Histology of Digestive System PDF

JIGJIGA UNIVERSITY Histology of Digestive System For Medicine Students  Digestive System Consists of: Digestive tract (gastrointestinal (GI) tract or alimentary canal) Oral cavity Esophagus Stomach Small and Large intestines Accessory digestive organs (as...

JIGJIGA UNIVERSITY Histology of Digestive System For Medicine Students  Digestive System Consists of: Digestive tract (gastrointestinal (GI) tract or alimentary canal) Oral cavity Esophagus Stomach Small and Large intestines Accessory digestive organs (associated glands) Salivary glands Liver Gall bladder Pancreas  Function of digestive tract includes:  Ingestion: introduction of food and liquid into the oral cavity. Mastication or chewing: divides solid food into digestible pieces. Motility: muscular movements of materials through the tract. Secretion: secretion of mucus, digestive enzymes, acidic and alkaline fluids, and bile.  Function of digestive tract cont… Hormone release: for local control of motility and secretion. Chemical digestion: enzymatic degradation of large macromolecules in food to smaller molecules and their subunits. Absorption: of the small molecules and water into the blood and lymph. Elimination: of indigestible, unabsorbed components of food.  General Structure of the digestive tract A wall made up of four main layers: Mucosa Submucosa Muscularis and Serosa Structures of the Alimentary Canal Anatomy of digestive system for 7 Nursing  Mucosa (Mucus membrane) The mucosa comprises: An epithelial lining Lamina propria: Made up of loose connective tissue rich in blood vessels, lymphatics, lymphocytes and smooth muscle cells Muscularis mucosae A thin layer of smooth muscle usually separating mucosa from submucosa. The submucosa Contains: Denser connective tissue with many blood and lymph vessels The submucosal (Meissner) plexus of autonomic nerves.  It may also contain glands and lymphoid tissue Diagram showing the structure of the small intestine portion of the digestive tract, with the four main layers and their major components listed on the left. Muscularis layer: Is composed of inner circular and outer longitudinal smooth muscle cells Contains: Blood and lymph vessels Myenteric (Auerbach) nerve plexus Contractions of the muscularis are generated and coordinated by the myenteric plexus. The serosa/adventitia: It is a thin sheet of loose connective tissue Rich in blood vessels, lymphatics, and adipose tissue Covered with a simple squamous covering epithelium or mesothelium,  Neural innervation of GI tract 1. Enteric nervous system: extend from esophagus to anus and grouped in to two. A. Myenteric plexus(plexus of aurbach): found between longitudinal and circular layer of muscularis. B. Sub mucosal plexus(meissners plexus): found within sub mucosa. 2. Autonomic nervous system Sympathetic NS = ↓GI function, ↓Motility ↓Secretions Parasympathetic NS = ↑GI function, ↑Motility, ↑Secretions  Medical Application Hirschsprung disease (congenital aganglionic megacolon): plexuses in the digestive tract’s, enteric nervous system are absent Chagas disease (trypanosomiasis, infection with the protozoan Trypanosoma cruzi): plexuses in the digestive tract’s, enteric nervous system are severely injured. This disturbs digestive tract motility and produces dilations in some areas  Oral Cavity Lined with stratified squamous epithelium, keratinized or nonkeratinized, depending on the region. The keratin layer: Protects the oral mucosa from damage during masticatory function It is best developed on the gingiva (gum) and hard palate. Nonkeratinized squamous epithelium covers The soft palate Cheeks The floor of the mouth Pharynx  Histology of lips Has three zones: 1. The inner zone: has lining mucosa with a thick, nonkeratinized epithelium and many minor labial salivary glands. 2. The outer zone: has thin skin, consisting of epidermal and dermal layers, sweat glands, and many hair follicles with sebaceous glands.  Histology of lips cont… 3. The vermilion zone: covered by very thin keratinized stratified squamous epithelium and is transitional between the oral mucosa and skin. This region lacks salivary or sweat glands and is kept moist with saliva from the tongue. The underlying connective tissue is very rich in both sensory innervation and capillaries, which impart the pink color to this region. The Hard and Soft Palate Separate the oral cavity from nasal cavity. On nasal side: both palates covered by pseudostratified ciliated columnar epithelium with goblet cells; Glands are of mixed type (both mucous and serous) On oral side: Soft palate – non-keratinized stratified squamous epith; Hard palate – keratinized stratified squamous epith; Glands are purely mucous  Tongue It is a mass of striated muscle covered by a mucous membrane. The dorsal surface is irregular, having hundreds of small protruding papillae on its anterior two-thirds and The massed lingual tonsils on the posterior third, or root of the tongue. The papillary and tonsillar areas of the lingual surface are separated by a V-shaped groove called the sulcus terminalis.  