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Liver Histology

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Liver Diseases

Abstract

The basic histological structure of the liver consists of closely intertwined epithelial cell cords that make it a cordonal gland. The classic hepatic lobule with the portal spaces in the periphery and the centrilobular vein in the center is the simplest and most versatile representation of the morpho-functional unit of the organ. Aspects of liver physiology and metabolism show a heterogeneous distribution along the porto-central axis of the lobule determining the basis of the metabolic zonation, that characterizes the functional attitude and the ultrastructural features of the different liver cell types. The main hepatic cell type is the hepatocyte with its different specialized domains, such as the sinusoidal, the lateral and the canalicular. Between hepatocytes cordons there are tortuous vascular channel named sinusoids, lined by fenestrated endothelial cells allowing blood plasma freely moving from vessel to perisinusoidal space of Disse facing the hepatocytes. In the Disse’s space, hepatic stellate cells, storing vitamin A, localize in a quiescent phenotype and they activate in response to chronic hepatic damage. The sinusoid endothelial cells and the hepatic stellate cells are also able to respond to vasoactive substances modifying the sinusoidal diameter. Resident macrophages, such as Kupffer cells and circulating monocyte, together with lymphocytic cells, such as NK cells, play roles in the maintenance of immune tolerance in the liver or in the activation of pro-inflammatory responses. Cholangiocytes lining the lumen of the biliary tree are responsible for the modification of the bile composition, are heterogeneous in size, regulation and response to biliary damage. The blood supplying the hepatic lobule is distributed by the branches of the portal vein and the hepatic artery, the latter terminating in a peribiliary plexus around the bile ducts. The wall of extra hepatic biliary tracts is formed by mucosal, muscle and serosal layers. The gallbladder with its mucosal folds is able to reabsorbs water and solutes fluids in order to concentrate bile.

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References

  1. Kiernan F. The anatomy and physiology of the liver. Philos Trans R Soc Lond. 1833;123:711–70.

    Article  Google Scholar 

  2. Mall FP. A study of the structural unit of the liver. Am J Anat. 1906;5:227–308.

    Article  Google Scholar 

  3. Rappaport AM. The structural and functional unit in the human liver (liver acinus). Anat Rec. 1958;130:673–89.

    Article  CAS  PubMed  Google Scholar 

  4. Monga SP. β-Catenin signaling and roles in liver homeostasis, injury, and tumorigenesis. Gastroenterology. 2015;148:1294–310. https://doi.org/10.1053/j.gastro.2015.02.056.

    Article  CAS  PubMed  Google Scholar 

  5. Benhamouche S, Decaens T, Godard C, Chambrey R, Rickman DS, Moinard C, Vasseur-Cognet M, Kuo CJ, Kahn A, Perret C, Colnot S. Apc tumor suppressor gene is the "zonation-keeper" of mouse liver. Dev Cell. 2006;10:759–70.

    Article  CAS  PubMed  Google Scholar 

  6. Matsumoto T, Kawakami M. The unit-concept of hepatic parenchyma—a re-examination based on angioarchitectural studies. Acta Pathol Jpn. 1982;32(Suppl 2):285–314.

    PubMed  Google Scholar 

  7. Hofmann AF. The choleohepatic circulation of unconjugated bile acids: an update. In: Paumgartner G, Stiehl A, Gerok W, editors. Bile acids and the hepatobiliary system: from basic science to clinical practice. Dordrecht: Kluwer Academic Publishers; 1993. p. 143–60.

    Google Scholar 

  8. Ekataksin W, Zou ZZ, Wake K, et al. HMS, hepatic microcirculatory subunits in mammalian species. Intralobular grouping of liver tissue with definition enhanced by drop out sinusoids. In: Wisse E, Knook DL, Wake K, editors. Cells of the hepatic sinusoid. Leiden: Kupffer Cell Foundation; 1995. p. 247–51.

    Google Scholar 

  9. Cao H, Krueger EW, McNiven MA. Hepatocytes internalize trophic receptors at large endocytic “Hot Spots”. Hepatology. 2011;54:1819–29. https://doi.org/10.1002/hep.24572.

    Article  CAS  PubMed  Google Scholar 

  10. Mazzone A, Tietz P, Jefferson J, Pagano R, LaRusso NF. Isolation and characterization of lipid microdomains from apical and basolateral plasma membranes of rat hepatocytes. Hepatology. 2006;43:287–96.

