Histology Gastro 1st PDF

CHAPTER GENERAL STRUCTURE OF THE DIGESTIVE 15 Digestive Tract SMALL INTESTINE...

CHAPTER GENERAL STRUCTURE OF THE DIGESTIVE 15 Digestive Tract SMALL INTESTINE 314 TRACT 295 Mucosa 314 ORAL CAVITY 298 Other Layers 317 Tongue 298 LARGE INTESTINE 318 Teeth 300 SUMMARY OF KEY POINTS 326 ESOPHAGUS 305 ASSESS YOUR KNOWLEDGE 328 STOMACH 307 Mucosa 307 Other Layers 314 he digestive system consists of the digestive tract Absorption of thesmall molecules and water into the oral cavity, esophagus, stomach, small and large intes blood and lymph, tines, and anusand its associated glandssalivary Elimination of indigestible, unabsorbed componentsof glands, liver, and pancreas (Figure 15-1). Also called the food. gastrointestinal (GI)tract or alimentarycanal, its function is to obtain from ingested food the molecules necessary for the maintenance, growth, and energy needs of the body. During > GENERAL STRUCTURE OF THE digestion proteins, complex carbohydrates, nucleic acids, and DIGESTIVE TRACT fats are broken down into their small molecule subunits that are easily absorbed through the small intestine lining. Most All regions of the GI tract have certain structural features in water and electrolytes are absorbed in the large intestine. In common. The GI tract is a hollow tube with a lumen of vari addition, the inner layer of the entire digestive tract forms an able diameter and a wall made up of four main layers: the important protectivebarrier between the content of the tract's mucosa, submucosa, muscularis, and serosa. Figure 15-2 lumen and the internal milieu of the body's connective tissue showsa general overview of these four layers; key features of and vasculature. each layer are summarizedhere. Structures within the digestive tract allow the following: The mucosa consists of an epithelial lining; an under Ingestion, or introduction of food and liquid into the lying lamina propria of loose connective tissue rich in oral cavity, blood vessels, lymphatics, lymphocytes, smooth muscle Mastication, or chewing, which divides solid food into cells, and often containing small glands; and a thin layer digestible pieces, of smooth muscle called the muscularis mucosae Motility, muscular movements of materials through the separating mucosa from submucosaand allowing local tract, movements of the mucosa. The mucosa is also frequently Secretion of lubricatingand protective mucus,digestive called a mucous membrane. enzymes, acidic and alkaline fluids, and bile, The submucosa contains denser connective tissue with Hormone release for local control of motility and larger blood and lymph vessels and the submucosal secretion, (Meissner) plexus of autonomicnerves. It may also Chemical digestion or enzymatic degradation of large contain glands and significant lymphoid tissue. macromolecules in food to smaller molecules and their The thick muscularis (or muscularis externa) is composed subunits, of smoothmuscle cells organized as two or more sublayers. FIGURE 15-1 The digestive system. Accessory digestive organs Gastrointestinal tract (digestive organs) Parotid salivary gland Teeth Oral cavity Tongue Pharynx Sublingual salivary gland Submandibular salivary gland Esophagus Liver Stomach Gallbladder Pancreas Large intestine Small intestine Anus The digestive system consists of the tract from the mouth (oral this tract, primarily the salivary glands, liver, and pancreas. These cavity) to the anus, as well as the digestive glands emptying into accessory digestive glands are described in Chapter 16. In the internal sublayer (closer to the lumen), the fiber luminal contents forward, are generated and coordinated orientation is generally circular; in the external sublayer by the myenteric plexus. it is longitudinal.The connective tissue between the The serosa is a thin layer of loose connective tissue, rich in and lymph vessels, as muscle sublayers contains blood blood vessels, lymphatics, and adipose tissue, with a simple well as the myenteric (Auerbach)nerve plexus of squamous covering epithelium or mesothelium. In the many autonomic neurons aggregated into small ganglia abdominal cavity, the serosa is continuous with mesenteries, and interconnected by pre- and postganglionic nerve thin membranes covered by mesothelium on both sides that fibers. This and the submucosal plexus together comprise support the intestines. Mesenteries are continuous with the enteric nervous system of the digestive tract. Con the peritoneum, a serous membrane that lines that cay tractions of the muscularis, which mixand propel the ity. In places where the digestive tract is not suspended in 309/573  FIGURE 15-2 Major layers and organization