15. UPPER DIGESTIVE SEGMENT a General outline of the digestive or alimentary tube ‘Swallowing, digestion, and absorption take place through the digestive or alimentary tube, a 7-10 10-13 hollow rauscular conduit. The digestive pro- cess converts foex! material into a soluble form easy to absorb by the small intestine. The elimination of insoluble residues an! other materials is the fanetion of the large intestine. “Histologically, the digestive tube consists of four major layers: (1) an inner mucosal layer encircling the Iumen, (2) a submucosal layet, (3) a ‘muscularis extema layer and (4) a serosal/advencitial layer. “The inner mucosa layer shows significant vaiiations along the digestive tube. Ie is subdivided into dhrce components (1) an epithelial layer, (2) « connective tissue lamina propria, and (3) a smooth muscle muscularis mucosae. The upper digestive segment: Mouth, esophagus, and stomach We have divided the diseussion of the digestive system into. two compo rents or chapters: Chapter 15 is focused on the upper digestive segment and includes the mouth, esophagus, and stomach. Chapter 16 deseribes the lower digestive segment (small and lange intestine). This division is ‘based on the distinctive functions of the upper digestive segment (swallow- ing and digestion) and lower digestive seyment (absorption) The mouth “The mouth is the entrance to the digestive tube. Ingestion, partial diges- ton, and lubrication of the food, or bolus, ate the main functions ofthe ‘mouth and its asociated salivary glands. We study the salivary glands in Chapter 17, Digestive Glands. “The mouth, or oral cavity, includes the lips, checks, teeth, gums, rongue, and palate, Except for the tecth, the mouth is lined by « stratified squa- ‘mous epithelium, with a submucosa present only in certain regions. ‘The lips consist of three regions: (1) the cutaneous region, (2) the red region, and (3) the oral mucosa region, The cutancousregion is covered by thin skin (keratinized stratified squa- ‘mous epithelium with haie follicles and sebaceous and sweat glands). The red region is lined by a stratified squamous epithelium supported by tall papillae containing blood vessels responsible for the red color ofthis te- ‘gion. The oral mucosa region is continuous with the mucosa of the cheeks and gums. “The stratified squamous epithelium covering the inner suiface of the lips ‘and cheeks issupported by a dense lamina propria and a submucesa, closely bound by connective tissue fibers to the underlying skeletal muscks. “The gums, or gingivae, are similar to the ted region of the lips, excepeon the frce margin, where significant keratinization is seen. The lamina pro- pria ofthe gums binds tightly o the periosteum of the alveolar processes of the maxillae and mandible and to the periodontal membrane. ‘The gums lack submucosa or glands. “The hard palate is lined by a keratiniding stratified squamous epithelium similar to that of the ree margins of the gums, A submucosa is present in394 | 15. UPPER DIGESTIVE SEGMENT The tongue the midline bur absent in the area adjacent to the gums. Collagenous fibess inthe submucose bind dhe mucosa to the periosteum of the hard palate The soft palate and uvula are lined by a nonkeratinizing stratified squamous epithelium extending into the oropharynx where it becomes continuous with the pseuclostratified ciliated columnar epithelium of the upper respiratory tact. The submucosa is loose and contains. abundant mucus and scrous glands. Skeletal muscle fibers 2re present in the sofe palate and uvula. Figure 15-1 Circumvallate papillae are located in front othe V-shaped ‘suleus terminalis. They are associated vith Ebner's glands.15, UPPER DIGESTIVE SEGMENT | 395, Teton The tongue ‘The antetior two thirds of the tongue consists of @ core mass of skeletal emuscle criented in thee directions: longitudinal, transverse, and oblique. The posterior ‘one third displays aggregations of lymphatic tissue, the Fingual tonsils. TThe dorsal surface of the tongue is covered by a nonkeratinizing stratified squamous epithelium supported by a lamina propria associated with the muscle core of the tongue, Serous and mucus glands extend across the lamina propria and the muscle. Their duets open into the erypts and furrows of the lingual tonsils and cireurvallae papillae, respectively “The dorsal surface ofthe congue contains numerous mucosal projections called Tingual papillae (Figure 15-1). Each lingual papilla is formed by a highly vascu- Jar connective tissue core and a covering layer of stratified squamous epithelium. According to theit shape, lingual papillae can be divided into four types: (1) fill form papillae (narrow conical), the most abundant; (2) Fungiform papillae (mush- room-shaped); (3) circunvallate papillae; and (4) foliate papillae (lef-shaped), rudimentary in humans but well developed in rabbits and monkeys “Taste buds are found in all lingual papillae excepr the filiforen papillae Taste buds are harre-shaped epithelial stuctures containing chemosensory cells called ‘gustatory receptor cells. Gustatory receptor cells are in synaptie contact with the terminals of the gustatory nerves, ‘Circumwallate(walHike) papillae are located in the posterior part ofthe tongue, aligned in front of the sulcus terminalis. The cireumvallate papilla occupies & recess in the mucosa and, therefore itis surrounded by acireular Furrow or tench, Serous glands, or Ebner’ glands, in the connective tissue, in contact with the underlying muscle, are asociated with the circurnvallae papilla. ‘The duets of Exner’s glands open into the floor of the circular furrow. “The sides of the circumvallate papilla and the facing wall of furrow contain several taste buds, Each taste bud, depending on the species, consists of 50 10 150. cells, with its narrow apical ends extending into a taste pore. taste bud has three call components (Figure 15~2): (1) taste receptor cells, (2) supporting cells (or immature taste cells), and (3) preeursor cells (or base cel). “Taste receptor cells have alfe span of 10t0 14 days. Precursor cals give rise to supporting cells (or immature taste cell) which, in tum, become mature taste receptor cells. The basal portion of a taste receptor cell makes contact with an afferent nerve terminal derived (rom neurons inthe sensory ganglia ofthe Facial, lossopharyngeal, and vagus nerves. ‘Sweet, sour, bitter, and salty ae the four classic taste sensations. A ff taste is ‘umami (the taste of monosodium glutamate). A specific taste sensation is gener ated by specific taste receptor cells. The facial nerve cartes the five tase sensa- tions; the glossopharyngeal nerve carries sweet and bitter sensations. ‘ase is initiated when soluble