cases, leading to bile duct paucity and intrahepatic that can extend to gallbladder or dysgenesis. This autosomal dominant disorder disrupts Notch signaling essential for biliary development, resulting in narrowed or absent ducts and associated cardiac, vertebral, and facial anomalies. Early confirms JAG1 involvement, guiding management. Incidence of major gallbladder anomalies like underscores their rarity yet clinical urgency, with prenatal enabling early detection through signs such as non-visualization or abnormal size/shape of the gallbladder in the second or third trimester. In cases of non-visible fetal gallbladder, about 3% progress to , prompting postnatal hepatobiliary or for confirmation. Timely intervention, such as the Kasai portoenterostomy, improves outcomes when performed before 60 days of age.

Physiology

Bile storage and concentration

The gallbladder serves as a reservoir for bile, a digestive fluid continuously produced by the liver at a rate of approximately 500 to 1000 mL per day, while the organ itself stores 30 to 50 mL of this bile at any given time. During periods between meals, bile enters the gallbladder intermittently through the cystic duct, driven by pressure gradients in the biliary system when the sphincter of Oddi is closed. This storage phase is maintained by low neural tone, which promotes gallbladder relaxation and accommodates the incoming bile without significant contraction. A primary function of the gallbladder is to concentrate bile, reducing its volume by 5- to 20-fold through active absorption of sodium (Na⁺) and chloride (Cl⁻) ions across the epithelial lining via specialized transporters. This is followed by passive movement of water osmotically, facilitated by aquaporins such as AQP1 and AQP8 in the epithelial cells, which enable efficient transepithelial water reabsorption while preserving the iso-osmolarity of the lumen. The columnar epithelium features abundant microvilli that increase the surface area for these absorptive processes, allowing up to 90% of the water and electrolytes in hepatic bile to be removed. As a result, gallbladder bile becomes highly concentrated, with key components including bile salts (for fat emulsification), bilirubin (a breakdown product of heme), and cholesterol, while maintaining an alkaline pH of approximately 7 to 8.

Bile release and digestion

The release of bile from the gallbladder is primarily triggered postprandially by , a secreted by enteroendocrine cells in the in response to the presence of fats and proteins in the . CCK binds to CCK-1 receptors on gallbladder cells, initiating contraction that increases intraluminal pressure to approximately 10-20 cm H₂O, thereby expelling concentrated through the into the . Concurrently, CCK promotes relaxation of the , facilitated by the release of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) from non-adrenergic non-cholinergic neurons, which inhibits tone and allows to flow into the without resistance. Neural regulation modulates this process through the autonomic nervous system. Parasympathetic innervation via the vagus nerve enhances gallbladder contraction by releasing acetylcholine, which acts on muscarinic receptors to amplify CCK-induced motility. In contrast, sympathetic innervation from the celiac plexus provides inhibitory input, releasing norepinephrine to suppress contraction and maintain gallbladder tone during fasting periods. Overall, human bile flow into the duodenum averages 0.5-1 L per day, delivered in boluses during meals to match digestive demands. In the , bile salts perform a critical role in by emulsifying dietary into smaller droplets, increasing the surface area for pancreatic to hydrolyze triglycerides into monoglycerides and free fatty acids. These products, along with bile salts, spontaneously form mixed micelles—spherical aggregates with a hydrophobic core and hydrophilic exterior—that solubilize the and facilitate their across the unstirred water layer to the for absorption. This micellar transport enhances the efficiency of absorption, preventing the accumulation of undigested . Feedback mechanisms fine-tune bile release to prevent excessive contraction when bile acid levels are low. , released from duodenal S cells in response to acidic , stimulates bicarbonate-rich fluid secretion from cholangiocytes but also indirectly reduces gallbladder contractility by counteracting CCK effects, thereby conserving bile when enterohepatic recirculation is insufficient. Following , the absence of the gallbladder leads to adaptive changes where bile flows continuously from the liver directly into the duodenum at a lower concentration, relying on hepatic production rates without storage-mediated boluses; this alters postprandial lipid digestion but maintains overall bile-dependent absorption through increased enterohepatic cycling.

