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Semin Liver Dis 2002; 22(3): 213-226
DOI: 10.1055/s-2002-34508
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Development of the Intrahepatic Biliary Tree

James M. Crawford
  • Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida
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Publication History

Publication Date:
02 October 2002 (online)

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ABSTRACT

The liver develops from two anlages: the hepatic diverticulum, which buds off the ventral side of the foregut, and the septum transversum, which is the mesenchymal plate that partially separates the embryonic thoracic and abdominal cavities. The endodermal cells of the hepatic diverticulum invade the septum transversum, forming sheets and cords of hepatoblasts arrayed along the sinusoidal vascular channels derived from the vitelline veins emanating from the yolk sac. The vitelline veins fuse to form the portal vein, which ramifies as tributaries within the liver along mesenchymal channels termed portal tracts. Those hepatoblasts immediately adjacent to the mesenchyme of the portal tracts differentiate into a ductal plate, a single circumferential layer of biliary epithelial cells. Mesenchymal cells interpose between the ductal plate and the remaining parenchymal hepatoblasts, which differentiate into hepatocytes. By week 7 the ductal plate begins to reduplicate, forming a double layer of cells around the portal tract. Lumena form between the two cell layers of the ductal plate, forming peripheral biliary tubular structures. These peripheral tubules remodel and, with continued proliferation of the mesenchyme, by the 11th week begin to become more centrally located within portal tracts as terminal bile ducts with a circular cross-section. The remaining ductal plate resorbs, leaving behind only tethers of bile ductules connecting the terminal bile ducts to the parenchyma. Abutting and within the parenchyma are the canals of Hering, ductular structures half-lined by hepatocytes and half-lined by biliary epithelial cells. Maturation of the intrahepatic biliary tree to the mature tubular treelike architecture occurs from the hilum of the liver outward, beginning around the 11th week of gestation and continuing past birth for several months. The architecture of maturation is the same regardless of gestational age or radial location in the liver. Importantly, the immature intrahepatic biliary system maintains patency and continuity with the extrahepatic biliary tree throughout gestation, with no evidence of a solid phase of development. Thus, from the earliest time of hepatocellular bile formation beginning around the 12th week, there is a patent passage to the alimentary canal.

