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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

Invertebrates,thegallbladder,also known as thecholecyst,is a small holloworganwherebileis stored and concentrated before it is released into thesmall intestine.In humans, the pear-shaped gallbladder lies beneath theliver,although the structure and position of the gallbladder can vary significantly among animal species. It receives bile, produced by the liver, via thecommon hepatic duct,and stores it. The bile is then released via thecommon bile ductinto theduodenum,where the bile helps in the digestion offats.

The gallbladder can be affected bygallstones,formed by material that cannot be dissolved – usuallycholesterolorbilirubin,a product ofhemoglobinbreakdown. These may cause significant pain, particularly in the upper-right corner of the abdomen, and are often treated with removal of the gallbladder (called acholecystectomy).Cholecystitis,inflammation of the gallbladder, has a wide range of causes, including result from the impaction of gallstones, infection, and autoimmune disease.

Structure

[edit]

The human gallbladder is a hollow grey-blueorganthat sits in a shallow depression below the right lobe of theliver.[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 thecystic duct.[4]The gallbladder is divided into three sections: thefundus,body,andneck.Thefundusis the rounded base, angled so that it faces theabdominal wall.Thebodylies in a depression in the surface of the lower liver. Thenecktapers and is continuous with thecystic duct,part of thebiliary tree.[2]The gallbladder fossa, against which the fundus and body of the gallbladder lie, is found beneath the junction ofhepatic segmentsIVB and V.[5]The cystic duct unites with thecommon hepatic ductto become thecommon 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 lowerhepatic lymph nodes.All the lymph finally drains intoceliac lymph nodes.

Microanatomy

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Micrographof 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 ofcolumnar cellswith abrush borderofmicrovilli,very similar to intestinal absorptive cells.[2]Underneath the epithelium is an underlyinglamina propria,amuscular layer,an outer perimuscular layer andserosa.Unlike elsewhere in the intestinal tract, the gallbladder does not have amuscularis mucosae,and the muscular fibres are not arranged in distinct layers.[6]

Themucosa,the inner portion of the gallbladder wall, consists of aliningof asingle layer of columnarcells, with cells possessing small hair-like attachments calledmicrovilli.[2]This sits on a thin layer of connective tissue, thelamina propria.[6]The mucosa is curved and collected into tiny outpouchings calledrugae.[2]

A muscular layer sits beneath the mucosa. This is formed bysmooth 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 ofRokitansky–Aschoff sinuses,deep outpouchings of the mucosa that can extend through the muscular layer, and which indicateadenomyomatosis.[7]The muscular layer is surrounded by a layer of connective andfattissue.[2]

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

Variation

[edit]
Abdominal ultrasonographyshowing 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 aseptummay 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]

Ananatomical variationcan occur, known as aPhrygian cap,which is an innocuous fold in the fundus, named after its resemblance to thePhrygian cap.[12]

Development

[edit]

The gallbladder develops from anendodermaloutpouching of the embryonic gut tube.[13]Early in development, the human embryo has threegerm layersand abuts an embryonicyolk sac.During the second week ofembryogenesis,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 thisforegutbegin to differentiate into the organs of the gastrointestinal tract, such as theesophagus,stomach,andintestines.[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 theduodenum.By the end of the fourth week, the developing duodenum begins to spout a small outpouching on its right side, thehepatic diverticulum,which will go on to become thebiliary tree.Just below this is a second outpouching, known as thecystic diverticulum,that will eventually develop into the gallbladder.[13]

Function

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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.Rightandleftlobes ofliver
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 leftkidneys
The front border of the liver has been lifted up (brown arrow).[14]

The main functions of the gallbladder are to store and concentratebile,also called gall, needed for the digestion of fats in food. Produced by the liver, bile flows through small vessels into the largerhepatic ductsand ultimately through thecystic duct(parts of thebiliary tree) 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 thedigestive tract,it stimulates thesecretionofcholecystokinin(CCK) fromI cellsof the duodenum and jejunum. In response to cholecystokinin, the gallbladder rhythmically contracts and releases its contents into thecommon bile duct,eventually draining into theduodenum.The bileemulsifiesfats in partly digested food, thereby assisting their absorption. Bile consists primarily of water andbile salts,and also acts as a means of eliminatingbilirubin,a product ofhemoglobinmetabolism, 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 theactive transportof sodium and chloride ions[17]across the epithelium of the gallbladder, which creates anosmotic pressurethat also causes water and other electrolytes to be reabsorbed.[15]