chemicals, called tastants, diffuse through the taste pore and inretact with the G-protein G, B, and ysubunits (called gustducin) linked to the taste receptors (designated TRI and TR2), present in the apical microvilli of the taste receptor cells. As we diseussed in Chapter 3, Cell Signal ing, guanosine wiphosphate (GTP) binding wo the & subunit of the G-protein complex activates target molecules (ion channels in the taste receptor cells). onic changes within taste cells cause ether depola (Gee Figure 15-2) or hyper polarization of the receptor cells. An increase in intracellular Ca” triggers the release of neurotransmitters atthe afferent synapse with the afferent nerve term nal, Some taste receptor cells respond co only one of the basic tase substances (Others are sensitive to more than one taste substance. The tooth In the adult human, dentition consists of 32 permanent teeth. ‘The 16 uppersoe) Urea igure 15-2 Furnow or trench ‘Serous (Ebners) glands (not shown), |! Lamina > 2 ‘serous secrtng glands ented irto | i propria : the muscle The secretory ducts cpan | i ) into the furow erttenches ofthe | [eg | cicumvatoterepite i | ‘Stratified squamous epithelium Tight junctions ae present atthe apical i [seme am 1 region ofthe taste receptor calls ot — Besa erin | | Statiied squamous ' \ cptholum Ne Tar poet proeaing rise Mates rompers : pan oo oo ; _miocts aaa gia Synapse between a receptor cell |! immefure taste or supporting | | ZUanetrnteene wmia Tho ata rare eho i as apa ‘cna eurotranemiter-contaring vesicios in the basal region ofthe cytoplasm, ‘The coll maturation pathway ie Indicate by te arows Sc GD Atastant ite sou sty sweet or anise TA oT eer aferent rane BESEE ] terminals Nat ca? al i BB Tre complex so cated gusioucin EJ Tho suit GTP complex i because ofits similarity to transducin in pens end closes ion channels to EB Ce?" tiggers the release Photoreceptor cells of the retina) is activated by make the interior of the taste cell _, of neurotransmitters from the GTP binding tothe ex subunit of te G complex. positvely charged (depolarization). taste cel.15, UPPER DIGESTIVE SEGMENT | 397 “hetooth teeth are embedded in alveolar processes of the maxilla, The lower 16 teeth are embedded in similar alveolar processes of the mandible. The permanent denti- tion is preceded by a set of 20 deciduous teeth, aso called milk or baby teeth Deciduous teeth appear at about 6 months of age and the entre set is present by. age 6 to 8 years. The deciduous teeth are replaced between years 10 and 12 by the 32 permanent teeth. This replacement process ends at about age 18. Each of the several types of teeth has a distinctive shape and fimetion: incisors are specialized for cutting; canines, for puncturing and holding: and molars, for coushing. Each tooth consists of crown and either single or multiple roots (Figure 15— 23). The crown is covered by highly calified layers of enamel and dentin. The ‘outer surface of the toot is covered by another cakified tise ealled cementum The dentin forms the bull-of the tooth and contains a central charaber filled with soft tissue, che pulp. The pulp chamber opens at the apical foramen. into the bony alveolar process by the root canal. Blood vessels, nerves, and lymphatics ‘enter and leave the pulp chamber through the apieal foramen, Myelinated nerve fibers run along with the blood vessels. Tooth development and the differentiation of ameloblasts and odonto- blasts ‘The ectoderm, cranial neural crest and! mesenchyme contribute to the develop- ment ofthe tooth (Figure 15-4). Ameloblasts derive from the ectoderm. Odon- toblasts derive fiom the cranial neural trest. Cementocytes derive from the mesenchyme.398 | 15. UPPER DIGESTIVE seGMENT Teeth dvtopent Secreted signaling molecules—activin BA, fibroblast growth factor, and bone ‘morphogenetic proteins—mediate the interaction berween the dental epithelium and the mesenchyme during tooth morphogenesis, Figure 154 illustrates the Figure 15-4 y Tooth eruption fatunxardbone fret gow coca || Enamel pediediy | A i | natgrate goon ff anette moves dowrward | il ents {| endiuonw morpbogenate |: STs dentn eves et The dental sac gives ie : ee {i petense, end rane nis Cementosat, wih ee | {pete y he ptt | eines predentin a ee aes to erm dentin. The primitive dental pila becomes Celsofine || Athincelberstak the dental lamina, | -Thecapis the beginning le | 4 epintal icc bud | { connects he covnvasd-roving cls wth! edertogericergan ering te | proierate and | the ectodermal epelum. The cells at crown ofthe tooth The outer irwaginate riche {the growing end ofthe denial tud forma: genal epthetm becomes underyng cele suture filed with he neural |! guncunded by a nework ot mesodem (est neuroectodermal cls The epi’ capieries The inner centl | tooth buds ined by an outer and inner: epihefum develops into | dental epithelia. The tudo the | singe ayer of enamel secretin | emoloblests. Th cuermast ‘cls ofthe dental papala | ciferenite rio dent, {producing odontoblsts,Figure 15-6 15. UPPER DIGESTIVE SEGMENT | 399 relevant steps of tooth development. ‘Odontoblasts A layer of odontoblasts is present ac the periphery of the pulp. Odontoblasts are active seeretory cells chat synthesize and secrete collagen and noncollagencus ‘material, the organic components of the deni “The odontoblast is a columnar epithelial-like cell located at the inner side oF the dentin, in the pulp cavity (Figure 15-5). The apical cell domain is embedled in predentin, a nonmineralized layer of dentin-like material. The epical domain projects a main apical cll process that becomes enclosed within 2 canalicular § Aentinel tubule certains the edontotast apical process. The walls ofthe tubule re formed by aligned collagen fibers. the | end of he tubule, the bifurcated ends etend ino the ena. | Dentin consis 20% ecaie material. rai type | collagen, and 80% inorganic neti, mainly crystals of hhycronyapatite and fuoroepatit. Predentns he nonmineralized zone surrounding the apical processes ofthe odontobest. It cnt type | collagen resulting forthe released procollagen processed {nto tropocllagen. Topacolagen molec ies polyrenze to rode the type | colegen ter of predentin.400 | 15. UPPER DIGESTIVE SEGMENT eb Figure 18-6 Enamel rods Enamel contains 68% inongeric material, sini crystal o Iydeanyepatie, and 5 gant metre Enamel conics of: 1: vertical stack of ‘enamel rods. 2.An interrod region beeen the rods, ‘Ez od contains Pighly packed lydronyepatte cts, system just above the junctional complexes linking adjacent odontoblasts. ‘A well-developed rough endoplasmic reticulum and Golgi apparatus as well as sceretory geatules are found in the apical region ofthe odorwoblast. The sere- tory granules contain