Diseases and disorders

Gallstones

Gallstones, medically termed cholelithiasis, are hardened deposits that develop within the gallbladder from imbalances in bile components, primarily , , and calcium salts. These stones form through a multi-step process involving of bile, of crystals, and growth within a matrix. In Western populations, stones predominate, comprising about 75-80% of cases, while stones account for the remainder. Cholesterol stones arise from hepatic overproduction of relative to available salts and phospholipids, leading to bile supersaturation and precipitation of cholesterol monohydrate crystals. is promoted by glycoproteins secreted by the gallbladder , which trap and aggregate crystals, often exacerbated by gallbladder stasis. Pigment stones, in contrast, result from excess unconjugated ; black pigment stones form via calcium bilirubinate precipitation in hemolytic conditions like sickle cell anemia, whereas brown pigment stones develop from bacterial deconjugation of in the presence of and stasis. The prevalence of gallstones affects 10-15% of adults , with over 14 million women and 6 million men impacted, and rates exceeding 25% in women over age 60. Women experience gallstones at roughly twice the rate of men (2:1 ratio), influenced by hormonal factors. Key risk factors are encapsulated by the "4 Fs": female sex, age over forty, (fat), and fertility (multiple pregnancies). elevates risk twofold in women with BMI ≥30 kg/m² and sevenfold in those with BMI ≥45 kg/m²; rapid exceeding 1.5 kg/week or 25% of body weight increases incidence by promoting bile ; doubles to triples prevalence through and ; and genetic variants, such as ABCG8 rs11887534 (affecting ~12% of Europeans), heighten susceptibility by impairing transport. Approximately 80% of gallstones are , discovered incidentally during imaging for unrelated issues. Symptomatic gallstones manifest as , with intense, episodic right upper quadrant or epigastric pain radiating to the back or shoulder, typically lasting 30 minutes to several hours after fatty meals, due to obstruction and gallbladder contraction against the stone. A significant complication is choledocholithiasis, the migration of stones into the , affecting 10-15% of symptomatic cases and potentially leading to biliary obstruction.

Cholecystitis

Cholecystitis refers to of the gallbladder, which can manifest in acute, chronic, or acalculous forms, primarily triggered by gallstone-related obstruction or other factors leading to bile stasis and secondary complications. In most cases, it arises as a of disease, where obstruction promotes inflammatory cascades that may progress to severe outcomes if untreated. Acute cholecystitis accounts for the majority of cases and is characterized by sudden inflammation, typically due to obstruction by a in approximately 95% of instances. This obstruction causes stasis, mucosal ischemia from increased intraluminal pressure, and subsequent bacterial overgrowth, predominantly involving enteric pathogens such as and species. The inflammatory response involves release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which exacerbate tissue damage and can lead to complications like or in 10-20% of severe cases. Clinically, patients present with right upper quadrant (RUQ) that may radiate to the , fever, and a positive —elicited as inspiratory arrest during palpation of the RUQ due to gallbladder tenderness. Diagnostic often reveals gallbladder wall thickening greater than 4 mm and pericholecystic fluid, supporting the diagnosis alongside clinical features. Chronic cholecystitis develops from repeated episodes of low-grade inflammation, usually associated with persistent gallstone irritation, resulting in progressive and thickening of the gallbladder wall. Over time, this leads to mucosal , hypertrophy, and impaired gallbladder contractility, often presenting with recurrent rather than acute distress. Acalculous cholecystitis, comprising 5-10% of all cases, occurs without s and is prevalent in critically ill patients, such as those post-trauma, undergoing prolonged , or receiving total . It arises from gallbladder stasis, hypoperfusion, and ischemia rather than mechanical obstruction, heightening risks in intensive care settings. The annual incidence of acute cholecystitis is approximately 1% among patients with gallstones, based on long-term progression data showing symptomatic development in about 20% over 20 years. In the United States, it affects roughly 200,000 individuals annually, underscoring its clinical significance in gallstone disease management.