KEYWORDS

bile duct - development - liver - canal of Hering - ductal plate - anatomy

REFERENCES

  • 1 Kiernan F. The anatomy and physiology of the liver.  Philos Trans R Soc London Biol Sci . 1833;  123 711-770
    PubMedGoogle Scholar
  • 2 Roskams T, Van Eyken P, Desmet V. Human liver growth and development. In: Strain A, Diehl AM, eds. Liver Growth and Repair London: Chapman & Hall 1998: 541-557
    Google Scholar
  • 3 Ekataksin W, Wake K. New concepts in biliary and vascular anatomy of the liver.  Prog Liver Dis . 1997;  15 1-29
    PubMedGoogle Scholar
  • 4 Kawarada Y, Das B C, Taoka H. Anatomy of the hepatic hilar area: the plate system.  J Hepatobiliary Pancreat Surg . 2000;  7 580-586
    CrossrefPubMedGoogle Scholar
  • 5 Nakanuma Y, Hoso M, Sanzen T, Sasaki M. Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply.  Microsc Res Tech . 1997;  38 552-570
    CrossrefPubMedGoogle Scholar
  • 6 Healey J E, Schroy P C. Anatomy of the biliary ducts within the human liver.  Arch Surg . 1953;  66 599-616
    PubMedGoogle Scholar
  • 7 Desmet V J. Congenital diseases of intrahepatic bile ducts: variations on the theme ``ductal plate malformation''.  Hepatology . 1992;  16 1069-1083
    CrossrefPubMedGoogle Scholar
  • 8 Terada T, Nakanuma Y, Ohta G. Glandular elements around the intrahepatic bile ducts in man: their morphology and distribution in normal livers.  Liver . 1987;  7 1-8
    PubMedGoogle Scholar
  • 9 Saxena R, Theise N D, Crawford J M. Microanatomy of the human liver: exploring the hidden interfaces.  Hepatology . 1999;  30 1339-1346
    CrossrefPubMedGoogle Scholar
  • 10 Landing B H, Wells T R. Considerations of some architectural properties of the biliary tree and liver in childhood. In: Abramowsky CR, Bernstein J, Rosenberg HS, eds. Transplantation Pathology-Hepatic Morphogenesis Perspectives in Pediatric Pathology, Vol 14. Basel: S. Karger 1991: 122-142
    Google Scholar
  • 11 Ludwig J, Ritman E L, LaRusso N F, Sheedy P F, Zumpe G. Anatomy of the human biliary system studied by quantitative computer-aided three-dimensional imaging techniques.  Hepatology . 1998;  27 893-899
    CrossrefPubMedGoogle Scholar
  • 12 Elias H, Pauly J E. Human Microanatomy, 3rd ed. Philadelphia: Davis . 1966: 223
    Google Scholar
  • 13 Miyake M, Okudaira M, Sato T, Kitagawa M, Hisauchi T. The blood vessels of the liver.  Nippon Byori Gakkai Kaishi Trans Soc Pathol Jap . 1960;  49 589-632
    PubMedGoogle Scholar
  • 14 Godlewski G, Gaubert-Cristol R, Rouy S, Prudhomme M. Liver development in the rat and in man during the embryonic period (Carnegie stages 11-23).  Microsc Res Tech . 1997;  39 314-327
    CrossrefPubMedGoogle Scholar
  • 15 Haratake J, Hisaoka M, Furuta A, Horie A, Yamamoto O. A scanning electron microscopic study of postnatal development of rat peribiliary plexus.  Hepatology . 1991;  14 1196-1200
    CrossrefPubMedGoogle Scholar
  • 16 Terada T, Nakanuma Y. Development of peribiliary capillary plexus: a lectin-histochemical and immunohistochemical study.  Hepatology . 1993;  18 529-536
    CrossrefPubMedGoogle Scholar
  • 17 Sergi C, Adam S, Kahl P, Otto H F. The remodeling of the primitive human biliary system.  Early Hum Dev . 2000;  58 167-178
    CrossrefPubMedGoogle Scholar
  • 18 Hammar J A. Uber die erste Entstehung der nicht kapillaren intrahepatischen Gallenganage beim Menschen.  Z Mikro Anat Forsch . 1926;  f 59-89
    PubMedGoogle Scholar
  • 19 Koga A. Morphogenesisi of intrahepatic bile ducts of the human fetus. Light and electron microscopic study.  Z Anat Entwickl Gesch . 1971;  135 156-184
    CrossrefPubMedGoogle Scholar
  • 20 Desmet V J. Intrahepatic bile ducts under the lens.  J Hepatol . 1985;  1 545-559
    CrossrefPubMedGoogle Scholar