procollagen. When procollagen is released from the odon- oblast, ic is enzymatically processed to tropocollagen, which aggregates into type collagen fibril. Predentin is the layer of dentin adjacent to the odontoblast cell body and processes. Precentin is nonmineralized and consists mainly of collagen fibrils that will become covered (mineraliaed) by hydroxyapatite crystals in the dentin re sion. A demarcation mineralization front separates predentin from dentin. ‘The pulp consists of blood vessels, nerves, and lymphatics surrounded by fibroblasts and mesenchyme-like extracellular elements. Blood vessels (arterioles) branch into a capillary nerwork among the ecll bodies of the odontoblasts. An15, UPPER DIGESTIVE SEGMENT | 401 reba inflammation in che pulp causes swelling and pain. Because there is no space for ‘swelling inthe pulp cavity. the blood supply is suppressed by compression, lead ing rapidly co the death of the cells ofthe pulp. Cementum The cementum isa bonelike mineralized tissue covering the outer surface of the 100, Like bone, the cementum consists of calcified collagenous fibrils and trapped ‘osteocyte like cells called cementocytes. “The cementum meets the enamel at the cementoenamel junction and separates the crown from the roor ac the neck region of the wooth. The outermost layer of the cementum is uncaleifed and is produced! by eementoblasts in concact with the periodontal ligament, a collagen and fibroblastrich and vascularized. sus pensory ligamentholding the tooth in the sockets of the alveolar bone. The strength of che periodontal ligament fibers gives tecth mobility and strong bone attach- iment, both usefal in orthodontic treatment. Ameloblasts ‘Ameloblasts are enamel-producing cells present only during tooth development. ‘The ameloblast (Figure 15-6) is @ polarized cofunmar cell with mitochondria and a nucleus present in the basal region of ‘the cell. ‘The supranuclear region contains numerous cisternae of rough endoplasmic reticulum and Golgi appara- ‘Beyond apical junctional complexes joining contiguous ameloblasts che apical domain displays a broad provess. Tomes process, in proximity to the calcified ‘enamel mattix. The apical damain has abundant secretory granules containing glycoprotein precursors of the enamel maerix. ‘The enamd is the hardest substance found in the body. About 99% of the ‘enamel is composed of crystals of hydroxyapatite; less than 1% is protein. The newly secreted enamel contains a high content of protein (about 309%), whose concentration decreases to 1% during enamel mineralization, ‘Two clases of pro- ‘eins have been identified: amelogenin and enamedin ‘Amelogenin is the major constituent, unique to the developing enarncl. Enamelin is @ ttinor component. Amelogenesis imperfecta is an inherited dis- cease affecting the formation of the tooth enamel; affected enamel does nor attain its normal thickness. It is caused by'a mutation of the amelogenin gene. Electron microscopic examination shows that the enamel consists of thin un- ulated enamel sods separated by an interrod region with a structure similar 10 that of the enamel rods but with its crystals oriented ina different direction. Each rod is coated with a thin layer of organic mattx, called the rod sheath. General organization of the digestive or alimentary tube Although we will study each segment of the digestive or alimentary tube sepa rately itis important to discuss first the general organization of the tube to un- derstand that each segment does not function as an independent unit. ‘We start with the common histologic features of the digestive tube by indicat- ing chat, except for che oral cavity, the digestive tube has @ uniform histologic organization. This organization is characterized by distince and significane strue- ‘tural variations reflecting changes in functional activity Aficr the ora cavity, the digestive tube is differentiated into four major organs: esophagus, stomach, smal inte made up of four concentric layers (Figure 15 cosa, (3) the muscularis, and (4) the advent ‘The mucosa has three components: a lining epithelium, an underlying lamina and large intestine. Fach of these organs is ): (1) the mucosa, (2) the submu- OF SerOS2. propria consiscing of 2 vascularized loose tonnective tissue, and a thin layer of smooth muscle, the muscularis mucosaeia] ative eine The dgestve be Figure 15-7 Lymphatic nodules and scattered immunocompetent cells lymphocytes, plasma cells, and macrophages) are present in the lamina propria. The lamina propria of the small and large intestines isa relevant ste of immune responses (see Chapter 16, Lower Digestive Segment). ‘The lining epithelium invaginates vo form glands, excending into che lamina propria (mucosal glands) or submucosa (submucosal glands), or ducts. crans- porting secretions from the liver and pancreas through the wal of the digestive tube (duodenum) into it Lumen. In the stomach and small intestine, both the mucese and submucos extend into che lumen as folds, called rugae and plicae, respectively. In other instances, the mucosa alone extends into the lumen as fingers, ot villi, Mucosal glands increase the sceretory capacity, whereas villi increase the absorptive capacity of the digestive tube. “The mucosa shows significant variations from segment to segmenc of the di- gestive tract. The submucosa consists of a dense irregular connective rissue with lange blood vessels, Iyraphatics, and nerves branching into the mucosa and mus- cularis. Glands are present in the submucosa of the esophagus and duodenum. “The muscularis contains two layers of smooth muscle: the smooth muscle fibers of the inner layer are arranged around the tube lumen (circular layer); fibers ofthe outer layer are disposed along the tube (longitudinal layer). Conerac- tion of the smooth fibers ofthe ciceular layer reduces the lumen: contraction of the fibers of the longitudinal layer shortens the tube. Skeletal muscle fibers are present in the upper esophagus and che anal sphincter: ‘The adventitia of the digestive tract consists of several layers of connective tissue continuous with adjacent connective tissues. When the digestive tube is stispended by the mesentery or peritoneal fold, the adventitia is covered by a mesothelium (simple squamous epithelium) supported by a thin connective ts- sue layet, together forming a serosa, oF serous membrane.Figure 15-8 Lear OSeT | Aes ot and vere soy Cet Gastric mucosa ‘lineal significance Gast artery 27 Dense regular connective Hsu othe submucosa Gest dena Calin venue Fenestra capillary bed Anastomosis GD Gastric arteries for a subsersal pens _ajacent capillary ‘ha inks to the intarruscular plenus. beds G Te highy developed inramusculer peas