Gallbladder cancer

Gallbladder cancer, also known as gallbladder carcinoma, is a rare but aggressive malignancy originating from the epithelial lining of the gallbladder. It represents approximately 0.6% of all new cancer cases and 0.9% of cancer-related deaths globally (GLOBOCAN 2022). In 2022, an estimated 122,491 new cases and 89,055 deaths occurred worldwide, with the highest burden in South Central Asia and Eastern/South-Eastern Asia. Incidence rates vary geographically, ranging from 1-2 per 100,000 in Western countries to much higher levels in high-risk regions such as (~7.6 per 100,000 nationally for females, up to ~15 per 100,000 in southern regions) and parts of (around 10-15 per 100,000 in northeastern areas). The disease disproportionately affects women, with a global female-to-male ratio of about 1.8:1 (64% of cases in females), though ratios up to 3:1 occur in endemic regions. Major risk factors include chronic gallstones, present in 70-90% of cases, which promote through persistent inflammation and irritation. , characterized by intramural calcification, carries an elevated risk, with recent studies reporting malignancy rates of 0-15% in affected individuals, though prophylactic is recommended. Anomalous pancreaticobiliary duct junction, an anatomical variant allowing bile reflux into the , is associated with 10-17% of cases and increases susceptibility due to chronic exposure to pancreatic enzymes. Histologically, accounts for over 90% of gallbladder cancers, typically arising from glandular and subdivided into papillary, mucinous, and other subtypes. , comprising up to 3% of cases, originates from metaplastic squamous and is linked to chronic . Staging follows the TNM system, where T1 tumors are confined to the mucosa (T1a) or muscle layer (T1b), T2 involves perimuscular , T3 extends to adjacent organs like the liver, and T4 indicates invasion of major structures such as the or multiple organs. Symptoms often manifest late due to the gallbladder's anatomical location and lack of early warning signs, commonly including right upper quadrant pain, , anorexia, and significant . Many cases (0.2-3%) are discovered incidentally during histopathological examination following for presumed benign conditions like gallstones. The cancer spreads primarily through direct invasion into the liver bed (in up to 70% of advanced cases), lymphatic dissemination to regional lymph nodes (45-60%), and peritoneal seeding, leading to widespread . is poor, with overall 5-year survival rates around 19%; for advanced stages (III-IV), this drops to less than 5%, reflecting late and limited therapeutic options. At the molecular level, TP53 mutations occur in 40-70% of tumors, disrupting tumor suppression and promoting genomic instability. ERBB2 (HER2) amplification is identified in 10-16% of cases, particularly in Latin American cohorts, driving aggressive growth via HER2 signaling pathways. Recent advances include targeted therapies such as HER2 inhibitors; for instance, phase II trials of and combinations (e.g., MyPathway trial) in ERBB2-amplified cancers, including gallbladder carcinoma, reported objective response rates of ~23% (as of 2023), while (DESTINY-PanTumor02) showed ~37% ORR (as of 2024), offering improved outcomes for molecularly selected patients.

Diagnosis and management

Diagnostic tests

Abdominal ultrasound serves as the first-line imaging modality for evaluating suspected gallbladder conditions due to its non-invasive nature, availability, and high accuracy in detecting gallstones, with a reported sensitivity of approximately 95% for cholelithiasis. It also identifies gallbladder wall thickening greater than 3 mm, which may indicate , and detects as echogenic material layering within the lumen. Hepatobiliary (HIDA) scan, also known as , is a test that assesses the patency of the by tracking the flow of radiotracer from the liver through the biliary system to the gallbladder. Non-visualization of the gallbladder on HIDA scan indicates obstruction, supporting a of acute with high specificity. Additionally, calculation of the gallbladder after cholecystokinin stimulation, where values below 35% suggest or chronic dysfunction, aids in evaluating functional disorders. Computed tomography (CT) and (MRI) are utilized to identify complications such as abscesses, perforations, or local invasion in , and they play a key role in staging by assessing tumor extent, involvement, and distant metastases. (MRCP), a non-invasive MRI variant, excels at delineating biliary duct anatomy, detecting strictures, and visualizing choledocholithiasis without the risks associated with contrast injection. Laboratory tests complement imaging by providing supportive evidence of gallbladder . Elevated serum and levels are characteristic of biliary obstruction, reflecting impaired flow and . In cases of inflammation such as , indicated by increased count and elevated may occur, particularly if is concurrent. For suspected , serum tumor markers like CA 19-9 can be measured, though elevations are non-specific and also seen in other biliary malignancies or benign obstructions. Endoscopic ultrasound (EUS) is employed for detailed evaluation of gallbladder masses, particularly in suspected malignancy, where it facilitates or for histopathological confirmation with high diagnostic accuracy. This procedure offers superior resolution for assessing wall invasion and adjacent structures compared to . Esophagogastroduodenoscopy (EGD) combined with (ERCP) provides both diagnostic visualization of the biliary tree and therapeutic options, such as stone extraction, for stones originating from the gallbladder. ERCP is particularly valuable when ductal obstruction is confirmed by prior imaging, allowing sphincterotomy and stent placement if needed.

