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Anatomy and Embryology of the Liver

  • Sergio MoriniEmail author
  • Guido Carpino
  • Simone Carotti
  • Eugenio Gaudio
Chapter

Abstract

This chapter deals in the first part with the anatomy of the liver, highlighting in particular the clinical anatomy and the relevant morphological aspects of practical interest to the physician, including the presence of the most frequent anatomical variations. Particular emphasis is given to the vascular organization that determines the subdivision into segments, whose understanding is fundamental in clinical diagnostics and in surgical practice. In the second part of the chapter the phenomena related to the morphogenesis of the liver are described in order to show the peculiar organization of the liver both at a macroscopic level and at a structural level. Moreover, the recent acquisitions on key signaling pathways and molecular mechanisms underlying the complex tissue interactions in hepatogenesis are briefly described. Due to the central regulatory role of the liver in many metabolic functions, this knowledge form the basis for the modern approaches to gene and molecular therapy of the liver. They may also contribute to understand how to promote liver regeneration, to engineer the replacement of functional liver tissues, or how to lead to therapeutically useful tissue for transplantation.

Keywords

Liver anatomy Portal vein Liver segmentation Biliary tract Liver embryology Liver development Hepatocytes Cholangiocytes 

Notes

Acknowledgments

Thanks are due to Mr. Francesco Mastrostefano for his help in the artwork generation.

