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Download 20. Liver Pancreas
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Liver and Pancreas - Liver + + + + + + + Lobule and portal area (triad) Hepatic acinus Hepatocyte Sinusoids Canaliculi Bile duct and galebladder Functions of the liver - Pancreas + Definitions + Lobule and acinus + Pancreatic duct system + Islets + Functions of the pancreas - Objectives - Liver + + + + + + + Lobule and portal area (triad) Hepatic acinus Hepatocyte Sinusoids Canaliculi Bile duct and galebladder Functions of the liver - Pancreas + Definitions + Lobule and acinus + Pancreatic duct system + Islets + Functions of the pancreas - Objectives Liver - All nutrients and liquids absorbed in the intestines enter the liver through the hepatic portal vein - Absorbed products first go through liver capillaries called sinusoids - Nutrient-rich blood in the hepatic portal vein first brought to the liver before it enters general circulation - However, venous blood from digestive organs in hepatic portal vein poor in oxygen - Consequence: hepatic artery from aorta supplies liver cells with oxygenated blood, giving dual blood supply to the liver Lobule - Liver exhibits hexagonal units called liver (hepatic) lobules - In the center of each lobule: central vein - Plates of liver cells, hepatocytes, and sinusoids radiate from central vein to periphery, where, branches of hepatic artery, hepatic portal vein, bile duct and lymph vessels form portal areas or triads in connective tissue - In human liver, 3 to 6 portal areas can be seen per lobule - The liver is bounded by a connective tissue capsule which extends into its substance as highly branched septae. The afferent blood vessels and lymphatics follow this connective tissue highway throughout the liver. Efferent vessels traverse a route separate from connective tissue scaffolding Capsule Septa Capsule and septae are stained blue , while hepatocytes are magenta (Masson’s trichrome). The connective tissue septae invaginating from the capsule delineate hepatic lobules, the structural unit of the liver CV: central vein; *: pa: portal area Lobules of the liver (primate) - The connective tissue septae invaginating from the capsule delineate hepatic lobules, the structural unit of the liver - A lobule is a roughly hexagonal arrangement of plates of hepatocytes radiating outward from a central vein (CV) in the center - At the vertices of the lobule are regularly distributed portal triads (also known as portal areas). Examination of a triad in cross section reveal a bile duct and branches of the hepatic artery and hepatic portal vein cv: central vein; pa: portal area bd: bile duct; v: branch of hepatic portal vein; a: branch of hepatic artery Liver lobule- Portal area (triad) - Due to plane of section, one can often observe more than one of each of these structures in a given triad or absence of one or more structures - Lobules are almost impossible to miss in some species, but one should also be able to recognize them in other species. The precise boundaries of lobules are sometimes difficult to discern - Venous and arterial blood from peripheral areas first mix in the liver sinusoids as it flows towards the central vein - From here, blood enters the general circulation through the hepatic veins that leave the liver and enter the inferior vena cava Hepatic acinus - The lobule is the structural unit of the liver and rather easy to observe - In contrast, the hepatic acinus is more difficult to visualize, but represents a unit that is of more relevance to hepatic function because it is oriented around the afferent vascular system The acinus consists of an irregular shaped, roughly ellipsoidal mass of hepatocytes aligned around the hepatic arterioles and portal venules just as they anastomose into sinusoids The acinus is roughly divided into zones that correspond to distance from the arterial blood supply - those hepatocytes closest to the arterioles (zone 1) are the best oxygenated, while those farthest from the arterioles have the poorest supply of oxygen. This arrangement also means that cells in the center of the acinus (zone 1) are the first to "see" and potentially absorb blood-borne toxins absorbed into portal blood from the small intestine - - Hepatocytes - The parenchymal cells of the liver are hepatocytes. Roughly 80% of the mass of the liver is contributed by hepatocytes - These polygonal cells are joined to one another in anastomosing plates, with borders that face either the sinusoids (sinusoidal face) or adjacent hepatocytes (lateral faces) - A portion of the lateral faces is modified to form bile canaliculi. Microvilli are present abundantly on the sinusoidal face and project sparsely into bile canaliculi - Hepatocytes are the chief functional cells of the liver and perform an astonishing number of metabolic, endocrine and secretory functions. The ultrastructure appearance of hepatocytes reflects their function as metabolic superstars, with abundant rough and smooth endoplasmic reticulum, and Golgi membranes - Glycogen granules and vesicles containing very low density lipoproteins are seen - Hepatocyte nuclei are distinctly round, with one or two prominent nucleoli. A majority of cells have a single nucleus, but binucleated cells are common - Hepatocytes are exceptionally active in synthesis of proteins and lipids for export. As a consequence of these activities, examination of hepatocytes reveals bountiful quantities of both rough and smooth endoplasmic reticulum - Hepatocytes typically contain many stacks of Golgi membranes. Golgi vesicles are particularly numerous in the vicinity of the bile canaliculi, reflecting transport of bile constituents into those channels - Another important function of hepatocytes is to synthesize and secrete very low density lipoproteins - Another type of particle observed in copious quantities in liver is glycogen. Glycogen is a polymer of glucose and the density of glycogen aggregates in hepatocytes varies dramatically depending on whether the liver is examined shortly after a meal (abundant glycogen) or following a prolonged fast (minimal quantities of glycogen) Glycogen (Electron microscopy) Fasted Fed - When stained with using the periodic acid-Schiff (PAS) technique, glycogen stains bright pink in color. Left panel: mouse that fasted overnight and thus had very low levels of glycogen in liver. Right panel: from mouse that stuffed himself on mouse chow 2 hours prior to fixing the liver, and thus had high levels of hepatic glycogen. These accumulations are seen as pink areas of PAS-positive material throughout the section Glycogen granules in liver cells (PAS staining) Sinusoids - Hepatocytes make contact with blood in sinusoids: distensible vascular channels lined with highly fenestrated endothelial cells and populated with phagocytic Kupffer cells. The space between endothelium and hepatocytes is called the Space of Disse which collects lymph for delivery to lymphatic capillaries - Sinusoids are low pressure vascular channels that receive blood from terminal branches of the hepatic artery and portal vein at the periphery of lobules and deliver it into central veins. Sinusoids are lined with endothelial cells and flanked by plates of hepatocytes Endothelial cells Blood cells Hepatocyte - The space between sinusoidal endothelium and hepatocytes is called the space of Disse. Sinusoidal endothelial cells are highly fenestrated, which allows virtually unimpeded flow of plasma from sinusoidal blood into the space of Disse. This arrangement has at least two important consequences: + Hepatocytes are bathed in plasma derived in large part from venous blood returning from the small intestine. Following meals, that plasma is nutrient-rich + Plasma which collects in the space of Disse flows back toward the portal tracts, collecting in lymphatic vessels and forming a large fraction of the body's lymph en: Endothelial cells cv: Central vein H: Hepatocyte K: Kuppfer cell S: Sinusoid - Another important feature of hepatic sinusoids is that they house an important part of the phagocytic system. Sinusoids are populated by numerous Kupffer cells, a type of fixed macrophage. Identifying Kupffer cells in conventionallystained sections of liver is not easy. However, they stand out sharply when full of phagocytosed ink particles. They can be immunostained by different markers Kuppfer cells (H&E) Kuppfer cells (immunostained for CD68) Kuppfer cells in a liver lobule (india ink preparation) Canaliculi - Hepatocytes secrete bile into tiny channels called bile canaliculi located between hepatocytes - Bile originates as secretions from the basal surface of hepatocytes, which collect in channels called canaliculi. Canaliculi converge at the periphery of lobules into the portal area as bile ducts. The bile