Lingual Papillae Papillae are elevations of the oral epithelium and lamina propria that assume various forms and functions. There are four types: 1. Filiform Papillae Have an elongated conical shape Are quite numerous and are present over the entire surface of the tongue. Their epithelium is keratinized. Does not contain taste buds They provide a rough surface that facilitates movement of food during chewing. Lingual Papillae cont… 2. Fungiform Papillae Resemble mushrooms in that they have a narrow stalk and a smooth-surfaced, dilated upper part. These papillae contain scattered taste buds on their upper surfaces Are irregularly interspersed among the filiform papillae. 3. Foliate Papillae Poorly developed in humans. They consist of two or more parallel ridges and furrows on the dorsolateral surface of the tongue Contain many taste buds 4. Vallate (circumvallate) papillae Are the least numerous and largest lingual papillae with diameters of 1 to 3 mm. Contains over half the taste buds on the human tongue. Eight to twelve vallate papillae are normally aligned just in front of the terminal sulcus. Vallate (circumvallate) papillae cont… Ducts from several serous salivary (von Ebner) glands empty into the deep groove that surrounds each vallate papilla. This provides a continuous flow of fluid over the taste buds, washing away food particles so that the taste buds can receive and process new gustatory stimuli. These glands also secrete a lipase that prevents the formation of a hydrophobic film over the taste buds that would hinder their function.  Taste buds Are ovoid structures, within the stratified epithelium of the tongue. Approximately 250 taste buds are present on the lateral surface of each vallate papilla. with many others present on fungiform and foliate papillae. They are not restricted to papillae and also widely scattered elsewhere on the dorsal and lateral surfaces of the tongue. Taste buds cont… A taste bud has 50 to 100 cells, about half of which are elongated gustatory (taste) cells. Three types of cells are identified: 1. Gustatory (taste) cells Are elongated cells Turn over with a 7- to 10-day life span. 2. Supportive cells: Are slender, immature cells Taste buds cont… 3. Basal stem cells: Which divide and give rise to the other two types. The base of each bud rests on the basal lamina and Is entered by afferent sensory axons that form synapses with the gustatory cells. At the apical ends of the gustatory cells microvilli project through an opening called the taste pore. Molecules (tastants) dissolved in saliva contact the microvilli through the pore and interact with cell surface taste receptors  Taste buds cont… Taste buds detect at least five broad categories of tastants: Sodium ions (salty); Hydrogen ions from acids (sour); Sugars and related compounds (sweet); Alkaloids and certain toxins (bitter); and Amino acids such as glutamate and aspartate (umami; Jap. umami, savory). Salivary Glands It is exocrine glands in the mouth Produce saliva With a usual pH of 6.5–6.9. There are three pairs of major salivary glands: – Parotid glands – The submandibular – Sublingual glands Minor glands in mucosa and submucosa throughout the oral cavity which secrete 10% of the total volume of saliva Major salivary gland: Surrounded by connective tissue capsule The parenchyma of each consists of: – Secretory end pieces on a branching duct system arranged in lobules separated by connective tissue septa – The secretion of each gland is either serous, seromucous, or mucous: Saliva from the parotids is serous and watery. The submandibular and sublingual glands produce a seromucous secretion The minor glands is mostly mucous.  