Histology Gastro 3rd PDF

Organs Associated CHAPTER SALIVARY GLANDS 16 329 with the Digestive...

Organs Associated CHAPTER SALIVARY GLANDS 16 329 with the Digestive Tract BILIARY TRACT & GALLBLADDER 345 PANCREAS 332 SUMMARY OF KEY POINTS 346 LIVER 335 ASSESS YOUR KNOWLEDGE 348 Hepatocytes & Hepatic Lobules 338 Structure & Function in the Liver 343 he organs associated with the digestive tract include the A connective tissue capsule surrounds each major sali major salivary glands, the pancreas, the liver, and the vary gland. Theparenchymaof each consists of secretory units gallbladder. Products of these organs facilitate transport on a branching duct system arranged in lobules, separated by and digestion of food within the gastrointestinal The main tract. septa of connective The secretion of each gland is either tissue. functions of the salivary glands are to moisten and lubricate serous, seromucous, or mucous, depending on its content of ingested food and the oral mucosa, to initiate the digestion of the glycoprotein mucin. Saliva from the parotids is serous carbohydrates and lipids with amylase and lipase, and to secrete and watery. The submandibular and sublingual glands pro innate immune components such as lysozyme and lactoferrin. duce a seromucoussecretion, while that of the minor glands The pancreas secretes digestive enzymes that act in the is mostly mucous. Saliva is modified by the cells of the duct small intestine andhormones important for the metabolisnm of system draining the secretory units, with much Na" and ClI the absorbed nutrients.Bile, whose componentsare necessary reabsorbed while certain growth factors and digestiveenzymes for digestion and absorption of fats, is made in the liver but are added. stored and concentrated in the gallbladder.The liver also plays Three epithelial cell types comprise the salivary secretory a major role in carbohydrate and protein metabolism, inacti units: vates many toxic substances and drugs, and synthesizes most plasma proteins and factors necessary for blood coagulation. Serous cells are polarized protein-secreting cells, usu ally pyramidal in shape, with round nuclei, well-stained RER, and apical secretory granules (Figures16-2 > SALIVARY GLANDS through 16-4). Joined apicallyby tight and adherent junctions, serous cells form a somewhat spherical unit Exocrine glands in the mouth produce saliva, which has diges called an acinus(L. grape), with a very small central tive, lubricating, and protective functions. With a normal pH lumen (Figure 16-2). Serous acinar cells secrete enzymes of 6.5-6.9, saliva also has an important buffering function and other proteins. and in some species is also important for evaporative cool Mucous cells are somewhat more columnarin shape, ing. There are three pairs of large salivaryglands: the parotid, with more compressed basal nuclei (Figures 16-2 and submandibular, and sublingual glands (Figure 16-1), in 16-4). Mucous cells contain apical granules with hydro addition to the numerous minor or intrinsic salivary glands philic mucins that provide lubricating properties in located throughout most of the oral mucosa which secrete saliva but cause poor cell staining in routine preparations about 10% of the total saliva volume. (Figure l16-5). Mucous cells are most often organized as cylindrical tubules rather than acini. Mixed salivary >> MEDICAL APPLICATION glands have tubuloacinar secretory units with both serous and mucous secretion. Inadequate saliva production,leading to dry mouth or xerosto Myoepithelial cells, described in Chapter 4, are found mia, can be caused by various factors affecting the major salivary inside the basal lamina surrounding acini, tubules, and glands, such as mumps viral infection, radiation of the glands, or the normal side effect of drugs such as antihistamines. the proximal ends of theduct system (Figures 16-2 and 16-4). These small, flattened cells extend several FIGURE 16-1 Major salivary glands. Parotid salivary gland Parotid duct There are three bilateral pairs of major sali vary glands, the parotid, submandibular, Masseter muscle and sublingualglands,which together produce about 90% of saliva. Their loca tions, relative sizes, and excretory ducts are shown here. These glands plus microscopic Mucosa (cut) minor salivary glands located throughout Sublingual ducts the oral mucosa produce 0.75-1.50 L of Submandibularduct saliva daily. -Sublingual salivary gland muscle (cut) -Mylohyoid -Submandibular salivary gland FIGURE 16-2 Epithelial components of a submandibulargland lobule. Myoepithelial cells Intercellular Myoepithelial cells secretory canaliculi Serous acinus "Serous demilune" Intercalated duct of a mixed acinus Intercalated ducts Striated ducts Basal laminae Mucous tubule The secretory portions are composed of pyramidal serous (violet) also occur, combining short mucous tubules with distal clusters and mucous (tan) cells. Serous acini consist of typical protein of serous "serousdemilune."The cells called short intercalated secreting cells with rounded nuclei, basal accumulation of RER, ducts are lined with low cuboidal epithelium. The striated ducts and apical ends filled with secretory granules. The cells of mucous consist ofcolumnar cells with characteristics of ion-transporting tubules have flattened, basal nuclei with condensed chromatin. cells: basal membrane invaginations with mitochondrial accumu In the submandibular gland mixed tubuloacinar secretory units lations. Myoepithelial cells are shown around the serous acini.  