of thedigestive tract. CHAP TER Mucosa Epithelium Lamina propria 15 Muscularis mucosae Mesentery Digestive Tract Vein Artery Lymph vessel Submucosa Submucosal gland Blood vessel Lumen General Submucosal nerve plexus Muscularis Structure Inner circular layer of the Myenteric nerve plexus Outer longitudinal layer Digestive Tr Serosa < > Diagram showing the structure of the small intestine portion large intestine are suspended by mesenteries that are the sites ofthe digestive tract, with the four main layers and their major of nerves, blood vessels and lymphaticsfrom the stomach and components listed on the left. The stomach, small intestine, and intestines. a cavity but bound directly to adjacent structures, such as protein produced by the epithelial cells. This IgA complex in the esophagus (Figure 15-1), the serosa is replaced by a resists proteolysis by digestive enzymes and provides impor thick adventitia, a connective tissue layer that merges with tant protection against specific viral and bacterial pathogens. the surrounding tissues and lacks mesothelium. > MEDICAL APPLICATION The numerous free immune cells and lymphoid nodules in the mucosa and submucosa constitute the MALT described In diseases such as Hirschsprung disease (congenital agan in Chapter 14. The digestive tract normally contains thou glionic megacolon) or Chagasdisease (trypanosomiasis, sands of microbial species, including both useful inhabitants infection with the protozoan Trypanosoma cruzi), plexuses of the gut as well as potential pathogens ingested with food in the digestive tract's enteric nervous system are absent or and drink. The mucosa-associated immune defense system severely injured, respectively. This disturbs digestive tract provides an essential backup to the thin physical barrier ofthe motility and produces dilations in some areas. The rich auto epithelial lining. Located just below the epithelium, the lam nomic innervation of the enteric nervous system also provides ina propria is rich with macrophagesand lymphocytes, many an anatomic explanation of the well-known actionsof emo for production of IgA antibodies. Such antibodies undergo tional stress on the stomach and other regions of the GI tract. transcytosis into the intestinal lumen bound to the secretory 298 CHAPTER 15 Digestive Tract ORAL CAVITY FIGURE 15-3 Lip. Theoral cavity (Figure15-1) is lined with stratified squamous epithelium, which may be keratinized, partially keratinized, or nonkeratinized depending on the location. Epithelial dif ferentiation, keratinization, and the interface between the epithelium and lamina propria are similar to those features in the epidermis and dermis and are discussed more exten M sively with skin (see Chapter 18). Like the keratinized sur face cells of epidermis, the flattened superficial cells of the oral epithelium undergo continuous desquamation, or loss at the surface. Unlike those of the epidermis, the shed cells of the nonkeratinizedor parakeratinized oral epithelium retain their nuclei. OM >> MEDICAL APPLICATION Viral infections with herpes simplex 1 cause death of infected epithelial cells that can lead to vesicular or ulcerating lesions of the oral mucosa or skin near the mouth. In the oral cavity such areas are caled canker sores, and on the skin they are usually called cold sores or fever blisters. Such lesions, often painful and clustered, occur when the immune defenses are Low-magnification micrograph of a lip section showingone side weakened by emotional stress, fever, illness, or local skin covered by typical oral mucosa (OM),the opposite side covered damage, allowing the virus, present in the local nerves, to by skin (S) containing hair follicles (F) and associated glands. move into the epithelial cells. Between the oral portion of the lips and normal skin is the vermil ion zone (V), where epidermis is very thin, lightly keratinized, and transparent to blood in the rich microvasculature of the underly ing connective tissue. Because this region lacks the glands for oil The keratinized cell layers resist damage from abrasion and sweat, is and chapping in cold, prone to excessive dryness it and are best developed in the masticatory mucosa on the dry weather. Internally, the lips contain much striated muscle (M) gingiva (gum) and hard palate. The lamina propria in these and many minor salivary glands (G). (X10; H&E) regions rests directly on the periosteum of underlying bone. Nonkeratinized squamous epithelium predominates in the lining mucosa over the soft palate, cheeks, the floor of the mouth, and the pharynx (or throat), the posterior region of The outer surface has thin skin, consisting of epidermal the