Three epithelial cell types comprise the salivary secretory units: a. Serous cells: – Are polarized protein-secreting cells – Pyramidal in shape, with round nuclei – Well-stained RER, and apical secretory granules – Joined apically by tight and adherent junctions – Serous cells form a spherical unit called an acinus, with a very small central lumen – Serous acinar cells largely produce digestive enzymes and other proteins. b. Mucous cells: – More columnar in shape, with more compressed basal nuclei. – Are mucus-secreting cells, containing hydrophilic glycoprotein mucins which are important for the moistening and lubricating functions of the saliva. – Organized as tubules rather than acini – Produce mostly mucins  c. Myoepithelial cell Are found inside the basal lamina surrounding acini, tubules, and the proximal ends of the duct system It is small, flattened cells that extend several contractile processes around the associated secretory unit or duct. – It is important for moving secretory products into and through the ducts.  Parotid gland A branched acinar gland with secretory portions composed exclusively of serous cells surrounding very small lumens Serous cells of parotid glands secrete: – Abundant α-amylase that initiates hydrolysis of carbohydrates and – Proline-rich proteins with antimicrobial properties.(a) Micrograph of a parotid gland shows densely packed serous acini (A) with ducts. Secretory granules of serous cells are clearly shown in this plastic section, as well as an intercalated duct (ID) and striated duct (SD), both cut transversely. (b) Striations of a duct (SD) are better seen here, along with a septum (CT) and numerous serous acini (A). The connective tissue often includes Submandibular Gland It is a branched tubuloacinar gland with secretory portions containing both mucous and serous cells. The serous cells are the main component of this gland. – Easily distinguished from mucous cells by their rounded nuclei and basophilic cytoplasm. Serous cells of the submandibular gland secrete: – α-amylase – Proline-rich proteins & – Lysozyme for bacterial wall hydrolysis. (a) shows well-stained serous acini (A) and serous demilunes (S) and pale- staining mucous cells (M) grouped as tubules in this tubuloacinar gland. Small intralobular ducts (ID) drain each lobule.  Sublingual gland The smallest of the major gland It is a branched tubuloacinar gland Formed of serous and mucous cells Mucous cells predominate Produce mucus The serous cells - secrete amylase and lysozyme (b) The sublingual gland is a mixed but largely mucous gland with a tubuloacinar arrangement of poorly stained mucous cells (M). Small intralobular ducts (ID) are seen in connective tissue, as well as small fascicles of lingual striated muscle (SM).  Esophagus It is a muscular tube whose function is to transport food from the mouth to the stomach Has the same 4 layers as the rest of the digestive tract The mucosa has nonkeratinized stratified squamous epithelium with stem cells scattered throughout the basal layer Esophagus cont… The submucosa contains small mucus-secreting glands, the esophageal glands. Secretions of which facilitate the transport of food (lubricate) and protect the mucosa. Near the stomach the mucosa also contains groups of glands, the esophageal cardiac glands, which secrete additional mucus. Esophagus cont… In approximately the upper one-third of the esophagus, the muscularis is exclusively skeletal muscle. The middle portion of the esophagus has a combination of skeletal and smooth muscle fibers, and In the lower third the muscularis is exclusively smooth muscle. Esophagus cont… Only the distal 1-2 cm of the esophagus, is covered by serosa. The rest is enclosed by the loose connective tissue of the adventitia.  Mucosa consisting of nonkeratinized stratified squamous epithelium (SSE), lamina propria (LP), and smooth muscles of the muscularis mucosae (MM). Submucosa containing esophageal mucous glands (GL) that empty via ducts (D) onto the luminal surface  The muscularis halfway along the esophagus reveals a combination of large skeletal or striated muscle fibers (St) and smooth muscle fibers (Sm) in the outer layer, which is cut transversely here.  Medical Application The lubricating mucus produced in the esophagus offers little protection against acid that may move there from the stomach. Such movement can produce heartburn or reflux esophagitis. An incompetent inferior esophageal sphincter may result in chronic heartburn, which can lead to erosion of the esophageal mucosa or gastroesophageal reflux disease (GERD). Untreated GERD can produce metaplastic changes in the stratified squamous epithelium of the esophageal mucosa, a condition called Barrett esophagus Stomach It is a mixed exocrine-endocrine organ that digests food and secretes hormones. The main functions are: To continue the digestion of carbohydrates initiated by the amylase of saliva To add an acidic fluid to the ingested food and mixing