    Article  CAS  PubMed  Google Scholar 

  11. Wang MJ, Chen F, Lau JTY, Hu YP. Hepatocyte polyploidization and its association with pathophysiological processes. Cell Death Dis. 2017;8:e2805. https://doi.org/10.1038/cddis.2017.167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Czaja MJ. Functions of autophagy in hepatic and pancreatic physiology and disease. Gastroenterology. 2011;140:1895–908. https://doi.org/10.1053/j.gastro.2011.04.038.

    Article  PubMed  Google Scholar 

  13. Liu K, Czaja MJ. Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ. 2013;20:3–11. https://doi.org/10.1038/cdd.2012.63.

    Article  CAS  PubMed  Google Scholar 

  14. Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G. Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood. 1996;87:4568–80.

    Article  CAS  PubMed  Google Scholar 

  15. Poisson J, Lemoinne S, Boulanger C, Durand F, Moreau R, Valla D, Rautou PE. Liver sinusoidal endothelial cells: physiology and role in liver diseases. J Hepatol. 2017;66:212–27. https://doi.org/10.1016/j.jhep.2016.07.009.

    Article  CAS  PubMed  Google Scholar 

  16. Ding BS, Nolan DJ, Butler JM, James D, Babazadeh AO, Rosenwaks Z, Mittal V, Kobayashi H, Shido K, Lyden D, Sato TN, Rabbany SY, Rafii S. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature. 2010;468(7321):310–5. https://doi.org/10.1038/nature09493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Carotti S, Morini S, Corradini SG, Burza MA, Molinaro A, Carpino G, Merli M, De Santis A, Muda AO, Rossi M, Attili AF, Gaudio E. Glial fibrillary acidic protein as an early marker of hepatic stellate cell activation in chronic and posttransplant recurrent hepatitis C. Liver Transpl. 2008;14:806–14. https://doi.org/10.1002/lt.21436.

    Article  PubMed  Google Scholar 

  18. Carotti S, Perrone G, Amato M, Vespasiani Gentilucci U, Righi D, Francesconi M, Pellegrini C, Zalfa F, Zingariello M, Picardi A, Onetti Muda A, Morini S. Reelin expression in human liver of patients with chronic hepatitis C infection. Eur J Histochem. 2017;61:2745. https://doi.org/10.4081/ejh.2017.2745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88:125–72. https://doi.org/10.1152/physrev.00013.2007.

    Article  CAS  PubMed  Google Scholar 

  20. Carpino G, Franchitto A, Morini S, Corradini SG, Merli M, Gaudio E. Activated hepatic stellate cells in liver cirrhosis. A morphologic and morphometrical study. Ital J Anat Embryol. 2004;109(4):225–38.

    PubMed  Google Scholar 

  21. Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, de Bruijn MF, Geissmann F, Rodewald HR. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature. 2015;518(7540):547–51. https://doi.org/10.1038/nature13989.

    Article  CAS  PubMed  Google Scholar 

  22. Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50:261–74. https://doi.org/10.1002/hep.22950.

    Article  CAS  PubMed  Google Scholar 

  23. González-Domínguez É, Samaniego R, Flores-Sevilla JL, Campos-Campos SF, Gómez-Campos G, Salas A, Campos-Peña V, Corbí ÁL, Sánchez-Mateos P, Sánchez-Torres C. CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo. J Leukoc Biol. 2015;98:453–66. https://doi.org/10.1189/jlb.3HI1114-531R.

    Article  CAS  PubMed  Google Scholar 

  24. Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol. 2013;14:996–1006.

    Article  CAS  PubMed  Google Scholar 

  25. Peng H, Wisse E, Tian Z. Liver natural killer cells: subsets and roles in liver immunity. Cell Mol Immunol. 2016;13:328–36. https://doi.org/10.1038/cmi.2015.96.

    Article  CAS  PubMed  Google Scholar 

  26. Alvaro D, Mancino MG, Glaser S, Gaudio E, Marzioni M, Francis H, Alpini G. Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver. Gastroenterology. 2007;132:415–31.