A function of the gallbladder appears to be protection againstcarcinogenesisas 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 cholecystecomy 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
3D still showing gallstones

Gallstonesform when the bile issaturated,usually with eithercholesterolorbilirubin.[20]Most gallstones do not cause symptoms, with stones either remaining in the gallbladder or passed along thebiliary system.[21]When symptoms occur, severe "colicky" pain in the upper rightquadrantof the abdomen is often felt.[20]If thestone blocks the gallbladder,inflammation known ascholecystitismay result. If the stone lodges in the biliary system,jaundicemay occur; if the stone blocks thepancreatic duct,pancreatitismay occur.[21]Gallstones are diagnosed usingultrasound.[20]When a symptomatic gallstone occurs, it is often managed by waiting for it to be passed naturally.[21]Given the likelihood of recurrent gallstones, surgery to remove the gallbladder is often considered.[21]Some medication, such asursodeoxycholic 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 ascholecystitis,inflammation of the gallbladder is commonly caused by obstruction of the duct with gallstones, which is known ascholelithiasis.Blocked bile accumulates, and pressure on the gallbladder wall may lead to the release of substances that cause inflammation, such asphospholipase.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 positiveMurphy's sign.Cholecystitis is often managed with rest and antibiotics, particularlycephalosporinsand, 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

Acholecystectomyis a procedure in which the gallbladder is removed. It may be removed because of recurrent gallstones and is considered anelective procedure.A cholecystectomy may be anopenprocedure, or alaparoscopicone. In the surgery, the gallbladder is removed from the neck to the fundus,[22]and so bile will drain directly from the liver into thebiliary tree.About 30 percent of patients may experience some degree ofindigestionfollowing the procedure, although severe complications are much rarer.[21]About 10 percent of surgeries lead to a chronic condition ofpostcholecystectomy syndrome.[23]

Complication

[edit]
Main articles:Biliary injuryandBiloma

Biliary injury (bile duct injury) is the traumatic damage of thebile ducts.It is most commonly aniatrogeniccomplication ofcholecystectomy— surgical removal ofgall bladder,but can also be caused by other operations or bymajor trauma.The risk of biliary injury is more 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 inendoscopy,radiologyand surgery.[24]

Biloma is collection ofbilewithin theabdominal cavity.It happens when there is a bile leak, for example after surgery for removing the gallbladder (laparoscopic 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 polypsand 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 testsmay be elevated, particularly involvingGGTandALP,with ultrasound and CT scans being consideredmedical imaginginvestigations 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 polypsare mostly benign growths or lesions resembling growths that form in the gallbladder wall,[26]and are only associated with cancer when they are larger in size (>1 cm).[21]Cholesterol polyps, often associated withcholesterolosis( "strawberry gallbladder", a change in the gallbladder wall due to excesscholesterol[27]), often cause no symptoms and are thus often detected in this way.[21]

Tests

[edit]
Abdominal ultrasonographyshowingbiliary sludgeandgallstones

Tests used to investigate for gallbladder disease includeblood testsandmedical imaging.Afull blood countmay reveal an increased white cell count suggestive of inflammation or infection. Tests such asbilirubinandliver function testsmay reveal if there is inflammation linked to the biliary tree or gallbladder, and whether this is associated with inflammation of the liver, and alipaseoramylasemay be elevated if there ispancreatitis.Bilirubin may rise when there is obstruction of the flow of bile. ACA 19-9level may be taken to investigate for cholangiocarcinoma.[21]

