Liver Anatomy PDF

LIVER Fat metabolism —> oxidation of triglycerides to produce energy, synthesis of plasma lipoproteins, synthesis of cholesterol and phospholipids Carbohydrate metabolism —> converting carbohydrates and proteins into...

LIVER Fat metabolism —> oxidation of triglycerides to produce energy, synthesis of plasma lipoproteins, synthesis of cholesterol and phospholipids Carbohydrate metabolism —> converting carbohydrates and proteins into fatty acids and triglycerides, regulation of blood glucose concentration (glycogenesis, glycogenolysis and gluconeogenesis) Protein metabolism —> synthesis of albumin and clotting factors (plasma proteins), synthesis of non-essential amino acids, contributes to the detoxification of waste products (deamination of amino acids and production of urea) Storage —> iron, glycogen and vitamins Intermediary metabolism —> detoxification of drugs and toxins such as alcohol Secretion —> synthesis and secretion of bile and conjugated bilirubin with glucuronic acid. Bilirubin is produced in the spleen and then conjugated to glucuronic acid in the liver. The liver is in our supramesocolic compartment and it is mostly to the right (right hypochondrium) but a part of it also reaches the centre (epigastrium) and the left side (left hypochondrium). Part of the stomach is covered by the liver. The liver is an intraperitoneal organ. The internal arrangement of the liver is homogeneous and the main cell population is hepatocytes. It is a very densely cellular organ. The connective tissue that divides hepatocytes forms the so called reticulin network and it is made of collagen type III. The liver parenchyma is characterised by a huge amount of capillaries and of sinusoids. The capsule surrounding the liver is called Glisson’s capsule and it is mostly made of collagen and elastic fibers. Outside of the Glisson’s capsule we can find the peritoneum, which envelops the liver almost completely (the liver is intraperitoneal but the bare area of the liver doesn’t present peritoneum as it touches the diaphragm) The liver weights 2kg on average of which 400-800g are blood. It is around 26-28cm in transverse diameter. TEPEE forms The liver is divided into a diaphragmatic surface (superior, anterior and posterior portion) and a visceral surface (in contact with other organs, inferior portion) The liver grows in the ventral mesogastrium and it grows so much that it comes in contact with the developing septum transversum and becomes bare in a section (bare area of the liver, in contact with the future diaphragm, no peritoneum). Here the peritoneum will form the coronary ligament (connects the inferior part of the diaphragm to the superior part of the liver). The lesser omentum will instead form the hepatogastric and hepatoduodenal ligaments. The liver can be divided into 4 lobes ANATOMICALLY SPEAKING. The right lobe is the large lobe of the liver (anterior) and it is connected to the left lobe by the falciform ligament (which also connects the liver to the anterior abdominal wall). At the base of the falciform ligament there is the round ligament of the liver, which is made of connective tissue. The round ligament or ligamentum teres is a remnant of the umbilical vein Am an At the apex of the coronary ligament the peritoneum forms the right refugees triangular ligament and the left triangular ligament. On the visceral layer of the liver we can appreciate the other two lobes, which are the quadrate lobe and the caudate lobe. These two lobes are separated by the porta hepatic (hilum of the liver). We can also see a system of grooves (sulci) —> right sagittal fissure and left sagittal fissure + porta hepatis (H-shaped system) The right sagittal fissure contains the gallbladder anteriorly and the inferior vena cava posteriorly while the left sagittal fissure contains the round ligament (remnant of umbilical vein) anteriorly and the ligamentum venosum (remnant of the ductus venosus) posteriorly. The porta hepatis (hilum) corresponds to the place where the portal vein, the hepatic artery and the bile duct pass. enters enters exits On the surface there are impressions caused by the adjacent organs during development —> gastric impression, oesophageal impression, renal impression, colic impression (by the bending of the ascending colon) and suprarenal impression (by the adrenal gland) Surgically the liver is divided into 8 segments BLOOD SUPPLY TO THE LIVER 75% of the blood comes from the portal vein —> collects blood from the small intestine, stomach, large intestine and