Gastrointestinal Tract - Gallbladder Development

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Introduction

Early embryonic gallbladder (Carnegie stage 13, Week 4)

This section of notes gives an overview of gallbladder (gall bladder, gall-bladder) and billary tree development, histology and abnormalities associated with the biliary system. In the adult, the gallbladder is a site of bile salt storage and concentration, to then be released into the duodenum 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 gallbladder.

The hepatic diverticulum divides into two parts: pars hepatica (larger cranial part, primordium of the liver) and pars cystica (smaller ventral invagination, primordium of gallbladder).


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. There are several opinions as to whether the duct has a solid phase or remains patent throughout development.[1][2]

Note that in some animals, for example horse and elephant, the gall bladder is normally absent.


See also: Gallbladder Histology.


GIT Links: Introduction | Medicine Lecture | Science Lecture | endoderm | mouth | oesophagus | stomach | liver | gallbladder | Pancreas | intestine | mesentery | tongue | taste | enteric nervous system | Stage 13 | Stage 22 | gastrointestinal abnormalities | Movies | Postnatal | milk | tooth | salivary gland | BGD Lecture | BGD Practical | GIT Terms | Category:Gastrointestinal Tract
GIT Histology Links: Upper GIT | Salivary Gland | Smooth Muscle Histology | Liver | Gallbladder | Pancreas | Colon | Histology Stains | Histology | GIT Development
Historic Embryology - Gastrointestinal Tract  
1878 Alimentary Canal | 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs | 1902 The Organs of Digestion | 1903 Submaxillary Gland | 1906 Liver | 1907 Development of the Digestive System | 1907 Atlas | 1907 23 Somite Embryo | 1908 Liver and Vascular | 1910 Mucous membrane Oesophagus to Small Intestine | 1910 Large intestine and Vermiform process | 1911-13 Intestine and Peritoneum - Part 1 | Part 2 | Part 3 | Part 5 | Part 6 | 1912 Digestive Tract | 1912 Stomach | 1914 Digestive Tract | 1914 Intestines | 1914 Rectum | 1915 Pharynx | 1915 Intestinal Rotation | 1917 Entodermal Canal | 1918 Anatomy | 1921 Alimentary Tube | 1932 Gall Bladder | 1939 Alimentary Canal Looping | 2008 Liver | 2016 GIT Notes | Historic Disclaimer
Human Embryo: 1908 13-14 Somite Embryo | 1921 Liver Suspensory Ligament | 1926 22 Somite Embryo | 1907 23 Somite Embryo | 1937 25 Somite Embryo | 1914 27 Somite Embryo | 1914 Week 7 Embryo
Animal Development: 1913 Chicken | 1951 Frog

Historic: Halpert B. and Lee H. The gall bladder and the extrahepatic biliary passages in late embryonic and early fetal life. (1932) Anat. Rec. 54(1): 29-42.

Some Recent Findings

  • Anatomy of rodent and human livers: What are the differences?[3] "The size of the liver of terrestrial mammals obeys the allometric scaling law over a weight range of >3 ∗ 106. Since scaling reflects adaptive changes in size or scale among otherwise similar animals, we can expect to observe more similarities than differences between rodent and human livers. Obvious differences, such as the presence (rodents) or absence (humans) of lobation and the presence (mice, humans) or absence (rats) of a gallbladder, suggest qualitative differences between the livers of these species. After review, however, we conclude that these dissimilarities represent relatively small quantitative differences. The microarchitecture of the liver is very similar among mammalian species and best represented by the lobular concept, with the biggest difference present in the degree of connective tissue development in the portal tracts. Although larger mammals have larger lobules, increasing size of the liver is mainly accomplished by increasing the number of lobules. The increasing role of the hepatic artery in lobular perfusion of larger species is, perhaps, the most important and least known difference between small and large livers, because it profoundly affects not only interventions like liver transplantations, but also calculations of liver function."
  • The fate of the vitelline and umbilical veins during the development of the human liver[4] "Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.
  • Fate mapping of gallbladder progenitors in posteroventral foregut endoderm of mouse early somite stage embryos[5] "In early embryogenesis, the posteroventral foregut endoderm gives rise to the budding endodermal organs including the liver, ventral pancreas and gallbladder during early somitogenesis. Despite the detailed fate maps of the liver and pancreatic progenitors in the mouse foregut endoderm, the exact location of the gallbladder progenitors remains unclear. In this study, we performed a DiI fate-mapping analysis using whole-embryo cultures of mouse early somite-stage embryos. Here, we show that the majority of gallbladder progenitors in 9-11-somite-stage embryos are located in the lateral-most domain of the foregut endoderm at the first intersomite junction level along the anteroposterior axis. This definition of their location highlights a novel entry point to understanding of the molecular mechanisms of initial specification of the gallbladder."
More recent papers  
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Search term: Gallbladder Embryology | Gallbladder Development | Bile Embryology