Anultrasoundis often the firstmedical imagingtest performed when gallbladder disease such as gallstones are suspected.[21]Anabdominal X-rayorCT scanis another form of imaging that may be used to examine the gallbladder and surrounding organs.[21]Other imaging options include MRCP (magnetic resonance cholangiopancreatography),ERCPand percutaneous or intraoperativecholangiography.[21]Acholescintigraphyscan is anuclear imagingprocedure used to assess the condition of the gallbladder.[28]

Other animals

[edit]

Mostvertebrateshave 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 ofmammals(includinghorses,deer,rats,andlaminoids),[29][30]several species ofbirds(such as pigeons and somepsittacinespecies),lampreysand allinvertebratesdo not have a gallbladder.[31][32]

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

History

[edit]

Depictions of the gallbladder and biliary tree are found inBabylonianmodels found from 2000 BCE, and in ancientEtruscanmodel 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 ofThebesdating to 1500 BCE.[35][36]Some historians believe the death ofAlexander the Greatmay 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 theRenaissance,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 theeponymousCourvoisier's law,stated that in an enlarged, nontender gallbladder, the cause ofjaundiceis 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 occurringbiliary fistula.[35]Stough Hobbs in 1867 performed the first recordedcholecystotomy,[37]although such an operation was in fact described earlier by French surgeonJean Louis Petitin the mid eighteenth century.[35]German surgeonCarl Langenbuchperformed the first cholecystectomy in 1882 for a sufferer of cholelithiasis.[36]Before this, surgery had focused on creating afistulafor 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 ofcontrast mediumandCT scanswere used to view the gallbladder.[35]The firstlaparoscopiccholecystectomy performed byErich Müheof 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 theChinese medicine,the gallbladder (Đảm) is associated with theWuxingelement of wood, in excess its emotion is belligerence and in deficiency cowardice and judgement, in the Chinese language it is related to a myriad ofidioms,including using terms such as "a body completely [of] gall" (Hồn thân thị đảm) to describe a forward person, and "single, alone gallbladder hero" (Cô đảm anh hùng) to describe a lone hero, or "they have a lot of gall to talk like that".[40]

In theZangfutheory ofChinese medicineit is an extraordinary Fu oryangorgan, 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

[edit]