References

  1. 1.
    Krumm P, Schraml C, Bretschneider C, Seeger A, Klumpp B, Kramer U, Claussen CD, Miller S. Depiction of variants of the portal confluence venous system using multidetector row CT: analysis of 916 cases. Rofo. 2011;183:1123–9.  https://doi.org/10.1055/s-0031-1281745.CrossRefPubMedGoogle Scholar
  2. 2.
    Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Kamiya K, Ota M, Setoguchi T, Takehara Y, Nasu H, Nakamura S, Konno H. Analysis of anatomic variants of mesenteric veins by 3-dimensional portography using multidetector-row computed tomography. Am J Surg. 2010;200:15–22.  https://doi.org/10.1016/j.amjsurg.2009.05.017.CrossRefPubMedGoogle Scholar
  3. 3.
    Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited: digital subtraction angiography performed in 600 patients. Radiology. 2002;224:542–7.  https://doi.org/10.1148/radiol.2242011283.CrossRefPubMedGoogle Scholar
  4. 4.
    Saba L, Mallarini G. Anatomic variations of arterial liver vascularization: an analysis by using MDCTA. Surg Radiol Anat. 2011;33:559–68.  https://doi.org/10.1007/s00276-011-0778-x.CrossRefPubMedGoogle Scholar
  5. 5.
    Fang CH, You JH, Lau WY, Lai EC, Fan YF, Zhong SZ, Li KX, Chen ZX, Su ZH, Bao SS. Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects. World J Surg. 2012;36:120–4.  https://doi.org/10.1007/s00268-011-1297-y.CrossRefPubMedGoogle Scholar
  6. 6.
    Hribernik M, Trotovšek B. Intrahepatic venous anastomoses with a focus on the middle hepatic vein anastomoses in normal human livers: anatomical study on liver corrosion casts. Surg Radiol Anat. 2014;36:231–7.  https://doi.org/10.1007/s00276-013-1198-x.CrossRefPubMedGoogle Scholar
  7. 7.
    Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291:643–52.  https://doi.org/10.1002/ar.20681.CrossRefGoogle Scholar
  8. 8.
    McCuskey RS. Anatomy of efferent hepatic nerves. Anat Rec A Discov Mol Cell Evol Biol. 2004;280:821–6.  https://doi.org/10.1002/ar.a.20087.CrossRefPubMedGoogle Scholar
  9. 9.
    Covey AM, Brody LA, Getrajdman GI, Sofocleous CT, Brown KT. Incidence, patterns, and clinical relevance of variant portal vein anatomy. AJR Am J Roentgenol. 2004;183:1055–64.  https://doi.org/10.2214/ajr.183.4.1831055.CrossRefPubMedGoogle Scholar
  10. 10.
    Onishi H, Kawarada Y, Das BC, Nakano K, Gadzijev EM, Ravnik D, Isaji S. Surgical anatomy of the medial segment (S4) of the liver with special reference to bile ducts and vessels. Hepato-Gastroenterology. 2000;47:143–50.PubMedGoogle Scholar
  11. 11.
    Couinaud C. Le foie; études anatomiques et chirurgicales. Paris: Masson; 1957.Google Scholar
  12. 12.
    Delattre JF, Avisse C, Flament JB. Anatomic basis of hepatic surgery. Surg Clin North Am. 2000;80:345–62.  https://doi.org/10.1016/S0039-6109(05)70409-6.CrossRefPubMedGoogle Scholar
  13. 13.
    Chaib E, Kanas AF, Galvão FH, D'Albuquerque LA. Bile duct confluence: anatomic variations and its classification. Surg Radiol Anat. 2014;36:105–9.  https://doi.org/10.1007/s00276-013-1157-6.CrossRefPubMedGoogle Scholar
  14. 14.
    Lamah M, Karanjia ND, Dickson GH. Anatomical variations of the extrahepatic biliary tree: review of the world literature. Clin Anat. 2001;14:167–72.  https://doi.org/10.1002/ca.1028.CrossRefPubMedGoogle Scholar
  15. 15.
    Chen WJ, Ying DJ, Liu ZJ, He ZP. Analysis of the arterial supply of the extrahepatic bile ducts and its clinical significance. Clin Anat. 1999;12:245–9.  https://doi.org/10.1002/(SICI)1098-2353(1999)12:4<245::AID-CA2>3.0.CO;2-W.CrossRefPubMedGoogle Scholar
  16. 16.
    Zorn AM. Liver development. In: StemBook, editor. The stem cell research community. Cambridge: StemBook; 2008.  https://doi.org/10.3824/stembook.1.25.1. http://www.stembook.org.CrossRefGoogle Scholar
  17. 17.
    Gordillo M, Evans T, Gouon-Evans V. Orchestrating liver development. Development. 2015;142:2094–108.  https://doi.org/10.1242/dev.114215.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gruppuso PA, Sanders JA. Regulation of liver development: implications for liver biology across the lifespan. J Mol Endocrinol. 2016;56:R115–25.  https://doi.org/10.1530/JME-15-0313.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ober EA, Lemaigre FP. Development of the liver: Insights into organ and tissue morphogenesis. J Hepatol. 2018;68:1049–62.  https://doi.org/10.1016/j.jhep.2018.01.005.CrossRefPubMedGoogle Scholar
