Accessory Glands of Digestive System PDF

Accessory Glands of Digestive System SALIVARY GLANDS, PANCREAS, LIVER & GALL BLADDER  SALIVARY GLANDS- produce saliva Major salivary glands  SALIVA (0.75- ꟷ A complex hypotonic ) 1.50L/day fluid, with a usual pH of 6.5–6.9, & has digestive,...

Accessory Glands of Digestive System SALIVARY GLANDS, PANCREAS, LIVER & GALL BLADDER  SALIVARY GLANDS- produce saliva Major salivary glands  SALIVA (0.75- ꟷ A complex hypotonic ) 1.50L/day fluid, with a usual pH of 6.5–6.9, & has digestive, lubricative, cleansing & protective functions Functions of Salivary Glands The main functions of the salivary glands are to: ꟷ wet and lubricate the oral mucosa and ingested food ꟷ initiate the digestion of carbohydrates and lipids, by means of α-amylase and lingual lipase respectively ꟷ secrete protective bacteriostatic substances such as the immunoglobulin A (IgA), lysozyme, and lactoferrin ꟷ buffering function & forms protective pellicle on the teeth by means of calcium-binding proline-rich salivary proteins ꟷ for cooling the body by evaporation (in nonhuman Minor Salivary glands ꟷ nonencapsulated glands distributed through out the mucosa and submucosa of oral cavity (labial, buccal, lingual, palatine & pharyngeal) ꟷ Continuous secretion to wet the oral cavity ꟷ secrete 10% of the total volume of saliva, but account for about 70% of the mucus secreted ꟷ saliva is produced by small groups of secretory units and is conducted to the oral cavity by short ducts, with little modification of its content ꟷ they are mixed muco-serous glands, mostly mucous type ꟷ the small serous glands present in the posterior region of the tongue (von Ebner's glands) are pure serous type ꟷ lymphocyte aggregates are commonly observed within minor salivary glands, associated with IgA secretion.  Major salivary glands ꟷexperience intermittent secretion, when stimulated only ꟷopen by long ducts into mouth cavity ꟷthese glands plus minor salivary glands throughout the oral mucosa produce 0.75 to 1.50 L of saliva daily ꟷaccount about 90% of the total saliva produced ꟷReduced function of the major salivary glands due to diseases or radiotherapy is associated with dental caries, atrophy of the oral mucosa and speech difficulties ꟷinclude three bilateral pairs of salivary glands: 1.Parotid glands 2.Submandibular (submaxillary) & 3.Sublingual glands  Major Salivary glands ꟷ Surrounded by dense fibrous connective tissue capsule, rich in collagen fibers, surrounds the large salivary glands ꟷ the capsule sends numerous septa which subdivide the gland into several lobules ꟷ the septa also convey blood an lymphatic vessels into or out of the gland & house the interlobular ducts ꟷ The parenchyma of the glands consists of secretory end pieces and a branching duct system ꟷ The secretory end pieces present two types of secretory cells: serous and mucous, as well as the nonsecretory myoepithelial cells. ꟷ The secretory portion is followed by a duct system whose components modify & conduct the saliva to the oral cavity.  Major Salivary Glands  General Structure:  Morphological: Parenchyma:  Compound glandular epithelium branched acinar lining the secretory end pieces and the branching  Parotid gland duct system  Compound Stroma: branched tubulo- Supporting connective acinar tissue framework  Submandibular & including Sublingual glands Capsule Septa (Trabecula) contains many lymphocytes and plasma cells Submaxillary gland illustration, at right group of mucous tubules, at left serous acini Regions of salivary glands Secretory portions Duct portions Secretory portions -consists of three types of cells  Serous cells  Mucous cells &  Myoepithelial cells called basket cells Duct portions Consists of two types of cells  Ductal cells &  Myoepithelial cells  mucous, or mixed seromucous, depending on its glycoprotein-mucin content. ꟷ Saliva from the parotids is serous and watery. ꟷ The submandibular and sublingual glands produce a seromucous secretion, with mostly mucous from the minor glands. ꟷ Saliva is modified by the cells of the duct system draining the secretory units, with much Na+ and Cl– reabsorbed while certain growth factors and digestive enzymes are added. ꟷ Two major kinds of secretory cells occur, arranged in separate units: Serous and  Serous – cellsprotein-secreting polarized cells, – Pyramidal or cuboidal in shape with a broad base resting on the basal lamina and a narrow apical surface facing the lumen – single, fairly central round nucleus – Basophilic basal cytoplasm – Well developed RER, Golgi complex, basal mitochondria, – possess apically situated secretory granules rich in polypeptides and glycoproteins – Intercellular canaliculi  Serous Cells ………..con’t ꟷ Adjacent cells are joined together by junctional complexes (desmosomes & tight junctions) and usually form a spherical mass of cells called an acinus (Serous Acini), with a very small lumen in the center. ꟷ Acini and their duct system resemble grapes attached to a stem; the stem corresponds to the duct system. ꟷ Serous acinar cells largely produce digestive enzymes and other proteins.  