    Article  CAS  PubMed  Google Scholar 

  27. Roskams TA, Theise ND, Balabaud C, Bhagat G, Bhathal PS, Bioulac-Sage P, Brunt EM, Crawford JM, Crosby HA, Desmet V, Finegold MJ, Geller SA, Gouw AS, Hytiroglou P, Knisely AS, Kojiro M, Lefkowitch JH, Nakanuma Y, Olynyk JK, Park YN, Portmann B, Saxena R, Scheuer PJ, Strain AJ, Thung SN, Wanless IR, West AB. Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology. 2004;39:1739–45.

    Article  PubMed  Google Scholar 

  28. Alpini G, Roberts S, Kuntz SM, Ueno Y, Gubba S, Podila PV, LeSage G, LaRusso NF. Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver. Gastroenterology. 1996;110:1636–43.

    Article  CAS  PubMed  Google Scholar 

  29. Maroni L, Haibo B, Ray D, Zhou T, Wan Y, Meng F, Marzioni M, Alpini G. Functional and structural features of cholangiocytes in health and disease. Cell Mol Gastroenterol Hepatol. 2015;1:368–80.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Glaser SS, Gaudio E, Rao A, Pierce LM, Onori P, Franchitto A, Francis HL, Dostal DE, Venter JK, DeMorrow S, Mancinelli R, Carpino G, Alvaro D, Kopriva SE, Savage JM, Alpini GD. Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium. Lab Investig. 2009;89:456–69. https://doi.org/10.1038/labinvest.2009.6.

    Article  CAS  PubMed  Google Scholar 

  31. Mancinelli R, Franchitto A, Gaudio E, Onori P, Glaser S, Francis H, Venter J, Demorrow S, Carpino G, Kopriva S, White M, Fava G, Alvaro D, Alpini G. After damage of large bile ducts by gamma-aminobutyric acid, small ducts replenish the biliary tree by amplification of calcium-dependent signaling and de novo acquisition of large cholangiocyte phenotypes. Am J Pathol. 2010;176:1790–800. https://doi.org/10.2353/ajpath.2010.090677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gaudio E, Chaberek S, Montella A, Pannarale L, Morini S, Novelli G, Borghese F, Conte D, Ostrowski K. Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver. J Anat. 2005;207:107–15.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Gaudio E, Onori P, Pannarale L, Alvaro D. Hepatic microcirculation and peribiliary plexus in experimental biliary cirrhosis: a morphological study. Gastroenterology. 1996;111:1118–24.

    Article  CAS  PubMed  Google Scholar 

  34. Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol. 2010;16:6046–57.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lautt WW. Relationship between hepatic blood flow and overall metabolism: the hepatic arterial buffer response. Fed Proc. 1983;42:1662–6.

    CAS  PubMed  Google Scholar 

  36. Reynaert H, Thompson MG, Thomas T, Geerts A. Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. Gut. 2002;50:571–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, University Campus Bio-Medico of Rome, Rome, Italy

    Simone Carotti & Sergio Morini

  2. Department of Motor, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy

    Guido Carpino

  3. Department of Anatomical, Histological, Locomotor and Legal Medicine Sciences, Sapienza University, Rome, Italy

    Eugenio Gaudio

Authors
  1. Simone Carotti
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  2. Sergio Morini
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  3. Guido Carpino
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  4. Eugenio Gaudio
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Corresponding author

Correspondence to Sergio Morini .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Florentina Radu-Ionita

  2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

    Nikolaos T. Pyrsopoulos

  3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Mariana Jinga

  4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Ion C. Tintoiu

  5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

    Zhonghua Sun

  6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

Self Study

Self Study

1.1 Questions

  1. 1.

    Which statement(s) is/are true?

    1. (a)

      The portal lobule is a morpho-functional liver unit obtained by joining different portal tracts each other and placing in the center the centri-lobular vein.

    2. (b)

      Glucose metabolism at the hepatocytes level shows heterogeneous localization, with gluconeogenesis occurring mainly in the periportal while glycolysis in the pericentral region.

    3. (c)

      The sinusoidal domain of hepatocyte through microvilli has only functions of absorption.

    4. (d)

      The fenestrations of sinusoidal endothelial cells are provided with diaphragms; hence the solutes don’t pass freely within the space of Disse and selective transcitosis is always required.

    5. (e)

      In the normal liver hepatic stellate cells are α-SMA-expressing cells that produce large amount of collagen and matrix proteins.