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Fate mapping of gallbladder progenitors in posteroventral foregut endoderm of mouse early somite stage embryos[5] "In early embryogenesis, the posteroventral foregut endoderm gives rise to the budding endodermal organs including the liver, ventral pancreas and gallbladder during early somitogenesis. Despite the detailed fate maps of the liver and pancreatic progenitors in the mouse foregut endoderm, the exact location of the gallbladder progenitors remains unclear. In this study, we performed a DiI fate-mapping analysis using whole-embryo cultures of mouse early somite-stage embryos. Here, we show that the majority of gallbladder progenitors in 9-11-somite-stage embryos are located in the lateral-most domain of the foregut endoderm at the first intersomite junction level along the anteroposterior axis. This definition of their location highlights a novel entry point to understanding of the molecular mechanisms of initial specification of the gallbladder."
  • Embryology of the biliary tract[2] "A hepatic diverticulum appears in the ventral wall of the primitive midgut early in the 4th week of intrauterine life in the development of the human embryo. This small diverticulum is the anlage for the development of the liver, extrahepatic biliary ducts, gallbladder, and ventral pancreas. By the 5th week, all elements of the biliary tree are recognizable. Marked elongation of the common duct occurs with plugging of the lumen by epithelial cells. Recanalization of the lumen of the common duct starts at the end of the 5th week and moves slowly distally. By the 6th week, the common duct and ventral pancreatic bud rotate 180 degrees clockwise around the duodenum. Early in the 7th week, the bile and pancreatic ducts end in closed cavities of the duodenum. Between the early 8th and 12th week, hepatopancreatic ducts have both superior and inferior orifices."
  • Muscularis mucosae versus muscularis propria in gallbladder, cystic duct, and common bile duct: smoothelin and desmin immunohistochemical study[6] "The muscle layer in the cystic duct and common bile duct is not well defined, and it is unresolved whether it represents muscularis mucosae or muscularis propria. ... Based on our findings, we conclude that, in the gallbladder wall, the muscle layer is muscularis propria and there is no muscularis mucosae present. In the cystic duct and common bile duct, only an attenuated and incomplete muscle layer of muscularis mucosae is present; because there is no muscularis propria, there probably is limited contractile function."

Embryonic Development

Stage 13

Stage 13 image 076.jpg

Stage 13 image 077.jpg

Early embryonic gallbladder (Carnegie stage 13, Week 4)

Stage 22

Stage 22 image 084.jpg

Late embryonic gallbladder (Carnegie stage 22, Week 8)

Historic

Grosser O. Lewis FT. and McMurrich JP. The Development of the Digestive Tract and of the Organs of Respiration. (1912) chapter 17, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

Gall-bladder Human Embryo (CRL)

  • 7.5 mm - epithelium is surrounded by a layer of mesenchyma, and the entire structure is so imbedded in the under surface of the liver that it causes only a slight swelling of the peritoneal surface. Above and on the sides the mesenchyma is in direct relation with the hepatic trabecular, and it receives a few prolongations of the venous capillaries. Below it is covered by the peritoneal epithelium except on the left, where that layer is reflected to the abdominal walls in connection with the falciform ligament. In later stages the gall-bladder is separated from the hepatic trabecular on either side, and is attached to the liver only along its upper surface.
  • 16 mm mesenchyma surrounding the gall-bladder is still undifferentiated.
  • 22.8 mm forms two broad concentric zones, of which the inner is darker and more compact than the outer.
  • 29 mm certain cells in the peripheral part of the dark zone form a third layer, which is thin and somewhat interrupted. As seen in later stages these cells are myoblasts, so that at 29 mm all three layers of the adult gall-bladder are indicated. These are the mucosa, muscularis, and serosa. The layers become gradually less distinct toward the hepatic duct.

Abnormalities

LB20.1 Structural developmental anomalies of gallbladder

LB20.10 Agenesis, aplasia or hypoplasia of gallbladder

LB20.10 Agenesis, aplasia or hypoplasia of gallbladder

Bile Ducts

LB20.2 Structural developmental anomalies of bile ducts

LB20.20 Choledochal cyst

LB20.21 Biliary atresia

LB20.21 Biliary atresia - Biliary atresia is a rare disease characterised by an inflammatory biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. Untreated, this condition leads to cirrhosis and death within the first years of life.