spleen. It contains nutrients and toxins (from intestine) and bilirubin (from spleen). The portal vein is composed of the superior mesenteric vein, inferior mesenteric vein, splanchnic vein and gastric vein. Venous blood (non oxygenated) 25% of the blood comes from the hepatic artery (originated from the celiac trunk) —> brings  oxygenated blood IMPORTANT When the portal vein and hepatic artery enter the liver they branch to reach all the sinusoids of the liver. The liver sinusoids run among the hepatocytes and contain both venous blood and arterial blood (mixed blood). The hepatic veins drain blood into the inferior vena cava Hepatic sinusoids —> special capillaries located among hepatocytes that contain mixed blood. Mixing of blood takes place at the periphery of the liver lobule. Hepatocytes work on the venous blood to detoxify it but at the same time need oxygenated blood to survive. Mixed blood flows in the sinusoids towards a central vein b Arteriosinusoidal branch (anastomosis) —> the blood flowing in the sinusoids is a mixture of venous blood coming from the portal vein and arterial blood coming from the hepatic artery Hepatic sinusoids are a special type of capillary and are about 10-15 microns in diameter. The endothelium is continuous but the endothelial cells are loosely attached to one another (and so fluids can leak through the intercellular junctions into the space of Disse). The endothelium is fenestrated and the fenestrations are not closed by diaphragms (to allow free passage) and they occur in groups called sieve plates), the basal lamina is discontinuous and there are macrophages (Kupffer cells) associated to the endothelial cells verypermeable The liver parenchyma is organised in lobules (like hexagonally shaped tiles attached to one another) Classic lobule of the liver —> Hexagonal shape in cross section — > at each vertex there is a portal space containing a vascular triad (or portal triad), made by a small branch of the hepatic artery, a small branch of the portal vein and a bile duct or ductule + lymphatics (not part of the portal triad). At the centre there is the centrilobular vein. At the vertex there is the mixing mechanism and connection with sinusoids A classic lobule is a polyhedral structure consisting in layers of hepatocytes organised in cords. In between cords there are sinusoids draining into the centrilobular vein. In the human liver it is very hard to recognise the different lobules (the hexagons aren’t delimited clearly) while in other animals it is easier (for example in pigs, where there is more connective tissue) The portal space is the space where the vessels of the portal triad reside. Hepatocytes have a peculiarity —> some of them are binucleated 2nuclei 0 In the classic lobule we can recognise two flows with opposite directions —> Blood flow (from periphery to centrilobular vein) and Bile flow (collected by conduit system from hepatocytes and sent to the gallbladder, stored there) HEPATOCYTES An hepatocytes can be compared to a cuboidal structure (6 faces) —> 2 of the faces can be called vascular faces because on that site of the plasma membrane the hepatocytes are in relationship with sinusoids, the other 4 faces are called biliary faces because on these sides the plasma membrane is indented and when hepatocytes are apposed to each other a lumen is formed (bile canaliculi, where bile will be released when synthesised). is soso.si isomerases iinee hepatocyte comaof hepatocytes SPACE OF DISSE —> tiny space in between the surface of the hepatocytes (vascular face) and the sinusoids. The purpose of the space of Disse is that of allowing exchanges, for this reason there must collagen fibers and the sinusoids have to present a discontinuous basal lamina. In the space of Disse we can find: Ito cells (or stellate cells) —> they store vitamine A (lipid soluble) and produce collagen and ECM present in the Disse space ECM Collagen fibers Hepatocytes’ microvilli In the space of Disse the double-way exchange between blood and hepatocytes takes place (so there’s oxygen in there). There’s an exchange of bilirubin produced in the spleen as well The macrophages lining the endothelial cells of the fenestrated sinusoids are called Kupffer cells When things go wrong —> in alcoholic patients or in patients with inflammations related to the liver Itos’ cells (or stellate cells) can transform and start to produce a lot of collagen and ECM (like fibroblasts) and become similar to myocontractile cells. Ito cells then replicate and damage the plasma membrane of the