its contents into a viscous mass called chyme. To begin digestion of triglycerides by a secreted lipase, and To promote the initial digestion of proteins with the enzyme pepsin Stomach cont… Four major regions make up the stomach: The cardia, Fundus, Body, and Pylorus Stomach cont… Cardia & pylorus are primarily involved with mucus production and are similar histologically. Fundus and body regions are identical in microscopic structure and are the sites of gastric glands releasing acidic gastric juice. The mucosa and submucosa of the empty stomach have large, longitudinally directed folds called rugae. This flatten when the stomach fills with food. (a) The major stomach regions are the cardia, fundus, body, and pylorus, all with longitudinal gastric folds, or rugae. The muscularis has three layers. (b) At the esophagogastric junction, stratified squamous epithelium (SSE) lining the esophagus is abruptly replaced by simple columnar epithelium (SCE) of the stomach. Also seen here are the mucous esophageal cardiac glands (ECG) beneath the lamina propria (lP) and muscularis mucosae (MM). Mucosa Consists of a simple columnar epithelium: That invaginates into the lamina propria, forming gastric pits The gastric pits lead to long, branched, tubular glands. The surface mucous cells that line the lumen and gastric pits: Secrete a thick, adherent, and highly viscous mucous layer that is rich in bicarbonate ions and Protects the mucosa from both abrasive effects of intraluminal food and the corrosive effects of stomach acid. (c) The mucosa of the stomach wall contains invaginations called gastric pits that lead into gastric glands. These structures are lined by simple columnar epithelium containing five functional cell types. Mucosa cont… Stem cells for the epithelium that lines the glands, pits, and stomach lumen are found: In a narrow segment (isthmus) between each gastric pit and the gastric glands. The pluripotent stem cells divide produce progenitor cells for all the other epithelial cells. Some of progenitor cells  surface mucous cells, which have a turnover time of 4 to 7 days. Other progenitor cells  secretory cells of the glands (mucous neck cells and parietal, chief, and enteroendocrine cells). The turnover is much slower than the surface mucous cells. Mucosa cont… The vascularized lamina propria: That surrounds and supports the gastric pits and glands contains smooth muscle fibers and lymphoid cells, capillaries, and lymphatic. Separating the mucosa from the underlying submucosa is a layer of smooth muscle, the muscularis mucosae Regional differences in the stomach mucosa The mucosa of cardia & pylorus contains tubular glands, usually branched, with coiled secretory portions called cardial glands and pyloric glands The pits leading to these glands are longer in the pylorus. In both regions the glands secrete abundant mucus, as well as lysozyme, an enzyme that attacks bacterial walls  In the fundus and body: The mucosa is filled with branched, tubular gastric glands Each gastric gland has: An isthmus A neck and A base The distribution of epithelial cells in the glands is not uniform  The isthmus: near the gastric pit, contains differentiating mucous cells and a few parietal (oxyntic) cells The neck of the glands: consists of stem cells, mucous neck cells, and parietal cells The base of the glands: contains parietal cells and chief (zymogenic) cells. Various enteroendocrine cells are dispersed in the neck and the base of the glands.  Cells of gastric glands Has 4 major types 1. Mucous neck cells: Are present in clusters or as single cells between parietal cells in the necks of gastric glands Irregular in shape With the nucleus at the base of the cell and the secretory granules near the apical surface. Their mucus secretion is acidic and quite different from that of the surface epithelial mucous cells. 2. Parietal cells Present mainly in the upper half of gastric glands, with fewer in the base. Large rounded or pyramidal cells, each with one central spherical nucleus and cytoplasm i.e., intensely eosinophilic due to the high density of mitochondria Parietal cells cont… Secrete both hydrochloric acid (HCl) and intrinsic factor, a glycoprotein required for uptake of vitamin B12 in the small intestine. Secretory activity of parietal cells is stimulated both by Cholinergic nerve endings (parasympathetic stimulation) & Histamine and a polypeptide called gastrin, both secreted by local enteroendocrine cells 3. Chief (zymogenic) cells: Predominate in the lower region of the tubular glands The cytoplasmic granules contain