contractile processes around the associatedsecretory striated duct (Figure 16-2). The more columnar striated unit or duct and their activity is important for moving duct cells have many infoldings of their basolateral mem secretory products into and through the ducts. brane, all aligned with numerous mitochondria that, by light microscopy, appear as faint basal striations radiating toward the nuclei (Figure 16-6). Striated ducts reabsorb Na ions >> MEDICAL APPLICATION from the initial secretion and their folded cell membranes present a large surface area with ion transporters, facilitat Excessive saliva production,or sialorrhea,is associatedwith ing rapid ion transcytosis and making the secretion slighty theautonomic activity of nausea, inflammation within the hypotonic. oral cavity, and rabies viral infection. Plasma cells in the connective tissue surrounding the small intralobularducts release lgA,which forms a complex with the secretory component synthesized by the epithelial In the intralobular duct system, secretory acini and cells of the serous acini and intralobularducts. Transferred tubules empty into short intercalated ducts, lined by cuboj into the saliva, the gA complex released into the saliva pro dal epithelial cells, and several of these ducts join to form a vides defense against specific pathogens in the oral cavity.  stimulation, usually through the smell or taste of food, FIGURE 16-4 Ultrastructure of serousand elicited mucous cells. provokes a copious watery secretion with relatively little organic content. Sympathetic stimulation inhibits such secre tion and produces the potential for dry mouth often associated with anxiety. Features specific to each group of major salivary glands include the following: Parotid glands,located in each cheek near the ear, are branched acinar glands with exclusively serous acini (Figure 16-3). Serous cells of parotid glands secrete abundanta-amylase that initiates hydrolysis of carbo hydrates and proline-rich proteins with antimicrobial and other protective properties. Submandibular glands,which produce two-thirds of M all saliva, are branched tubuloacinar glands, having pri marily serous acini, many mixed tubuloacinar but with secretory units (Figures 16-4 and 16-5a). Within the mixed units groupedserous cells occur distally on short mucous tubules and often assume a crescent-shaped arrangementcalled a serousdemilune (Figure 16-5a). In addition to a-amylase and proline-rich proteins, serous cells of the submandibular gland secrete lyso zyme for hydrolysis of bacterial walls. My Sublingualglands,the smallest of the major glands, are also considered branched tubuloacinar glands, but here secretory tubules of mucous cells predominate and the A micrograph of a mixed acinus from a submandibular gland main product ofthe gland is mucus (Figure 1l6-5b).The shows both serous and mucous cells surrounding the small lumen (L). Mucous cells (M) have large, hydrophilic granules like few serous cells present add amylase and lysozyme to the those of goblet cells, while serous cells (S) have small, dense secretion. granules. Small myoepithelial (My) extend cells contractile processes around each acinus. (X2500) As described in Chapter 15, small, nonencapsulated sali (Used with permission from Dr John D. Harrison, King's College vary glands are distributed throughout the oral mucosa and London Dental Institute, London, UK.) submucosa with short ducts to the oral cavity. These mino v salivary glands are usually mucous,except for the small serous glands at the bases of circumvallate papillae. Plasma cells releasing IgA are also common within the minor salivary Ducts from each lobule converge and drain into inter glands. lobular excretory ducts with increasing size and thicker connective tissue layers. The lining of these ducts is unusual, combining various epithelial types, including simple cuboidal > PANCREAS or columnar, stratified cuboidal or columnar, and pseudostrat ified epithelia, distributed in no apparent pattern. These atypi The pancreas is a mixed exocrine-endocrine gland that pro cal epithelia may reflect their composition of cells with many duces both digestive enzymesand hormones.It an elongated is diverse functions, including cells for ion reabsorption, cells retroperitoneal organ, with a large head near the duodenum for secretion of mucin and other proteins, enteroendocrine and more narrow body and tail regions that extend to the left cells, and basal stem cells, all in highly branched ducts of small (Figure 16-7). The pancreas has a thin capsule of connec diameter. Before emptying into the oral cavity, the main duct tive tissue, from which septa extend to cover the larger ves of each gland is lined with nonkeratinized stratified squamous sels and ducts and to separate the parenchyma into lobules epithelium. (Figure 16-8). The secretory acini are surrounded bya basal Vessels and nerves enter the large salivary glands at a lamina that is supported only by a delicate sheath of reticu hilum and gradually branch into the lobules. A rich vascular lar fibers with a rich capillary network. Endocrine function of and nerve plexus surrounds the secretory and duct compo the pancreas involves primarily smaller cells similar to entero nents ofeach lobule. The capillaries surrounding the secretory endocrine cells located in variously sized clusters called the units provide fluid important for saliva production, which is pancreatic islets (islets of Langerhans). These are described stimulated by the autonomicnervous system. Parasympathetic with the endocrine organs in Chapter 20.  > MEDICALAPPLICATION although the pancreas lacks striated ducts and the parotid glands lack islets of endocrine tissue. Each pancreatic aci Pancreatic cancer,which is usually a carcinoma of duct nus consists of several serous cells surrounding a very small cells, can arise anywhere in the gland but occurs most often lumen, without myoepithelial cells (Figure 16-9). The acinar in the head of the organ near the duodenum. The tumor is cells are polarized, with round basal nuclei, and numerous usually asymptomatic until growth and metastasis are well zymogen granules apically, typical of protein-secretingcells advanced, leading to the low rate of early detection and sub (Figure l6-10). sequent high rate of mortality. Metastasis may be facilitated Each acinus is drained by a short intercalated duct of by the relatively sparseconnective tissue around the ducts simple squamous or low cuboidal epithelium. The initial cells and vasculature of the pancreas. of these small ducts extend into the lumen of the acinus as small pale-stainingcentroacinar cells that are unique tothe The digestive enzymes are produced by cells serous acini of pancreas. Cells of the intercalated ducts secrete a large volume in the larger exocrine portion of the pancreas (Figure 16-9a). of fluid, rich in HCO, (bicarbonate ions), which alkalinizes This somewhat resembles the parotid gland histologically, and transports hydrolytic enzymes produced in the acini. The intercalated ducts merge with intralobular ducts and The higher pH in the acini and duct system due to larger interlobular ducts, which have increasinglycolumnar HCO, secretedby the centroacinar and intercalated epithelia before joining the main pancreatic duct that runs the duct cells, which helps keep all the enzymes inactive. length of thegland. The exocrine pancreas secretes approximately 1.5 L of alkalinepancreatic juice per day and delivers it directly into > MEDICAL APPLICATION the duodenum where the HCO, ions neutralize the acidic In acute pancreatitis, the proenzymes may be activated and chyme entering there from the stomach and establish the pH digest pancreatic tissues, leading to very serious complica foroptimal activity of the pancreatic enzymes. These digestive tions. Possible causes includeinfection, gallstones, alcohol enzymes include severalproteases,a-amylase, lipases, and and trauma. Chronic pancreatitiscan produce ism, drugs, nucleases (DNAase and RNAase). The proteasesaresecreted progressivefibrosis and loss of pancreatic function. as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase, kallikreinogen,and procarboxipeptidases). Tryp sinogen is cleaved and activated by enteropeptidases in the Exocrine secretion in the pancreas is regulated mainly duodenum, generating trypsin that activates the other prote through two polypeptide hormones produced by enteroendo ases in a cascade. Pancreatic tissue is protected against autodi crine cells ofthe small intestine: gestion by the following: Restricting protease activation to the duodenum,. Cholecystokinin (CCK) stimulatesenzymesecretion by the acinar cells. Trypsin inhibitor, which is copackaged in the secretory Secretin promotes water and HCO, secretion by the granules with trypsinogen, duct cells.  FIGURE 16-7 Pancreas and duodenum. CHAPTER Body of pancreas Main pancreatic duct Common bile duct 16 -Tail of pancreas Duodenum Organs Accessory pancreatic duct Duodenojejunal flexure Hepatopancreatic Associated ampulla with Major duodenal. Pancreatic< papilla the acini Jejunum Head of pancreas Digestive (a)Duodenum and pancreas, anterior view Tract Liver Pancreatic islet Acinar cell Pancreatic acinus (b) (a) The main regionsofthe pancreas are shownin relation to the (b)Micrographs show a pancreatic islet and several pancreatic two pancreatic ducts and the duodenum. acini. (X75 and X200; H&E) Autonomic (parasympathetic) nerve fibers also stimulate > LIVER secretion from both acinar and duct cells. The liver is the largest internal organ, in adults averaging > MEDICAL APPLICATION about 1.5 kg or 2% of the body weight. Located in the right upperquadrant of the abdomen just below the diaphragm (see the normal liver most dense connective tissue is found Figure 15-1), the liver has major left and right lobes with two only in the portal areas, surrounding the blood vessels and smaller inferiorlobes, most ofwhich are covered by a thin cap bile ductule. In liver cirrhosis, which occurs late in chronic sule andmesotheliumof the visceralperitoneum. The capsule liver disease, fibrosis and proliferation of fibroblasts and thickens at the hilum (or porta hepatis) on the inferior side, hepatic stellate cells occur beyond the portal areas. The where the dual blood supply from the hepatic portal vein excessive connective tissue may disruptthe normal hepatic and hepatic artery enters the organ and where the hepatic architecture and interfere with liver function. vein, Iymphatics, and common hepatic (bile)duct exit.  