supplies brarches to he submucesal pleas and the layers ofthe musculatis. EF The sutmucosa phous supleseneiles tothe mucosa Teepe ener BJ pes teone ero cts mesenteric vers thin the gastric mucesa ard ecund the ‘Subserosal plows wih each other. Gastic mctocraiaen isleart the pathogenesis peptic ulcet disease ardite _€D Cotectingreraies crane copia ito Protection a the gastric mucosa from the agcression of roche acid ard pepsin __subnucosal venules of he submucosal vencus actity. Inaruscular plows glands. Poiglendularcepilary beds anastomose | planus. | Microvasculature of the digestive tube We stare our discussion with the microcirculation of the stomach. [n Chapter 16, Lower Digestive Segment, we describe the microcirculation of the small intestine and point out differences (sce Figute 16-3). Bloed! and lymphatic vessels and nerves teach the walls ofthe digestive ibe through the supporsing mesentery or the surrounding tissues. After entering the walls of the scomach, arteries organize three arterial networks: the subseross, inteamusculas, and submucosal plexuses (Figute 15-8). Some branches from the plexuses run longitudinally in the muscularis and submucosa; other branches extend perpendicularly into the mucosa and muscularis. In the mucosa, arterioles derived from the submucosa plexus supply a bed of fenestrated capillaies around the gastric glands and anastomese laerally with cach other. The fenestrated natu ofthe capillaies facilitates bicarbonate deiv- ery 1 provect che surface epithelial cells against hydrochloric acid damage (see Figure 15-17). Collecting venules descend from che mucosa into the subraucesa ae veins, leave the digestive tube tough the mesentery, and dian into the splenic and superior mesenteric eins. Mesenteric veins dein into the portal vein, leading tothe liver (Gee Chapter 17, Digestive Glands). Clinical significance: Gastric microcirculation and gastric ulcers ‘As we discuss later in this chapter, gastric microcirculation plays a role in the protection of the integrity of the gastric mucosa. A breakdewnoF | are eee aioe lod an nave spy Figure 15 Inner muscle lye (cular, Aajacent smocth ruse ces ar erica coupled and conta syictercsl when site. ‘The autonomic nervous system is presented inthe alimentary tube by two distinct interemmected neuronal networks: the myenteric plexus of Auerbach cated between he circar ard longiudnal muscle layers and innervating the muscle {vers andthe submucosel plexus of Meissner (bund betneen te musculatis and the mucosa and inervatg the sectetory glen). The to plenses at linke by axons ano consist of senscry «and motor neurons connected by interneurons. Although they ; ; an function indepeneily of ho CHS, they ae equated by os a pregargjionic fives of parasympathetic neurens ofthe vagus ‘and pelvic nerves and postganglionic bets of sympathetic euros ofthe spinal cord and preveribral ganglia, ‘Some ol he chemical neurcransmittersfcunc inthe enteric nerves are acetylcholine (excitatory), the two major inhibitory nitric ovide and vasoactive intestinal peptide (VIP), and tachykinins (suchas substance P). Serotonin ari ‘somatostatin are products of interneurons. protective mechanism, including mocus and bicarbonate secretion, allows the destructive action of hydrochloric acid and pepsin and bacterial infection. leading to peptic ulcer disease (PUD). PUD includes a group of disorders characterized bya pantial or cota loss of the mucosal surface of the stomach or duodenum or both, ‘The tich blood supply to the gastric mucosa is of considerable significance in ‘understanding bleeding associated with stress ulcers. Stress leery are superficial gastric mucosal erosions observed after severe tauma or severe illness and afier|15, UPPER DIGESTIVE SEGMENT | 405 The esophagus long-term use of aspirin and corticosteroids. In mast cases, stres ulcers are cini- «ally asymptomatic and ate detected only when they cause severe bleeding. Nerve supply of the digestive tube “The digestive tube is innervated by the autonomic nervous system (ANS). The ‘ANS consists of an extrinsic component (the parasympathetic and sympathetic innervation) and an intrinsic. or enterie, component. Sympathetic nerve fibers derive from the thoracic and lumbar spinal cord. Parasympathetic nerve fibers derive from the vagal dorsal motor nucleus of the medulla oblongata. Visceral sensory fibers exiginat® in the spinal dorsal root gan- la. The intrinsic or enteric innervation is represented by two distinct intercon rected neuronal eicuits formed by sensory and motor neurons linked by inecr ‘neurons: (1) the submucosal plewus of Meissner, present in the submucosa, aed (2) the myenteric plexus of Auerbach (Figure 15-9), located between the inner circular and outer longitudinal layees of the muscularis, ‘Neurons and interneurons of the plexuses give off axons that branch to form the networks. The plexuses are connected to the extrinsic sympathetic and para- sympathetic ANS: the plexuses of Auerbach and Meissner receive preganglionic axons of the parasympathetic system and postganglionic axons of the sympa- thetie system. TThe intrinsic or enteric nervous system enables the digestive tube to respon t0 both local stimuli and inpuc from extrinsic nerves of the ANS. ‘The integrated extrinsic and intrinsic enteric) networks regulate and concrol (1) peristaltic con tractions of the muscularis and movements of the muscularis mucosae, and (2) secretory activities of the mucosal and submucosal glands. For example, stimu- lacion of preganglionic parasympathetic nerve fibers (cholinergic terminals) of the muscularis causes increased motility as well as glandular secretory activity. Scimulation of postganglionic sympathetic nerve fibers (adrenergic terminals) ‘on the smooch muscle cells causes decreased motility. ‘The esophagus “The esophagus is a muscular tube linking the pharynx to che stomach. Ie cuns through the thorax, crosses the diaphragm, and enters the stomach. Contractions ‘of the muscularis propel the food down the esophagus—in about 2 seconds. At this velocity, changes of pressure and volume within the thorax are minimal. No disruption of respiration and cardiopulmonary cixculation takes place. TThe esophageal mucosa consists ofa. steatified squamous epithelium overly ing a lamina propria with numerous connective tissue papillae (Figure 15-10). ‘The museailaris mucosae isnot present in the upper portion of the esophagus, but icbecomes exganized near the stomach. Both the mucosa and the submucosa in the undistended esophagus form longieudinal folds thae give the lumen an inegular outline. As the bolus of food moves down the esophagus, the folds dis appear transiently and then are restored by the recoil