the inactive enzyme pepsinogen. Converted into the highly active proteolytic enzyme pepsin after being released into the acid environment of the stomach. Chief cells also produce gastric lipase, which digests many lipids 4. Enteroendocrine cells: An epithelial cell type in the mucosa throughout the digestive tract, In the fundus enterochromaffin cells (EC cells) are found on the basal lamina of gastric glands Secrete principally serotonin (5-hydroxytryptamine), which increase gut motility The pylorus and lower body of the stomach contains G-cells which produce the polypeptide gastrin. Gastrin stimulates the secretion of acid by parietal cells. Other layers of the stomach The submucosa: It is composed of connective tissue containing blood and lymph vessels Infiltrated by lymphoid cells, macrophages, and mast cells The muscularis: Composed of smooth muscle fibers oriented in three main directions. The external layer is longitudinal, the middle layer is circular, and the internal layer is oblique At the pylorus, the middle layer is greatly thickened to form the pyloric sphincter The stomach is covered by a thin serosa MEDICAL APPLICATION In autoimmunity, parietal cells may be damaged to the extent that insufficient quantities of intrinsic factor are secreted and vitamin B12 is not absorbed adequately. This vitamin is a cofactor required for DNA synthesis Low levels of vitamin B12 can reduce proliferation of erythroblasts, producing pernicious anemia.  Gastric and duodenal ulcers are painful erosive lesions of the mucosa that may extend to deeper layers. Their causes includes: Bacterial infections with Helicobacter pylori, Effects of nonsteroidal anti-inflammatory drugs, Overproduction of HCl or pepsin, and Lowered production or secretion of mucus or bicarbonate. Small Intestine The small intestine is the site where the digestive processes are completed and where the nutrients (products of digestion) are absorbed by cells of the epithelial lining. It is relatively long ~ 5 - 8 m Consists of three segments: Duodenum Jejunum and Ileum These segments have many characteristics in common. Mucous membrane The lining of the small intestine shows a series of permanent circular or semilunar folds (plicae circulares) consisting of mucosa and submucosa and, which are best developed in the jejunum Intestinal villi are 0.5- to 1.5-mm-long mucosal outgrowths (epithelium plus lamina propria) and project into the lumen Villi are covered by a simple columnar epithelium of absorptive cells and goblet cells. Between the villi are the openings of short tubular glands called intestinal glands or crypts (crypts of lieberkühn). Submucosa (SM); Plicae circulsris (P); Villi (V); Muscularis (M); Serosa (S).  The epithelium of the intestinal glands have the following cells: 1. Enterocytes (the absorptive cells): Are tall columnar cells, each with an oval nucleus located basally. At the apex of each cell is a homogeneous layer called the striated (brush) border. On the striated border the projections are microvilli Each absorptive cell is estimated to have an average of 3000 microvilli and 1 mm2 of mucosa contains about 200 million of these structures (c) shows microvilli and densely packed mitochondria of enterocytes (E), and enteroendocrine cells (EC) with basal secretory granules can be distinguished along the basal lamina. 2. Goblet cells: Interspersed between the absorptive cells Are less abundant in the duodenum More numerous in the ileum. Produce glycoprotein mucins that are hydrated and cross-linked to form mucus. The main function is to protect and lubricate the lining of the intestine 3. Paneth cells: Located in the basal portion of the intestinal crypts below the stem cells They are exocrine cells with large, eosinophilic secretory granules in their apical cytoplasm Paneth cell release lysozyme, phospholipase, and hydrophobic peptides called defensins. All of which bind and breakdown membranes of microorganisms and bacterial walls. Paneth cells have an important role in innate immunity and in regulating the microenvironment of the intestinal crypts. 