oral cavity leading to the esophagus. Lining mucosa over and dermal layers, sweat glands, and many hair follicles a thick submucosa containing lies many minor salivary glands, with sebaceous glands. which secrete continuously to keep the mucosal surface wet, and diffuse lymphoid tissue. Throughout the oral cavity, the Tongue epithelium contains transient antigen-presenting cells and The tongue is a mass of striated muscle covered by mucosa, rich sensory innervation. which manipulates ingested material during mastication and The well-developed core of striated muscle in the lips, or Swallowing. The muscle fibers are oriented in all directions, labia, (Figure 15-3) makes these structures highly mobile for allowing a high level of mobility. Connective tissue between ingestion, speech, and other orms of communication. Both the small of muscle is penetrated fascicles by the lamina pro lips have three differently covered surfaces: pria, which makes the mucous membrane strongly adherent to The internal mucous surface has lining mucosa with a the muscular core. The lower surface ofthe tongue is smooth, thick, nonkeratinizedepithelium and many minor labial with typical lining mucosa. The dorsal surface is irregular, hav salivary glands. ing hundreds small protruding papillae of various types on of The red vermilion zone of each lip is covered by very its anterior two-thirds and the massed lingual tonsils on the thin keratinized squamous epithelium stratified and posterior third, or root of thetongue (Figure 15-4). The papil is transitional between the oral mucosa and skin. This lary and tonsillar areas of the lingual surface are separated by a region lacks salivary or sweat glands and is kept moist V-shaped groove called the sulcus terminalis. with saliva from the tongue.The underlyingconnective The lingual papillae are elevations of the mucous mem tissue is very rich in both sensory innervation and capil brane that assume various forms and functions. There are four laries, which impart the pink color to this region. types (Figure 15-4): 311/573  FIGURE 15-4 Tongue, lingual papillae, and taste buds. CHAPTER Stratified squamous epithelium of tongue surface Lingual 15 tonsil Epithelium Gustatory Sulcus cell terminalis -Gustatory microvillus Taste pore Digestive Tract -Supporting celi Sensory Basal cell Oral nerve (b)Vallate papilla (c) Taste bud Nuclei of Taste Cavity gustatory cells pore Apex of tongue Epithelium Taste bud Taste bud Epithelium Epithelium Nuclei of supporting cells Filiform papilla Fungiform papilla Foliate papilla (a) Dorsal surface of tongue (d) Histology of taste bud On its dorsal surface (a), the posterior third of the tongue has the (c) Diagram of a single taste bud shows the gustatory(taste) cells, lingual tonsils and the anterior portion has numerous lingual the supporting cells whose function is not well understood, and papillae of four types. Pointed filiform papillae provide friction the basal stem cells. Microvilli at the ends of the gustatory cells to help move food during chewing. Ridge-like foliate papillae project throughan opening in the epithelium, the taste pore. Affer on the sides of the tongue are best developed in young children. ent sensory axons enter the basal end of taste buds and synapse Fungiform papillae are scattered across the dorsal surface, and with the gustatory cells. In the stratified squamous epithelium of 8-12 large vallate papillae (b)are present in a V-shaped line the tongue surface, taste buds form as distinct clusters of cells that near the terminal sulcus. Taste buds are present on fungiform are recognizable even at low magnification (d). At histologically and foliate papillae but are much more abundant on vallate higher power the taste pore may be visible, as well as the elongated papillae. nuclei of gustatory and supporting cells. (140Xand 500X;H&E) Filiform papillae (Figure 15-5) are very numer with well-vascularizedand innervated cores of lamina ous, have an elongated conicalshape, and are heavily propria. keratinized, which gives their surface a gray or whitish Foliate papillae consist of several parallel ridges on appearance. They provide a rough surface that facilitates each side ofthe tongue, anterior to the sulcus termi movement of food during chewing. nalis, but are rudimentary in humans, especially older Fungiform papillae (Figure 15-5) are much less individuals. numerous, lightly keratinized, and interspersed among Vallate (orcircumvallate) papillae (Figure 15-5) are the filiform papillae. They are mushroom-shaped the largest papillae, with diameters of 1-3 mm. Eight to  twelve vallate papillae are normally aligned justin front give rise the other