hepatocytes as well, causing the disappearance of microvilli. The basement membrane of the sinusoids then becomes continuous due to the scar tissue. Kupffer cells are then activated and worsen the problem. The fibrosis of the liver is reversible up to a certain point. cell His Oxygen is more concentrated close to the portal space (because it is then gradually delivered to hepatocytes) and less concentrated in the centrilobular vein. When oxygen is scarce the hepatocytes close to the centrilobular vein suffer the most BILE CANALICULI They’re extracellular canals between hepatocytes formed by the union of the denting on the plasma membrane of the two adjacent hepatocytes (apical domain). Bile is an emulsifying agent for lipids that will be mixed with food in the duodenum. At the level of the hepatocytes bilirubin (then contained in bile) is conjugated to an acid (glucuronic acid) and is then called conjugated bilirubin. Bilirubin comes from the destruction of erythrocytes in the spleen. Except from the places of indentation, hepatocytes are attached together by junctional devices, so that bile isn’t able to flow wherever it wants but just in the bile canaliculi  I Damage to hepatocytes can cause INTRAHEPATIC JAUNDICE (means that it is caused by problems in the liver parenchyma) —> this leads to an excessive presence of unconjugated or conjugated bilirubin in blood. There is too much free (unconjugated) bilirubin, which is toxic, and when it is too much it starts to deposit in peripheral tissues thus giving the yellowish appearance to the person. Free bilirubin is very toxic to the brain (if it deposits it can give rise to kernicterus) too bilirubinin much blood preaepariceauna.ie finery king rocaestroyeatoosestaff.sn egintraheparicjaunaicegoes8Et FEE  eswhitishstoolsanddarkurine Faeces and urine may change colour when there is a problem in bilirubin metabolism At the periphery of the hepatic lobule there is a region called limiting place (outermost layer of hepatocytes packed together). The fluids present in the space of Disse are drained in the space of Mall, which is in connection with the lymphatic vessels in which fluids have to be drained. At the periphery of the lobule the bile canaliculi communicate with the canal of Hering (or cholangiole) that in turn drains into the bile duct of the portal space hepatocytes Endocrine function of the liver —> The cytoplasm of hepatocytes is very dense, there is a lot of RER (protein synthesis —> coagulating factors, lipoproteins and albumin. A problem in the liver might cause problems in coagulation. If there isn’t enough albumin the patient can develop an edema) and a lot of SER (the liver is also a storage site, SER functions as glycogen storage and takes part in the detoxifying action of the liver) Other kinds of lobules: Portal lobule —> it has a triangular shape and at the vertex there are centrilobular veins. It is called portal lobule because inside it there is a portal space. It includes portions of lobules whose bile canaliculi drain into the same bile ductule in the portal space Liver acinus/lobule of Rappaport —> best correlation between blood perfusion, metabolic activity (closer to centrilobular vein or to portal space) and pathologies. Hepatocytes are metabolically different depending on their location (closer to portal space or to centrilobular vein) LIVER ACINUS —> It is centred around the arterial blood supply and it is based on the metabolic gradient of oxygen and different substances from the portal space to the central veins. The liver acinus is the smallest functional unit of the liver and it is made of two wedge- shaped masses of liver parenchyma that are supplied by two neighbouring branches of the portal vein and hepatic artery and drained by two central veins and by terminal branches of the bile duct. The liver acinus can be divided in 3 zones: Zone 1 (periportal zone) —> here blood is more oxygenated and hepatocytes are metabolically more active (gluconeogenesis and cholesterol synthesis). This zone is prone to most toxic injuries Zone 2 (midlobular zone) —> intermediate Zone 3 (pericentral zone) —> receives least oxygenated blood, it is more prone to hypoxic injuries. In this zone there is glycogen storage, lipogenesis, metabolism of drugs and chemicals. It is the detoxifying zone strike intranepatic BILIARY TREE Blessing adf.ae iiafIgugiieiiIeE rightesthepatic ducts The common bile duct, also called COLEDOCUS, is made by the convergence of the common hepatic duct and the cystic duct (connection with the gallbladder). The