Surgical treatments

Laparoscopic cholecystectomy is the gold standard surgical treatment for most gallbladder disorders, including symptomatic gallstones and , and has been widely adopted since the late 1980s, comprising over 90% of all performed today. The procedure involves creating and inserting four ports: one 10-mm supraumbilical port for the camera, one subxiphoid port for retraction, and two in the right upper quadrant for dissection. The and are identified, doubly clipped proximally and distally with metal clips, and divided, followed by dissection and removal of the gallbladder using electrocautery or a harmonic scalpel. This minimally invasive approach results in shorter hospital stays, reduced postoperative pain, and faster recovery compared to open . Open cholecystectomy is reserved for cases where laparoscopic conversion occurs due to complications such as severe , adhesions, , or unclear , or for planned procedures in patients with , extensive prior abdominal surgeries, or . The surgery entails a right subcostal or upper midline incision to access the gallbladder, with ligation and division of the and artery using hemoclips, followed by gallbladder excision and potential intraoperative . Conversion from laparoscopic to open occurs in 2-10% of cases, and open procedures carry a higher overall complication rate of approximately 16% compared to 9% for laparoscopic approaches. For acute cholecystitis, early within 72 hours of symptom onset is preferred over delayed (typically 6-12 weeks after initial management), as it reduces length of stay, costs, complication rates, and recurrence risk. Studies show that performing the procedure within 24 hours of admission further lowers leak incidence (0.4% vs. 5.9%) and conversion rates (2.2% vs. 6.9%). Common complications of cholecystectomy include bile leak (occurring in up to 1% of laparoscopic cases), bile duct injury (0.5% overall, with 0.13% requiring major reconstruction), and post-cholecystectomy , which encompasses persistent biliary symptoms due to retained stones, dysfunction, or other causes in 10-15% of patients. Bile duct injuries are slightly more frequent in laparoscopic (0.5%) than open (0.15%) surgery. In , radical is indicated for T2 or higher stage tumors and includes en bloc removal of the gallbladder, wedge resection of the adjacent liver bed, extrahepatic resection, and regional dissection (portal and hepatoduodenal ligament nodes). Liver resection is essential for T2+ disease to address potential microscopic invasion, with residual disease found in 57% of T2 re-resections (31% nodal, 10% hepatic). Five-year survival rates post-radical resection are 42.5% for node-negative T2-T4 tumors and 31% for node-positive cases. Overall, achieves success in over 95% of cases for benign disease, with 30-day morbidity around 11% and mortality under 0.5%. Robotic-assisted variants, particularly for radical procedures, have emerged in the , offering enhanced precision via 3D imaging and instrumentation; in experienced centers, they yield R0 resection rates of 96.8%, complication rates of 6.8%, and 2-year survival of 60.5-100% for , though long-term oncologic data remain limited.