of the elastic fibers of the The submucosa contains a network of collagen and clastic fibers and many small blood vessels, Ac the lower end of the esophagus, submucosal venous plex tuses diain into both the systemic venous system and the portal venous system, ‘An increase in pressure in the portal venous system, caused by chronic liver die «ase, results in dilation of the submucous venous sinuses and the formation of ‘esophageal varices. Ruprute ofthe varices or ulceration of the averlying mucosa an produce hemoxthage into the etophagus and stomach, afin causing vomit ing (hematemesis). submacoea glands are found inthe exphagus Their functions406 | _15-UPPER DIGESTIVE SEGMENT ‘The esophopss Figure 15-10 { The contraction of he muscularis mucosae produces | longitudinal mucosal folds. ipa enophagal pine | Fels are ransenty eased during he trait of the (UES) ion’ anatemicaly as {ood boius. The reel action elastic ers in the _aleaqeanas ‘submucosa restores the folds. ‘Striated (skeletal) muscle — Muscufaris . rrucosae Both striated (skeletal) . = and smooth muscle cosa i —Adventitia ai ‘Muscularis mucosae Muscularis: y; 3 Predominantly smooth f muscle A Bi ‘sphincter (LES);no eee {a serosa surrounds ute a be t ns a i “cs ss eae the esophagus only longitudinal: i i teenies) below the ciaphragm. | layer Inner deur layer Longjteinal mucosed The muscularis consists inner crear ard ‘cuter longitudinal layers of muscle. Inthe iia! “ | peri lhe eseotagus, bth ges ae stited | Submucosal glands are vane rule. Deep the ssid muse, smooth ‘ubuloacner lends rruscle appear nthe mile thie. nite lower || trang in sal cules, tid, both eyers consist ol smooth muscle. | dained by single uc. | acca nucceae15, UPPER DIGESTIVE SEGMENT | 407 The eopbags Figure 15-11 —_— Fei hs on mec nee ee _gards, sumounded by a lamina propria em... = containing capillaries, and the muscularis: i : z i i & ; i i i i E The paste mucosa is caver ty a protective layer of mucus that protects the surface eptelum ron rmecharical erosion by the ingested food aro the | cesinctve elect of acid and ydayc enzymes | present inthe gastic ice. ‘cara ‘The orad area and the LES relax uring swallowing, The caudad areais involved he regulation of gastric emplying. ‘The sorachis usualy died int the cardia, fundus, body, ard antrum. Based on the moti patterns ofthe sth, tan be Gvded into an rad area—consising of the fundus, and pron ofthe body—erd a caudad area—consitng othe distal body an th artru. to produce continuously a thin layer of mucus that lubticares the surface of the epithelium. ‘The mucosal tubular glands, restricted to the lamina propria, resemble the cardiac glands of the stomach and are called eandiae esophageal glands (Figure 15-10). Their excretory ducts join larger duct that opens atthe tip of a papilla. ‘The submucosal rubuloacinar glands, found in the submucosa just hencath the muscularis mucosae, are organized into small lobules drained bya single duct. ‘Theacini are lined by evo secretory cell ypes: a mucous and a serous cell ype, the later with secretory granules éontaining lysuzyme. “The composition of the inner circumferential or citcular and outer longitudi- nal layers of the muscularis shows segment-dependent variations, In the upper third of the esophagus, both layers consist of striated muscle. [nthe middle third,408 | 15-UPPER DIGESTIVE SEGMENT ‘he somach smooth muscle fibers can be seen deep to the striated muscle. In the lower third, bout layers of the muscularis contain smooth muscle eels. Clinical significance: The mechanism of swallowing and dysphagia “The esophagus has two sphincters: (1) ‘The anatomically defined upper esoph- aageal sphincter (UES), of cricopharyngeal sphincter, (2) ‘The functionally de- fined lower esophageal sphincter (LES), or gastroesophageal sphincter. The UES participates in the initiation of swallowing, The LES prevents reflux of gastric contents into the esophagus. Because the esophageal stratified squamous lining epithelium may be replaced at the lower end by 2 poorly resistant columnar epithelium, 2 reflux of acidic gastric secretions causes chronic inflammation (reflux esophagitis) or ulceration and difficulty in swallowing (dysphagia). This persistent condition leads to fibro- sis and eventual stricture ofthe lewser esophagus. ‘When the esophageal hiatus in the diaphragm does nor clese entitely during development, a hiatus hernia enables a portion of the stomach to move into the thotacie cavity. In sliding hiatus hernia, he stomach procrudes through the di phragmatic hiatus, normally occupied by the lower esophagus. Reflux esophagitis and peptic uleeration in the intrathoracic portion ofthe stomach and lower esopha gus determines difficulty in swallowing and che feeling of lump in the throat. ‘This condition, commonly seen in family practice patients, affects young and middle-aged! women in particular, ‘The movements involved in swallowing are coordinated by nerves from the ‘cervical and thoracic sympathetic trunks, forming plexuses in the submucass and in berween the inner and outer layers of the muscularis. Diseases affecting this neuromuscular systern may result in musele spasm, and substernal pain. Figure 15-12 Cardiac glands Catia dards ar simple tubular an coiled atthe hols tower end. es ris to sectioned ard prolies at diferent angles. ‘The called nature of cardac glands results in eross and cblque sections. Cardac dards af ined ty mucussceraing cls ard CHEE fave asmler suture tothe esepeageal cardlac dhnds urdin he evince oe excohagus15, UPPER DIGESTIVE SEGMENT | 409 Figure 15-13 © AsSple coturnar epithelium | consisting of surfece mucous | stomach and the pits. Suface | muoaus cals fer fram goblet calls: er rucleus is ovel- cals spay a tered nucleus inthe basal porto ofthe cl. {inthe nattow peton othe {gland neat the gasp. THs rao region s known a the + lttimus of geste gland fedora inthe fonds : fe reer a body ofthe stomach. 