  • 21 Jorgensen M J. The ductal plate malformation. A study of the intrahepatic bile duct lesion in infantile polycystic disease and congenital hepatic fibrosis.  Acta Pathol Microbiol Scand . 1977;  257 1-88
    PubMedGoogle Scholar
  • 22 Terada T, Nakanuma Y. Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development.  Am J Pathol . 1995;  146 67-74
    PubMedGoogle Scholar
  • 23 Van Eyken P, Sciot R, Callea F, Van Der Steen K, Moerman P, Desmet V J. The development of the intrahepatic bile ducts in man: a keratin immunohistochemical study.  Hepatology . 1988;  8 1586-1595
    PubMedGoogle Scholar
  • 24 Shiojiri N. Development and differentiation of bile ducts in the mammalian liver.  Lab Invest . 2001;  81 17-25
    CrossrefPubMedGoogle Scholar
  • 25 Desmet V J, Van Eyken P, Sciot R. Cytokeratins for probing cell lineage relationships in developing liver.  Hepatology . 1989;  15 125-135
    PubMedGoogle Scholar
  • 26 Sell S. Heterogeneity and plasticity of hepatocyte lineage cells.  Hepatology . 2001;  33 738-750
    CrossrefPubMedGoogle Scholar
  • 27 Cocjin J, Rosenthal P, Buslon V. Bile ductule formation in fetal, neonatal, and infant livers compared with extrahepatic biliary atresia.  Hepatology . 1996;  24 568-574
    PubMedGoogle Scholar
  • 28 Faa G, Van Eyken P, Roskams T. Expression of cytokeratin 20 in developing rat liver and in experimental models of ductular and oval cell proliferation.  J Hepatol . 1998;  29 628-633
    CrossrefPubMedGoogle Scholar
  • 29 Van Eyken P, Sciot R, Desmet V J. Intrahepatic bile duct development in the rat: a cytokeratin-immunohistochemical study.  Lab Invest. 1988a;  10 52-58
    PubMedGoogle Scholar
  • 30 Van Eyken P, Sciot R, Callea F. The development of the intrahepatic bile ducts in man: a keratin-immunohistochemical study.  Hepatology . 1988b;  8 1586-1595
    PubMedGoogle Scholar
  • 31 Roskams T, Desmet V J. Parathyroid hormone-related peptide and development of intrahepatic bile ducts in man.  Int Hepatol Commun . 1994;  2 121-127
    PubMedGoogle Scholar
  • 32 Blakolmer K, Jaskiewicz K, Dunsford H A, Robson S C. Hematopoietic stem cell markers are expressed by ductal plate and bile duct cells in developing human liver.  Hepatology . 1995;  21 1510-1516
    CrossrefPubMedGoogle Scholar
  • 33 Vijayan V, Tan C EL. Developing biliary system in three dimensions.  Anat Rec . 1997;  249 389-398
    PubMedGoogle Scholar
  • 34 Tan C EL, Moscoso G J. The developing human biliary system at the porta hepatis level between 29 days and 8 weeks of gestation: a way to understanding biliary atresia. Part 1.  Pathol Int . 1994;  44 587-599
    PubMedGoogle Scholar
  • 35 Tan C EL, Moscoso G J. The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: a way to understanding biliary atresia. Part 2.  Pathol Int . 1994;  44 600-610
    PubMedGoogle Scholar
  • 36 Tan C EL, Chan V SW, Yong R YY. Distortion in TGFb1 peptide immunolocalisation in biliary atresia: comparison with the normal pattern in the developing human intrahepatic bile duct system.  Pathol Int . 1995;  45 815-824
    PubMedGoogle Scholar
  • 37 Morgan J D, Hartroft W S. Juvenile liver.  Arch Pathol . 1961;  71 86-88
    PubMedGoogle Scholar
  • 38 Washington K, Clavien P-A, Killenberg P. Peribiliary vascular plexus in primary sclerosing cholangitis and primary biliary sclerosis.  Human Pathol . 1997;  28 791-795
    PubMedGoogle Scholar
  • 39 Crawford A R, Lin X Z, Crawford J M. The normal adult human liver biopsy: a quantitative reference standard.  Hepatology . 1998;  28 323-331
    CrossrefPubMedGoogle Scholar
  • 40 Cascio S, Zaret K S. Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation.  Development . 1991;  113 217-225
    PubMedGoogle Scholar