Mucous –cells are somewhat more cuboidal or columnar in shape, with single, basally located flattened nucleus – they exhibit the characteristics of mucus- secreting cells – less extensive RER, fewer mitochondria but greater Golgi complex – abundant apically situated secretory granules, containing hydrophilic glycoprotein mucins which are important for the moistening and lubricating functions of the saliva. – are most often organized as tubules (Mucous Tubules) rather than acini and produce mostly mucins. – pale-staining Electron micrograph of a mixed acinus from a human sub-mandibular gland: Note the difference between the serous (lower part) and mucous (upper part) secretory granules. Mucous cells Serous cells  Myoepithelial ꟷ arecells found inside the basal lamina of the secretory units and (to a lesser extent) the initial part of the duct system. ꟷ surrounding the secretory portion myoepithelial cells are well developed and branched (and are sometimes called basket cells), whereas ꟷ those associated with the initial ducts are spindle-shaped and lie parallel to the duct's length. ꟷ myoepithelial cells prevent distention of the endpiece when the lumen fills with  Myoepithelial cells cells Myoepithelial (basket cells) – Share the basal laminae of the secretory cells – Envelop acinus and intercalated ducts – Cytoplasmic process are rich in actin and myosin → resemble smooth muscle → contract → facilitating release of secretory product  Myoepithelial cells Functions – Support secretory cells and ductal cells – Contraction may aid in the rupture of secretory cells – In ducts, contraction may widen the diameter of the ducts or shorten their length  Duct Portions Secretory potions → intercellular ductules (canaliculi) → intercalated ducts → striated ducts → intralobular ducts → interlobular ducts → intralobar ducts → interlobar ducts → terminal (principal) duct Salivon –functional unit of a salivary gland –Acinus + intercalated duct + striated duct ꟷ In the intralobular duct system, secretory endpieces empty into intercalated ducts, Intercalated Ducts ꟷ Small diameter ꟷ Lined by small cuboidal cells and myoepithelial cells (simple cuboidal epithelium), ꟷ Nucleus located in the center ꟷ Well-developed RER, Golgi apparatus, occasionally secretory granules, few microvilli ꟷ Myoepithelial cells are also present ꟷ Intercalated ducts are prominent in salivary glands having a watery secretion, e.g- parotid ꟷ Several intercalated ducts join to form striated duct. The Striated ducts: ꟷ Lined by simple columnar epithelium ꟷ The columnar cells of striated ducts often show radial striations extending from the cell bases to the level of the nuclei. ꟷ the striations consist of infoldings of the basal plasma membrane ꟷ Numerous mitochondria are aligned parallel to the infolded membranes which contain ion transporters. ꟷ Such folds greatly increase the cell surface area, facilitating ion absorption, and are characteristic of cells specialized for ion transport Columnar Striated cells ꟷ Centrally located Ducts nucleus ꟷ Some RER and some Golgi, short microvilli ꟷ The striated ducts of each lobule converge and drain into ducts located in the connective tissue septa separating lobules- interlobular ducts  Interlobular ducts ꟷ near the striated ducts, they have the same histology as the striated ducts, but have CT sheath ꟷ distally, lined with pseudostratified or stratified cuboidal epithelium, ꟷ more distally they become the interlobar ducts - lined with stratified columnar epithelium containing a few mucous cells, & supported by CT sheath. The Terminal/Principal/Main duct ꟷ the terminal duct of each large salivary gland SUBMAXILLARY GLAND DUCTS (lined by stratified cuboidal)  Terminal Excretory As the duct ducts reaches the oral mucosa the lining becomes stratified squamous Oral mucosa, with CT sheath ꟷ Vessels and nerves enter the large salivary glands at a hilum and gradually branch into the lobules. ꟷ A rich vascular and nerve plexus surrounds the secretory and ductal components of each lobule. ꟷ The capillaries surrounding the secretory endpieces are very important for the secretion of saliva. ꟷ These glands are stimulated by the autonomic NS. ꟷ Parasympathetic stimulation, usually elicited through the smell or taste of food, provokes  Parotid Gland ꟷ the largest of the three major salivary glands ꟷ located in each cheek in front of the ear ꟷ pure serous type in humans ꟷ abundant scattered adipose tissue fat in the adults ꟷ have well defined capsule ꟷ acini are formed of pyramidal shaped cells with basally placed oval nucleus and apical secretory vesicles ꟷ Intercellular secretory canaliculi are present ꟷ Prominent, long intercalated duct system usually associated with myoepithelial cells, lined with simple cuboidal epithelium ꟷ Striated ducts- lined by columnar cells  Normal Parotid Gland capsule a lobule Trabecula Trabecula Parotid gland, stratified cuboidal columnar epithelium is visible in IL ducts surrounded by connective tissue sheath  Parotid ꟷ Gland……..con’t Interlobar and excretory duct-lined at first with stratified cuboidal and later becomes columnar. ꟷ mostdistal part of its single main duct (Stensen’s duct) is lined with stratified squamous