Histology of the liver and the biliary system - PDF document

Histology of the liver, and the biliary system http://www.mgtowforums.com/forums/lads - night - inn/3969 - give - your - liver - art.html Dr. Zsuzsanna Tóth Semmelweis University Department of Anatomy , Histology and Embryology What does liver do? More than 500 vital functions have been identified with the liver. Conversion excess glucose into glycogen and vica versa in need. Gluconeogenezis.

Regulation of blood levels of amino acids. Production of bile which helps carry away waste (ie. bilirubin) and break down fats in the small intestine during digestio n. Production of plazma proteins (albumin, fibrinogen, blood coagulation factors, transferrin). Organization of lipid metabolism production of cholesterol. Progressing hemoglobin for use of its iron, storing iron and cupper. Stor

age of vitamins (A, B12, folic acid). Resisting infections by producing immune factors and removing bacteria from the bloodstream . Clearing the blood of drugs and other poisonous substances . Conversion of poisonous ammonia to urea . Production and conversion of signal molecules and hormones. (erytropoetin, angiotensinogen, hepcidin, IGF1,2, trijodtyronin). Special circulation of the live

r has a basic importance 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: • hepatic veins → inferior vena cava Dual blood supply of the liver The

liver is the first organ for the absorbed material to reach from the gut . Complex lipids (chylomicrons) reach the liver through the lymph vessels. • 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 int

o 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. Glisson ’s capsule Glisson ’s capsule The liver tissue is organized into units called lobules Hepatic lobule • Hexagonal shaped functional unit consisting of mainly hepatocytes. • Lobules are separ

ated 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 hepatic vein. portal triad s ublobular veins interlobular septa v ena cava interlobular artery interlobular duct i nterlobular vein Intensive blood supply facilitates the work of hepatocytes This is an idealized structure . interlobular duct portal ( Glisson ’s) triad : interlobular artery interlobular vein central vein perilobular artery perilob

ular vein hepatic plates sinusoids • Hepatic cells in the lobule form on cell layer - thick plates . • Within the plates hepatocytes are arranged in radial cords. • The cords are actually branching, interconnected sheets . • Sinusoids are dilatated capillaries. • Blood from the perilobular vessels falls into the sinusoids and from them to the central vein . • Arterial and venous bloo

d get mixed in the sinusoids . • Sinusoids separate the hepatic plates . • T hey form anastomoses , thus at least two surfaces of a hepatocyte is surrounded by blood . It may contain lymph vessels and nerves too . 3 • It collects blood from the sinusoids . • It enters to the sublobular vein . peribiliar plexus • Run in the connective tissue at the edges. • Lateral branch of the in

terlobular vein . • Forms anastomoses with each other . • Continous with the sinusoids . • Lateral branch of the interlobular artery . • Forms anastomoses with each other . • Continous with the sinusoids . • Supplies also the interlobular duct . • Network of fine arteries . • After supplying the interlobular duct joins to the sinusoids . Overview of the hepatic circulation v ena ca

va Perilobular vessels Perilobular vessels Pig liver tissue hematoxylin - eosin staining central vein portal triad interlobular septum hepatic lobule Lobules can have irregular shape, portal triads cannot be find at every edge. Human liver tissue central vein portal ( hepatic ) triad hepatic lobule Interlobular septa are less definitive in humans . The site at which blood enters the lobule and bi

le leaves it. Portal triad interlobular artery • round or oval shape • muscular media • may contain red blood cells interlobular vein • irregular shape • thin wall , only endothelial lining • surrounding pericytes • may contain red blood cells interlobular bile duct • round or oval shape • s imple cuboidal (small ones) or columnar (larger ones) epithelium lymph vessel • i rregul

ar shape • very delicate wall • no red blood cells capsule • connective tissue Nerves may be present. Hepatocytes : • main cell type in the parenchyma • h ave large , round euchromatic nuclei, and one or more nucleoli • Poyploidia : b inucleate cells are common (paired nuclei) Central vein with hepatic cords and sinusoids CV Cell Death Dis. 2017 May; 8(5): e2805. doi : 10.1038/cddis.2

