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LIVER, GALLBLADDER, AND PANCREAS by Dr. Suhair Majeed The liver, gallbladder, and pancreas are accessory organs of the digestive tract that deliver their secretory products to the small intestine by excretory ducts. The common bile duct from the liver and the main pancreatic duct from the pancreas join in the duodenal loop to form a single duct common to both organs. CONT. This duct then penetrates the duodenal wall and enters the lumen of the small intestine. The gallbladder joins the common bile duct via the cystic duct. Thus, bile from the gallbladder and digestive enzymes from the pancreas enter the duodenum via a common duct. 1- LIVER The liver is invested by a delicate connective tissue capsule . The capsule contains numerous elastic fibers and is covered by a mesothelium . The liver is composed of epithelial cells, the hepatocytes, arranged in branching and anastomosing plates separated by blood sinusoids. Both form a radial pattern about a central vein. CONT. The spokelike arrangement of hepatic plates about a central vein constitutes the basis of the classic hepatic lobule, which appears hexagonal in cross section, with a central vein at the center and portal areas at the corners. CONT. A portal area contains : - a branch of the portal vein, -a branch of the hepatic artery, -a bile duct, - a lymphatic channel. All are enclosed in a common investment of connective tissue . HEPATIC SINUSOIDS Hepatic sinusoids are larger and more irregular in shape than ordinary capillaries. The sinusoidal lining consists of a simple layer of squamous epithelium supported by connective tissue. Three types of cells are associated with the sinusoidal lining: endothelial cells, stellate cells (Kupffer cells or hepatic macrophages), and fatstoring cells (lipocytes). CONT. The sinusoidal lining is separated from the liver cells by a narrow perisinusoidal space (of Disse) . the perisinusoidal space has considerable significance in the exchange of materials between the liver and plasma. HEPATOCYTES The parenchyma of the liver consists of large polyhedral hepatocytes arranged in plates that radiate from the region of the central vein. The surfaces of an individual hepatocyte either contact an adjacent liver cell or border on a perisinusoidal space. This latter surface bears numerous well developed microvilli. The nuclei of hepatocytes are large and round and occupy the center of the cell. CONT. Inclusions such as glycogen and lipid are common in the cytoplasm. Hepatocytes secrete bile into tiny channels called bile canaliculi located between individual hepatocytes. BILE DUCTS Bile canaliculi unite with bile ducts in the portal canals by small, interconnecting channels called bile ductules. They are small and have thin walls, lined by a low cuboidal epithelium. The terminal ductules empty into interlobular bile ducts of the portal areas. Interlobular ducts unite to form the extrahepatic ducts. CONT. Two large extrahepatic ducts, the left and right hepatic ducts, exit the lobes of the liver and unite to form the major excretory duct of the liver, the common hepatic duct. It is joined by the cystic duct from the gallbladder to form the common bile duct, which empties into the duodenum. The major extrahepatic ducts are lined by a tall columnar, mucus-secreting epithelium. FUNCTIONAL CORRELATIONS: LIVER : The liver performs hundreds of functions. Hepatocytes perform more functions than any other cell in the body, and perform both endocrine and exocrine roles. - Exocrine Functions -Endocrine Functions 1- EXOCRINE FUNCTIONS: One major exocrine function of hepatocytes is to synthesize and release 500 to 1,200 mL of bile into the bile canaliculi per day. From these canaliculi, bile flows through a system of ductules and ducts to enter the gallbladder, where it is stored and concentrated by removal of water. Release of bile from the liver and gall bladder is primarily regulated by hormones. CONT. Bile flow is increased when a hormone such as cholecystokinin is released by the mucosal enteroendocrine cells, stimulated when dietary fats in the chyme enter the duodenum. This hormone causes contraction of smooth muscles in the gallbladder wall and relaxation of the sphincter, allowing the bile to enter the duodenum. CONT. Bile salts in the bile emulsify fats in the duodenum. This process allows for more efficient digestion of fats by the fat-digesting pancreatic lipases produced by the pancreas. The digested fats are subsequently absorbed by cells in the small intestine and enter the blindending lymphatic lacteal channels located in individual villi. From the lacteals, fats are carried into larger lymphatic ducts that drain into the major veins. CONT. Hepatocytes also excrete bilirubin, a toxic chemical formed in the body after degradation of worn-out erythrocytes by liver macrophages, (Kupffer cells ). Bilirubin is taken up by hepatocytes from the blood and excreted into bile. CONT. Hepatocytes also have an important role in the immune system. Antibodies produced by plasma cells in the intestinal lamina propria are taken from blood by hepatocytes and transported into bile canaliculi and bile. From here, antibodies enter the intestinal lumen, where they control the intestinal bacterial flora. 