epithelium, that becomes continuous with the lining epithelium of the cheek ꟷ Stensen’s duct opens finally into the vestibule opposite the 2nd upper molar tooth ꟷ Serous cells contain secretory granules with abundant–α amylase and proline-rich proteins. ꟷ Amylase activity is responsible for most of the hydrolysis of ingested carbohydrates which begins in the mouth. ꟷ Proline-rich proteins, the most abundant factors in parotid saliva, have antimicrobial properties and Ca2+ binding properties that may help maintain the surface of enamel. PAROTID STRIATED DUCT AND NEARBY CAPILLARY Parotid gland, lobules are separated by fat cells, duct lining cells stain more palely  Submandibular ꟷ (Submaxillary) Gland a mixed, but mostly serous, compound branched tubuloacinar gland ꟷ lies beneath the base of the tongue in the floor of the mouth, where its principal duct (Wharton’s duct) also empties ꟷ the serous cells are the main component of this gland and are easily distinguished from mucous cells by their rounded nuclei and basophilic cytoplasm. ꟷ In humans, 90% of the end pieces of the submandibular gland are serous acinar, whereas 10% consist of mucous tubules capped with crescent-shaped serous cells called serous demilunes. ꟷ Lateral and basal membrane infoldings of the serous cells increase the ion-transporting surface area and facilitate electrolyte and water transport: Because of these folds, the cell boundaries are indistinct.  Submandibular Gland…………… Con’t ꟷ Serous cells are responsible for the weak amylolytic activity present in this gland and its saliva. ꟷ The cells that form the demilunes secrete the enzyme lysozyme, whose main activity is to hydrolyze the walls of certain bacteria. ꟷ Some acinar and intercalated duct cells in large salivary glands also secrete lactoferrin, which binds iron, a nutrient necessary for bacterial growth. ꟷ The striated ducts of the submandibular gland are much longer than those of parotid or sublingual gland → display many cross sectional profiles of striated duct but intercalated ducts are very short. ꟷ Its CT capsule forms abundant septa, which subdivide the gland into lobes and lobules Normal Submandibular gland SUBMANDIBULAR GLAND NORMAL SUBMANDIBULAR GLAND Submandibular A= gland serous acinus S= serous demilunes M= mucous tubule ID = intercalate d duct  Sublingual ꟷ lie in front ofgland the submandibular glands ꟷ like the submandibular gland, is a branched tubuloacinar gland formed of serous and mucous cells. ꟷ composed of mucous tubular secretory units capped by serous demilunes. ꟷ mucous cells predominate in this gland; serous cells are present almost exclusively as demilunes only. ꟷ produce mixed, but mostly mucous saliva ꟷ as in the submandibular gland, cells that form the demilunes in this gland secrete lysozyme. ꟷ Intralobular ducts are not as well developed as in other major salivary glands. ꟷ scant CT, and its duct system doesn’t form terminal duct. ꟷ several ducts open into the floor of mouth cavity and into the duct of the submandibular gland Sublingual gland M= mucous tubule ID = intercalated duct SM= small fascicles of tongue skeletal muscle HISTOLOGICAL DIFFERENCES BETWEEN SUBMANDIBULAR AND SUBLINGUAL GLANDS  MEDICAL APPLICATION ꟷ Xerostomia or dry mouth is a common condition associated with difficulties in chewing, swallowing, tasting, and speaking, dental caries, and atrophy of the oral mucosa. ꟷ The most common causes are the use of certain systemic medications (mostly in the elderly), high doses of radiation, and certain diseases such as Sjogren's syndrome. ꟷ This syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands. ꟷ Clinical features may involve the skin, eyes, oral cavity, and salivary glands, as well as the nervous, musculoskeletal, genitourinary, and  PANCREAS ꟷ a mixed exocrine-endocrine gland ꟷ produces digestive enzymes (pancreatic juices) by its exocrine portion-- pancreatic acini & several hormones by its clusters of endocrine cells known as Islets of Langerhan’s. ꟷ has thin, delicate, transparent CT capsule ꟷ the capsule sends numerous septa which sudivide the gland into several lobules. ꟷ the septa also convey blood an lymphatic vessels into or out of the gland & house the interlobular ducts. Pancreas and duodenum: (a) The main regions of the pancreas are shown in relation to the two pancreatic ducts and the duodenum. (b) Micrographs show a pancreatic islet and several pancreatic acini.  