Histology of the liver - Maha Hammady.pptx

classical hepatic lobule
The Portal Tract
Hepatic sinusoids
Space of Disse
perisinusoidal space
Lymphatic pathway
Hepatocyte

1. Maha Hammady,MBBCh,MMSc

2. Liver Histology part 2 By/ Maha Hammady Hemdan MBBCh- MMSc - Faculty of Medicine, Alexandria University. 2015

3. Blood Vessels of the parenchyma

4. Blood Vessels of the parenchyma 4 Blood flow trough the classical hepatic lobule The larger interlobular vessels branch into distributing vessels that are located at the periphery of the lobule. These distributing vessels send inlet vessels to the sinusoids the blood flows centripetally toward the central vein (CV), also termed “ terminal hepatic venule” CV empties into a sublobular vein. Several sublobular veins converge to form larger hepatic veins that empty into the inferior vena cava. Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017 Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

5. 1-The portal tract

6. Blood Vessels of the parenchyma 6 The Portal Tract Standring S. Gray'sanatomy : The anatomical basis of clinical practice. 42th ed. Philadelphia: Elsevier; 2020 The portal tract is a small area found at the periphery of a liver lobule. Covered by connective tissue sleeve which is continuous with the connective tissue of the porta hepatis .

7. Blood Vessels of the parenchyma 7 The Portal Tract It typically consists of three main structures: 1-Branch of the portal vein: The lumen is much larger than that of the artery associated with it. 2-Branch of the hepatic artery: Th e structure of the hepatic artery is like that of other arteries (i.e., it has a thick muscular wall). 3-branch of the bile duct: lined by simple cuboidal epithelium. The term "portal triad" is commonly used in anatomy to refer to a specific arrangement of structures in the liver. In reality, the hepatic portal triad is not always comprised of just three structures . It often includes additional components such as lymphatic vessels, nerves, and small branches of other blood vessels. Therefore, the term "portal triad" fails to capture the full extent of the structures present in this region. Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017

8. Blood Vessels of the parenchyma 8 The Portal Tract Young B, O'Dowd G, Woodford P. Wheater's functional histology. 7th edition ed. New York: Elsevier; 2022

9. Blood Vessels of the parenchyma 9 The Portal Tract Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

10. Blood Vessels of the parenchyma 10 The Portal Tract Misdraji J. Embryology, anatomy, histology, and developmental anomalies of the liver. Sleisenger and fordtran's gastrointestinal and liver disease. 11th ed: Elsevier; 2020. p. 1201-6. e1.

11. 2-The Hepatic sinusoids

12. The Hepatic sinusoids 12 The Hepatic sinusoids sinusoidal capillaries (sinusoids), are vascular channels between the plates of hepatocytes. The blood vessels of the portal triads send distributing branches along the sides of the lobule, and these branches open into the hepatic sinusoids. Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

13. The Hepatic sinusoids 13 The Hepatic sinusoids Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017 The hepatic sinusoids are characterized by a thin and discontinuous endothelium, with a basal lamina that is also discontinuous, particularly in larger areas where it is absent. One distinctive feature of hepatic sinusoids is the presence of stellate sinusoidal macrophages, known as Kupffer cells, which are a regular component of the vessel lining. These Kupffer cells are part of the mononuclear phagocytic system and originate from monocytes. Through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), it is evident that Kupffer cells contribute to the lining of the sinusoid, contrary to earlier beliefs that they resided solely on the luminal surface of endothelial cells. Although the processes of Kupffer cells may overlap with endothelial cells, they do not form junctions with them. Furthermore, these Kupffer cell processes often extend across the sinusoidal lumen and can even partially obstruct it. Fig. 2. Scanning microscopy of a Kupffer cell in the sinusoid. The cell extends several microvilli or pseudopodia on its surface. 3000 Naito, M., Hasegawa, G., Ebe , Y.  et al.  Differentiation and function of Kupffer cells.  Med Electron Microsc   37 , 16–28 (2004). https://doi.org/10.1007/s00795-003-0228-x

14. The Hepatic sinusoids 14 The Hepatic sinusoids Carl von Kupffer and a scanning electron micrograph demonstrating a Kupffer cell (KC) from rat liver. Because activated cells appear ruffled (K), Carl von Kupffer called them sternzellen (‘star cells’) but everyone since then has called them Kupffer cells. S, sinusoid; h, hepatocyte. Images obtained from the Clending History of Medicine Library ( http://clendening.kumc.edu ) and from Lemasters et al., Ann Rev Pharmacol Toxicol 1997; 37: 327–38. Bilzer , M., Roggel , F. and Gerbes , A.L. (2006), Role of Kupffer cells in host defense and liver disease. Liver International, 26: 1175-1186.  https://doi.org/10.1111/j.1478-3231.2006.01342.x