The main digestive function of the liver is production In addition to an exocrine function in the secretion of bile of bile, a complex substance required for the emulsification, components, hepatocytes and other liver cells process the con hydrolysis, and uptake of fats in the duodenum. The liver is tents ofblood, with many specific functions: also the major interfacebetween the digestivesystem and the Synthesis and endocrine secretioninto the blood of the blood, as the organ in which nutrientsabsorbed in the small major plasma proteins, including albumins, fibrinogen, intestine are processed before distribution throughout the apolipoproteins,transferrin, and many others body. About 75% of the blood entering the liver is nutrient Conversion of amino acids into glucose rich (but O,-poor) blood from the portalvein arising from the (gluconeogenesis); stomach, intestines, and spleen;the other 259% comes from the Breakdown (detoxification) and conjugation of hepatic arteryand suppliesthe organ'sO,. ingested toxins, including many drugs; Hepatocytes (Gr.hepar, liver), the key cells of this organ, Amino acid deamination, producing urea removed are among the most functionally diverse cells of the body. from blood in kidneys;  Storage of glucose in glycogen granulesand triglycerides exocrine, and endocrine functions. Hepatocytes are large in small lipid droplets; cuboidal or polyhedral epithelial cells, with large, round cen Storage of vitamin A (in hepatic stellate cells) and tral nuclei and eosinophilic cytoplasm rich in mitochondria. other fat-soluble vitamins; The cells are frequently binucleated and about 50% of them Removal of effeteerythrocytes(by specialized macrophages, are polyploid,with two to eight times the normal chromosome or Kupffer cells); number. Storage of iron in complexes with the protein ferritin. The parenchyma is organized as thousands of small liver (~0.7 x 2 mm) hepatic lobules in which hepatocytes form hundreds of irregular plates arranged radially arounda small Hepatocytes& Hepatic Lobules central vein (Figures 16-11 through l6-13). The hepa The liver's unique histologic organization and microvascu tocyte plates are supported by a delicate stroma of reticulin lature allow hepatocytes to perform their diverse metabolic, fibers (Figure 16-13b). Peripherallyeach lobule has three to six portal areas with more fibrous connective tissue, each of perisinusoidal space (orspace of Disse) and directly bathe which contains three interlobularstructuresthat comprise the the many irregularmicrovilliprojecting from the hepatocytes portal triad (Figures 16-11 and 16-13d): into this space (Figure 16-14). This direct contact between A venule branch of the portalvein, with blood rich in hepatocytes and plasma facilitates most key hepatocyte func tions that involve uptake and release of nutrients, proteins, nutrientsbut low in O,, and potential toxins. An arteriole branch of the hepatic artery that Two other functionallyimportant cells arefound with the supplies O, sinusoids ofhepatic lobules: One or two small bile ductules of cuboidalepithelium, branches of the bile conducting system. Numerous specialized stellate macrophages, usually called Kupffer cells, are found within the sinusoid lin Most of the peripheral portal areas also contain lymphat ics and nerve fibers and in some species (eg,pigs) extend thin ing (Figure l6-15). These cells recognize and phagocy sheets of fibrous connective tissue completely around the lob tose aged erythrocytes,freeingheme and iron for reuse ules,making individual lobules easier to distinguish than in or storage in ferritin complexes. Kupffer cells are also humans (Figure 16-12b). antigen-presentingcells and remove any bacteria or debris Between all of the anastomosing plates of hepatocytes of a present in the portal blood. hepatic lobule are important vascular sinusoids that emerge In the perisinusoidalspace are hepaticstellate cells (or from the peripheral branches of the portal vein and hepatic lipid droplets that storevitaminA Ito cells) with small artery and converge on the lobules central vein (Figuresl6-11 and other fat-solublevitamins (Figure 16-15b). These through 16-13c). The venous and arterial blood mixes in these mesenchymal cells, which are difficult to see in routine irregularhepatic sinusoids.The anastomosing sinusoids have preparations,also produce extracellular matrix (ECM) thin, discontinuous linings of fenestrated endothelial cells components (becoming myofibroblasts after liver surrounded by sparse basal lamina and reticular fibers. The injury)and cytokines that help regulateKupffer cell discontinuities and fenestrationsallow plasma to filla narrow activity.  