Exocrine ꟷ Pancreas formed by pancreatic acini (singular, acinus) ꟷ Compound branched acinar gland ꟷ 40 – 50 pancreatic acinar cells (form a round to oval acinus with a very small lumen ꟷ 3 – 4 centroaciner cells occupied acinar lumen → beginning of the duct system ꟷ Each acinus is surrounded by a basal lamina that is supported by a delicate sheath of reticular fibers and a rich capillary network. ꟷ Occasional M cells for presenting antigens ꟷ Lack myoepithelial cells ꟷ similar in structure to the parotid & lacrimal glands ꟷ they can be distinguished histologically by the absence of striated ducts and the presence of the islets & centroacinar cells in the pancreas. Schematic drawing of the structure of pancreatic acini. Acinar cells are pyramidal, with granules at their apex and rough endoplasmic reticulum at their base. The intercalated duct partly penetrates the acini. These duct cells are known as centroacinar cells. Note the absence of myoepithelial cells. Pancreatic acini (A)  Exocrine Pancreas Zymogenic Cells ꟷ are pancreatic acinar secretory cells of serous type ꟷ highly polarized typical protein-secreting cells ꟷ truncated pyramidal cells with a spherical (round) fairly central nucleus; basophilic basal cytoplasm (ergastoplasm)- due to prominent RER & many free ribosomes forming polyribosomes ꟷ apex, facing the lumen, is filled with zymogen granules (eosinophilic). ꟷ number of secretory granules diminished after meal, granules increase during fasting. ꟷ basal cell membranes have receptors for secretin, cholecystokinin and acethylcholine ꟷ may release their contents individually or several granules may fuse each other, forming a channel to the lumen  The Golgi complex varies in size in inverse relation to the zymogen granule concentration – Smaller when zymogen granules are numerous – Larger after the granules release their content Zymogen granules (secretory granules) – are membrane-bounded & densely packed in the apical cytoplasm of the Zymogenic cells – stain eosinophilic i.e. acidophilic in H & E stain – contain pancreatic enzymes, which degrade proteins, carbohydrates, lipids & nucleic acids by the process of luminal digestion – proteolytic enzymes are stored as inactive zymogens in the secretory granules of acinar cells ꟷ After secretion, trypsinogens are cleaved and activated by enterokinase only in the lumen of the small intestine, generating trypsins. ꟷ The trypsins activate other proteases in a cascade. ꟷ This, along with production of protease inhibitors by the acinar cells, prevents the pancreas from digesting itself. Centroacinar cells: ꟷ low cuboidal cells with pale cytoplasm, because of very few G. apparatus & RER, i.e. not synthetic cells ꟷ form incomplete border of initial (intra- acinar) part of intercalated ducts. Pancreas Sections Centroacinar cells: – Small, pale-staining, low cuboidal epithelial cells, with pale cytoplasm, because of very few G.apparatus & RER, i.e. not synthetic cells – form simple low cuboidal epithelium – constitute the initial intra-acinar portion of the intercalated ducts – found only in pancreatic acini – form incomplete border of initial part of intercalated duct (open-ended) – probably elaborate the water and bicarbonate component of pancreatic secretion (increase PH) Pancreatic Acinar cell (secretory cells) Pancreatic Acinar Duct System Centroacinar cells of acini intercalated duct → intralobular ducts → interlobular ducts → main pancreatic duct → common bile duct → papilla of Vater 1. Intercalated ducts ꟷ each duct has intra-acinar & inter- acinar parts ꟷ lined by simple cuboidal epithelium ꟷ begin within the acini by centroacinar cells, and converge into a small number of larger intra-lobular ducts ꟷ are tributaries of the larger  2. Intralobular ꟷ Ducts formed by convergence of several intercalated ducts in the lobule ꟷ similar in histology to intercalated ducts except being larger in size ꟷ lined by simple cuboidal epithelium ꟷ empty the secretion into interlobular ducts 3. Interlobular Ducts ꟷ located between lobules in the connective tissue septa containing blood vessels ꟷ lined by simple columnar epithelium, supported by a loose connective tissue sheath empty into the main or accessory pancreatic duct IC= Intercalated duct, ILD= Intralobular duct IC ILD  4. Main pancreatic duct (of Wirsung) and Accessory Pancreatic Duct ꟷ formed in the tail of pancreas, by convergence of several interlobular ducts in dense connective tissue septa ꟷ lined with stratified cuboidal epithelium ꟷ supported in a dense connective tissue sheath ꟷ receive a series of interlobular ducts along its course ꟷ deliver secretions of the exocrine part of pancreas into the duodenum at the major (papilla of Vater) or minor papilla ꟷ the main pancreatic duct receives the common bile duct just proximal to the papilla of Vater  MEDICAL APPLICATION ꟷIn acute necrotizing pancreatitis, the proenzymes may be activated and digest pancreatic tissues, leading to very serious complications. ꟷ Possible causes include infection, gallstones, alcoholism, drugs, and trauma. ꟷIn conditions of extreme malnutrition, such as kwashiorkor, pancreatic acinar cells and other active protein-secreting cells atrophy and lose much of their RER,  Endocrine Portion of ꟷ Pancreas Islets of Langerhans ꟷ Richly vascularized spherical conglomeration of about 300 cells ꟷ Cells:  (A,alpha),  (B, beta),  (D, delta), PP (F) cells ꟷ Difficult to differentiate by routine examination → readily differentiated using IHC, EM ꟷ Each islet is surrounded by reticular fibers, which also enter the islet to encircle the capillaries that pervade it. ꟷ Endocrine portion, the islets of Langerhans is developed together with the exocrine portion. They are most numerous in the tail of the pancreas. ꟷ It consists of clumps or cords of secretory cells, supported by fine collagenous network with numerous fenestrated capillaries. ꟷ Cells are poorly stained with H and E stain, and have granular cytoplasm. Islet of Langerhans Islet of Langerhans Islet of Langerhans  Table: Major cell types and hormones of pancreatic islets. Cell Quantity Hormone Hormone Hormone Function Type Produced Structure and Size A ~20% Glucagon Polypeptide; Acts on several tissues to make 3500 Da energy stored in glycogen and fat available through glycogeno- lysis and lipolysis; increases blood glucose content B ~70% Insulin Dimer, Acts on several tissues to cause chains with entry of glucose into cells and S-S bridges; promotes decrease of blood 5700-6000 glucose content Da ∂ or D 5–10% Somato- Polypeptide; Inhibits release of other islet cell statin 1650 Da hormones through local paracrine action; inhibits release of GH and TSH in anterior pituitary and HCl secretion by parietal cells F or PP Rare Pancreatic Polypeptide; Stimulates activity of gastric polypeptide 4200 Da chief cells; inhibits bile secretion, pancreatic enzyme  LIVER ꟷa large dark-brown internal organ with a soft spongy texture ꟷthe second-largest organ of the body (next to the skin), weighing about 1.5 kg; is about 15 cm thick ꟷThe liver is unique among the body organs in that it receives both arterial and venous blood. ꟷIt is the organ in which nutrients absorbed in the digestive tract are processed and stored for use by other parts of the body. ꟷIt is thus an interface between the digestive system and the blood. ꟷ Most of its blood (70-80%) comes from the portal vein, arising from the stomach, intestines, and spleen; the smaller percentage (20-30%) is supplied by the hepatic artery, which arise from the celiac trunk. ꟷ Venous drainage of the liver occurs via the left and right hepatic veins to the inferior vena cava.. ꟷ the portal vein carries venous blood laden with nutrients absorbed from digestive tract ꟷ All the materials absorbed via the intestines reach the liver through the portal vein, except the complex lipids (chylomicrons), which are transported mainly by lymph vessels. ꟷ The position of the liver in the circulatory system is optimal for gathering, transforming, and accumulating metabolites and for  secretion of the liver that is important for lipid digestion. ꟷ The liver also has the very important function of producing plasma proteins, such as albumin, carrier proteins, coagulation factors, and growth factors. Liver Stroma ꟷ The liver is covered by a thin connective tissue capsule (Glisson's capsule) that becomes thicker at the hilum (porta hepatis). ꟷ At the porta hepatis, the hepatic artery and the portal vein enter the liver, and the right and left hepatic ducts and  Liver Stroma……………..Con’t ꟷthe hepatic artery, the portal vein, the right and left hepatic ducts and lymphatics are surrounded by connective tissue all the way to their termination (or origin) in the portal spaces between the liver lobules. ꟷAt this point, a delicate reticular fiber network that supports the hepatocytes and sinusoidal endothelial cells of the liver lobules is formed.  Liver…..cont ꟷ Has both exocrine (bile) and endocrine functions (by hepatocytes) ꟷ Is enveloped by peritoneum ꟷ Simple squamous epithelium ꟷ Dense irregular CT capsule (Glisson’s capsule) ꟷ Hepatocytes are arranged in hexagon- shaped lobules (classical lobules) – Longitudinal axis is occupied by central (centrolobular) vein – Portal areas (triads): where 3 classical lobules are in contact each other, and CT elements are increased house hepatic artery, portal vein; interlobular bile ducts; lymph vessels  In some animals (e.g., pigs), the lobules are separated from each other by a layer of prominent connective tissue, making them easy to distinguish. In humans (b), the lobules are in close contact along most of their length and it is more difficult to establish the exact limits between different lobules. Microscopic Structure of the Liver Classic Liver Lobules (pig) Centrolobular region of classic liver lobule A portal space with its characteristic small artery, vein, lymph vessel, and bile duct surrounded by CT. H&E stain  HEPATOCYTES ꟷ are polyhedral, with six or more surfaces, ꟷ have a diameter of 20-30 µm. ꟷ Eosinophilic cytoplasm with H&E stains, mainly because of the large number of mitochondria and some smooth endoplasmic reticula. ꟷ Hepatocytes located at different distances from the portal spaces show differences in structural, histochemical, and biochemical characteristics. ꟷ The surface of each hepatocyte is in contact with the wall of the sinusoids, through the space of Disse, and with the surfaces of other hepatocytes. ꟷ Wherever two hepatocytes abut, they delimit a  HEPATOCYTES ꟷ disposed and are arranged like the bricks of a wall. ꟷ These cellular plates are directed from the periphery of the lobule to its center and anastomose freely, forming a labyrinthine and sponge-like structure ꟷ The space between these plates contains capillaries, the liver sinusoids Liver Sinusoidal capillaries ꟷ are irregularly dilated vessels composed solely of a discontinuous layer of fenestrated endothelial cells. ꟷ the fenestrae are about 100 nm in diameter, have no diaphragm, and are grouped in ꟷ A subendothelial space