Non-surgical interventions

Non-surgical interventions for gallbladder conditions primarily target symptom relief, stone dissolution, infection control, and prevention of recurrence, particularly in patients unsuitable for surgery. These approaches include pharmacological treatments, minimally invasive procedures, and lifestyle modifications, often used for gallstones (cholelithiasis), biliary colic, and acute cholecystitis. Ursodeoxycholic acid (UDCA), a bile acid medication, is employed to dissolve small cholesterol gallstones, typically those less than 1 cm in diameter, by reducing cholesterol saturation in bile. Clinical studies indicate that UDCA achieves complete dissolution in approximately 50% of suitable patients over 6 to 24 months of treatment, with higher success rates (up to 80%) for radiolucent stones in select cases. It also alleviates biliary pain and reduces the risk of gallstone-related complications during long-term use. UDCA is particularly beneficial for patients with symptomatic gallstones who are poor surgical candidates, though recurrence can occur after discontinuation. For managing pain associated with , nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or , serve as first-line therapy due to their efficacy in reducing and . NSAIDs have been shown to significantly alleviate compared to or spasmolytic agents alone, with fewer side effects than opioids and a lower risk of subsequent complications like . Antispasmodics, including hyoscine or derivatives, are often combined with NSAIDs to relieve spasms in the , providing rapid symptom control during acute episodes. These medications are administered orally or parenterally, with NSAIDs preferred for their properties in uncomplicated cases. In acute cholecystitis, especially among high-risk patients where surgery is contraindicated, antibiotics are a cornerstone of conservative management to combat bacterial . Common regimens include intravenous combined with , providing broad-spectrum coverage against gram-negative and anaerobic pathogens prevalent in biliary infections. This combination has demonstrated appropriateness as empirical therapy for moderate to severe cases, with equivalent efficacy to other options like fluoroquinolones in community-acquired infections. Treatment duration typically spans 4 to 7 days for mild cases, extending longer if percutaneous drainage is required, and is guided by clinical response and culture results. Percutaneous cholecystostomy involves ultrasound- or CT-guided insertion of a drainage tube into the gallbladder, offering a minimally invasive alternative for decompressing the organ in acute acalculous cholecystitis, particularly in critically ill ICU patients. This procedure is effective as a definitive treatment in the majority of cases, achieving resolution in over 80% of moderate to severe acute acalculous cholecystitis without subsequent surgery. It is preferred for high-risk individuals, allowing gallbladder drainage and antibiotic delivery directly, with low complication rates and the option for tube removal once inflammation subsides. Extracorporeal shock wave lithotripsy (ESWL) uses high-energy shock waves to fragment gallstones, reserved for rare cases involving solitary stones smaller than 2 cm that are radio-opaque and located in a functioning gallbladder. While once more common, ESWL's role has diminished due to lower overall compared to other methods, succeeding in stone clearance for small solitary stones (under 16 mm) in about 50-70% of patients after multiple sessions, often combined with UDCA to aid dissolution of fragments. It is considered for patients unfit for or , though recurrence remains a concern without . Endoscopic interventions, such as sphincterotomy performed during (ERCP), address choledocholithiasis by incising the to facilitate stone extraction from the . This procedure is safe and effective, achieving stone clearance in over 90% of cases, with long-term success in preventing recurrence when the is not markedly dilated. It is particularly valuable for common bile duct stones, reducing the need for open surgery and associated risks. Lifestyle modifications play a key role in preventing gallstone formation and recurrence, emphasizing a to minimize bile supersaturation with and gradual to avoid rapid loss. Diets rich in and moderate in fats, along with regular , can reduce symptomatic gallstone risk by up to 30% in at-risk populations, while avoiding very low-calorie regimens (under 800 kcal/day) prevents stone development during weight reduction. Maintaining a healthy body weight through balanced and exercise is recommended, as increases gallstone incidence, but slow loss (1-2 pounds per week) mitigates this risk.

Comparative anatomy

In non-human mammals

The gallbladder is present in the majority of mammalian , serving as a reservoir for concentration and storage to facilitate intermittent . For instance, it is found in carnivores such as dogs and cats, where it typically exhibits a pear-shaped structure with a fundus, body, and neck that transitions into the , allowing for expansion to hold up to 1.2 mL/kg of in dogs and 1.0–1.2 mL/kg in cats during interdigestive periods. In contrast, it is absent in certain including rats, deer, , camels, and whales, where flows continuously from the liver directly into the without storage. This absence is particularly noted in like rats and pocket gophers, while closely related such as mice retain a gallbladder located between the liver's medial lobes. Structural variations among mammals with a gallbladder reflect dietary adaptations. In carnivores like dogs and cats, the organ is relatively larger and more robust, adapted for efficient fat digestion through bile concentration up to 10-fold, with mucosal folds aiding absorption and a flexible enabling postprandial expansion. Pigs, as omnivores, possess a gallbladder with similar basic morphology, though its size correlates with liver mass. Some , such as mice, show a compact, embedded form within liver fissures, while variations in shape—such as bilobed or multilobed configurations—occur sporadically across species, often as developmental anomalies rather than consistent traits. Functionally, the gallbladder in possessing mammals concentrates and releases in response to meals, triggered by hormones like cholecystokinin, to emulsify fats in the . In species lacking it, such as , secretion is continuous to support steady of fibrous, low-fat diets from , bypassing the need for concentration. This ensures a constant supply to the without storage, aligning with uninterrupted feeding patterns in herbivores. Diseases affecting the gallbladder occur across species, with gallstones (cholelithiasis) being prominent. In dogs, these are commonly cholesterol-based or mixed with pigments and calcium, often forming in saturated and leading to obstruction or , particularly in middle-aged females. Pigs develop choleliths composed of pigments, cholesterol, calcium, and acids, which can cause intrahepatic issues or blockages. Surgical removal () is a standard veterinary intervention for such conditions in dogs and cats, with laparoscopic approaches showing good short-term outcomes in managing benign diseases and restoring flow. The absence or vestigial nature of the gallbladder in some herbivores, such as deer and , is linked to evolutionary adaptations for fiber-rich, continuous diets that require steady rather than episodic bile release, reducing the selective pressure for a .

Evolutionary perspectives

The gallbladder emerged as a synapomorphy among extant vertebrates, coinciding with the of the liver and in early chordates, with primitive forms present in jawless such as and larval lampreys, where it stores C27 alcohols rather than concentrated acids. In more derived like ray-finned species, the organ supports concentration for , though less specialized than in tetrapods. This structure likely originated over 500 million years ago during the Cambrian-Ordovician transition, facilitating the storage and release of in response to feeding patterns in aquatic environments. A more fully developed gallbladder appears in amphibians and reptiles, where a SOX17-positive biliary bud forms from the hepatic to enable intermittent storage and , adapting to sporadic prey capture in terrestrial predators. Fossil evidence for this configuration is inferred from the anatomy of reptilian ancestors around 300 million years ago, during the early radiation, when -storing organs would have supported feast-famine cycles in ectothermic lineages transitioning to land. In the mammalian radiation, the gallbladder is retained in the majority of , but has been independently lost in several lineages, including some like rats, due to failure of the biliary bud to form, often linked to reduced SOX17 expression and favoring continuous from the liver. This loss is exemplified in through genetic modifications that prevent gallbladder , mirroring adaptations in with steady feeding habits. The adaptive significance of the gallbladder lies in its role in energy efficiency for predators facing irregular meals, allowing concentration and rapid release to digest large, infrequent boluses, as seen in carnivorous reptiles and mammals. Conversely, in herbivores with constant grazing, the organ's absence reduces the risk of stasis and , promoting a steady flow that aligns with continuous , though this has led to its evolutionary forfeiture in groups like equids and certain perissodactyls. Developmentally, the organ's formation is governed by conserved transcription factors such as HNF6 (also known as OC-1), which is essential for biliary bud outgrowth and across vertebrates; its disruption in model organisms like mice results in gallbladder , underscoring a shared genetic framework from to mammals. In modern humans, post-cholecystectomy adaptation to continuous hepatic flow parallels the of gallbladder-less species, enabling enterohepatic recirculation without storage, though it may increase susceptibility to certain digestive imbalances.