ducts drain into larger hepatic ducts that carry bile out of the liver - By contrast, blood flows in the sinusoids toward the central vein. As a result, bile and blood do not mix Bile canaliculi in liver lobule (osmic acid staining) Reticular fibers - Supporting connective tissue: fine reticular fibers made of collagen type III - Reticular fibers line sinusoids, support endothelial cells and form dense network of reticular fibers in wall of central vein - Merge with collagen fibers in interlobular septum where they surround portal vein and bile duct Reticular fibers in liver lobule (reticulin method) Bile duct and gallbladder - Bile flows out of the liver through hepatic ducts, which join and extend as the common bile duct (also known as the bile duct) to traverse the wall of the duodenum and deliver bile into its lumen. In species with a gallbladder, the hepatic ducts join with the cystic duct, which conveys bile to and from the gall bladder - The gallbladder is a distensible sac and, when not distended, its mucosa is thrown into many folds. The lumen of the gallbladder is lined with a high columnar epithelium. The connective tissue wall contains abundant elastic fibers and layers of smooth muscle Wall of gallbladder Exocrine functions of the liver - Liver synthesizes and releases bile into bile canaliculi. Bile flow regulated by hormones such as cholecystokinin (CCK). Stimulated when dietary fats in the chyme enter the duodenum. CCK causes contraction of smooth muscles in gallbladder, allowing bile to enter duodenum - Bile salts emulsify fats in the duodenum allowing more efficient digestion of fats by the fat-digesting pancreatic lipases - Hepatocytes excrete bilirubin, a toxic chemical formed in the body after degradation of worn-out erythrocytes by liver macrophages, Kuppfer cells. Bilirubin is taken up by hepatocytes from the blood and excreted into bile - Hepatocytes have role in 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 Endocrine functions of the liver - Hepatocytes are also endocrine cells - They synthesize numerous plasma proteins, including albumin and the blood-clotting factors prothrombin and fibrinogen - Liver stores fats, vitamins, carbohydrates as glycogen - When the cells need glucose, glycogen stored in the liver is converted into glucose and released in the bloodstream - Hepatocytes also detoxify blood of drugs and harmful substances - Kupffer cells are specialized liver phagocytes derived from blood monocytes. They filter and phagocytose particulate material, cellular debris and damaged erythrocytes - Liver performs vital functions in life: in the fetus, the liver is the site of hematopoiesis Section of liver taken from a 100 day sheep fetus. The clusters of cells in sinusoids are various types of basophilic immature blood cells. In the fetus, the liver is a major site of hematopoiesis, or formation of blood cells. Hepatic hematopoiesis is not normally seen after birth, although it can occur under certain pathologic conditions - Liver + + + + + + + Lobule and portal area (triad) Hepatic acinus Hepatocyte Sinusoids Canaliculi Bile duct and galebladder Functions of the liver - Pancreas + Definitions + Lobule and acinus + Pancreatic duct system + Islets + Functions of the pancreas - Objectives Pancreas - Most of the pancreas is an exocrine gland - Exocrine secretory units, or acini, contain pyramidal-shaped acinar or zymogenic cells. Serous acini: well stained acini on HE - Each cell of acini has its apex filled with secretory granules - Granules contain the precursors of several pancreatic digestive enzymes secreted into the excretory ducts in an inactive form - Secretory acini subdivided into lobules and bound together by loose connective tissue - Excretory ducts start from within the center of individual acini (pale-staining centro-acinar cells), and continue into short intercalated ducts - Intercalated ducts merge in intralobular ducts, forming then interlobular ducts that empty into main pancreatic duct - Endocrine units of the pancreas are scattered among the exocrine acini as isolated, pale staining vascularized units called pancreatic islets (of Langerhans) - Four cell types can be identified by immunocytochemistry in each islet: alpha, beta, delta and pancreatic polypeptide (PP) cells - Alpha cells constitue 20% of the islets and located primilarly at the periphery of islets. Produce glucagon - Beta cells are more