known as the space of Disse separates the endothelial cells from the hepatocytes. ꟷ The fenestrae and discontinuity of the endothelium allow the free flow of plasma but not of cellular elements into the space of Disse, permitting an easy exchange of molecules (including macromolecules) from the sinusoidal lumen to the hepatocytes and vice versa. ꟷ This exchange is physiologically important not only because of the large number of macromolecules (e.g, lipoproteins, albumin, fibrinogen) secreted into the blood by hepatocytes but also because the liver takes Hepatic Sinusoids and Perisinusoidal Hepatic Space sinusoids: occupy the spaces of Disse between the plates of hepatocytes – Sinusoidal lining endothelial cells (endothel) – Fenestrated 0.5 µm – Discontinuous endothelial cells – No basal lamina – Macrophage → Kupffer Cells Endothelial cells are separated from hepatocytes by perisinusoidal space (Space of Disse) – is subendothelial space, contains – Collagen III; – Nonmyelinated nerve fibers – Fat storing cells (Ito Cells/Stellate cells) grouped fenestrations. At the border are seen cut edges of the endothelial cell (E) in this discontinuous sinusoid and hepatocytes (H). Between these two cells is the thin perisinusoidal space (PS), into which project microvilli from the Hs surface. Blood plasma passes freely through the fenestrations into the PS, where the voluminous membrane of Hs acts to remove many high and low molecular weight blood components and nutrients for storage and processing. Proteins synthesized and secreted from Hs, such as albumin, fibrinogen, and other blood proteins, are released into the PS. X6500. Ito Cells Hepatocytes, Kupffer Cells Stellate macrophages are seen as black cells in a liver lobule from a rat injected with particulate India ink.  Space of Disse Kupffer Cells Liver Liver performs more than 500 different types of secretary, metabolic, storage and excretory functions (Worman, 2006) 1.To synthesize and store energy in the form of glycogen. ꟷ Through a process called gluconeogenesis, the liver fabricates glucose from ingested carbohydrate & from non-carbohydrate sources such as amino acids and fatty acids ꟷ It also removes excess glucose molecules from the blood, by converting them into glycogen. ꟷ When the amount of glucose in the blood falls below the level required to meet the body’s need, the liver 2.Producing bile, a yellowish-brown liquid containing salt necessary for the digestion of lipids. 3.From the nutrient-rich blood in the hepatic portal vein, liver collects and stores elemental iron, and vitamins A, D, E, B12 & K. 4.Liver also functions as the body’s chemical factory. ꟷ Several important proteins found in the blood are produced in the liver, including albumin, globins, one of the two components that form ꟷ Certain globulins, a group of proteins including antibodies, fibrinogen and prothrombin, as well as cholesterol ꟷ Cholesterol is a key component of cell membranes that transports fats in the bloodstream to body tissues. 5. The liver is also site of hematopoiesis during fetal life and destruction of spent red blood cells and reclamation of their constituents. absorb and modify various drugs and toxic substances into products that can be readily removed through the bile or urine. ꟷ If toxins accumulate in the body faster than the liver can process them, then liver damage will result ꟷ Hepatocytes, cells with high degree of metabolic activities, are susceptible to circulating toxic agents and drugs. ꟷ In acute toxicosis, they exhibit histological cell responses such as fatty changes, cloudy swelling, and necrosis. ꟷ Inflammatory cell infiltration, vascular abnormalities, and fibrosis are other  H H BR K I CV PV I K S Liver toxicity, see severe inflammations (arrows) around central vein and portal vein  Functions of Hepatocytes………… con’t ꟷ Functionally, the hepatocyte may be the most versatile cell in the body. ꟷ The hepatocyte has an abundant endoplasmic reticulum—both smooth and rough. Rough ER ꟷ Impart cytoplasmic basophilia ꟷ for synthesis of plasma proteins, which is often more pronounced in hepatocytes near the portal areas Liver glycogen ꟷ a depot for glucose and is mobilized if the blood glucose level falls below normal. ꟷ The hepatocyte frequently contains deposits of  Functions of Hepatocytes…………….. Con’t ꟷ hepatocytes maintain a steady level of blood glucose, one of the main sources of energy for the body. SYNTHESIS AND STORE OF LIPIDS Smooth ER ꟷ distributed diffusely throughout the cytoplasm ꟷ Various important processes take place in it ꟷ is responsible for the processes of oxidation, methylation, and conjugation required for inactivation or detoxification of various substances before their excretion. ꟷ The smooth ER is a labile system that reacts promptly to the molecules received by the  Functions of Hepatocytes…………….. Con’t ꟷHepatocytes do not usually store proteins in secretory granules but continuously release them into the bloodstream. About 5% of the protein exported by the liver is produced by the sinusoidal stellate macrophages. ꟷThe hepatocyte is responsible for converting lipids and amino acids into glucose by means