5 I accu neckosts Fenestrate capilaryin the lamina propia © Chit ‘cots peconince inte | lover orton ca gost “Their basal domain és basophilic ance apie coma coiaies relory granules (pepsinoger Enetoendoctine cell wit an apical ‘ueleus and ight cytoplasm “The stomach extends from the esophagus to the duodenum. Av the gastrocsoph- ageal junction, the epichelium changes from stratified squamous to a simple co- lumnar type. ‘The muscularis mucosae of the esophagus is continuous with that of the stomach. However, the submucosa does not havea clear demarcation line, and glands from the cardiac portion ofthe stomach may extend under the strati- fed squamous epithelium ard contact the esophageal cardiac glands. “The funetion of the stomach is to homogenize and chemically process the swallowed semisolid food. Both the contractions of the muscular wall of the stomach and the acid and enzymes secreted by the gasttic mucosa contribute €0410 15. UPPER DIGESTIVE SEGMENT Thestanect this Function. Once the food is tansformed into a thick flu ally into the duodenum. Four regions are recognized in the stomach: (1) the cardia, @ 2- ro 3-cm-wide zone surrounding the esophageal opening, (2) the fundus, projecting co the leftof the epening ofthe esophagus, (3) the body, an extensive central region, and (4) the pyloric antrum (Gk. gplres, gatekeeper), ending at the gastroduodenal o fice. Based on the motility characteristics ofthe stomach, the orad area, consist- ing of the fundus and the upper part of the body, relaxes during swallowing. The caudad area, consisting of the lower portion ofthe body and the antrum, partici- iis released pradu- ‘Surfae rucous cells ricer sectioned at diferent anges ‘Mucous surface cells have apical ‘el nzdton, abundant mitochondr ‘wih carbonic corning ‘lyecprteins (mucins). Mucins caine wih water on ‘the surface of he gastric mucosa to form a protective iategether tothe formation cf bicarorat ions to increase the pH of the protective gel ‘Vagal nerve stirultion and acatycholine increase the cecretion ol soluble mucus by | neckcels—ocaed hee the gland cpensiro the pi. Lethe macs produced by a ie ee nee ee eee a a ese yy eKeacag the glandular and mucosal surface.15. UPPER DIGESTIVE SEGMENT ya Chil and pst cals Niechoraia = ‘estan receptor alana Rough endoplasmic reticulum The gastic lands ofthe fundus-body region contain tao major cel types: The che er peptic cells produce and secrete pepsinogen (42.5 kDa) which gies ‘ise othe predic enzyme pepsin (35 KDa) inthe gastic tice hen the pH ‘is below 5.0. Pepsin can catalyze the formation of addtional pein fom persnogen. Acetylcholine stulats the secretion of pepsinagen The parietal or oxyntic cels secrete hydrochloric acid ard intrinsic factor in humans (m some species, chet cells secrete innsc fact). The cytoplasm of paetal calls displays numerous tubulovesicles and an intracellular ‘canaliculus coniruous wit the lumen ofthe gastric gland. fer stimulation, te tubulovesices fuse with the plasma menbrane of the intraceldar ‘analicus. Carbonic anhydrese and H’,K"-ATPase are localized in the ‘mctovil projecting nto the lumen ole intrecelar caries.ai2 15, UPPER DIGESTIVE SEGMENT het and past eas pates in the regulation of gastric emptying, "The empry stomach shows gastric muicosal folds, or rugae, covered by gastric pits or foveolae (Figure 15-11). A gastric mucosal barrier, produced by surface ‘mucus eels, protects the mucosal surface. The surface mucus cells contain apical lic acidSchif (PAS)-positive granules and are linked to each other by api- «al tight junctions. Cardia region Glands of the cardia region are tubular, with 2 coiled end and an opening con ‘tinuous with the gastric pits (Figure 1512). A mucus-secreting epithelium lines the cardiac glands. Fundus-body region: The gastric gland Gastric glands of the fundus-body region are the major contributors to the gastric juice, Abour 15 million gastric glands open into 3.5 million gastric pits. From ‘wo t0 seven gastric glands open into a single gastric pit, or foveola. ‘A gastric gland consists of hree regions (Figure 15-13: (1) The pit, or foveola, lined by surface muicous cells: (2) the neck, containing raucous neck cells mitoti- cally active stem calls, and parietal cells; and (3) the body, representing the major length of the gland. ‘The upper and lower portions of the body contain different proportions of cells lining the gastric gland TThe surface mucous cells line the surface ofthe gastric mucosa and the gastric pits (sce Figures 1513 and 15-14) ‘The gastric glands proper house five major cell types: (1) mucous neck cells (sce Figure 15-13), (2) chief cells (also called peptic eells), (3) parietal cells (aso called exyntic cells), (4) stem cells, and (5) enteroendoerine eels ‘The upper portion of the main body of the gastric gland contains abundant parietal cells. Chief eels and enteroendocrine cells predominate in the lower por- tion (sce Figure 15-13). ‘The gastric mucosa of the fundus-body has ewo classes of mucus-producing cells (Figure 15-14): (1) the surface mucous cells lining the pits, and (2) the ‘mucous neck cells locared ar the opening of the gastric gland into the pit. Both calls produce mucins, glycoproteins with high molecular mass. A mucus layers containing 95% water and 5% mucins, forms an insoluble gel thar acraches ro the surface of the gastric mucosa, forming & 100-sim-thick protective gastric mucosal barrier. This protective mucus blanket traps bicarbonate ions and neutralizes the ‘microenvironment adjacent ro the apical region of the mucous surface cells to an alkaline pH (about 7.0). Na‘, K’, and CI” are additional constituents of the protective mucosal barir. Patients with chronie vorniting or undergoing continuous aspiration of gastric juice require intravenous replacement of NaCI, dextrose, and K* ro prevent hy- pokalemie metabolic acidosis. Chief cells (Figure 15-15) predominate in the lower third of the gastric gland, Chief cells are not present in cardiac glands and are seldom found in the pyloric antrum. Chief ells havea structural similarity to the zymogenie cells ofthe exo cine pancreas: the basal region of the cytoplasm contains an extensive rough endoplasmic reticulum. Pepsinogen-containing secretory granules (zymogen gran- ules) are observed in the apical region ofthe cell. Pepsinogen, a proenayme stored in the zymogen granules, i released ineo the lumen ofthe gland and converted in the acid environment of the siomach to pepsin, a proicolysic enzyme capable of esting most proteins. Exocytosis of pepsinogen is rapid and. stimulated by ing (afer fasting) 2 Parieal cells predominate in the neck and fundus ofthe gastee gland and arePernicious anemia In autoimmune gastritis, antibodies produced ‘grin HY, K*-ATPase cause a reduction in hycro- hlovcacidin the gastric juice (achlorhydria) and lack of synthesis of intrinsic fact. The resulting Vi- ‘amin 42 deficiency osrupts the formation of rec ‘blood cells inthe bone marron, leading to a cond tion knawn 2s pernicious anemia. 