This section of notes gives an overview of Gall Bladder development, histology and abnormalities associated with the biliary system. In the adult, the gall bladder is a site of bile salt storage and concentration, to then be released into the small intestine where they act to solubilize dietary lipids by their detergent effect. Bile salts are a cholesterol derivative (breakdown product).
The transverse septum differentiates to form the hepatic diverticulum and the hepatic primordium, these two structures together will go on to form different components of the mature liver and gall bladder.
Embryo (stage 13/14) showing gall bladder and liver
The hepatic diverticulum divides into two parts: pars hepatica (larger cranial part, primordium of the liver) and pars cystica (smaller ventral invagination, primordium of gall bladder).
The pars cystica vacuolates and expands, the stalk becoming the cystic duct. This structure is initially hollow, then solid (by proliferation of epithelial lining), and then recanalized occurs by vacuolation of this expanded epithelium. (some text above modified from Bani-Hani KE., 2005)
Embryo (stage 22) showing gall bladder and liver
Introduction | Components of Gall Bladder Formation | Bile Secretion | Intrahepatic Bile Ducts | Histology | Molecular | Abnormalities | References | WWW Links | Glossary
primitive endoderm
(table modified from The Anatomical Basis of Mouse Development Kaufman and Bard, 1999 Academic Press)
The pathway below describes the production and passage of bile for final excretion into the duodenum:
hepatocytes produce bile
secreted into bile canaliculi
connected to intrahepatic bile ducts
intrahepatic bile ducts connect to the hepatic duct
then the cystic duct for storage in the gallbladder
then the common bile duct into the duodenum
The term extrahepatic bile ducts (EHBDs) is used to describe the hepatic, cystic, and common bile ducts.
Intrahepatic bile ducts (IHBDs) transport bile secreted from hepatocytes to the hepatic duct and are are lined with biliary epithelial cells (BECs). Biliary epithelial cells are generated from the bipotent hepatoblasts surrounding the portal vein.
There are several excellent internet Histology resources, below are external links to some histology images of mainly adult gall bladder.
Virtual Microscope - Gall Bladder (slide 278) | Gall Bladder (slide 67)
UWA Blue Histology - Gall Bladder images and notes
Forkhead Box F1 (Foxf1) forkhead genes are transcription factors, Foxf1 is expressed in embryonic septum transversum and gallbladder mesenchyme. Knockout Foxf1 +/- mice showed severe gallbladder structural abnormalities. (See Kalinichenko etal, 2005) (More? OMIM FORKHEAD BOX F1; FOXF1)
Gallbladder Agenesis is a rare (10–75 per 100, 000 population) congenital biliary anomaly, that can be associated with other biliary (lack of cystic duct) and extrabiliary congenital anomalies. The first case was historically described by Lemery in 1701 and often is not discovered until adulthood with new diognostic screening techniques. (See Bani-Hani KE., 2005 Fayad LM etal, 2005)
Left-Sided Gallbladder is a rare congenital biliary anomaly often associated with other abnormal anatomy in the hepatobiliary system (e.g. congenital hypoplasia of left liver lobe, intrahepatic portal branching). (See Noritomi T etal, 2004)
Triplication of Gallbladder extremely rare congenital anomaly (only nine reported cases to date, 2003).
Septate Gallbladder usually asymptomatic, but can cause recurrent attacks of abdominal pain or become complicated by cholelithiasis.
Cholestasis inflammation of the gall bladder generally caused by gallstones obstructing the duct from gall bladder to common bile duct and can occur in maternal gall bladder during pregnancy. (More? Acute cholecystitis (Gallstones) | The Merck Manual Cholecystitis)
Obstetric cholestasis "Obstetric cholestasis (or intrahepatic cholestasis of pregnancy) remains widely disregarded as an important clinical problem, with many obstetricians still considering its main symptom, pruritus, a natural association of pregnancy. Obstetric cholestasis is associated with cholesterol gallstones. It may be extremely stressful for the mother but also carries risks for the baby. (Abstract from Milkiewicz P etal, 2002) "Intrahepatic cholestasis of pregnancy (ICP) affects about 0.7% of deliveries in Britain. It is regarded as a benign condition for the mother but is associated with increased fetal mortality in late pregnancy and early delivery is advised." (Abstract from Howard and Murphy, 2003)
Myotonic Dystrophy Type 1 can lead to gallstone formation as a result of increased tone of the gall bladder sphincter, preventing or decreasing emptying. (More? GeneReviews- Myotonic Dystrophy Type 1)
Reviews
Duncan SA. Transcriptional regulation of liver development. Dev Dyn. 2000 Oct;219(2):131-42. Review.
Shiojiri N. Development and differentiation of bile ducts in the mammalian liver. Microsc Res Tech. 1997 Nov 15;39(4):328-35. Review.
Darlington GJ. Molecular mechanisms of liver development and differentiation. Curr Opin Cell Biol. 1999 Dec;11(6):678-82. Review.
Costa RH, Kalinichenko VV, Holterman AX, Wang X. Transcription factors in liver development, differentiation, and regeneration. Hepatology. 2003 Dec;38(6):1331-47. Review. No abstract available.
Strick-Marchand H, Weiss MC. Embryonic liver cells and permanent lines as models for hepatocyte and bile duct cell differentiation. Mech Dev. 2003 Jan;120(1):89-98. Review.
Bani-Hani KE. Agenesis of the gallbladder: difficulties in management. J Gastroenterol Hepatol. 2005 May;20(5):671-5.
Fayad LM, Kamel IR, Mitchell DG, Bluemke DA. Functional MR cholangiography: diagnosis of functional abnormalities of the gallbladder and biliary tree. AJR Am J Roentgenol. 2005 May;184(5):1563-71.
Noritomi T, Watanabe K, Yamashita Y, Kitagawa S, Oshibuchi M, Shirakusa T. Left-sided gallbladder associated with congenital hypoplasia of the left lobe of the liver: a case report and review of literature. Int Surg. 2004 Jan-Mar;89(1):1-5.
Milkiewicz P, Elias E, Williamson C, Weaver J. Obstetric cholestasis. BMJ. 2002 Jan 19;324(7330):123-4.
Howard PJ, Murphy GM. Bile acid stress in the mother and baby unit. Eur J Gastroenterol Hepatol. 2003 Mar;15(3):317-21.
Kalinichenko VV, Zhou Y, Bhattacharyya D, Kim W, Shin B, Bambal K, Costa RH. Haploinsufficiency of the mouse Forkhead Box f1 gene causes defects in gall bladder development. J Biol Chem. 2002 Apr 5;277(14):12369-74. Epub 2002 Jan 23.
Kinoshita T, Miyajima A. Cytokine regulation of liver development. Biochim Biophys Acta. 2002 Nov 11;1592(3):303-12. Review.
Earlier References
Darlington GJ. Molecular mechanisms of liver development and differentiation. Curr Opin Cell Biol. 1999 Dec;11(6):678-82. Review.
Biochemistry. Berg, Jeremy M.; Tymoczko, John L.; and Stryer, Lubert. New York: W. H. Freeman and Co.; 2002. Figure 26.23. Synthesis of Bile Salts.
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This page is currently under development (this notice removed when complete).
This section of gastrointestinal tract notes gives an overview of Gall Bladder development. There is still controversy as to the embryonic origins of some gall bladder components.
Please email Dr Mark Hill if you wish to make a comment about this current project.