cell types. The base of each bud rests on to of the terminal sulcus.Ducts of severalsmall,serous the basal lamina and is entered by afferent sensory axons that salivary (von Ebner) glands empty into the deep, form synapses with the gustatory cells. At the apical ends of the moatlike groove surrounding each vallate papilla. This gustatory cells, microvilli project toward a 2-um-wide open provides a continuous flow of fluid over the taste buds ing in the structurecalled the taste pore. Molecules (tastants) that are abundant on the sidesof these papillae, washing dissolved in saliva contact the microvilli through the pore and away food particles so that the taste buds can receive and interact with cell surface taste receptors (Figure 15-4). Secretionsfrom these and Taste buds detect at least five broad categories oftastants: process new gustatory stimuli. other minor salivary glands associated with taste buds sodium ions (salty); hydrogen ions from acids (sour);sugars contain a lipase that preventsthe formation of a hydropho and related compounds (sweet);alkaloids and certain tox bic film on these structures that would hinder gustation. ins (bitter); and amino acids such as glutamate and aspartate (umami; Jap. umami, savory). Salt and sour tastes are pro Taste buds are ovoid structures within the stratified duced by ion channels and the other three taste categories are epithelium on the tongue's surface, which sample the general mediated by G-protein-coupled receptors. Receptor binding chemical composition of ingested material (Figures 15-4 and produces depolarizationof thegustatory cells, stimulatingthe 15-5). Approximately 250 taste buds are present on the lat the brain for sensory nerve fibers that send information to eral surface of each vallate papilla, with many others present processing. Conscious perception of tastes in food requires on fungiform and foliate (but not the keratinized fliform) olfactoryand other sensationsin additionto taste bud activity. papillae. They are not restricted to papillae and are also widely scattered elsewhere on the dorsal and lateral surfacesof the Teeth tongue, where they are also continuously flushedby numerous minor salivary glands. In the adult human there are normally 32 permanent teeth, A taste bud has 50-100 cells, about half of which are elon arranged in two bilaterally symmetric arches in the maxillary gated gustatory (taste) cells, which turn over with a 7- to and mandibular bones (Figure 15-6a).Each quadrant has eight 10-day life span. Other cells present are slender supportive teeth: two incisors, one canine,two premolars, and three per cells, immature cells, and slowly dividing basal stem cells that manent molars. Twenty of the permanent teeth are preceded  FIGURE 15-6 Teeth. CHA Central incisor (7-8 y) Lateral incisor (8-9 y) Canine (11-12 y) PTER Crown 1st premolar (10-11 y) Enamel 2nd premolar (10-12 y)F Gingiva Upper teeth 1st molar (6-7 y) Neck 15 Dentin 2nd molar (12-13 y) Pulp cavity 3rd molar (17-25 y) Hard palate Digestive Root canal Root 3rd molar (17-25 y) Tract 2nd molar (11-13 y) Cementum 1st molar (6-7 y) Lower teeth Periodontal Oral 2nd premolar (11-12 y) ligaments 1st premolar (10-12 y) Dental alveolus Cavity Canine (9-10 y) Lateral incisor (7-8 y) Central incisor (6-7 y) (a) Permanent teeth (b)Molar All teeth are similar embryologically and histologically. constricted neck where the enamel and cementum coverings (a) The dentition of the permanent teeth is shown, as well as the meet at the gingiva. Most ofthe roots and neck consists of dentin. approximate age at eruption for each tooth. A pulp cavity extends into the neck and is filled with well vascularized, well-innervated mesenchymal connective tissue. Blood (b) Diagram ofa molar's internal structure is similar to that of all vessels and nerves enter the tooth through apical foramina at the teeth, with an enamel-coveredcrown, cementum-covered roots root tips. Periodontal ligaments hold the tooth to bone of the jaw. anchoringthe tooth to alveolar bone of the jaw, and a slightly by primaryteeth (deciduous or milk teeth) that are shed; the Dentin others are permanent molars with no deciduous precursors. Dentin is a calcified tissue harder than bone, consisting of Each tooth has a crown exposed above the gingiva, a constricted 70% hydroxyapatite. The organic matrix contains type I col neck at the gum, and one or more roots that fit firmly into bony lagen and proteoglycans secreted from the apical ends of sockets in the jaws called dental alveoli(Figure 15-6b). odontoblasts, tall polarized cells derived from the cranial The crown is covered by very hard, acellular enamel and neural crest