References

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  1. ^Ginsburg, Ph.D., J.N. (August 22, 2005)."Control of Gastrointestinal Function".In Thomas M. Nosek, Ph.D. (ed.).Gastrointestinal Physiology.Essentials of Human Physiology. Augusta, Georgia, United States:Medical College of Georgia.pp.p. 30.Archived fromthe originalon April 1, 2008.RetrievedJune 29,2007.
  2. ^abcdefghijklGray's Anatomy 2008,p. 1187-81.
  3. ^Jon W. Meilstrup (1994).Imaging Atlas of the Normal Gallbladder and Its Variants.Boca Raton: CRC Press. p. 4.ISBN978-0-8493-4788-7.
  4. ^Nagral, Sanjay (2005)."Anatomy relevant to cholecystectomy".Journal of Minimal Access Surgery.1(2): 53–8.doi:10.4103/0972-9941.16527.PMC3004105.PMID21206646.
  5. ^Shakelford's Surgery of Alimentary Tract, ed.7. 2013
  6. ^abcdYoung, Barbara; et al. (2006).Wheater's functional histology: a text and colour atlas(5th ed.). [Edinburgh?]: Churchill Livingstone/Elsevier. p.298.ISBN978-0-443-06850-8.
  7. ^Ross, M.; Pawlina, W. (2011).Histology: A Text and Atlas(6th ed.). Lippincott Williams & Wilkins. p.646.ISBN978-0-7817-7200-6.
  8. ^Leeuw, Th.G.; Verbeek, P.C.M.; Rauws, E.A.J.; Gouma, D.J. (September 1995). "A double or bilobar gallbladder as a cause of severe complications after (laparoscopic) cholecystectomy".Surgical Endoscopy.9(9): 998–1000.doi:10.1007/BF00188459.PMID7482221.S2CID2581053.
  9. ^Segura-Sampedro, JJ; Navarro-Sánchez, A; Ashrafian, H; Martínez-Isla, A (February 2015)."Laparoscopic approach to the intrahepatic gallbladder. A case report".Revista Espanola de Enfermedades Digestivas.107(2): 122–3.PMID25659400.Archived fromthe originalon March 4, 2016.
  10. ^Dhulkotia, A; Kumar, S; Kabra, V; Shukla, HS (March 1, 2002)."Aberrant gallbladder situated beneath the left lobe of liver".HPB.4(1): 39–42.doi:10.1080/136518202753598726.PMC2023911.PMID18333151.
  11. ^Naganuma, S.; Ishida, H.; Konno, K.; Hamashima, Y.; Hoshino, T.; Naganuma, H.; Komatsuda, T.; Ohyama, Y.; Yamada, N.; Ishida, J.; Masamune, O. (March 6, 2014). "Sonographic findings of anomalous position of the gallbladder".Abdominal Imaging.23(1): 67–72.doi:10.1007/s002619900287.PMID9437066.S2CID30176379.
  12. ^Meilstrup JW; Hopper KD; Thieme GA (December 1991)."Imaging of gallbladder variants".AJR Am J Roentgenol.157(6): 1205–8.doi:10.2214/ajr.157.6.1950867.PMID1950867.
  13. ^abcSchoenwolf, Gary C.; et al. (2009). "Development of the Gastrointestinal Tract".Larsen's human embryology(4th ed.). Philadelphia: Churchill Livingstone/Elsevier.ISBN978-0-443-06811-9.
  14. ^Standring S, Borley NR, eds. (2008).Gray's anatomy: the anatomical basis of clinical practice.Brown JL, Moore LA (40th ed.). London: Churchill Livingstone. pp. 1163, 1177, 1185–6.ISBN978-0-8089-2371-8.
  15. ^abcGuyton, Arthur C.; Hall, John E. (2005).Textbook of medical physiology(11th ed.). Philadelphia: W.B. Saunders. pp. 802–4.ISBN978-0-7216-0240-0.
  16. ^KO, CYNTHIA (2005)."Biliary Sludge Is Formed by Modification of Hepatic Bile by the Gallbladder Mucosa".Clinical Gastroenterology and Hepatology.3(7): 672–8.doi:10.1016/s1542-3565(05)00369-1.PMID16206500.S2CID27488720.
  17. ^Meyer, G.; Guizzardi, F.; Rodighiero, S.; Manfredi, R.; Saino, S.; Sironi, C.; Garavaglia, M. L.; Bazzini, C.; Bottà, G. (June 2005). "Ion transport across the gallbladder epithelium".Current Drug Targets. Immune, Endocrine and Metabolic Disorders.5(2): 143–151.doi:10.2174/1568008054064805.PMID16089346.
  18. ^Mu L, Li W, Ren W, Hu D, Song Y (June 2023)."The association between cholecystectomy and the risk of colorectal cancer: an updated systematic review and meta-analysis of cohort studies".Transl Cancer Res.12(6): 1452–1465.doi:10.21037/tcr-22-2049.PMC10331452.PMID37434692.