2- ENDOCRINE FUNCTIONS : Hepatocytes are also endocrine cells. The arrangement of hepatocytes in a liver lobule allows them to take up, metabolize, accumulate, and store numerous products from the blood. Hepatocytes then release many of the metabolized or secreted products back into the bloodstream, as the blood flows through the sinusoids and comes in direct contact with individual hepatocytes. CONT. The endocrine functions of the liver hepatocytes involve synthesis of numerous plasma proteins, including albumin and the blood-clotting factors prothrombin and fibrinogen. The liver also stores fats, various vitamins, and carbohydrates as glycogen. When the cells of the body need glucose, glycogen that is stored in the liver is converted back into glucose and released into the bloodstream. CONT. Hepatocytes also detoxify the blood of drugs and harmful substances as it percolates through the sinusoids. Kupffer cells in the sinusoids are specialized liver phagocytes derived from blood monocytes. These large, branching cells filter and phagocytose particulate material, cellular debris, and worn-out or damaged erythrocytes that flow through the sinusoids. The liver also performs vital functions early in life. In the fetus, the liver is the site of hemopoiesis. 2- GALLBLADDER The gallbladder is a saclike structure on the inferior surface of the liver, It is joined to the common hepatic duct by the cystic duct, whose mucous membrane forms prominent spiraling folds that contain bundles of smooth muscle. These folds make up the spiral valve that prevents the collapse or distention of the cystic duct during sudden changes in pressure. CONT. The wall of the gallbladder consists of a mucous membrane, a muscularis, and a serosa or adventitia. The mucous membrane of the gallbladder wall consists of a simple columnar epithelium and an underlying lamina propria. The oval nuclei are located basally in the cells and the luminal surfaces show numerous short microvilli . CONT. The mucosa of the nondistended gallbladder forms large irregular folds called rugae, which flatten out as the gallbladder fills with bile. There is no submucosa in the gallbladder. The muscularis consists of bundles of smooth muscle that spiral around the lumen of the gallbladder. The smooth muscle cells contain numerous receptors for cholecystokinin. . CONT. Gaps between the smooth muscle bundles are filled with reticular, and elastic fibers. Because of the musculoelastic wall and the rugae, gallbladder has the capacity for distention CONT. The surrounding fibroconnective tissue of the adventitia is dense and is continuous with the connective tissue of the liver capsule. The gallbladder stores and concentrates bile, which is elaborated continuously by the liver. On stimulation by cholecystokinin, gallbladder wall contracts and the sphincters of the common bile duct and ampulla relax, allowing bile to be released into the duodenum. FUNCTIONAL CORRELATIONS: THE GALLBLADDER : The primary functions of the gallbladder are to collect, store, concentrate, and expel bile when it is needed for emulsification of fat. Bile is continually produced by liver hepatocytes and transported via the excretory ducts to the gallbladder for storage. Here, sodium is actively transported through the simple columnar epithelium of the gallbladder into the extracellular connective tissue, creating a strong osmotic pressure. CONT. Release of bile into the duodenum is under hormonal control. In response to the entrance of dietary fats into the proximal duodenum, the hormone cholecystokinin (CCK) is released into the bloodstream by enteroendocrine cells located in the intestinal mucosa. CCK is carried in the bloodstream to the gallbladder, where it causes strong rhythmic contractions of the smooth muscle in its wall. CONT. Water and chloride ions passively follow, producing concentrated bile. At the same time, the smooth sphincter muscles around the neck of gallbladder relax. The combination of these two actions forces the bile into the duodenum via the common bile duct. 3- PANCREAS The pancreas is a soft, elongated organ located posterior to the stomach. The head of the pancreas lies in the duodenal loop and the tail extends across the abdominal cavity to the spleen. It lacks a definite capsule but is covered by a thin layer of connective tissue that extends delicate septa into the substance of the pancreas and subdivides it into numerous small lobules. Blood vessels, nerves, lymphatics, and excretory ducts course through the septa. . CONT. The pancreas consists of an exocrine portion, which elaborates numerous digestive enzymes and bicarbonate, and an endocrine portion, whose secretions are important in carbohydrate metabolism. Unlike the liver, the exocrine and endocrine functions of the pancreas are performed by different groups of cells. 