common hepatic duct is E made by the fusion of the right and left hepatic ducts, which in turn I receive bile from the canals of Hering (or cholangiole) at the periphery of each lobule (connection between canalicula and extranopari portal space, goes through the limiting plate). The coledocus then communicates with the pancreas and duodenum (major duodenal papilla). The bile canalicula are made of hepatocytes while from canals of Hering to extrahepatic bile ducts the composition changes —> lined by special epithelial cells called cholangiocytes. Intrahepatic portion —> from inside to the hilum of the liver Extrahepatic portion —> from the hilum of the liver to outside Post-hepatic jaundice —> can be caused by an obstruction of the I extrahepatic portion of the biliary tree that leads to the release of conjugated bilirubin in the bloodstream Cholangiocytes regulate the flow, composition and pH of the primary bile generated at the canaliculi of hepatocytes through different mechanisms. The cholangiocyte’ primary cilium acts as a mechanosensor (direction of bile flow), chemosensor (sense composition or pH of bile) and osmosensor (osmolarity of bile) detecting signals in bile and subsequently modifying cell biology, bile flow and its composition. Modification of bile happens both in the liver and in the gallbladder formedbyhepatocytes Bile ductules in the portal space are only made by cholangiocytes and a thin layer of connective tissue. The bile ductules then come together to form larger and larger conduits to eventually form the right and left hepatic ducts. As bile ducts grow larger their wall becomes thicker with denser connective tissue (with elastic fibers) and with smooth muscle fibers. In bitsL extrahepatic conduits all layers of the intestinal tract are present with the exception of the muscolaris mucosae and submucosa COMMUNICATION OF THE COMMON BILE DUCT (coledocus) WITH THE DUODENUM The coledocus descends until it reaches the main pancreatic duct (Wirsung duct). In many cases these two ducts come together in the hepatopancreatic ampulla (ampulla of Vater), but in some other cases they open independently at the level of the major and minor duodenal papilla. The smooth muscle layer organisation is sophisticated: there is a complex sphincteric device that takes the name of sphincter of Oddi. At the level of the main pancreatic and hepatic duct there are also other specific sphincteric devices to regulate the flow of each substance. Some fibers surround specifically the pancreatic and coledocus sphincters, while others surround the sphincter of Oddi. The ampulla of Vater marks the place of transition between the part of GI tract originating from the foregut and that originating from the midgut (and so where the celiac trunk artery stops supplying and is replaced by the superior mesenteric artery) GALLBLADDER Bile is stored into the gallbladder. The gallbladder is a saccular organ divided into a fundus, body and neck. The neck is the place in communication with the cystic duct (communication with the common bile duct). Bile is released in the duodenum after eating, especially if many lipids have been eaten (emulsifying agent). The gallbladder presents a mucosa with folds and with a simple columnar epithelium with microvilli (to absorb water and electrolytes for bile concentration, to make it more efficient), there is no muscolaris mucosae and the submucosa is practically absent. The underlying smooth muscle is very thick. GALLSTONES The mucosa can invaginate in the muscle layer due to a weakness of the wall leading to the formation of diverticula. Bacteria can accumulate in diverticula causing cystitis (inflammation that can cause the formation of gallstones). If the gallstones move around and reach the cystic duct they can block it causing cholestatic itterus or jaundice Gallstones may cause no signs or symptoms. If a gallstone lodges in a duct and causes a blockage then the resulting signs and symptoms may include: Sudden and rapidly intensifying pain in the upper right portion of the abdomen Sudden and rapidly intensifying pain in the centre of the abdomen Back pain between shoulder blades Pain in right shoulder Nausea or vomiting These signs and symptoms are a consequence of the extreme contractions of the ducts performed to try to eject the blocking object The cystic duct and its communication with the neck of the gallbladder present inner mucosal folds that take the name of SPIRAL VALVES OF HEISTER, which are still being investigated to assess if they’re functional or not