  20. 20.
    Yin C. Molecular mechanisms of Sox transcription factors during the development of liver, bile duct, and pancreas. Semin Cell Dev Biol. 2017;63:68–78.  https://doi.org/10.1016/j.semcdb.2016.08.015.CrossRefPubMedGoogle Scholar
  21. 21.
    Bossard P, Zaret KS. GATA transcription factors as potentiators of gut endoderm differentiation. Development. 1998;125:4909–17.PubMedGoogle Scholar
  22. 22.
    Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS. Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev. 1996;10:1670–82.CrossRefGoogle Scholar
  23. 23.
    Tremblay KD, Zaret KS. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol. 2005;280:87–99.  https://doi.org/10.1016/j.ydbio.2005.01.003.CrossRefPubMedGoogle Scholar
  24. 24.
    Wilkins BJ, Pack M. Zebrafish Models of Human Liver Development and Disease. Compr Physiol. 2013;3:1213–30.  https://doi.org/10.1002/cphy.c120021.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Nemer G, Nemer M. Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol. 2003;254:131–48.  https://doi.org/10.1016/S0012-1606(02)00026-X.CrossRefPubMedGoogle Scholar
  26. 26.
    Shin D, Shin CH, Tucker J, Ober EA, Rentzsch F, Poss KD, Hammerschmidt M, Mullins MC, Stainier DY. Bmp and Fgf signaling are essential for liver specification in zebrafish. Development. 2007;134:2041–50.  https://doi.org/10.1242/dev.000281.CrossRefPubMedGoogle Scholar
  27. 27.
    Zhao R, Duncan SA. Embryonic development of the liver. Hepatology. 2005;41:956–67.  https://doi.org/10.1002/hep.20691.CrossRefPubMedGoogle Scholar
  28. 28.
    McLin VA, Rankin SA, Zorn AM. Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development. 2007;134:2207–17.  https://doi.org/10.1242/dev.001230.CrossRefPubMedGoogle Scholar
  29. 29.
    Ober EA, Verkade H, Field HA, Stainier DY. Mesodermal Wnt2b signalling positively regulates liver specification. Nature. 2006;442:688–91.  https://doi.org/10.1038/nature04888.CrossRefPubMedGoogle Scholar
  30. 30.
    Serls AE, Doherty S, Parvatiyar P, Wells JM, Deutsch GH. Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development. 2005;132:35–47.  https://doi.org/10.1242/dev.01570.CrossRefPubMedGoogle Scholar
  31. 31.
    Margagliotti S, Clotman F, Pierreux CE, Beaudry JB, Jacquemin P, Rousseau GG, Lemaigre FP. The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. Dev Biol. 2007;311:579–89.  https://doi.org/10.1016/j.ydbio.2007.09.013.CrossRefPubMedGoogle Scholar
  32. 32.
    Ganiatsas S, Kwee L, Fujiwara Y, Perkins A, Ikeda T, Labow MA, Zon LI. SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis. Proc Natl Acad Sci U S A. 1998;95:6881–6.CrossRefGoogle Scholar
  33. 33.
    Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ, Talianidis I. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006;20:2293–305.  https://doi.org/10.1101/gad.390906.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Matsumoto K, Yoshitomi H, Rossant J, Zaret KS. Liver organogenesis promoted by endothelial cells prior to vascular function. Science. 2001;294:559–63.  https://doi.org/10.1126/science.1063889.CrossRefPubMedGoogle Scholar
  35. 35.
    Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010;18:175–89.  https://doi.org/10.1016/j.devcel.2010.01.011.CrossRefPubMedGoogle Scholar
  36. 36.
    Hata M, Nanno M, Doi H, Satomi S, Sakata T, Suzuki R, Itoh T. Establishment of a hepatocytic epithelial cell line from the murine fetal liver capable of promoting hemopoietic cell proliferation. J Cell Physiol. 1993;154:381–92.  https://doi.org/10.1002/jcp.1041540222.CrossRefPubMedGoogle Scholar
  37. 37.
    Miyajima A, Kinoshita T, Tanaka M, Kamiya A, Mukouyama Y, Hara T. Role of Oncostatin M in hematopoiesis and liver development. Cytokine Growth Factor Rev. 2000;11:177–83.CrossRefGoogle Scholar
  38. 38.
    Wang Y, Wimmer U, Lichtlen P, Inderbitzin D, Stieger B, Meier PJ, Hunziker L, Stallmach T, Forrer R, Rülicke T, Georgiev O, Schaffner W. Metal-responsive transcription factor-1 (MTF-1) is essential for embryonic liver development and heavy metal detoxification in the adult liver. FASEB J. 2004;18:1071–9.  https://doi.org/10.1096/fj.03-1282com.CrossRefPubMedGoogle Scholar
