DIGESTIVE GLANDS II Mr. Babatunde D.E Liver ❖ Is the second largest organ in the body. ❖ Is composed of a single type of parenchymal cell, the hepatocyte. Hepatocyte ❖ Possess a myriad of both endocrine and exocrine functions. Figure 16—18. Ultrastructure of a hepatocyte. RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum. x10,000. Glisson’s Capsule ❖ Is composed of thin connective tissue that subdivides the liver into lobes and lobules. Blood Supply ❖ Of the liver is derived from two sources: abdominal aorta, via the hepatic artery; portal vein, which brings nutrient-laden blood from the alimentary tract and the spleen. Porta Hepatis ❖ Is the region where the hepatic artery and the portal vein enter and the hepatic ducts leave the liver. Drainage ❖ Of blood is via the hepatic vein. ❖ Hepatic vein is formed by the union of numerous sublobular veins. ❖ Sublobular veins collect blood from the central vein of each classical liver lobule. Bile ❖ Leaves the liver via the hepatic ducts. ❖ Is delivered to the gallbladder. Liver Lobules ❖ There are three types of liver lobules: classical (hexagonal in histologic section); portal lobule (triangular in histological section); liver acinus of Rappaport (liver acinus; diamond shaped in histologic section). CENTRAL VEIN PORTAL CANAL Classical Lobule ❖ Is based on the pig’s liver, where connective tissue elements clearly delineate it. ❖ Portal area (portal canal; triad) is present at each corner of the lobule. ❖ Portal area contains branches of the portal vein, hepatic artery, bile duct, and lymph vessel. Figure 16—12. Three- dimensional aspect of the normal liver. In the upper center is the central vein; in the lower center, the portal vein. Note the bile canaliculus, liver plates, Hering’s canal, Kupffer cells, sinusoid, fat-storing cell, and sinusoid endothelial cells. (Courtesy of M Muto.) Figure 16—11. Schematic drawing of the structure of the liver. The liver lobule in the center is surrounded by the portal space (dilated here for clarity). Arteries, veins, and bile ducts occupy the portal spaces. Nerves, connective tissue, and lymphatic vessels are also present but are (again, for clarity) not shown in this illustration. In the lobule, note the radial disposition of the plates formed by hepatocytes; the sinusoidal capillaries separate the plates. The bile canaliculi can be seen between the hepatocytes. The sublobular (intercalated) veins drain blood from the lobules. (Redrawn and reproduced, with permission, from Bourne G: An Introduction to Functional Histology. Churchill, 1953.) Figure 16—13. Photomicrograph of the liver. A: A central (centrolobular) vein. Note the liver plates that anastomose freely, limiting the space occupied by the sinusoids. PT stain. Medium magnification. B: A portal space with its characteristic small artery, vein, lymph vessel, and bile duct surrounded by connective tissue. PT stain. Medium magnification. C: Collagen III reticular fibers in the lobule, forming a scaffold for the hepatic tissue. Silver impregnation. Medium magnification. Plates of Hepatocytes ❖ Compose the bulk of the lobule. ❖ Are arranged in a radial fashion, radiating from the region of a central vein. ❖ Blood flows from the periphery of the lobule toward the central vein. Figure 16—13. Photomicrograph of the liver. A: A central (centrolobular) vein. Note the liver plates that anastomose freely, limiting the space occupied by the sinusoids. PT stain. Medium magnification. Bile Canaliculi ❖ Are slender intercellular spaces between neighboring hepatocytes. ❖ Convey bile to canals of Herring. ❖ Canals of Herring deliver bile ducts in the portal area at the periphery of the classical lobule. ❖ Flow of bile and blood occurs in opposite directions. Figure 16—18. Ultrastructure of a hepatocyte. RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum. x10,000. Figure 16—19. Electron micrograph of a bile canaliculus in rat liver. Note the microvilli in its lumen and the junctional complexes (arrows) that seal off this space from the remaining extracellular space. x54,000. (Courtesy of SL Wissig.) Figure 16—20. The confluence of bile canaliculi and bile ductules, which are lined by cuboidal epithelium. The ductules merge with bile ducts in the portal spaces. Sinusoids ❖ Are endothelial-lined spaces between neighboring plates of hepatocytes. ❖ Receive blood from the vessels in the portal area and deliver it to the central vein. Figure 16—12. Three- dimensional aspect of the normal liver. In the upper center is the central vein; in the lower center, the portal vein. Note the bile canaliculus, liver plates, Hering’s canal, Kupffer cells, sinusoid, fat-storing cell, and sinusoid endothelial cells. (Courtesy of M Muto.) Endothelial Cells ❖ Lining sinusoids have large