  2. 2.

    Which statement(s) is/are true?

    1. (a)

      The intrahepatic bile ducts have their roots in the bile canaliculi with cholangiocytes lining their wall.

    2. (b)

      Secretin receptor (SR), cystic fibrosis transmembrane conductance regulator (CFTR) and anion exchanger 2 (AE2) are expressed both by large and small cholangiocytes and are responsible for most of the biliary fluid secretion that occurs through the Ca2+ activated signaling pathways.

    3. (c)

      The ramifications of the hepatic artery follow substantially those of the portal system penetrating the organ through it and directly terminating into sinusoidal bed.

    4. (d)

      The main site of the regulation of hepatic microcirculation seems to be represented by sinusoids themselves.

    5. (e)

      The function of the gallbladder is only to contain the bile waiting for the bile to be pushed into the common bile duct and fed into the duodenum after a meal.

1.2 Answer

  1. 1.

    Which statement(s) is/are true?

    1. (a)

      The portal lobule is a structural unit in which the portal space is at the center and the centrilobular veins in the periphery. The morpho-functional unit with the portal spaces in the periphery and the centrilobular vein in the center is the classic hepatic lobule.

    2. (b)

      (CORRECT) Many aspects of liver physiology and metabolism show a heterogeneous distribution along the porto-central axis of the lobule determining the so-called liver zonation. Hepatocytes located in the periportal area are more involved in gluconeogenesis and lipid metabolism whereas those located in the pericentral are the most able to detoxify and are involved in glycolysis.

    3. (c)

      At the level of the sinusoidal domain of the hepatocyte, the plasma membrane has abundant microvilli and secretion vacuoles that open at their base, responsible for the processes of exocytosis; hence both functions of absorption and secretion are exerted.

    4. (d)

      The fenestrations of sinusoidal cells are not provided with diaphragms and the basal membrane is lacking on the deep surface of the endothelial cell; hence, the solutes pass freely through the fenestrations within the space of Disse and arrive in contact with the plasma membrane of hepatocytes. However, sinusoidal endothelial cells exhibit also endocytotic capacity and part of the molecules that are taken by endocytosis are modified and reach the hepatocytes by transcytosis.

    5. (e)

      In the normal liver, the stellate cells are quiescent; they only produce moderate levels of collagen proteins and matrix glycoproteins. The liver damage induces activation of stellate cells affecting aspects such as proliferation, migration, contractility and increased matrix production; a feature of stellate cell activation is the de novo expression of the muscle-smooth isoform of α-actin (α-SMA).

  2. 2.

    Which statement(s) is/are true?

    1. (a)

      The bile canaliculi run between adjacent hepatocytes that form the canaliculi’s wall with their canalicular domain; at the boundary of the portal space the canaliculi continue in the bile ductules, whose wall initially consists partly of hepatocytes and partly of cholangiocytes; then interlobular bile ducts in the portal tract are lined by cholangiocytes.

    2. (b)

      Secretin receptor (SR), cystic fibrosis transmembrane conductance regulator (CFTR) and anion exchanger 2 (AE2) are expressed only by large cholangiocytes and are responsible for most of the biliary fluid secretion that occurs through the activation of a cyclic dependent AMP pathway; on the other hand, in small cholangiocytes, the Ca2+ activated signaling pathways is predominant.

    3. (c)

      The ramifications of the hepatic artery follow substantially those of the portal system; however, the termination of the hepatic artery is a peribiliary vascular plexus at the level of the intrahepatic bile ducts; then the peribiliary plexus drains mainly in the hepatic sinusoids.

    4. (d)

      (CORRECT) The sinusoidal endothelial cells are able to respond to a series of vasoactive substances which modify the sinusoidal diameter, by determining their partial contraction or their relative relaxation. Even the stellate cells with their long processes that embrace the sinusoidal wall, are able to respond to mediators with a vasoconstricting action.

    5. (e)

      The reabsorption of water and solutes fluids for the concentration of bile is a fundamental role of the gallbladder; thus, it is not designed only to storing bile.

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Carotti, S., Morini, S., Carpino, G., Gaudio, E. (2020). Liver Histology. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_2

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  • DOI: https://doi.org/10.1007/978-3-030-24432-3_2

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  • Online ISBN: 978-3-030-24432-3

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