of a complex enzymatic process called gluconeogenesis (Gr. glykys, sweet, + neos, new, + genesis, production). ꟷliver is also the main site of amino acid deamination, resulting in the production of urea which is transported in blood to the kidney and is  Functions of Hepatocytes…………….. Con’t ꟷHepatocyte lysosomes: are important in the turnover and degradation of intracellular organelles. ꟷPeroxisomes : are also abundant and are important for ꟷ oxidation of excess fatty acids, ꟷ breakdown of the hydrogen peroxide generated by this oxidation (by means of catalase activity), ꟷ breakdown of excess purines to uric acid, and ꟷ participation in the synthesis of cholesterol, bile acids, and some lipids relationships in liver ꟷStudies of liver microanatomy, physiology, and pathology have given rise to three related ways to view the liver's organization which emphasize different aspects of hepatocyte activity. (a): The classic lobule concept offers a basic understanding of the structure-function relationship in liver organization and emphasizes the endocrine function of hepatocytes as blood flows past them toward the central vein. (b): The portal lobule emphasizes the hepatocytes' exocrine function and the flow of bile from regions of three classic lobules toward the bile duct in the portal triad at the (c):The liver acinus concept ꟷ emphasizes the different oxygen and nutrient contents of blood at different distances along the sinusoids, with blood from each portal area supplying cells in two or more classic lobules. ꟷ Each hepatocyte's major activity is determined by its location along the oxygen/nutrient gradient: ꟷ periportal cells of zone I get the most oxygen and nutrients and show metabolic activity generally different from the pericentral hepatocytes of zone III, exposed to the lowest oxygen and nutrient concentrations. ꟷ Many pathological changes in liver are best  3 Concepts of Liver lobules Classical liver lobules – Concept: Blood flows from the periphery to the center of the lobule (central vein) – Bile enters into bile canaliculi and flows to the periphery of the lobule to the interlobular bile ducts of the portal areas Portal lobules – Concept: exocrine secretion (bile) flows to central lumen of acinus – Triangular region whose center is the portal area and whose periphery is bounded by imaginary straight line connecting the three surrounding central veins that form the three apices of the triangle Hepatic acinus (acinus of Rappaport) – Concept: blood flow from distributing arterioles → on the order in which hepatocytes degenerate subsequent to toxic or hypoxic insults – 3 concentric regions of hepatic parenchyma surrounding a distributing artery in the center: periportal (zone I), intermediate (zone II), & pericentral (zone III). 3 Concepts of Liver Lobules Concepts of structure-function relationships in liver Portal Acinus of Rappaport  BILIARY TRACT ꟷ Bile produced by the hepatocytes is directed to flow toward the periphery of the classic liver lobule (in opposite direction to the blood flow). ꟷ Bile is carried in a system of ducts, collectively called biliary tract, that commence at the bile canaliculi. ꟷ Has intrahepatic & extrahepatic portions based on their location. ꟷ The daily basal secretion of bile is about 500 ml. Intrahepatic tract 1.Bile canaliculus ꟷ Is a narrow intercellular space b/n adjacent hepatocytes.  Bile canaliculi ꟷ Receive the liver’s exocrine secretion (bile) & carries into bile ductules ꟷ Are tubular spaces 1-2 μm in dim ꟷ Limited only by the plasma membrane of two hepatocytes & have small microvilli in the interiors ꟷ the plasma membrane near canaliculi are firmly joined by tight junctions ꟷ The canaliculi form a complex anastomosing network progressing along the plates of the liver lobule and terminate in to bile ductules 2. Bile Ductules (Herring’s Canals) ꟷ very short, slender ducts ꟷ the first portion of the bile duct system ꟷ located near the portal spaces, at very periphery of the classic lobule ꟷ Composed of low cuboidal cells called Cholangiocytes and some ovoid cells (simple cuboidal epithelium) ꟷ the Cuboidal cells secrete a bicarbonate-rich fluid under influence of hormone secretin released by DNES cells of small intestine ꟷ after a short distance, the ductules cross the  Biliary Tract Bile canaliculi → labyrinthine tunnels →canals of Herring (bile ductules) → interlobular bile ducts at portal spaces) → right and left hepatic ducts→common hepatic duct →joined by cystic duct and becomes common bile duct →joins the main pancreatic duct and form hepatopancreatic ampulla Bile ductules  Hepatocytes 2 domains: lateral and sinusoidal Lateral/Exocrine domain – Form bile canaliculi – Fascia occludentes prevent leakage of bile from bile canaliculi – Short, blunt microvili project into bile canaliculi (exocrine secretion) – High levels of Na-K ATPase and adenylate cyclase – Isolated gap junctions Sinusoidal/Endocrine domains – Microvili projects into space of Disse – Endocrine secretion Bile Canaliculi Bile Canaliculus  Gall Bladder ꟷ a hollow, muscular pear-shaped organ, attached to the lower surface of the liver. ꟷ it stores bile, concentrate