4. Enteroendocrine cells Polypeptide-secreting cells of the digestive tract fall into two classes: A "closed" type, in which the cellular apex is covered by neighboring epithelial cells An "open" type, in which the apex of the cell has microvilli and contacts the intestinal lumen Produce peptides hormone with both endocrine and paracrine effects 5. M (microfold) cells: Specialized epithelial cells in the ileum overlying the lymphoid follicles of Peyer patches These cells are characterized by the presence of basal membrane invaginations or pockets containing many intraepithelial lymphocytes and antigen-presenting cells M cells selectively endocytose antigens and transport them to the underlying lymphocytes and dendritic cells. Then migrate to lymph nodes for an appropriate immune response Lamina Propria through Serosa The lamina propria: Composed of loose connective tissue with blood and lymph vessels, nerve fibers, and smooth muscle cells. Smooth muscle fibers inside the villi are responsible for their rhythmic movements, which are important for efficient absorption. The muscularis mucosae also produces local movements of the villi and plicae circulares. The muscularis composed of an internal circular layer and an external longitudinal layer The small intestine is covered by a thin serosa Figure: Microvasculature, lymphatics, and muscle in villi. The villi of the small intestine contain blood microvasculature (left), lymphatic capillaries called lacteals (center), and both innervation and smooth muscle fibers (right).  The proximal part of the submucosa of duodenum has, large clusters of branched tubular mucous glands, the duodenal (Brunner) glands Mucus from these glands is distinctly alkaline, which neutralizes chyme entering the duodenum from the pylorus In the ileum both the lamina propria and submucosa contain the lymphoid nodule aggregates known as Peyer patches. An important component of the MALT.  Celiac disease Celiac disease (celiac sprue) is a disorder of the small intestine mucosa that causes malabsorption and can lead to damage or destruction of the villi. The cause of celiac disease is an immune reaction against gluten or other proteins in wheat. The resulting inflammation affects the enterocytes, leading to reduced nutrient absorption.  Crohn disease Crohn disease is a chronic inflammatory bowel disease that occurs most commonly in the ileum or colon. Result from combination of immune, environmental, and genetic factors. Excessive lymphocytic activity and inflammation occur in any or all layers of the tract wall, producing pain, localized bleeding, malabsorption, and diarrhea  Large Intestine The Mucosa The mucosa has no folds except in its distal (rectal) portion and lack villi The mucosa is penetrated throughout its area by tubular intestinal glands lined by goblet and absorptive cells with a small number of enteroendocrine cells.  Large Intestine cont… The columnar absorptive cells or colonocytes have irregular microvilli and dilated intercellular spaces indicating active fluid absorption Goblet cells producing lubricating mucus become more numerous along the length of the colon and in the rectum. Epithelial stem cells are located in the bottom third of each gland. (a) Diagram shows the wall of the large intestine composed of the four typical layers. The submucosa is well vascularized. The muscularis has a typical inner circular layer, but the outer longitudinal muscle is only present in three equally spaced bands, the teniae coli. (b) The mucosa is occupied mostly by tubular intestinal glands extending as deep as the muscularis mucosae and by lamina propria rich in MALT.  The lamina propria Rich in lymphoid cells and in lymphoid nodules that frequently extend into the submucosa The richness in MALT is related to the large bacterial population of the large intestine The appendix has little or no absorptive function but is a significant component of MALT  Muscularis The muscularis of the colon has longitudinal and circular layers but differs from that of the small intestine, with fibers of the outer layer gathered in three separate longitudinal bands called teniae coli. Serosa Intraperitoneal portions of the colon are covered by serosa, which is characterized by small, pendulous protuberances of adipose tissue.  Anal canal At the rectoanal junction, the simple columnar mucosal lining of the rectum is replaced by stratified squamous epithelium. The mucosa and submucosa of the anal canal form several longitudinal folds, the anal columns. Near the anus, the circular layer of the rectum’s muscularis forms the internal anal sphincter. Defecation involves the action of voluntary muscle comprising the external anal sphincter.  