15. UPPER DIGESTIVE SEGHENT | 413 the petal cl Figure 15-16 (Chior, rysrogen, and potassium ns are actly UNensported ino the lumen of the canaliuts. HY K’- dependent ATPase provides the energy for is tonsir. BYR dependent iRREIBHET [Nac [20 | — By ation Man. re Byactve transport linked to chief cells by junctional complexes. Parietal cells produce the hydro chlorie acid of the gastric juice and intrinsic factor. glycoprotein thar binds to vitamin By» to facilitate its absorption in the upper smell imestine. Parietal cells have three distinctive features (sce Figure 15-15): (1) Abundant mitochondria, which occupy about 40% ofthe cell volume and provide the ad ‘enosine tiphosphace (ATP) required to pump H ions ino the lumen of the incracellalar canaliculus. (2) An intracellular eanaliculus, formed by an invagi- nation of the apical cell surface and continuous with che lumen of the gastric gland, which is lined by numerous microvilli, (3) An H’,K°-ATPase-rich tubulovesicular system, which is distibured along the secretory cansliculus dur- ing the resting state of the parietal cel ‘Alter stimulation, the tubulovesicular system fuses with the membrane of the secretory canaliculus, and numerous microvilli project into the canalicular space. Membrane fusion increases the amount of H'K°-ATPase and expands the intra- cellular canaliculus. H’,K’-ATPase represents about 80% of the protein content of the plasma membrane of the rerovill. Secretion of hydrochloric acid by parietal cells Parietal cells produce an acidic secretion (pH 0-9 (0 2.0) rich in hydrochloric acid, with a concentration of H’ ions one million times greater than that of blood (Figure 15-16). ‘The release of H* ions and Cl by the parietal cell in- volves the membrane fusion of the tubulovesicular system with the intracellulae canaliculus. “The parasympathetic mediator acetylcholine and the peptide gastrin, produced by enteroendocrine cells of the pyloric ancrum, stimulate parietal cells to secrete HC (see Figure 15-19). Acetylcholine also stimulates the release of gastrin. Hs414 15, UPPER DIGESTIVE SEGMENT “he gas peeve basket Figure 15-17 Some ofthe bicarbonate fons ottuse ino the mucus bark to increase the oH Fenostated caplary ‘Bicarbonate ions enter a fenestrated capillary in the tamina propria, with ‘oad flowing toward the surface ophehum tamine potentiates the efiets of acetylcholine and gastrits on parietal cell secre~ tion after binding to che histamine H,, receptor. Histamine is produced by en- terochromaffin-like (ECL) cells within the lamina propria surrounding the gas- tric plands. Cimetidine is an H, receptor antagonist that inhibits histamine-de- pendent acid secretion, H1',K*-dependent ATPase facilitates the exchange of H* and K", Cl and Na’ (derived from the dissociation of NaCl) are actively transporte of the intracellular canaliculus, leading to the production of HCI. K* and Na’ are reeycled back into the cell by separate pumps once H" has taken their place. ‘Omeprazole, with binding affinity to H’,*-dependent ATPase, inactivates acid secretion and isan effective agent in the treatment of peptic ule. ‘Water enters the cell by osmiésis—because of the secretion of ions into the ‘analiculus—and dissociates into H* and hydroxyl ions (HO). Carbon diox- ide, entering the cell from the blood or formed during metabolism of the cell, combines with HO to form earbonic acid under the influence of carbonic anhydrase. Carbonic acid dissociates into bicarbonate ions (HCO, ) and. hy- drogen ions. HCO, diffuses out of the cell into the blood and accounts for the increase in blood plasma pH! during digestion. Clinical significance: The gastric mucosal barrier and Helicobacter pylori infection Ie is convenient wo regard the gastric juice as a combination of rwo separate secre- tions: (1) an alkaline mucosal gel protective component, prodiced by surface mucous cells and! mucus neck cells and (2) HCI and pepsin, ewe parietal-chief cell potentially aggressive components. ‘The protective component is constitu-iS UP eH i475 utabocteplst Figure 15-18 ees Serta Hoot [pcr pee BB roth hea ty iio i Leeper men ‘decreases the accty ofthe gasttic fo ¥ ere High ce fra short Kesienaie carey ek tod fm, About six tage provide the ny = molly Dung tis ime. H por decrease the aciyby producing ammonia) by the actonol the enzyme urease. 6B stationary phase pet enter the mucus blanket preduce adesins, adhesion molecules wth binding aft to ueose-containingrecepors, and attache apical surfaces ofthe mucous epithelial als contig fcose-inding ‘tes, Cel attachment enables adherent H. ‘yf cbtain nutints rom epithe cells, which ator i. Colonization ‘Welknourished pyri detach rom the ‘apical surface ofthe mucus-secreting sufece cel, replicate within the mucus Danket and atch o sialic ‘acid-containing mucous proteins, Bacteria reenter he act phase (retity and NHs procucton end reintate rere Fucose: containing | receptor surface Hf ere | Caer | ar dace Torwnrston of ell cae meen wh bal arnt ne fe gar mace lamina propria develops when cells of the ‘Stem cells are mitotic-diividing calls present ‘surface epithelium are destroyed by H. adjacent to the neck region of the gastric gland pylori. ‘and ere responsible for the continuous renewal aes = ofthe gastric mucosa. Daughter cells derived fomte son cl mam eer nado tyes ees mses, eur wrt prt cls, a od puforunsndiatocas ‘Surface mucous cells havea lifespan of about ‘3 days; panetal and chiet cells have a filespan of tennant tive; tis always present. The aggressive component is faculative because hydro chloric acid and pepsin levels increase above bas! levels aftr food intake. The viscous, highly glycosylated gastric roucus blanket— produced by surface15. UPPER DIGESTIVE SEGMENT Castronterotndone cole a6 ‘mucous cells and mucous neck cells—maintains a neutral pH at the epithelial cell surfaces of the scomach. In addition, che mitochorsdrial-ich surface mucus cells (sce Figure 15-14) produce HCO” ions diffusing into the surface mucus gel. Recall the clinical significance during chronic vorsiting of Na’, K'. and CI” present in the protective mucosal bartier and gastric juice. HCOs ions, produced by parictal cells enter the fenestrated capillaries of the lamina propria. Some of the HCO ions diffuse into the mucus blanket and neutralize the low pH created by the HCI content of the gastric lumen at the vicinity of the surface mucous cells (Figure 15-17). Figure 15-19 chair (mescatc) neve &—_— Pestsynaptc, Yeausnene eur ss and release of peptide hormones synthe atte hormones by sasvo- Totarget cal GD Lic solute amino acids enter a gastroenteroendocrine ‘cal and are decerbosyated to form amines. Amines ee part of ‘Polypeptide hormores hat can simuate or iii target call ution, EB A poiypeptide hormone is released from the gasro- ‘entercendosrine cel into the surcunding lamin propria anc reaches the blood capil. {5B Bicod:totne papiies wil Lind to target cals to stimulate ‘orinhibit a cellular function. ‘gal stimulation of the pyle antrum causes the release of astrn-releasing peptide rom postsynepic neurons that strulate ‘rect the release of gastin from G cel presentin the ant, Sorratosiatin released from