fenestrations and also display discontinuous between neighboring cells. Figure 16—14. Scanning electron micrograph of the endothelial lining of a sinusoidal capillary in rat liver, showing the grouped fenestrations in its wall. At the borders, edges of cut hepatocytes are present, with their villi protruding into spaces of Disse. x6500. (Courtesy of E Wisse.) Kupffer Cells ❖ Are also present within the endothelial lining. ❖ Are phagocytic cells that are derived from monocytes. Figure 16—15. Liver section showing sinusoid capillaries with their endothelial cells close to the hepatocytes. The thin slit between the hepatocytes and the endothelium is the space of Disse. Kupffer cells can be seen inside the sinusoid. PT stain. High magnification. Space of Disse ❖ Is visualized by electron microscopy as a subendothelial space between the liver cells and the lining cells of the sinusoids. contains ❖ Stellate-shaped fat storing cells (which preferentially store vitamin A). ❖ Reticular fibers (which maintain the architecture of the sinusoids). ❖ Nonmyelinated nerve fibers. ❖ Short, blunt microvilli of hepatocytes. Functions ❖ In the exchange of material between the bloodstream and the hepatocytes (which do not contact the bloodstream) Basal Lamina ❖ Is not present in this space Figure 16—18. Ultrastructure of a hepatocyte. RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum. x10,000. Portal Lobule ❖ Is based on the liver’s exocrine function. In many exocrine glands, the duct is in the center of a lobule. ❖ Is a triangular region whose three apices are neighboring central veins, selected in such a fashion that the triangle thus constructed will have a portal area in its center. CENTRAL VEIN PORTAL CANAL The portal lobule has a portal canal in a central position and central veins at the edges of the cross-sectioned lobule Liver Acinus (of Rappaport) ❖ Is another interpretation of lobulation in the liver. ❖ Is based on blood flow. ❖ Is a diamond-shaped structure, envisioned as the amalgamation of two equilateral triangular areas derived from two adjoining classical lobules, where the bases of the two triangles parallel each other. ❖ Apices include the central vein of the first classical lobule, the two adjoining portal area that are shared by the two neighboring classical lobules, and the central vein of the second classical lobule. CENTRAL VEIN PORTAL CANAL The liver acinus has distributing vessels in the center and central veins at each pole of the cross-sectioned structure CENTRAL VEIN Zonation ❖ Blood enters the sinusoids from vessels located in the interface between the two neighboring classical lobules (the bases of the equilateral triangles) PORTAL CANAL Hepatocytes ❖ In the vicinity of this interface are the first to be “exposed” to the entering blood ❖ Nearer the central vein are the last to be “exposed” Three Zones ❖ Exist within each liver acinus of Rapport first in the immediate vicinity of the blood supply, third in the area of the central vein, and second in between these two areas Hepatocytes ❖ Are large, polyhedral cells that stain light pink with hematoxylin and eosin. ❖ Usually possess one (or two), centrally placed (occasionally enlarged polyploid) round nucleus. ❖ Frequently more than two nuclei may be present in a single cell. ❖ Bile canaliculi are evident between neighboring hepatocytes. Electron Micrographs of Liver Cells ❖ Demonstrate that these cells are rich in rough and smooth endoplasmic reticular and mitochondria and possess several Golgi regions. ❖ Demonstrate that both lysosomes and peroxisomes are well represented. ❖ Lipid droplets and glycogen are also abundant. Figure 16—23. Protein synthesis and carbohydrate storage in the liver. Carbohydrate is stored as glycogen, usually associated with the smooth endoplasmic reticulum (SER). When glucose is needed, glycogen is degraded. ❖ Proteins produced by hepatocytes are synthesized in the rough endoplasmic reticulum (RER), which explains why hepatocyte lesions or starvation lead to a decrease in the amounts of albumin, fibrinogen, and prothrombin in a patient’s blood. The impairment of protein synthesis leads to several complications, since most of these proteins are carriers, important for the blood’s osmotic pressure and for coagulation. Figure 16—24. Mechanism of secretion of bile acids. About 90% of bile acids are derived from the intestinal epithelium and transported to the liver. The remaining 10% are synthesized in the liver by the conjugation of cholic acid with the amino acids glycine and taurine. This process occurs in the smooth endoplasmic reticulum (SER). Figure 16—25. The secretion of bilirubin. The water- insoluble form of bilirubin is derived Bilirubin from the metabolism glucuronide of hemoglobin in macrophages.