  19. ^Choi YJ, Jin EH, Lim JH, Shin CM, Kim N, Han K, Lee DH (May 2022)."Increased Risk of Cancer after Cholecystectomy: A Nationwide Cohort Study in Korea including 123,295 Patients".Gut Liver.16(3): 465–473.doi:10.5009/gnl210009.PMC9099388.PMID35502586.
  20. ^abc"Cholelithiasis - Hepatic and Biliary Disorders - MSD Manual Professional Edition".MSD Manual Professional Edition.RetrievedOctober 18,2017.
  21. ^abcdefghijklmnopqNicki R. Colledge; Brian R. Walker; Stuart H. Ralston, eds. (2010).Davidson's principles and practice of medicine(21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 977–984.ISBN978-0-7020-3085-7.
  22. ^Neri V; Ambrosi A; Fersini A; Tartaglia N; Valentino TP (2007)."Antegrade dissection in laparoscopic cholecystectomy".Journal of the Society of Laparoendoscopic Surgeons.11(2): 225–8.PMC3015719.PMID17761085.
  23. ^nhs.uk,Complications of a gallbladder removal
  24. ^VK Kapoor (2007), "Bile duct injury repair: when? what? who?",Journal of Hepato-Biliary-Pancreatic Surgery,14(5): 476–479,doi:10.1007/s00534-007-1220-y,PMID17909716
  25. ^Dolan, R.D.; Storm, A.C.; Thompson, C.C. (2022)."Endoscopic management of acute biliary & pancreatic conditions".In Friedman, S.; Blumberg, R.S.; Saltzman, J.R. (eds.).Greenberger's CURRENT Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy(4e ed.). McGraw Hill Education.ISBN978-1-260-47343-8.
  26. ^"Gallbladder Polyps".MayoClinic.RetrievedMarch 19,2015.
  27. ^Strawberry gallbladder– cancerweb.ncl.ac.uk.
  28. ^"HIDA scan - Overview".Mayo Clinic.RetrievedOctober 18,2017.
  29. ^C. Michael Hogan. 2008.Guanaco: Lama guanicoe,GlobalTwitcher.com, ed. N. StrömbergArchivedMarch 4, 2011, at theWayback Machine
  30. ^Higashiyama, H; Sumitomo, H; Ozawa, A; Igarashi, H; Tsunekawa, N; Kurohmaru, M; Kanai, Y (2016)."Anatomy of the Murine Hepatobiliary System: A Whole-Organ-Level Analysis Using a Transparency Method".The Anatomical Record.299(2): 161–172.doi:10.1002/ar.23287.PMID26559382.
  31. ^Romer, Alfred Sherwood; Parsons, Thomas S. (1977).The Vertebrate Body.Philadelphia, PA: Holt-Saunders International. p. 355.ISBN978-0-03-910284-5.
  32. ^Hagey, L. R.; Vidal, N.; Hofmann, A. F.; Krasowski, M. D. (2010)."Complex Evolution of Bile Salts in Birds".The Auk.127(4): 820–831.doi:10.1525/auk.2010.09155.PMC2990222.PMID21113274.
  33. ^Actman, Jani (May 5, 2016)."Inside the Disturbing World of Bear-Bile Farming".National Geographic.Archived fromthe originalon May 5, 2016.RetrievedOctober 23,2017.
  34. ^Hance, Jeremy (April 9, 2015)."Is the end of 'house of horror' bear bile factories in sight?".The Guardian.RetrievedOctober 23,2017.
  35. ^abcdefghijEachempati, Soumitra R.; II, R. Lawrence Reed (2015).Acute Cholecystitis.Springer. pp. 1–16.ISBN978-3-319-14824-3.
  36. ^abcdJarnagin, William R. (2012).Blumgart's Surgery of the Liver, Pancreas and Biliary Tract E-Book: Expert Consult - Online.Elsevier Health Sciences. p. 511.ISBN978-1-4557-4606-4.
  37. ^abcBateson, M. C. (2012).Gallstone Disease and its Management.Springer. pp. 1–2.ISBN978-94-009-4173-1.
  38. ^Reynolds, Walker (January–March 2001)."The First Laparoscopic Cholecystectomy".Journal of the Society of Laparoendoscopic Surgeons.5(1): 89–94.PMC3015420.PMID11304004.
  39. ^Lifang, Qu (2020).Chinese Medicine Psychology: A Clinical Guide to Mental and Emotional Wellness.Jessica Kingsley Publishers.ISBN978-1-78775-276-4.
  40. ^abYu, Ning (January 1, 2003). "Metaphor, Body, and Culture: The Chinese Understanding of Gallbladder and Courage".Metaphor and Symbol.18(1): 13–31.doi:10.1207/S15327868MS1801_2.S2CID143595915.
Books
  • Standring S, Borley NR, eds. (2008).Gray's Anatomy: The Anatomical Basis of Clinical Practice.Brown JL, Moore LA (40th ed.). London: Churchill Livingstone.ISBN978-0-8089-2371-8.
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