15. The Hepatic sinusoids 15 The Hepatic sinusoids Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

16. The Hepatic sinusoids 16 The Hepatic sinusoids Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

17. The Hepatic sinusoids 17 The Hepatic sinusoids Fig. 1. Kupffer cell in rat liver. The cell adheres to the surface of endothelial cells and possesses several lysosomes and an ingested erythrocyte( R ) in the cytoplasm. Perfusion fixation. 10 000 Naito, M., Hasegawa, G., Ebe , Y.  et al.  Differentiation and function of Kupffer cells.  Med Electron Microsc   37 , 16–28 (2004). https://doi.org/10.1007/s00795-003-0228-x

18. The Hepatic sinusoids 18 The Hepatic sinusoids Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

19. The Hepatic sinusoids 19 The Hepatic sinusoids Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

20. 3-The space of Disse

21. The Hepatic sinusoids 21 The Space of Disse (perisinusoidal space) This space lies between the endothelial lining of the hepatic sinusoids and the hepatocytes, forming a crucial interface within the liver lobule. It contains plasma, and the microvilli of the hepatocytes are projecting into it. It is also filled with a loose network of reticular fibers, or collagen fibrils. These elements provide structural support. Ito cells (hepatic stellate cells) reside within the perisinusoidal space and play pivotal roles in liver function and pathology. They store vitamin A in lipid droplets and are involved in extracellular matrix remodeling and fibrosis in response to liver injury. Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

22. The Hepatic sinusoids 22 The Space of Disse (perisinusoidal space) Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

23. The Hepatic sinusoids 23 The Space of Disse (perisinusoidal space) Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020 Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

24. The Hepatic sinusoids 24 The Space of Disse (perisinusoidal space) Localization of Kupffer cells within the hepatic sinusoid in healthy and diseased liver. The Kupffer cell is located to the hepatic sinusoid and is therefore in close proximity to other cells in the sinusoid, including natural killer (NK) and natural killer T cells (NKT), as well as the liver sinusoidal endothelial cells (LSEC). Despite the barrier of the LSEC, Kupffer cell products, such as cytokines, chemokines, reactive nitrogen, and oxygen species, influence the activity of both stellate cells and hepatocytes. Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. Kupffer cells in the liver. Compr Physiol. 2013;3(2):785-97.

25. The Hepatic sinusoids 25 The Space of Disse (perisinusoidal space) Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017

26. The Hepatic sinusoids 26 The Space of Disse (perisinusoidal space) Color atlas of cytology, histology, and microscopic anatomy by Wolfgang Kuehnel

27. Lymphatic pathway

28. Lymphatic pathway 28 Lymphatic pathway Lymphatic drainage from the liver begins in the perisinusoidal space. Plasma remaining in this space flows into the periportal connective tissue, where a small cavity known as the periportal space (or space of Mall) exists between the portal canal stroma and the outermost hepatocytes (the limiting plate). From here, the fluid enters lymphatic capillaries that accompany the components of the portal triad. The lymph then proceeds through progressively larger vessels, moving in the same direction as bile—away from the hepatocytes, toward the portal canals, and ultimately reaching the liver hilum. It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains through sublobular and capsular lymphatic vessels.  Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52. Tanaka M, Iwakiri Y. The hepatic lymphatic vascular system: Structure, function, markers, and lymphangiogenesis . Cell Mol Gastroenterol Hepatol. 2016;2(6):733-49.

29. Lymphatic pathway 29 Lymphatic pathway Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52. “ There are spaces or channels which penetrate through the portal limiting plate with collagen fibers, independent of the blood vessels. In line with early studies by Mall ( 1901 ) and Viragh et al. ( 1978 )., these findings indicate that fluids in the space of Disse pass through the space between limiting plate hepatocytes to enter the space of Mall as well as through the space around the initial segment of the hepatic sinusoids (or inlet venules). “ “ We have examined the ultrastructure of the periportal limiting plate by the KOH-maceration/SEM method ( Ushiki and Ide, 1988 ). KOH-maceration at 60°C for 10 min followed by microdissection under a binocular microscope exposes the surface of the limiting plate (Ohtani et al., 2003 ). SEM of the samples shows many openings of channels extending through the limiting plate (Fig.  5 ). These openings are generally located in the areas where three hepatocytes meet. The density of the openings is approximately 1.3 × 10 3 /mm. Undigested collagen fibers can sometimes be observed to emerge from the channels between limiting plate hepatocytes. Accidentally fractured limiting plates also show channels containing undigested collagen fibers, which pass through the limiting plate to connect the space of Disse with the interstitial space of the portal tract (Ohtani et al., 2003 ). Thus, it is evident that the space of Disse is in continuity with the interstitial space of the portal tract or space of Mall through the channels traversing the periportal limiting plate as well as the space along the inlet venules. ”

30. Lymphatic pathway 30 Lymphatic pathway Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52. Scanning electron micrograph of the rat liver treated with the KOH-maceration technique, showing surface view of the portal tract side of limiting plate. There are many openings (arrowheads) of channels between limiting plate hepatocytes.