Mucosa of the rectoanal junction The simple columnar epithelium with tubular intestinal glands in the rectum (left side of photo) changes abruptly to stratified squamous epithelium in the anal canal (right side of photo), as seen in this longitudinal section. The connective tissue of the lamina propria is seen to contain many free lymphocytes  Medical Application Colorectal cancer is an adenocarcinoma that develops initially from benign adenomatous polyps in the mucosal epithelium. Such polyps usually occur in epithelium of the rectum, sigmoid colon, or distal descending colon. More common in individuals with low-fiber diets, which reduce the bulk of fecal material, and this in turn prolongs contact of the mucosa with toxins in feces. Screens for colorectal cancer include sigmoidoscopy or colonoscopy to see polyps and tests for fecal occult blood resulting from mucosal bleeding.  Medical Application Swollen blood vessels in the mucosa or submucosa of the anal canal can cause a painful disorder called hemorrhoids. This common condition typically results from a low-fiber diet, constipation, prolonged sitting, or straining at defecation Pancreas Both exocrine & endocrine gland Produces both digestive enzymes and hormones. Covered by a thin capsule of connective tissue and sends septa into it, separating the parenchyma into lobule. The secretory acini are surrounded by a basal lamina. – Supported by reticular fibers with a rich capillary network Endocrine function of the pancreas involves the pancreatic islets (islets of Langerhans). Low-power view of pancreas includes several islets (I) surrounded by many serous acini (A). The larger intralobular ducts (D) are lined by simple columnar epithelium. The ducts and blood vessels (V) are located in connective tissue, which also provides a thin capsule to the entire gland and thin septa separating the lobules of secretory acini  Pancreas cont… The digestive enzymes are produced by cells of serous acini. This somewhat resembles the parotid gland histologically, however; – the pancreas lacks striated ducts and – the parotid glands lack islets of endocrine tissue. Each pancreatic acinus consists of several serous cells surrounding a very small lumen, without myoepithelial cells.  Pancreas cont… Each acinus is drained by a short intercalated ducts. The initial cells of these ducts extend into the lumen of the acinus as centroacinar cells that are unique to the pancreas. Cells of the intercalated ducts secrete a large volume of fluid, rich in HCO3− (bicarbonate ions) This alkalinizes and transports hydrolytic enzymes produced in the acini. The intercalated ducts drain intralobular ducts drain into the interlobular ducts in the septa of the gland  main pancreatic duct The diagram shows the arrangement of cells more clearly. under the influence of secretin, the centroacinar and intercalated duct cells secrete a HCO3-- rich fluid that hydrates, flushes, and alkalinizes the enzymatic secretion of the acini. (a) Micrograph of exocrine pancreas shows the serous, enzyme-producing cells arranged in small acini (A) with very small lumens. Acini are surrounded by only small amounts of connective tissue with fibroblasts (F). each acinus is drained by an intercalated duct with its initial cells, the centroacinar cells (arrow), inserted into the acinar lumen.  Pancreas cont… The exocrine pancreas secretes approximately 1.5 L of alkaline pancreatic juice per day & – Delivers it directly into the duodenum where the HCO3- ions neutralize the acidic chyme entering there from the stomach and – Establish the pH for optimal activity of the pancreatic enzymes. These digestive enzymes include several proteases, α- amylase, lipases, and nucleases (DNAase and RNAase).  Pancreas cont… The proteases are secreted as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase, and procarboxipeptidases) Trypsinogen is cleaved and activated by enteropeptidases in the duodenum, – generating trypsin that activates the other proteases in a cascade.  Pancreas cont… Pancreatic tissue is protected against autodigestion by the following: Restricting protease activation to the duodenum, Trypsin inhibitor, which is copackaged in the secretory granules with trypsinogen, and The higher pH in the acini and duct system due to HCO3- secreted by the centroacinar and intercalated duct cells, which helps keep all the enzymes inactive.  Pancreas cont… Exocrine secretion in the pancreas is regulated mainly through two polypeptide hormones produced by enteroendocrine cells of the small intestine: – Cholecystokinin (CCK) stimulates enzyme secretion by the acinar cells. – Secretin promotes water and HCO3- secretion by the duct cells. – Autonomic (parasympathetic) nerve fibers also stimulate secretion from both acinar and duct cells. The Liver Is the largest internal organ The largest gland in the body The 2nd largest organ next to the skin Wt = 1.5 KG Constitute 2% of the total body wt The liver is covered by a thin fibrous capsule of connective tissue that becomes thicker at the hilum (porta hepatis). The main digestive function of the liver is production of bile.  