Histology of the liver, and the biliary system

Transcription

1 Histology of the liver, and the biliary system Dr. Zsuzsanna Tóth Semmelweis University Department of Anatomy, Histology and Embryology

2 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. Progressing hemoglobin for use of its iron, storing iron and cupper. Production of bile which helps carry away waste (ie. bilirubin) and break down fats in the small intestine during digestion. Storage of vitamins (A, B12, folic acid). Organization of lipid metabolism production of cholesterol. Regulation of blood levels of amino acids. Production of plazma proteins (albumin, fibrinogen, blood coagulation factors, transferrin). 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). Resisting infections by producing immune factors and removing bacteria from the bloodstream.

3 Special circulation of the liver has a basic importance The liver is the first organ for the absorbed material to reach from the gut. Input: 75% portal vein o o o o poor in oxygen rich in nutritions and pancreatic hormones ( from the bowels), rich in hemoglobin metabolites-bilirubin and heme (from the spleen) the liver is in a situation to be a key metabolic center 25% hepatic artery o Dual blood supply of the liver rich in oxigen Output: hepatic veins inferior vena cava Complex lipids (chylomicrons) reach the liver through the lymph vessels.

4 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.

5 The liver tissue is organized into units called lobules vena cava portal triad Hepatic lobule sublobular veins interlobular duct interlobular vein interlobular artery Hexagonal shaped functional unit consisting of mainly hepatocytes. 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 interlobular septa transports it to the sublobular vein, and then into the hepatic vein.

6 Intensive blood supply facilitates the work of hepatocytes sinusoids Sinusoids are dilatated capillaries. Blood from the perilobular vessels falls into the sinusoids and from them to the central vein. Arterial and venous blood get mixed in the sinusoids. Sinusoids separate the hepatic plates. They form anastomoses, thus at least two surfaces of a hepatocyte is surrounded by blood. hepatic plates 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. This is an idealized structure. central vein It collects blood from the sinusoids. It enters to the sublobular vein. portal (Glisson s) triad: It may contain lymph vessels and nerves too. peribiliar plexus interlobular artery interlobular vein interlobular duct Run in the connective tissue at the edges. perilobular vein perilobular artery 3 Lateral branch of the interlobular 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.

7 Overview of the hepatic circulation vena cava Perilobular vessels Perilobular vessels

8 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.

9 Human liver tissue portal (hepatic) triad central vein hepatic lobule Interlobular septa are less definitive in humans.

10 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 interlobular vein irregular shape thin wall, only endothelial lining surrounding pericytes may contain red blood cells interlobular bile duct round or oval shape simple cuboidal (small ones) or columnar (larger ones) epithelium Nerves may be present.

11 Central vein with hepatic cords and sinusoids around CV Hepatocytes: main cell type in the parenchyma have large, round euchromatic nuclei, and one or more nucleoli binucleate cells are common (paired nuclei)

12 Blood supply of the hepatic lobule cv 3. cv

13 Liver acinus acinus perilobular vessels 1/6 1/6 CV CV liver acinus perilobular vessels 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 last to respond to toxic substances and bile stasis Zone 2: intermediate zone

14 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.

15 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 large number of mitochondria RER - protein synthesis SER - detoxification, lipid biosynthesis glicogen granules, lipid droplets many peroxisomes - alcohol and hydrogen peroxide processing Golgi- secretional activity

16 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.

17 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.

18 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

19 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

20 Hemoglobin metabolism and storage of iron in the liver Kupffer cell - Hepcidin a hormone of hepatocytes inhibits iron mobilization from Kupffer cells Kupffer cells store most of the iron in form of hemosiderin - pigment hepatocytes store some iron in form of ferritin circulation 10% excretion with urine 90% Bilirubin is a yellow breakdown product of heme catabolism. Jaundice: increased blood level of bilirubin a sign of a liver, gallbladder, or pancreas disease

21 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 produce connective tissue of interlobular septa liver fibrosis lipid dropplet The liver of many arctic mammals contains poisonous amount of vitamin A.

22 The liver has strong self regenerating capacity Progenitor cells Canals of Hering In case of liver damage: differentiated hepatocytes and cholangiocytes (epithelial duct cells) proliferate first under chronic conditions progenitor cells start to proliferate into hepatocytes and cholangiocytes progenitor cells are in the canals of Hering and around the ducts.

23 The path of the bile within the liver portal vein interlobular bile duct canals of Hering (bile ductule) bile canaliculi form a network interlobular bile ducts le and right hepa c duct hylum of the liver

24 The way of the bile outside the liver spiral valves Extrahepatic ducts: simple columnar epithelium mucous glands in the submucosa the muscular layers thickens toward the duodenum the sphincter of Oddi regulates bile flow into the duodenum cystic duct

25 Histology of the gallbladder I. Serosa & subserosa The gallbladder stores, concentrates and releases bile. CCK (cholecystokinin): stimulates gallbladder contraction & emptying relaxes the sphincter of Oddi CCK is produced by enteroendocrine cells in the small intestine CCK is released by stimulation of dietary fat in the duodenum Note, the gall bladder does not have a layer of muscularis mucosae and submucosa!

26 Histology of the gallbladder II. secretory granules- mucin microvilli tight junctions intercellular space Absorbtive epithelial cells: microvilli transcellular water reabsorbtion many mitochondria intercellular spaces - paracellular pathway of water reabsorbtion

27 Enterohepathic circulation of bile salts Composition of the bile (IgA) (inorganic salts, copper) (lecithin) 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.

28 champagne Vodka-tonic pina colada tequila