017.167 Blood supply of the hepatic lobule 1. 2. 3. 4. 5. 6. 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 l ast to die in case of ishemia and the first to regenerate first to take up glucose to store as glycogen f

irst 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 l iver acinus acinus CV CV perilobular vessels perilobular vessels 1/6 1/6 Portal lobule • The area from where an interlobular bile duct collects bile. • Triang

ular shaped with bile duct at the center, central veins at the edges. 1/6 1/6 1/6 The h epatocyte is the main cell type in the liver • large nucleus, heterochromatin • large number of mitochondria • RER - protein synthesis • SER - detoxification, lipid biosynthesis 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 • glicogen granules , lipid droplets • many peroxisomes - alcohol and h ydrogen peroxide processing • Golgi - secretional activity The liver sinusoid and the perisinusoidal space Easy exchange of large molecules between hepatocytes and blood plasma is facilitated : • the sinu

soidal 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, â€

¢ 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 reticular fibers Silver impregnation of type III collagen fibers. • Reticular fibers are in connection with the interlobular connective tissue and with the connective tissue around the central veins. • The ratio of th

e 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 • Kupffer cells : in the sinusoids • Ito cells (hepatic stellate cells ): in the perisinusoidal space (= HSC) Kupffer cells are resident macrophages Kupffer cells: • triangular or star shaped , smaller , migrating cells in the si

nusoids • are part of the immune system – diffuse mononuclear phagocyte system (MPS ) • u ptake and degrade foreign and potentially harmful substances • p roliferate and enlarge in response to hepatocyte damage , bacterial toxins, etc. • uptake senescent red blood cells and break down hemoglobin Kupffer cells phagocyte ink particles added intravenously . Hemoglobin metabolism and s

torage of iron in the liver • Kupffer cells store most of the iron in form of hemosiderin - pigment • hepatocytes store some iron in form of ferritin Jaundice : • increased blood level of bilirubin • a sign of a liver , gallbladder, or pancreas disease circulation excretion with urine Bilirubin is a yellow breakdown product of heme catabolism . 10% 90% Hepcidin • a hormone of hepatoc

ytes • i nhibits iron mobilization from Kupffer cells - Kupffer cell Hepatic stellate cells (Ito cells) store vitamin A lipid dropplet 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 The liver of many arctic mammals contains

poisonous amount of vitamin A. Hepatic stellate cells are key components in liver fibrosis Cirrhosis : • i s the end stage of chronic liver diseases • i s caused by alcoholism, cancer, hepatitis C, etc. • the liver tissue is replaced by fibrous connective tissue Activated stellate cells turn into proliferative contractile myofibroblasts. induction of apoptosis stress In case of liver damag

e: • differentiated hepatocytes and cholangiocytes (epithelial duct cells) proliferate first • under chronic conditions progenitor cells start to proliferate into hepatocytes and cholangiocytes • p rogenitor cells are in the canals of Hering and around the ducts. Canals of Hering Progenitor cells The liver has strong self regenerating capacity The path of the bile within the liver inter

lobular bile duct canals of Hering (bile ductule) bile canaliculi form a network portal vein interlobular bile ducts → left and right hepatic duct →hylum of the liver The way of the bile outside the liver Extrahepatic ducts: • simple columnar epithelium • mucous glands in the submucosa • t he muscular layers thickens toward the duodenum • the sphincter of Oddi regulates bile flow into

the duodenum cystic duct spiral valves Common hepatic duct Common bile duct Cystic duct Histology of the gallbladder I. • The gallbladder stores , concentrates and releases bile. • CCK ( cholecystokinin ): • stimulates gallbladder contraction & emptying • r elaxes the sphincter of Oddi • CCK is produced by enteroendocrine cells in the small intestine • CCK is released by stimulation o

f dietary fat in the duodenum Note , the gall bladder does not have a layer of mu s cularis mucosae and submucosa ! Serosa & subserosa Histology of the gallbladder II. secretory granules - mucin microvilli i ntercellular space tight junctions Absorbtive epithelial cells: • microvilli – transcellular water reabsorbtion • many mitochondria • intercellular spaces - paracellular pathway of wat

er reabsorbtion Enterohepathic circulation of bile salts Composition of the bile (IgA) (inorganic salts, copper) • Bile components are secreted together into the duodenum in micelles . • Bile helps emulsify lipids, facilitating fat digestion by enzymes. • Bile acids, cholesterol and lecithin are recycled. ( lecithin ) champagne Vodka - tonic pina colada tequila Vater papilla Oddi sphincte