The endothelium of the centralvein in themiddle of each Blood always flows from the periphery to the center of hepatic lobule is supported by a very thin layer offibrous con each hepatic lobule. Consequently, oxygen and metabolites,as nective tissue (Figure 16-13c). Central venules from each lob well as all other toxicor nontoxic substances absorbed in the ule converge into larger veins, which eventually form two or intestines, reach the lobule's peripheral cells first and then the more large hepatic veins that empty into the inferior vena more central cells. This directionof blood flow partlyexplains cava. why the properties and function ofthe periportalhepatocytes differ from those of the centrolobular cells. Hepatocytes near secretethe plasma proteins,the smaller apical surfaces of the the portal areas can rely on aerobic metabolism and are often hepatocytes form bile canaliculi and are involved in exo more active in protein synthesis,while the more central cells crine secretion of bile (Figures 16-14 and 16-16). Within the are exposed to lower concentrations of nutrients and oxy hepatic plates hepatocytes adhere firmly with desmosomes gen and are more involved with detoxification and glycogen and junctional complexes. The apicalsurfacesoftwo adherent metabolism. hepatocytes are grooved and juxtaposed to form the canalicu While the sinusoidal (basolateral) domains of hepa lus, sealed by tight junctions,into which bile components are tocytes process nutrients and other blood components and secreted (Figure 16-14). These canaliculi are elongated spaces (total length > 1 km) with lumens only 0.5-l um in diameter into the bile canaliculi (Figure 16-16). Bile acids/salts have an with large surface areas due to the many short microvilli from important function in emulsifying the lipids in the duodenum the constituenthepatocytes (Figures 16-14 and 16-16). promoting their digestion and absorption. The bile canaliculi forma complex anastomosing network Bilirubin a pigmented breakdown product of heme that is of channels through the hepatocyte plates that end near the is released from splenic macrophages primarily, but also from portal tracts (Figures 16-1lb and 16-17). The bile flow there Kupffer cells, and carried to hepatocytes bound to albumen. foreprogresses in a directionopposite to that of the blood, that Released into the duodenum with bile, bilirubin is converted is, from the center of the lobule to its periphery. Bile canaliculi by intestinal bacteriainto other pigmented products, some of are the smallestbranches of the biliary tree or bile conducting which are absorbed in the intestinal mucosa to be processed system. They empty into bile canals of Hering (Figure l6-17) and excreted again in the liver or excreted into urine by the composed of cuboidal epithelial cells called cholangiocytes. kidneys. These bilirubin-related compounds give feces and The short bile canals quickly merge in the portal areas with urine theircharacteristic colors. the bile ductules lined by cuboidal or columnar cholangio cytes and with a distinct connective tissue sheath. Bile duct >> MEDICAL APPLICATION ules gradually merge, enlarge,and form right and left hepatic ducts leaving the liver. The fibrosis characteristic of cirrhosis produces connective Into the canaliculi hepatocytes continuously secretebile, a tissue that can fill the perisinusoidal space and interfere with mixture of bile acids (organicacids such as cholic acid), bile metabolic exchange between the hepatocytes and the sinu salts (the deprotonated forms of bile acids), electrolytes, fatty soids. Blockage of hepatocyte secretion into the blood can acids, phospholipids, cholesterol, and bilirubin. Some bile result in clotting disorders,hypoalbuminemia,and other components are synthesized in hepatocyte SER, but most are medical problems. taken up from the perisinusoidalspace; all are quickly secreted  FIGURE 16-16 Hepatocyte ultrastructure and major functions. CH A PTE R eLipid 10 Bile ARER canaliculus A diagram of hepatocyte cytoplasmic organization, SERie with major functions localized. (1) RER is primarily Tight engaged in synthesis of plasma proteins for release Organs Lysosomes (occluding) intothe perisinusoidal space. (2) Potentially toxic com junctions 2 pounds, bilirubin (bound to albumin) and bile acids Golgi Si(GolgiSO are taken up from the perisinusoidal space, processed SERI -Desmosome by enzymes in the tubulovesicular system of the SER, and secreted into the bile canaliculi. (3)Glucose is Associated Mitochondria taken up from the perisinusoidal space and stored in glycogen granules, with the process reversed when with glucose is needed. the RER Glycogen Microvilli Digestive Perisinusoidal space Endothelium. Iract Fenestration Reticular fibers Liver FIGURE 16-17 Bile ductules. Structure & Function in the Liver As mentioned previously, hepatocytes are highly versatile cells Bile canaliculi with diverse functions that are reflected in their structure (Figure 16-16). Abundant rough ER focused on synthesis of plasma proteins and causes cytoplasmic basophilia, which is pronounced in hepatocytes near the portal areas