  • 41 Terada T, Ohta T, Nakanuma Y. Expression of transforming growth factor-alpha and its receptor in human liver development and maturation.  Virchow Arch . 1994;  424 698-675
    PubMedGoogle Scholar
  • 42 Picolli D A, Spinner N B. Alagille syndrome and the jagged 1 gene.  Semin Liver Dis . 2001;  21 525-534
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Michalopoulos G K, Bowen W C, Mule K, Stolz D B. Histological organization in hepatocyte organoid cultures.  Am J Pathol . 2001;  159 1877-1887
    CrossrefPubMedGoogle Scholar
  • 44 Shah K, Gerber M. Development of intrahepatic bile ducts in humans: possible role of laminin.  Arch Pathol Lab Med . 1990;  114 597-600
    PubMedGoogle Scholar
  • 45 Johnson M, Koukoulis G, Matsumoto K, Nakamura T, Iyer A. Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells.  Hepatology . 1993;  17 1052-1061
    CrossrefPubMedGoogle Scholar
  • 46 Shiojiri N, Mizuno T. Normal development of extra- and intrahepatic bile ducts. Proceedings of the Fourth International Symposium on Biliary Atresia. Sendai, Japan 1986 : 3-9
    Google Scholar
  • 47 Dubois A M. The embryonic liver. In: Rouiller C, ed. The Liver, Vol 1 New York: Academic Press 1963: 1-39
    Google Scholar
  • 48 Shankle W R, Landing B H, Gregg J. Normal organ weights of infants and children: graphs of values by age, with confidence intervals.  Pediatr Pathol . 1983;  1 399-408
    PubMedGoogle Scholar
  • 49 Khan E, Markowitz J, Aiges H, Daum F. Human ontegeny of the bile duct to portal space ratio.  Hepatology . 1989;  10 21-23
    PubMedGoogle Scholar
  • 50 Alagille D. Intrahepatic biliary atresia (hepatic ductular hypoplasia). In: Berenberg SR, ed. Liver Diseases in Infancy and Childhood Dordrecht, The Netherlands: Martinez Nijhoff 1976: 129-142
    Google Scholar
  • 51 Elias H. A re-examination of the structure of the mammalian liver. II. The hepatic plate and its relation to the vascular and biliary systems.  Am J Anat . 1949;  85 379-456
    CrossrefPubMedGoogle Scholar
  • 52 Steiner J W, Carruthers J S. Studies on the fine structure of the terminal branches of the biliary tree. 1. The morphology of the normal bile canaliculi, bile pre-ductules (ducts of Hering) and bile ductules.  Am J Pathol . 1961;  38 639-661
    PubMedGoogle Scholar
  • 53 Theise N D, Saxena R, Portmann B C. Canals of Hering and hepatic stem cells in humans.  Hepatology . 1999;  30 1425-1433
    CrossrefPubMedGoogle Scholar
  • 54 Ekataksin W, Zou Z Z, Wake K. The hepatic microcirculatory subunits: an over-three-century-long-search for the missing link between an exocrine unit and an endocrine unit in mammalian liver lobules. In: Motta PM, ed. Recent Advances in Microscopy of Cells, Tissues and Organs Rome: University of Rome La Sapienza 1996: 375-380
    Google Scholar
  • 55 Gallin W J, Sanders E J. Development of bile canaliculi between chicken embryo liver cells in vivo and in vitro.  Exp Cell Res . 1992;  200 58-69
    PubMedGoogle Scholar
  • 56 Kanamura S, Kanai K, Watanabe J. Fine structure and function of hepatocytes during development [review].  J Electron Microsc Tech . 1990;  14 92-105
    CrossrefPubMedGoogle Scholar
  • 57 Gallin W J. Development and maintenance of bile canaliculi in vitro and in vivo.  Microsc Res Tech . 1997;  39 406-412
    CrossrefPubMedGoogle Scholar
  • 58 Suchy F J, Bucuvalas J C, Novak D A. Determinants of bile formation during development: ontogeny of hepatic bile acid metabolism and transport.  Semin Liver Dis . 1987;  7 77-84
    PubMedGoogle Scholar
  • 59 Terada T, Nakanuma Y. Development of human intrahepatic peribiliary glands. Histological, keratin immunohistochemical, and mucin histochemical analyses.  Lab Invest . 1993;  68 261-269
    PubMedGoogle Scholar