agjecert O ces (not shox) inhibits gastrnrelease. GE Histamine, leased by enterochromatfr-lke (ECL celsin the lina propia in response to aoetychine released by psigenghoric bers, binds othe Hp receptor on parietal cells Histamine potentiates the ete of acetycholne an gain on the secretion of hydrochloric acid by aia al15, UPPER DIGESTIVE SEGMENT | 417 cosroetemenderine et However, the mucus blanket fining the gastric epithelium, in particular in the pyloric antrum, is the sive where the flagellated bacteriurn Helicobacter pylori we sides in spite of the hostile environment. Hi, pylori survives and replicates in the gastric lumen. Its presence has been «associated with acid peptic ulcers and adenocarcinoma of the stomach. “Three phases define the pathogenesis of #7. pylori (Figure 15-18): 1. An active phase, in which motile bacteria increase the gastric pH! by pro ducing ammonia through the action of urease 2. A stationary phase, consisting in the bacterial attachment to fucose-con- taining receptors on the surface of mucous surface cells ofthe pyloric region. H. ‘plori attachment results in the production of eytotoxie proteases that ensure the bacteria a supply of nutrients from surface mucous cells and also aeract leuko- yes. Roth ammonia production and cytotonic proteases correlate with the de velopment of peptic ulcers of the pyloric mucosa. 3. During the last colonization phase, [2 pylori detach from he Fucose-con taining receptors of the surface mucus epithelium, increase in number by eplica: tion within the mucus blanket, and remain artached to glycoproceins containing sialic acid. Despite the rapid turnover of the gastric mucus-secreting cells, H. ‘li aveids being flushed sway with dead epithelial cells by producing urease and displaying high motility About 20% of the population are infected with H. pylori by age 20 years. The incidence of the infection inereases 16 about 60% by age 0. ‘Mest infected individuals do not have clinical symptoms. Increasing evidence for the infectious origin of acid peptic disease and chronic gastritis led to the implementation of a herapy for al leet patients shown to be infected with HL. pylori. ‘More recently, attention has been directed 10 adhesins and fucose-containing receptors as potential targets for drug action. ‘The objective is to prevent binding of pathogenic bacteria without interfering with the endogenous bacterial flora by the use of antibiotics, Gastroenteroendocrine cells ‘The function of the alimentary tube is epulated by peptide hormones, produced by gestroenteroendocrine cells, and neuroendocrine mediators, produced by new Peptide hormones are synthesined by gastrocntercendoctine cells dispersed thcoughout the mucosa from the stomach through the'colon. The population of | ‘gasuventeroendocrine cells $0 lange that the gastointestinal segmencis regarded as the langest endocrine organ in the body. Gastroenteroenddocrine cells are members of the APUD system. s» called be cause of the amine precursor uptake and decarboxylation propery of ino acids (Figure 15-19). Because not all the cells aceurmulate amine precursors, the designation APUD has been replaced by DNES (for diffuse neuroendocrine sys- tem). Neuroendocrine mediators are released from nerve terminals. For example, acetylcholine is released ac the terminals of postganglionic cholinergic nerves. Gastrin-releasing peptide is released by postsynaptic neurons activated by stimu- lation of the vagus nerve (see Figute 15-19). Peptide hormones produced by gastrointestinal endocrine cells have the fo lowing general funetions: (1) regulation of water, electrolyte metabolism and en- zyme secretion; (2) regulation of gastrointestinal motility and mucosal growth; and (3) stimulation of the release of other peptide hormones. ‘We will consider five major pepride gastrointestinal peptide neuroendocrine hormones: secretin, gastrin, cholecystokinin, gastric inhibitory peptide, and418 | 15. UPPER DIGESTIVE SEGMENT Py lands 1. Secretin was the first hormone to be discovered (in. 1902). Seceetin is re leased by cells in the duodenal mucosa when HCL-containing gastric juice enters the duodenum. Secretin is released when the pH in the duodenum is below 4.5, and reduces acid secretion (antacid effect). Sceretin stimulates panereatic biear- bonate and fluid secretion. Secretin, together with cholecystokinin, stimulates the growth of she exocrine pancreas. In addition, secretin (and acetylcholine) stimulates chief cells to secrete pepsinogen. 2. Gastrin, produced by G cells located in the pyloric antrum. Two forms of gastiin have been described: little gastrin, or G,, (which contains 17 amino ac ids), and big gastrin, or G,, (which contains 34 amino acids). G cells produce primarily G,.."The duodenal mucosa in humans contains G cells producing mainly G, The neuroendocrine mediator gastrin-releasing peptide regulates the release of gastrin, Somatostatin, produced by D cells, inhibits the release of gastrin when. the pyloric antral mucosa is acidified (see Figure 15~19) ‘The main function of gastrin isto stimulate the production of hydrochloric acid by parietal cells. Gastrin can also activate cholecystokinin recepeors to stimu late gallbladder contraction. Gastrin has a trophic effect on the mucoss of the small and large intestine and the fundic region of the stomach. Gastrin stimulates the growth of enterochromaffinclike cells of the stomach. ‘Continued hypersecretion of gastrin results in hyperplasia of ECL cells, ECL cells produce histamine by decarboxylation of histidine. Histamine binds to the hista- imine H, receptor on parietal cells to potentiate the effec of gastrin and acetyl- choline on HCI secretion (see Figure 15-19). Histamine H, recepcor blocking. drugs (such as cinietidine [Tagamet] and ranitidine [Zantae) are effective inhibi tors of acid secretion. 3. Cholecystokinin (CCK) is produced in the small intestine (duodenum andl jejunum) and stimulates gallbladder contraction triggered by the presence of fat in che small intestine. 4. Gastric inhibitory peptide (GIP), formerly called urogastrone, is produced in the small intestine (duodenum and jejunum) and inhibits gastic secretion Figure 15-20 Pylori region of the stomach Pylori glands are simple ‘tubular and branched atthe very lower end. ‘The pits are deeper than the cardiac gends and geste ‘lands of the fundus-body region. Prjltic wands are ined by ‘mucous-socreting cells, The continu othe poo lands Ath distal en, the contents ‘sifu to eaize in histologic tthe mucous-secreting cells sections because oftheir tortuous splace and fatten the mle path end highly branched nature ‘to the basal domain of the cel, Deep pltined by mucncs-secreting cals usculris mucosae