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Histology of the Liver, and the Biliary System

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Histology of the Liver, and the Biliary System Histology of the liver, and the biliary system Dr. Zsuzsanna Tóth Semmelweis University Department of Anatomy, Histology and Embryology http://www.mgtowforums.com/forums/lads-night-inn/3969-give-your-liver-art.html What does liver do? More than 500 vital functions have been identified with the liver. Organization of lipid metabolism Storage of vitamins Conversion excess glucose into production of cholesterol. glycogen and vica versa in need. (A, B12, folic acid). Gluconeogenezis. Regulation of blood levels of amino acids. Progressing hemoglobin for use of its iron, storing iron and cupper. Production of plazma proteins (albumin, fibrinogen, blood coagulation factors, transferrin). Production of bile which helps carry away waste (ie. bilirubin) and break down fats in the small Clearing the blood of drugs and other intestine during digestion. poisonous substances. Conversion of poisonous ammonia to urea. Production and conversion of signal Resisting infections by producing molecules and hormones. immune factors and removing (erytropoetin, angiotensinogen, bacteria from the bloodstream. hepcidin, IGF1,2, trijodtyronin). Special circulation of the liver has a basic importance Dual blood supply of the liver Input: • 75% portal vein o poor in oxygen o rich in nutritions and pancreatic hormones ( from the bowels), o rich in hemoglobin metabolites-bilirubin and heme (from the spleen) o the liver is in a situation to be a key metabolic center • 25% hepatic artery o rich in oxigen Output: The liver is the first organ for the absorbed • hepatic veins → inferior vena cava material to reach from the gut. Complex lipids (chylomicrons) reach the liver through the lymph vessels. Glisson’s capsule Glisson’s capsule • The liver is covered by a fibrous capsule called Glisson’s capsule. • At the hilum, where it is thicker, it wraps the portal vein, the hepatic artery and the bile duct. • Main branches called Glisson’s pedicles divide the liver into segments that has surgical importance. • Further arborization: branches of the hepatic duct, the portal vein and the hepatic artery are distributed in the parenchyma and remain together. The liver tissue is organized into units called lobules vena cava portal triad Hepatic lobule interlobular • Hexagonal shaped functional unit consisting of interlobular vein sublobular duct mainly hepatocytes. veins interlobular artery • Lobules are separated by connective tissue – interlobular septa. • Branches of the portal vein, the hepatic artery and the hepatic duct follow the corners of the hexagon and are called portal triad. • Blood flows from the perifery of the lobule toward the center (red arrows). • In the center of the hexagon there is a central vein. • The central (=centrilobular) vein gathers blood and transports it to the sublobular vein, and then into the interlobular septa hepatic vein. Intensive blood supply facilitates the work of hepatocytes sinusoids • Sinusoids are dilatated capillaries. portal (Glisson’s) triad: • Blood from the perilobular vessels It may contain lymph falls into the sinusoids and from vessels and nerves too. them to the central vein. • Arterial and venous blood get interlobular artery mixed in the sinusoids. interlobular vein 3 • Sinusoids separate the hepatic interlobular duct plates. • Run in the connective tissue • They form anastomoses, thus at at the edges. least two surfaces of a hepatocyte is perilobular vein surrounded by blood. • Lateral branch of the interlobular vein. hepatic plates • Forms anastomoses with each • Hepatic cells in the lobule form other. on cell layer-thick plates. • Continous with the sinusoids. • Within the plates hepatocytes perilobular artery are arranged in radial cords. • Lateral branch of the • The cords are actually branching, interlobular artery. interconnected sheets. • Forms anastomoses with each central vein other. • It collects blood from the sinusoids. • Continous with the sinusoids. • It enters to the sublobular vein. • Supplies also the interlobular duct. peribiliar plexus • Network of fine arteries. • After supplying the interlobular duct joins This is an idealized structure. to the sinusoids. Overview of the hepatic circulation vena cava Perilobular vessels Perilobular vessels Pig liver tissue hematoxylin-eosin staining portal triad central vein interlobular septum hepatic lobule Lobules can have irregular shape, portal triads cannot be find at every edge. Human liver tissue portal (hepatic) triad central vein hepatic lobule Interlobular septa are less definitive in humans. Portal triad The site at which blood enters the lobule and bile leaves it. capsule • connective tissue interlobular artery • round or oval shape • muscular media • may contain red blood cells lymph vessel • irregular shape • very delicate wall • no red blood cells Nerves may be present. interlobular vein interlobular bile duct • irregular shape • round or oval shape • thin wall, only endothelial lining • simple cuboidal (small ones) • surrounding pericytes or columnar (larger ones) epithelium • may contain red blood cells Central vein with hepatic cords and sinusoids CV Cell Death Dis. 2017 May; 8(5): e2805. doi: 10.1038/cddis.2017.167 Hepatocytes: • main cell type in the parenchyma • have large, round euchromatic nuclei, and one or more nucleoli • Poyploidia: binucleate cells are common (paired nuclei) Blood supply of the hepatic lobule 2. 