numerous (70% of the islets) and located in center of islets. Produce insulin - Remaining cells are few in number and located in various places. Delta cells produce somatostatin. Pancreatic polypeptide cells (PP) produce pancreatic polypeptide, which inhibits production of pancreatic enzymes and alkaline secretions The pancreas is surrounded by a very thin connective tissue capsule that invaginates into the gland to form septae, which serve as scaffolding for large blood vessels. Further, these septae divide the pancreas into distinctive lobules Connective tissue Islets Lobule Islet Exocrine and endocrine pancreas - The exocrine pancreas is classified as a compound tubuloacinous gland. The cells that synthesize and secrete digestive enzymes are arranged in grape-like clusters called acini, very similar to what is seen in salivary glands Centro-acinar cell - Acinus Centroacinar cells: excretory duct of each individual acinus. Continuous with epithelium of intercalated ducts Pancreatic duct system • Intralobular duct Intercalated duct (low cuboidal, almost squamous epithelium) (intercalated duct emptying in cuboidal intralobular duct) Small interlobular duct Large interlobular duct (columnar epithelium) A: Artery; V: vein: D: intralobular duct Islets The endocrine cells within islets are arranged as irregular cords around abundant capillaries, which receive the secreted hormones for delivery into the systemic circulation 1: acini; 2: islets; 3: interlobular connective tissue; 4: vessel 1: acini; 2: islets; 3: intralobular duct; 4: interlobular connective tissue Pancreas: endocrine (pancreatic islet) and exocrine regions Pancreatic islet Pancreaticp islet (Gomori’s chrome alum hematoxylin and phloxine Functional correlations: exocrine pancreas - Pancreas produces numerous digestive enzymes that exit the gland through major excretory duct - Both hormones and vagal stimulation regulate pancreatic exocrine secretions - Two intestinal hormones, secretin and cholecystokinin (CCK) secreted by cells (APUD) cells in the duodenum mucosa into the bloodstream regulate pancreatic secretions - Acidic chyme in duodenum induces release of secretin. Secretin triggers exocrine pancreas to produce watery fluid rich in sodium bicarbonate ions (role: to neutralize acidic chyme, stop action of pepsin in stomach, create a neutral pH in duodenum) - Fats and proteins in duodenum induce release of CCK into bloodstream. CCK stimulates acinar cells to secrete large amounts of pancreatic amylase for carbohydrate digestion, pancreatic lipase for lipid digestion, deoxyribonuclease and ribonuclease for digestion of nucleic acids, proteolytic enzymes trypsinogen, chymotrypsinogen - Pancreatic enzymes are first produced in acinar cells in an inactive form then activated in the duodenum by the hormone enterokinase secreted by intestinal mucosa. This hormone converts trypsinogen into trypsin which then converts all other pancreatic enzymes into active digestive enzymes Functional correlations: endocrine pancreas + Alpha cells produce the hormone glucagon. Released in response to low levels of glucose in the blood. Glucagon elevates blood glucose levels by accelerating the conversion of glycogen, amino acids and fatty acids in the hepatocytes into glucose + Beta cells produce insulin. Release stimulated by elevated blood glucose levels after a meal. Insulin lowers blood glucose levels by accelerating membrane transport of glucose into hepatocytes, muscle cells and adipose cells. Accelerates the conversion of glucose into glycogen in hepatocytes. Effects of insulin on blood glucose levels are opposite to the ones of glucagon + Delta cells secrete the hormone somatostatin. 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 pancreatic polypeptide which inhibits production of pancreatic enzymes and alkaline secretions - Liver + + + + + + + Lobule and portal area (triad) Hepatic acinus Hepatocyte Sinusoids Canaliculi Bile duct and galebladder Functions of the liver - Pancreas + Definitions + Lobule and acinus + Pancreatic duct system + Islets + Functions of the pancreas - Objectives - To know the architecture of the liver (lobule, triad, hepatic acinus, hepatocyte, sinusoids) - To know functional correlations of the liver - To know the architecture of the pancreas exocrine (lobules, acini) and endocrine (islets) - To know pancreatic ducts - To know functional correlations of the pancreas