31. Lymphatic pathway 31 Lymphatic pathway A schematic representation of pathways of fluid and migrating cells such as dendritic cells (Dc) extending from the sinusoids (S) through the space of Disse, channels in the limiting plate, and interstitial space of the portal tract to portal lymphatic vessels (L ). Arrows indicate the presumable flow direction. C, collagen fibers; iA, interlobular artery; iV , interlobular vein; iB , interlobular bile duct; F, fibroblast; I, Ito cell (or stellate cell); K, Kupffer cell; N, nerve; PbP , peribiliary capillary plexus; a, afferent vessel of PbP ; e, efferent vessel of PbP . Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52.

32. Lymphatic pathway 32 Lymphatic pathway Fig. 5. Terminal lymphatics of the periportal area. The thick arrows indicate the possible lymph flow, coming from the space of Disse and entering a terminal lymphatic. The continuity between the space of Disse and the periportal area is represented by collagen fibers. I, blood capillary entering the liver parenchyma; 2, terminal lymph vessel; 3, sinusoid; 4, periportal hepatocyte; 5, space of Disse; 6, space of Mall; 7, collagen fibers entering the limiting plate; 8, network of periportal collagen fibers; 9, anchoring filaments Trutmann M, Sasse D. The lymphatics of the liver. Anat Embryol ( Berl ). 1994;190(3):201-9. .

33. Lymphatic pathway 33 Lymphatic pathway Scanning electron micrograph of the lymphatic corrosion cast of the rabbit liver. The lymphatic network in the portal tract extends as far as terminal portal tract. Arrows indicate partially filled sinusoids in the vicinity of the portal tract. Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52.

34. Lymphatic pathway 34 Lymphatic pathway Jeong J, Tanaka M, Iwakiri Y. Hepatic lymphatic vascular system in health and disease. J Hepatol. 2022;77(1):206-18.

35. The Hepatocyte

36. The Hepatocyte 36 The Hepatocyte Hepatocytes comprise approximately 80% of the liver's cellular population. These cells are typically large and polygonal. surfaces face the perisinusoidal space called the sinusoidal domains. others face neighboring hepatocytes and bile canaliculi called the lateral domain Their nuclei, which are often spherical and large , are situated centrally within the cell. Many hepatocytes in adult liver tissue contain two nuclei , while most are tetraploid . Each nucleus contains two or more well-defined nucleoli. Hepatocytes are relatively long-lived cells compared to those found in other parts of the digestive system, with an average lifespan of about 5 months . Moreover, they exhibit remarkable regenerative capacity. The cytoplasm of hepatocytes typically stains acidophilic . Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

37. The Hepatocyte 37 The Hepatocyte Specific components within the cytoplasm can be distinguished: Many rER and free ribosomes. Many sER. Cells in zone 3 have a much richer sER than those in zone 1. numerous mitochondria, ranging from 800 to 1,000 per cell. Cells in zone 3 have nearly twice as many, but considerably smaller , mitochondria as hepatocytes in zone 1 of the liver acinus. multiple small Golgi complexes. There are as many as 50 Golgi units and they are concentrated near the bile canaliculus. they are believed to be associated with the exocrine secretion of bile. abundant peroxisomes. Hepatocytes have as many as 200 to 300 peroxisomes per cell. deposits of glycogen, which stain positively with PAS. Liver cells in zone 1display large clumps of β particles surrounded by sER , whereas hepatocytes in zone 3 exhibit diffuse glycogen deposits. Lipid droplets of various sizes. Lysosomes containing lipofuscin pigment, partially digested organelles, or myelin figures. Mescher A. Junqueira’s basic histology text and atlas. 15th ed. new york : McGraw-Hill Education; 2018

38. The Hepatocyte 38 The Hepatocyte Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017

39. The Hepatocyte 39 The Hepatocyte Young B, O'Dowd G, Woodford P. Wheater's functional histology. 7th edition ed. New York: Elsevier; 2022

40. The Hepatocyte 40 The Hepatocyte Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

41. The Hepatocyte 41 The Hepatocyte Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

42. The Hepatocyte 42 The Hepatocyte Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

43. Thank you 43