often mnore (Figure 16-12). Abundant smooth ER, distributed more evenly throughout the cytoplasm, contains the enzyme sys tems for the biotransformation or detoxification ofsubstances in blood, which are then usually excreted with bile. These include enzymes responsible for oxidation, methylation, and Bile ductule conjugation of steroids, barbiturates, antihistamines, anticon vulsants, and other drugs. Under some conditions prolonged presence of drugs can lead to increased amounts of SER in hepatocytes, thus improving the iver's detoxification capac ity.Other SER enzymes (glucuronosyl transferases) conjugate bilirubin to glucuronate, rendering it more soluble and facili tating its excretion in bile. Hepatocytes Bile canals Cholangiocytes Glycogen granules and small ipid droplets in hepa of Hering tocytes, and very small electron-dense ferritin complexes (hemosiderin) primarily in the Kupffer cells, respectively Near the periphery of each hepatic lobule, many bile canaliculi mediatetemporary storage of glucose, triglycerides,and iron. join with the much larger bile canals of Hering,which are lined Hepatocyte peroxisomes are also abundant and impor by cuboidal epithelial cells called cholangiocytes. These canals tant for oxidation of excess fatty acids, catalase-mediated soon join the bile ductules in the portal areas and drain into the biliary tree. breakdown of the hydrogen peroxide generated by fatty acid oxidation (by means of catalase activity), and conversion of excess purines to uric acid. Many Golgi complexes are also The different categories of hepatocyte functions present,involved in synthesis of both plasma proteins and bile including secretion of proteins into blood, the exocrine secre components. The numerous mitochondria provide energy for tion of bile, and the removal of diverse small compounds from all these activities (Figure 16-16). blood--have led to three ways of considering liver lobule structure,which are summarizedin Figure 16-18. >> MEDICAL APPLICATION The classic hepatic lobule (Figure 16-18a), with blood flowing past hepatocytes from the portal areas to a cen Fatty liver disease is a reversible condition in which large tral venule, emphasizes the endocrine function of the lipid droplets containing triglycerides accumulate abnormally structure producing factors for uptake by plasma. in hepatocytes via the process called steatosis. This disorder The concept of portal lobules of hepatocytes is more has multiplecauses,but it occurs most commonly in indi useful when considering the exocrine function of these viduals with alcoholism or obesity.Accumulation of fat in cells, that is, bile secretion. The portal area has the bile hepatocytes may produce a progressive inflammation of the ductule at the center, and bile, moving in the opposite liver, or hepatitis, in this case called steatohepatitis. direction as the blood, flows toward it from all the sur rounding hepatocytes. The tissue draining bile into FIGURE 16-18 Conceptsof structure-function relationships in liver. (a) Classic Hepatic Lobule (b) Portal Lobule (c) Hepatic Acinus Drains blood from the portal Drains bile from Supplies oxygenated vein and the hepatic artery to hepatocytes to the blood to hepatocytes the hepatic or the central vein bile duct Central vein Hepatic arteriole Zone IlII Bile duct least -Oxygenated Portal vein Zone Il Central Zone I (or hepatic) most venule Oxygenated Studies of liver microanatomy, physiology, and pathology have sinusoids,with blood from each portal area supplying cells in given rise to three related ways to view the liver's organization, two or more classic lobules. Major activity of each hepatocyte is which emphasize different aspects of hepatocyte activity. determined by its location along the oxygen/nutrient gradient: (a) The classic lobule concept offers a basic understandingof the periportal of zone Iget the most oxygen and nutrients and cells structure-function relationship in liver organization and empha show metabolicactivity generally different from the pericentral sizesthe endocrine function of hepatocytes as blood flows past hepatocytesof zone ll,exposed to the lowest oxygen and nutri them toward the central vein. ent concentrations. Many pathologic changes in the liver are best understood from the point of view of liver acini. (b)The portal lobule emphasizes the hepatocytes' exocrine (Usedwith permission from Boron WE, Boulpaep EL. Medical functionand the flow of bile from regions of three classic lobules Physiology:A Cellular and Molecular Approach.Philadelphia, PA: toward the bile duct in the portal triad at the center here. The area Saunders Elsevier, 2005.) drainedby each bile duct is roughly triangular. (c)The hepatic acinus concept emphasizes the different oxygen and nutrient contents of blood at different distances along the  each portal area duct is roughly triangular in shape, Besides proliferation of existing hepatocytes, a role for with the central veins of three classic lobules at its liver stem cells in regeneration has been shown in some angles (Figure 16-18b). experimental models. Such cells, often called oval cells, are CHA The hepaticacinus, a third way of viewing