1- EXOCRINE PANCREAS : Most of the pancreas is an exocrine gland. The exocrine secretory units or acini , each acinus consists of a single pyramidal cells whose narrow apices border on a lumen, while their broad bases lie on a thin basement membrane. whose apices are filled with secretory granules. These granules contain the precursors of several pancreatic digestive enzymes that are secreted into the excretory ducts in an inactive form. CONT. The secretory acini are subdivided into lobules and bound together by loose connective tissue. The excretory ducts in the exocrine pancreas start from within the center of individual acini as pale-staining centroacinar cells, which continue into the short intercalated ducts. DUCT SYSTEM An extensive duct system permeates the pancreas. At their beginnings, the ducts extend into the acini and are interposed between the acinar cells and the lumen. Ductal cells within the pancreatic acini are called centroacinar cells and appear as flattened, cells. The wall of the duct system formed by centroacinar cells is continuous outside the secretory unit with intercalated and intralobular ducts CONT. These ducts are tributaries of the interlobular ducts found in the loose connective tissue between lobules; the transition between ducts is gradual. The epithelial lining is simple squamous in the intercalated ducts, to cuboidal in the intralobular ducts, and columnar in the interlobular ducts. The interlobular ducts drain into the primary and accessory pancreatic ducts. CONT. The primary duct runs the length of the pancreas, increasing in size near the duodenum, where it runs parallel to the common bile duct, with which it often shares a common opening at the greater duodenal papilla . The intercalated ducts merge to form intralobular ducts in the connective tissue, which, in turn, join to form larger interlobular ducts that empty into the main pancreatic duct. 2- ENDOCRINE PANCREAS : The endocrine units of the pancreas are scattered among the exocrine acini as isolated, pale-staining vascularized units called pancreatic islets (of Langerhans). Each islet is surrounded by fine fibers of reticular connective tissue, four cell types can be identified in each pancreatic islet: alpha, beta, delta, and pancreatic polypeptide (PP) cells. CONT. Alpha cells constitute about 20% of the islets and are located primarily around the islet periphery. beta cells are most numerous, constituting about 70% of the islet cells, and are primarily concentrated in the center of the islet. The remaining cell types are few in number and are located in various places throughout the islets. FUNCTIONAL CORRELATIONS: EXOCRINE PANCREAS The exocrine and endocrine functions of the pancreas are performed by separate exocrine and endocrine cells. The pancreas produces numerous digestive enzymes that exit the gland through a major excretory duct, whereas the different hormones are transported via blood vessels. Both hormones and vagal stimulation regulate pancreatic exocrine secretions CONT. Two intestinal hormones, secretin and cholecystokinin (CCK), secreted by the enteroendocrine cells in the duodenal mucosa into the bloodstream, regulate pancreatic secretions. The release of the hormone secretin stimulates exocrine pancreatic cells to produce large amounts of a watery fluid rich in sodium bicarbonate ions. CONT. This fluid, which has little or no enzymatic activity, is primarily produced by centroacinar cells in the acini and by cells that line the smaller intercalated ducts. The main function of this bicarbonate fluid is to neutralize the acidic chyme, stop the action of pepsin from the stomach, and create a neutral pH in the duodenum for the action of the digestive pancreatic enzymes. CONT. In response to the presence of fats and proteins in the small intestine, CCK is released into the bloodstream. CCK stimulates the acinar cells in the pancreas to secrete large amounts of digestive enzymes: pancreatic amylase for carbohydrate digestion, pancreatic lipase for lipid digestion, deoxyribonuclease and ribonuclease for digestion of nucleic acids, and the proteolytic enzymes trypsinogen, chymotrypsinogen, and procarboxypeptidase. CONT. Pancreatic enzymes are first produced in the acinar cells in an inactive form and are only activated in the duodenum by the hormone enterokinase secreted by the intestinal mucosa. This hormone converts trypsinogen to trypsin, which then converts all other pancreatic enzymes into active digestive enzymes. FUNCTIONAL CORRELATIONS: ENDOCRINE PANCREAS Pancreatic islets secrete two major hormones that regulate blood glucose levels and glucose metabolism. Alpha cells in the pancreatic islets produce the hormone glucagon, which is released in response to low levels of glucose in the blood. CONT. Glucagon elevates blood glucose levels by accelerating the conversion of glycogen, amino acids, and fatty acids in the liver cells into glucose. CONT. Beta cells in pancreatic islets produce the hormone insulin, whose release is stimulated by elevated blood glucose levels after a meal. Insulin lowers blood glucose levels by accelerating membrane transport of glucose into liver cells,muscle cells, and adipose cells. Insulin also accelerates the conversion of glucose into glycogen in liver cells. The effects of insulin on blood glucose levels are opposite to that of glucagon. CONT. Delta cells secrete the hormone somatostatin. This hormone decreases and inhibits secretory activities of both alpha (glucagon-secreting) and beta (insulin-secreting) cells through local action within the pancreatic islets. Pancreatic polypeptide cells (PP) produce the hormone pancreatic polypeptide, which inhibits production of pancreatic enzymes and alkaline secretions. THANK YOU