Hepatocytes Hepatocytes, the key cells of liver, are among the most functionally diverse cells of the body. Hepatocytes and other liver cells have many specific functions: – Secretion of bile components, – Synthesis of the major plasma proteins, including albumins, fibrinogen, apolipoproteins, transferrin, and many others Function of hepatocytes and other liver cells cont… – Conversion of amino acids into glucose (gluconeogenesis) – Breakdown (detoxification) and conjugation of ingested toxins, including many drugs – Amino acid deamination, producing urea removed from blood in kidneys – Storage of glucose in glycogen granules and triglycerides in small lipid droplets Functions of hepatocytes and other liver cells cont…. Storage of vitamin A (in hepatic stellate cells) and other fat-soluble vitamins Removal of effete erythrocytes (by specialized macrophages, or Kupffer cells) Storage of iron in complexes with the protein ferritin Hepatocytes & Hepatic Lobules The structural unit of the liver can be considered as a conceptually simple hepatic lobule Hepatocytes are epithelial cells grouped in interconnected plates. Hepatocytes are arranged into thousands of small (~0.7 x 2 mm), polyhedral hepatic lobules. – This are the classic structural and functional units of the liver Hepatic Lobules cont… Peripherally each lobule has three to six portal areas with more fibrous connective tissue. Each of which contains three interlobular structures that comprise the portal triad: – A venule branch of the portal vein, with blood rich in nutrients but low in O2, – An arteriole branch of the hepatic artery that supplies O2, – One or two small bile ductules of cuboidal epithelium, branches of the bile conducting system central vein (C), hepatocytes (H), lymphatic (L), a portal venule (PV), hepatic arteriole (HA), and bile ductule (B).  Between all of the anastomosing plates of hepatocytes of a hepatic lobule are important vascular sinusoids – This emerge from the peripheral branches of the portal vein and hepatic artery and converge on the lobule’s central vein. The venous and arterial blood mixes in hepatic sinusoids.  Two functionally important cells are found with the sinusoids of hepatic lobules: 1. Stellate macrophages (Kupffer cells): are found within the sinusoid lining. These cells: – Recognize and phagocytose aged erythrocytes – Freeing heme and iron for reuse or storage in ferritin complexes. – Remove any bacteria or debris present in the portal blood. 2. Hepatic stellate cells (Ito cells) with small lipid droplets that: – Store vitamin A and other fat-soluble vitamins. – Produce extracellular matrix (ECM) components (becoming myofibroblasts after liver injury) and – Produce cytokines that help regulate Kupffer cell activity  Liver Regeneration The liver has a strong capacity for regeneration despite its slow rate of cell renewal. The loss of hepatic tissue from the action of toxic substances triggers a mechanism by which the remaining healthy hepatocytes begin to divide. Process is called compensatory hyperplasia, continuing until the original mass of tissue is restored.  Liver Regeneration cont.. Surgical removal of a liver portion produces a similar response in the hepatocytes of the remaining lobe(s). The regenerated liver tissue is usually well organized, and replaces the functions of the destroyed tissue. In humans this capacity is important because: – One liver lobe can often be donated by a living relative for surgical transplantation and – Full liver function restored in both donor and recipient.  Biliary Tract & Gallbladder The bile produced by the hepatocytes flows through the bile canaliculi, bile ductules, and bile ducts. These structures gradually merge, forming a network that converges to form the hepatic duct. The hepatic duct, after receiving the cystic duct from the gallbladder, continues to the duodenum as the bile duct. The gallbladder: – is a hollow, pear-shaped organ – attached to the lower surface of the liver – capable of storing 30–50 ml of bile. – The wall of the gallbladder 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 The gallbladder cont… The mucosa has abundant folds that are particularly evident when the gallbladder is empty Contraction of the smooth muscle of the gallbladder is induced by cholecystokinin (CCK). Release of CCK is, in turn, stimulated by the presence of dietary fats in the small intestine.