liver cells, present among cholangiocytes of the bile canals near portal emphasizes the nature of the blood supply to the hepa areas and produce progenitor cells for both hepatocytes and tocytes and the oxygen gradient from the hepatic artery cholangiocytes. PTER branch to the central vein. In a liver acinus hepatocytes make up an irregular oval or diamond-shaped area extending tral from two portal triads to the two closest veins (Figure 16-18c). Periportal hepatocytes nearest cen >>MEDICAL APPLICATION 6 the hepatic arteriole, comprising zone Iin the acinus, Most malignant tumors of the liver derive from hepatocytes get the nost oxygen and nutrients and can most readily or cholangiocytes of the hepatic ducts. The pathogenesis of carry out functions requiring oxidative metabolism such liver carcinoma is associated with a variety of acquired disor Organs ders, such as chronic viral hepatitis (Bor C) and cirrhosis. as protein synthesis. Hepatocytes in zone II, near the central vein, get the least oxygen and nutrients.They are the preferential sites of glycolysis, lipid formation, and drug biotransformations and are the Associated first hepatocytes to undergofatty accumulation and ischemic necrosis. In > BILIARY TRACT & GALLBLADDER with the intervening zone II, hepatocytes have an intermedi ate range of metabolic functions betweenthose in zones The bile produced by the hepatocytes flows through the bile the Iand I.The major activities in any given hepatocyte canaliculi, bile ductules, and bile ducts. These structures result from the cell adapting to the microenvironment gradually merge, forming a converging network that ulti produced by the contents of the blood to which it is mately formsthe common hepatic duct that joins the cystic Digestive exposed. duct from the gallbladder and continues to the duodenum as the common bile duct (Figure l6-19). Tract The hepatic, cystic, and common bile ducts are lined with >> MEDICAL APPLICATION a mucous membrane having a simple columnarepithelium of cholangiocytes. The lamina propria and submucosa are rela An important function of hepatocyte SER is the conjugation tively thin, with mucous glands in some areas of the cystic Biliary of hydrophobic (water-insoluble), yellow blirubin by glucuro and surrounded by a thin muscularis. This muscle layer duct, nosyl transferases to form water-soluble,nontoxic bilirubin becomesthicker near the duodenum and finally, in the duode & Tract glucuronide,which is excreted into the ble canaliculi. When nal papilla, forms a sphincter that regulates bile flow into the bilirubin glucuronide is not formed or excreted properly, vari small bowel. ous diseases characterizedby jaundice can result. The gallbladderis a hollow,pear-shaped organ (Figure 16-19) A frequent cause ofjaundice in newborns is an underde attached to the lower surface of the liver, capable of storing veloped state of the hepatocyte SER (neonatal hyperbilirubi 30-50 mL of bile that is concentrated during storage. The wall Gallbladder nemia). A treatment in these cases is exposure to blue light of the gallbladder consists of a mucosa composed of simple from ordinary fluorescent tubes, which transforms unconju columnar epithelium and lamina propria, a thin muscularis gated bilirubin into a water-soluble photoisomer that can be with bundles of muscle fibers oriented in several directions, excreted by the kidneys. and an external adventitia or serosa (Figure 16-20a). The mucosa has numerous folds that are particularlyevident when the gallbladder is emnpty. and pancreas, the liver has Unlike the salivary glands The lining epithelial cells of the gallbladder have promi a strong capacity for regeneration despite its normal slow nent mitochondria, microvilli,and large intercellular spaces, rate of cell renewal. Hepatocyte loss from the action of toxic all indicative of cells actively transporting water, in this case substances triggers mitosis in the remaining healthy hepa for concentrating The mechanism for bile (Figure 16-20b). tocytes in a proces of compensatory hyperplasia that this includes activity of Na pumps in the basolateral mem maintains the original tissue mass. Surgical removal of a branes, followed by passive movement of water from the bile. liver portion produces a similar response in the hepatocytes To move stored bile into the duodenum, contraction of the of the renmaining lobe(s). The regenerated liver tissue is usu gallbladder muscularis is induced by cholecystokinin (CCK) ally wellorganized, with the typical lobular arrangement, and released from enteroendocrine cells of the small intestine. replaces the functions of the destroyed tissue. This regenera Release of CCK is, in turn, stimulated by the presence of tive capacity is important clinically because one major liver ingested fats in the small intestine. Gallbladder removal due lobe can sometimesbe donated by a living relative for surgi to obstruction or chronic inflammation leads to the direct cal transplant and full liver function restored in both donor flow of bilefrom liver to gut, with few major consequences and recipient. on digestion.  