History

Early anatomical descriptions

The earliest recorded references to bile, a key component associated with the gallbladder, appear in ancient Egyptian medical texts. The , dating to approximately 1550 BCE, mentions in the context of enemas and therapeutic applications, reflecting an early recognition of its medicinal properties without detailed anatomical description of the organ itself. In ancient Greek thought, the gallbladder began to emerge as a distinct structure tied to humoral physiology. , in the 4th century BCE, described the gallbladder as a "small bag or sack" situated in the hollow of the liver, likening it to a due to its sac-like form and role in containing yellow , one of the four humors believed to govern bodily temperament and health. Building on this framework, the Roman physician in the 2nd century CE elaborated on the gallbladder's connection to the liver, positing it as a reservoir for choler or yellow , which he viewed as a hot and dry humor produced in conjunction with blood and black bile from the . Galen emphasized the gallbladder's subordinate yet essential role in humoral balance, influencing medical theory for centuries. The marked a shift toward empirical and visual representation of the gallbladder. In 1543, published De humani corporis fabrica, featuring accurate illustrations of the that depicted the gallbladder in relation to the liver, stomach, intestines, and ducts, based on direct human cadaver s that corrected prior misconceptions. Complementing Vesalius's work, Gabriele Falloppio in 1561 published Observationes anatomicae, a critique and expansion of Vesalius's findings. By the mid-17th century, Francis Glisson's Anatomia hepatis (1654) advanced observations, noting gallstones in human cadavers and their potential to obstruct ducts, causing pain—early insights into biliary derived from meticulous liver and gallbladder s. Throughout this period, anatomical studies of the gallbladder were constrained by the absence of , restricting observations to gross dissections visible to the and precluding any understanding of its histological structure or cellular composition.

Modern surgical advancements

In 1882, German surgeon Carl Johann August Langenbuch performed the first elective for gallstones at the Lazarus Hospital in , marking a pivotal shift from drainage procedures to complete removal of the gallbladder as a curative approach for cholelithiasis. This operation, conducted on a 43-year-old with chronic symptoms, demonstrated the feasibility of extirpation without immediate mortality, though initial adoption was cautious due to risks. During the early 1900s, Theodor Kocher introduced the Kocher maneuver, a mobilization technique involving incision of the lateral to the to expose the retroperitoneal structures, enhancing surgical access to the gallbladder and during open . First described in 1903, this procedure reduced operative trauma and improved visualization, contributing to broader acceptance of elective biliary surgery amid declining postoperative infection rates from emerging aseptic techniques. The introduction of laparoscopic cholecystectomy in the late 1980s revolutionized gallbladder surgery by enabling minimally invasive removal through small incisions, with Erich Mühe performing the first procedure in 1985 in , followed by Philippe Mouret's refinement in 1987 using fundus-first . This approach, which utilized video and , dramatically shortened recovery times and reduced wound complications, leading to global adoption by the early 1990s as the standard for symptomatic gallstones, with over 500,000 procedures annually alone by 1992. In the , intraoperative emerged as a routine adjunct during laparoscopic to map the biliary and prevent common bile duct injuries, which initially rose to 0.5-1% with the new technique's . By visualizing the junction and extrahepatic ducts in real-time via contrast injection, this imaging reduced injury rates by identifying anatomic variants in up to 20% of cases, establishing it as a quality benchmark in high-volume centers. The 2000s saw further minimally invasive innovations, including single-incision laparoscopic (SILC), first reported in 2008 using a single umbilical port for gallbladder extraction, which minimized scarring while maintaining standard laparoscopic outcomes. Concurrently, robotic-assisted with the , approved by the FDA in 2000 for general , offered enhanced precision through three-dimensional visualization and tremor-filtered instruments, particularly beneficial in complex cases with adhesions or , though adoption remained limited by cost. In the 2020s, (AI)-assisted technologies have enhanced visualization during gallbladder , such as autonomous cameras that improve surgical field stability and efficiency. For , extended resections combining with partial and have improved prognoses, achieving 5-year survival rates of 15-30% in R0-resected advanced cases, compared to less than 5% without . Overall, these advancements have transformed outcomes, with for declining from approximately 10% in the early 1900s—due to and hemorrhage—to 0.1-0.5% as of the late , reflecting improvements in , antibiotics, and procedural safety.

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