1. cv 3. cv 6. 4. 5. Liver acinus acinus perilobular vessels perilobular 1/6 1/6 perilobular vessels perilobular CV CV liver acinus According to the deacreasing oxygen gradient toward the central vein, the acinus is divided into 3 zones. Hepatocytes in the zones have different functions. Zone 1: first to receive both nutrients and toxins last to die in case of ishemia and the first to regenerate first to take up glucose to store as glycogen first to show morphological changes following bile duct occlusion Zone 3: first to show ischemic necrosis first to show fat accumulation in obese persons least vulnerable to toxic substances and bile stasis Zone 2: intermediate zone Portal lobule 1/6 1/6 1/6 • The area from where an interlobular bile duct collects bile. • Triangular shaped with bile duct at the center, central veins at the edges. The hepatocyte is the main cell type in the liver Polarization: • microvilli at the sinusoidal surface • bile canaliculi between the adjacent hepatocytes: -formed by plasma membranes -sealed by tight junctions on the two sides Microvilli extending into the bile canaliculus TJ TJ • large nucleus, heterochromatin • glicogen granules, lipid droplets • large number of mitochondria • many peroxisomes - alcohol and hydrogen peroxide processing • RER - protein synthesis • Golgi- secretional activity • SER - detoxification, lipid biosynthesis The liver sinusoid and the perisinusoidal space Easy exchange of large molecules between hepatocytes and blood plasma is facilitated: • the sinusoidal wall is lined with fenestrated endothel, • beside the intercellular fenestrae there are also intracellular pores in the endothelial cells, • the basal lamina is discontinous or missing, • the hepatocytes and the sinusoidal wall is separated by the perisinusoidal space – space of Disse, • plasma may enter, but red blood cells and platelets are exluded form the perisinusoidal space, • microvilli (increasing surface) of the hepatocytes extend into the space of Disse-this is the site of exchange. Reticular network supports hepatocytes in the space of Disse Silver impregnation of type III collagen fibers. reticular fibers • Reticular fibers are in connection with the interlobular connective tissue and with the connective tissue around the central veins. • The ratio of the interstitium and the parenchyma is small, therefore the liver is vulnerable to injuries. Kupffer and Ito cells are two other prominent cell types in the liver (= HSC) • Kupffer cells : in the sinusoids • Ito cells (hepatic stellate cells): in the perisinusoidal space Kupffer cells are resident macrophages Kupffer cells phagocyte ink particles added intravenously. Kupffer cells: • triangular or star shaped, smaller, migrating cells in the sinusoids • are part of the immune system – diffuse mononuclear phagocyte system (MPS) • uptake and degrade foreign and potentially harmful substances • proliferate and enlarge in response to hepatocyte damage, bacterial toxins, etc. • uptake senescent red blood cells and break down hemoglobin Hemoglobin metabolism and storage of iron in the liver Kupffer cell - Hepcidin • a hormone of hepatocytes • Kupffer cells store most of the iron in form of • inhibits iron mobilization from Kupffer cells hemosiderin - pigment • hepatocytes store some iron in form of ferritin circulation Jaundice: 10% excretion with urine • increased blood level of bilirubin 90% • a sign of a liver, gallbladder, or pancreas disease Bilirubin is a yellow breakdown product of heme catabolism. Hepatic stellate cells (Ito cells) store vitamin A hepatic stellate cell = Ito cell = perisinusoidal cell • are located in the space of Disse • cannot be seen on hematoxylin-eosin stained sections • strore and metabolize vitamin A • contribute to liver fibrosis lipid dropplet The liver of many arctic mammals contains poisonous amount of vitamin A. Hepatic stellate cells are key components in liver fibrosis stress induction of apoptosis Activated stellate cells turn into proliferative contractile myofibroblasts. Cirrhosis: • is the end stage of chronic liver diseases • is caused by alcoholism, cancer, hepatitis C, etc. • the liver tissue is replaced by fibrous
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