LB20.22 Congenital stenosis or stricture of bile ducts (Congenital hypoplasia of bile ducts)

LB20.23 Structural developmental anomalies of cystic duct

LB20.24 Accessory bile duct


Infections

These mainly relate to postnatal infections. Recent studies in the mouse have identified that gastrointestinal tract listeria infections can relocate to the gallbladder and reside there, leading to later reinfection of the gastrointestinal tract.


Links: Bacterial Infection


References

  1. Crawford JM. (2002). Development of the intrahepatic biliary tree. Semin. Liver Dis. , 22, 213-26. PMID: 12360416 DOI.
  2. 2.0 2.1 Ando H. (2010). Embryology of the biliary tract. Dig Surg , 27, 87-9. PMID: 20551648 DOI.
  3. Kruepunga N, Hakvoort TBM, Hikspoors JPJM, Köhler SE & Lamers WH. (2018). Anatomy of rodent and human livers: What are the differences?. Biochim Biophys Acta Mol Basis Dis , , . PMID: 29842921 DOI.
  4. Hikspoors JPJM, Peeters MMJP, Mekonen HK, Kruepunga N, Mommen GMC, Cornillie P, Köhler SE & Lamers WH. (2017). The fate of the vitelline and umbilical veins during the development of the human liver. J. Anat. , 231, 718-735. PMID: 28786203 DOI.
  5. 5.0 5.1 Uemura M, Igarashi H, Ozawa A, Tsunekawa N, Kurohmaru M, Kanai-Azuma M & Kanai Y. (2015). Fate mapping of gallbladder progenitors in posteroventral foregut endoderm of mouse early somite-stage embryos. J. Vet. Med. Sci. , 77, 587-91. PMID: 25648459 DOI.
  6. Raparia K, Zhai QJ, Schwartz MR, Shen SS, Ayala AG & Ro JY. (2010). Muscularis mucosae versus muscularis propria in gallbladder, cystic duct, and common bile duct: smoothelin and desmin immunohistochemical study. Ann Diagn Pathol , 14, 408-12. PMID: 21074688 DOI.


Reviews

Kruepunga N, Hakvoort TBM, Hikspoors JPJM, Köhler SE & Lamers WH. (2018). Anatomy of rodent and human livers: What are the differences?. Biochim Biophys Acta Mol Basis Dis , , . PMID: 29842921 DOI.

Lemaigre FP. (2010). Molecular mechanisms of biliary development. Prog Mol Biol Transl Sci , 97, 103-26. PMID: 21074731 DOI.

Causey MW, Miller S, Fernelius CA, Burgess JR, Brown TA & Newton C. (2010). Gallbladder duplication: evaluation, treatment, and classification. J. Pediatr. Surg. , 45, 443-6. PMID: 20152372 DOI.

Roskams T & Desmet V. (2008). Embryology of extra- and intrahepatic bile ducts, the ductal plate. Anat Rec (Hoboken) , 291, 628-35. PMID: 18484608 DOI.

Bani-Hani KE. (2005). Agenesis of the gallbladder: difficulties in management. J. Gastroenterol. Hepatol. , 20, 671-5. PMID: 15853977 DOI.

Delalande JM, Milla PJ & Burns AJ. (2004). Hepatic nervous system development. Anat Rec A Discov Mol Cell Evol Biol , 280, 848-53. PMID: 15382016 DOI.

Articles

Salazar MC, Brownson KE, Nadzam GS, Duffy A & Roberts KE. (2018). Gallbladder Agenesis: A Case Report. Yale J Biol Med , 91, 237-241. PMID: 30258310

Botsford A, McKay K, Hartery A & Hapgood C. (2015). MRCP imaging of duplicate gallbladder: a case report and review of the literature. Surg Radiol Anat , 37, 425-9. PMID: 25757833 DOI. Ahmed M & Aurangzeb. (2010). Triplication of gallbladder. J Coll Physicians Surg Pak , 20, 766-7. PMID: 21078254 DOI.

Blidaru D, Blidaru M, Pop C, Crivii C & Seceleanu A. (2010). The common bile duct: size, course, relations. Rom J Morphol Embryol , 51, 141-4. PMID: 20191134

Peloponissios N, Gillet M, Cavin R & Halkic N. (2005). Agenesis of the gallbladder: a dangerously misdiagnosed malformation. World J. Gastroenterol. , 11, 6228-31. PMID: 16273658

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Additional Images

See also Gall Bladder Histology

Chapter XVIII. The Organs of Digestion Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.

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Cite this page: Hill, M.A. (2019, July 23) Embryology Gastrointestinal Tract - Gallbladder Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Gastrointestinal_Tract_-_Gallbladder_Development

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G