FIGURE 16-19 Biliary tract and gallbladder. Left and right hepatic ducts Common hepatic duct D Left and right hepatic ducts merge to form a common hepatic duct. Cystic duct 2)Common hepatic and cystic ducts merge to form a common bile duct. Common bile duct Accessory pancreatic duct Stored bile Gallbladder Minor duodenal papilla Hepatopancreatic Main pancreatic duct ampulla with hepatopancreatic sphincter 3)Main pancreatic duct merges with common bileduct at the hepatopancreatic ampulla, Major duodenal which extends into the duodenum. papilla and pancreatic Bile juices enter Duodenum duodenum atthe major duodenal papilla. Bile leaves the liver in the left and right hepatic ducts, which The main pancreatic duct merges with the common bile duct merge to form the common hepatic duct,which connects to the at the hepatopancreaticampulla,which enters the wall of the cystic duct serving the gallbladder. The latter two ducts merge to duodenum at a major papilla (of Vater); the accessory pancreatic form a common bile duct. Allthese ducts carrying bile are lined by duct enters the duodenumat a minor papilla. Bile and pancreatic cuboidalor low columnar cells called cholangiocytes, similar to juices are mixed before release into the duodenal lumen. those of the small bile ductules in the live. >> MEDICAL APPLICATION common formation of cholesterol stones, the most form. Brownor black pigmentstones can form when bile contains Reabsorption of water from bile in the gallbladder is involved excessiveamountsof unconjugated bilirubin, which can the formation of gallstones in the lumen of the gallblad result from chronic hemolysis associated with disorders such der or biliary ducts, a condition called cholelithiasis. assickle cell anemia. Gallstones can lead to biliary obstruc This disorder usually originates with bile that already tion or more commonly to inflammation in acute or chronic contains excessive amountsof normal bile components. cholecystitis. Supersaturation of cholesterol in bile can lead to the Organs Associated with the Digestive Tract suMMARY OF KEY POINTS Salivary Glands Cells of striated ducts have mitochondria-lined, basolateral mem Salivary glands have secretory units of either protein-secreting brane folds specialized for electrolyte reabsorption from the secre serous cells, usually organized in round or oval acini, or of mucin tion; excretory ducts are unusual in having stratified cuboidal or columnar cells. secreting mucous cells in elongated tubules. Parotid glands have only serous acini; sublingual glands are Pancreas mixed but have primarily mucous tubules, some with serous Pancreatic islets of endocrine cells are embedded in exocrine serous demilunes; submandibular glands are also mixed but have acinar tisue, which comprises most of the pancreas and which mainly serous acini. the cells secrete hydrolytic digestive enzymes for delivery to the Salivary secretory units are drained by simple cuboidal intercalated duodenum. ducts that merge as simple columnar striated ducts, which merge as larger interlobular or excretory ducts. FIGURE 16-20 Gallbladder. CH A PTER 16 Organs M Associated with the Digestive Tract A Biliary The gallbladder a saclike structure that stores and concentrates (b)TEM of the epithelium shows cells specialized for water uptake & is Tract bile, and releases into the duodenum after a meal. across apical microvilli (MV) and release into the intercellular it (a)Its wallconsists largely of a highly folded mucosa, with a spaces (arrows) along the folded basolateral cell membranes. simple columnar epithelium (arrows)overlying a typical lamina From these spaces water is quickly removed by capillaries in the propria (LP); a muscularis (M) with bundles of muscle fibers lamina propria. Abundant mitochondria provide the energy for ori ented in directions to facilitate emptying of the organ; and an this pumping process. Scattered apical secretory granules (G) con all external adventitia (A) where it against the liver and a serosa tain mucus. (X5600) is Gallbladder where itis exposed. (X60; H&E) Each pancreatic acinar cell is pyramidal, with secretory (zymo Portal areas or tracts contain a small lymphatic and the portal triad: gen) granules in the narrow apical end and Golgi complexes, a portal venule branch from the portal vein, a hepatic arteriole much rough ER, and a large nucleus at the basal end. branch of the hepatic artery, and a bile ductule branch of the biliary Intercalatedducts draining pancreatic acini, including their initial tree. centroacinar cells that insert into the acinar lumen, secrete bicar In the lobules the portal venule and hepatic arteriole both branch bonate ions (HCO,)to neutralize chyme entering the duodenum into irregular sinusoids between the hepatic plates where the nutri from the stomach. ent-rich and O,-rich blood mixes, flows past hepatocytes, and drains to the central vein. Liver The endothelium of the hepatic sinusoids discontinuous and is Liver hepatocytes are large epithelial cells with large central nuclei fenestrated; between and the hepatocytes is the perisinusoidal it (polyploid and often binucleated), much smooth and rough ER, space (of Disse) where exchange occurs between the hepatocytes and many small Golgi compl