it by absorbing its water and releases it into the duodenum after a meal. ꟷ It can store 30–50 mL of bile ꟷ the presence of dietary fats and lipids in the small intestine (duodenum) promotes the secretion of cholecystokinin (CCK) released from enteroendocrine cells of the small intestine (duodenal mucosa). ꟷ this, in turn, stimulates contraction of the gall bladder & force bile into the duodenum. ꟷ its wall consists of a mucosa composed of simple columnar epithelium and lamina propria, a thin muscularis with bundles of muscle fibers oriented in several directions, and an external adventitia or serosa. ꟷ The mucosa has abundant folds that are particularly evident when the gallbladder is empty 1. Mucosa – Empty gallbladder is highly folded into tall, parallel ridges; bile distended gallbladder reduces the plications to a few short folds → smooth mucosa Epithelium: – Simple tall columnar epithelium: Lamina propria: is a vascularized loose CT occasional simple tubuloalveolar mucous glands- in the neck may produce a mucus which provide a protective surface film for the biliary tract 2. Muscularis: Smooth muscles are oriented in oblique, transverse & longitudinal directions (all directions) 3. Adventitia – Glisson’s capsule of Liver – peritoneum Histological Layers of Gall bladder wall Histological Layers of Gall bladder wall Biliary tract and gall bladder: Bile leaves the liver in the left and right hepatic ducts, which merge (1) to form the common hepatic duct, which connects to the cystic duct serving the gall bladder. The latter two ducts merge (2) to form a common bile duct. The main pancreatic duct merges with the common bile duct at the hepatopancreatic ampulla (3) which enters the wall of the duodenum. Bile and pancreatic juices together are secreted from the major duodenal papilla (of Vater) into the duodenal lumen (4). All these ducts carrying bile are lined by cuboidal or low columnar cells called cholangiocytes, similar to those of the small bile ductules in the liver Gall Bladder with a simple columnar epithelium (arrows) overlying a typical lamina propria (LP); a muscularis (M) with bundles of muscle fibers oriented in all directions to facilitate emptying of the organ; an external adventitia (A) where it is against the liver and a serosa where it is exposed. (b): TEM of the epithelium shows cells specialized for water uptake across apical microvilli (MV) and release into the intercellular spaces (arrows) along the folded basolateral cell membranes. Abundant mitochondria provide the energy for this pumping process. Scattered apical secretory granules (G) contain mucus  Gall Bladder ꟷThe lining epithelial cells have prominent mitochondria, microvilli, and intercellular spaces, all indicative of active absorptive cells. ꟷThis process depends on an active sodium-transporting mechanism in the gallbladder's epithelium, with water absorption from bile an osmotic consequence of the Na pump ꟷContraction of the smooth muscle of the gallbladder is induced by cholecystokinin (CCK) released from enteroendocrine cells of the small intestine (duodenal mucosa). ꟷRelease of CCK is, in turn, stimulated by the presence of dietary fats in the small intestine. ꟷRemoval of the gallbladder due to obstruction or chronic inflammation leads to direct flow of bile from liver to gut,  Histophysiology of Gall Bladder Store, concentrate, and release bile Epithelium – Luminal surface display short, irregular microvili coated by a thin layer of glycocalyx, account for unevenness of the luminal surface – Supranuclear: secretory granules containing mucinogen – Basal region is rich in mitochondria – the lining cells concentrate bile 5 to 10-fold by an active process, water being passed into a rich capillary network in the lamina propria the wall of the cystic duct is formed into twisted mucosa covered fold known as spiral valve of Heister.  Gall Bladder  MEDICAL APPLICATION Gallstones (Cholelithiasis) ꟷ formed by the concretion of normal and abnormal bile constituents. ꟷ Cholesterol and mixed stones comprise 80% of the gallstones, which are frequently caused by excessive cholesterol in relation to phospholipids and bile acids or gallbladder hypomotility. ꟷ can block bile flow and cause jaundice from the rupture of tight junctions around the bile canaliculi. Tumors of the Digestive Glands ꟷ Most malignant tumors of the liver derive from hepatic parenchyma or epithelial cells of the bile duct. ꟷ The pathogenesis of hepatocellular carcinoma is not completely understood, but it may be associated with a variety of acquired disorders, such as chronic viral hepatitis (B or C) and cirrhosis.  REVIEW QUESTIONS 1. Compare and contrast between the following (with respect to their histology) a. Enamel and dentine b. Dentine and cementum c. Cementum and bone d. Small intestine and large intestine 2. Describe histological differences between a. Minor (accessory) and major salivary glands b. Parotid and submandibular salivary glands c. parotid gland and pancreas 3. Which parts of the tubular digestive tract consists of submucosal glands? 4. Describe the differences between the cardiac, fundic and pyloric gland of stomach.