  39. 39.
    Zaret KS. Regulatory phases of early liver development: paradigms of organogenesis. Nat Rev Genet. 2002;3:499–512.  https://doi.org/10.1038/nrg837.CrossRefPubMedGoogle Scholar
  40. 40.
    Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS, Duncan SA. Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet. 2003;34:292–6.  https://doi.org/10.1038/ng1175.CrossRefPubMedGoogle Scholar
  41. 41.
    Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 2001;21:1393–403.  https://doi.org/10.1128/MCB.21.4.1393-1403.2001.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Martinez-Jimenez CP, Kyrmizi I, Cardot P, Gonzalez FJ, Talianidis I. Hepatocyte nuclear factor 4alpha coordinates a transcription factor network regulating hepatic fatty acid metabolism. Mol Cell Biol. 2010;30:565–77.  https://doi.org/10.1128/MCB.00927-09.CrossRefPubMedGoogle Scholar
  43. 43.
    Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev. 2004;14:582–90.  https://doi.org/10.1016/j.gde.2004.08.004.CrossRefPubMedGoogle Scholar
  44. 44.
    Tchorz JS, Kinter J, Müller M, Tornillo L, Heim MH, Bettler B. Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice. Hepatology. 2009;50:871–9.  https://doi.org/10.1002/hep.23048.CrossRefPubMedGoogle Scholar
  45. 45.
    Poncy A, Antoniou A, Cordi S, Pierreux CE, Jacquemin P, Lemaigre FP. Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts. Dev Biol. 2015;404:136–48.  https://doi.org/10.1016/j.ydbio.2015.05.012.CrossRefPubMedGoogle Scholar
  46. 46.
    Clotman F, Lannoy VJ, Reber M, Cereghini S, Cassiman D, Jacquemin P, et al. The onecut transcription factor HNF6 is required for normal development of the biliary tract. Development. 2002;129:1819–28.PubMedGoogle Scholar
  47. 47.
    Coffinier C, Gresh L, Fiette L, Tronche F, Schutz G, Babinet C, et al. Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development. 2002;129:1829–38.PubMedGoogle Scholar
  48. 48.
    Chen Y, Verfaillie CM. MicroRNAs: the fine modulators of liver development and function. Liver Int. 2014;34:976–90.  https://doi.org/10.1111/liv.12496.CrossRefPubMedGoogle Scholar
  49. 49.
    Lemaigre FP. Development of the biliary tract. Mech Dev. 2003;120:81–7.  https://doi.org/10.1016/S0925-4773(02)00334-9.CrossRefPubMedGoogle Scholar
  50. 50.
    Kamiya A, Gonzalez FJ. TNF-alpha regulates mouse fetal hepatic maturation induced by oncostatin M and extracellular matrices. Hepatology. 2004;40:527–36.  https://doi.org/10.1002/hep.20362.CrossRefPubMedGoogle Scholar
  51. 51.
    Jungermann K, Katz N. Functional specialization of different hepatocyte populations. Physiol Rev. 1989;69:708–64.  https://doi.org/10.1152/physrev.1989.69.3.708.CrossRefPubMedGoogle Scholar
  52. 52.
    Birchmeier W. Orchestrating Wnt signalling for metabolic liver zonation. Nat Cell Biol. 2016;18:463–5.  https://doi.org/10.1038/ncb3349.CrossRefPubMedGoogle Scholar
  53. 53.
    Kaestner KH. In the zone: how a hepatocyte knows where it is. Gastroenterology. 2009;137:425–7.  https://doi.org/10.1053/j.gastro.2009.06.020.CrossRefPubMedGoogle Scholar
  54. 54.
    Stanulović VS, Kyrmizi I, Kruithof-de Julio M, Hoogenkamp M, Vermeulen JL, Ruijter JM, Talianidis I, Hakvoort TB, Lamers WH. Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes. Hepatology. 2007;45:433–44.  https://doi.org/10.1002/hep.21456.CrossRefPubMedGoogle Scholar
  55. 55.
    Loo CK, Wu XJ. Origin of stellate cells from submesothelial cells in a developing human liver. Liver Int. 2008;28:1437–45.  https://doi.org/10.1111/j.1478-3231.2008.01788.x.CrossRefPubMedGoogle Scholar
  56. 56.
    Collardeau-Frachon S, Scoazec JY. Vascular development and differentiation during human liver organogenesis. Anat Rec (Hoboken). 2008;291:614–27.  https://doi.org/10.1002/ar.20679.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Sergio Morini
    • 1
    Email author
  • Guido Carpino
    • 2
  • Simone Carotti
    • 1
  • Eugenio Gaudio
    • 3
  1. 1.Department of Medicine and SurgeryUniversity Campus Bio-Medico of RomeRomeItaly
  2. 2.Department of Motor, Human and Health SciencesUniversity of Rome “Foro Italico”RomeItaly
  3. 3.Department of Anatomical, Histological, Locomotor and Legal Medicine SciencesSapienza UniversityRomeItaly

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