that line the tooth's pulp cavity (Figure 15-7a). the roots by a bone-like tissue called cementum. These two Mineralization of the predentin matrix secreted by odon coverings meet at the neck of the tooth. The bulk of a tooth is toblasts involves matrix vesicles in a process similar to that composed of another calcified material, dentin, which sur occurring in osteoid during bone formation (see Chapter 8). rounds an internal pulp cavity (Figure 15-6b). Dental pulp Long apical odontoblast processes extend from the is highly vascular and well-innervated and consists largely odontoblasts within dentinal tubules (Figure 15-7b) that of loose, mesenchymal connective tissue with much ground penetrate the full thickness of the dentin, gradually becoming substance, thin collagen fibers, fibroblasts, and mesenchymal longer as the dentin becomesthicker. Along their length, the stem cells. The pulp cavity narrows in each root as the root processes extend fine branches into smaller lateral branches canal, which extends to an opening (apical foramen) at the of the tubules (Figure 15-7c). The odontoblast processes are tip of each root for the blood vessels, lymphatics, and nerves of important for the maintenance of dentin matrix. Odontoblasts the pulp cavity. The periodontal ligaments are fibrous con continue predentin production into adult life, gradually reduc nective tissue bundles of collagen fibers inserted into both the ing the size ofthe pulp cavity, and are stimulated to repair den cementum and the alveolar bone. tin if the tooth is damaged. 314/573  Oral Cavity 303 Teeth are sensitive to stimulisuch as cold, heat, and acidic surrounded by a thinner layer of other enamel. Each rod pH, all of which can be perceived as pain.Pulp is highly inner extends through the entire thickness of the enamel layer, vated, and unmyelinated nerve fibers extend into the dental which averages 2 mm.The precise, interlockedarrangement of CHA tubules along with odontoblast processes near the pulp cavity the enamel rods is crucial forenamel'shardness and resistance (Figure 15-8). Such stimulican affect fluid insidethe dentinal to great pressures during mastication. tubules,stimulating these nerve fibers and producing tooth In a developing tooth bud, the matrix for the enamel PTER sensitivity. rods is secreted by tall, polarized cells, the ameloblasts (Figure 15-9a), which are part of a specialized epithelium >> MEDICAL APPLICATION in the tooth bud called the enamel organ. The apical ends 15 of the ameloblasts face those of the odontoblasts producing Immune defenses in the oral cavity cannot protect against predentine (Figure 15-10). An apical extension from each all infections. Pharyngitis and tonsillitis areoften due to ameloblast, the ameloblast (or Tomes) process, contains the bacterium Streptococcus pyrogenes.White excrescences numerous secretorygranules with the proteins of theenamel or leukoplakia on the sides of the tongue can be caused Digestive matrix. The secreted matrix undergoes very rapid mineral by Epstein-Barr virus. Oral thrush,a white exudate on the ization.Growth of the hydroxyapatite crystals to produce tongue's dorsal surface, is due to a yeast (Candidaalbicans) Tract each elongating enamel rod is guided by a small (20 kDa) infection and usualy affects neonates or immunocompro protein amelogenin, the main structuralprotein of develop mised patients. ing enamel. Oral Ameloblasts are derived from the ectodermal lining of Enamel the embryonic oral cavity, while odontoblasts and most tis the hardest component of the human body, Cavity Enamel is consist sues of the pulp cavity develop from neural crest cells and ing of 96% calcium hydroxyapatite and only 2%-3% organic mesoderm, respectively. Together, these tissues produce a material including very few proteins and no collagen. Other series of52 tooth buds in the developing oral cavity, 20 for the ions, such as fluoride, can be incorporated or adsortbed by primary teeth and 32 for the secondary or permanent teeth. the hydroxyapatite crystals; enamel containing fluorapatite is Primary teeth complete developmentand begin to erupt about more resistant to acidicdissolution caused by microorganisms, 6 months after birth. Development of the secondary tooth hence theaddition offluorideto toothpasteand water supplies. buds arrests at the "bell stage, shown in Figure 15-10a, until Enamel consists of uniform, interlockingcolumns called about 6 years of age, when these teeth begin to erupt as the enamel rods (or prisms), each about 5 um in diameter and primary teeth are shed.  >> MEDICAL APPLICATION than bone, cementocytes maintain their surrounding matrix and by graduallyremodeling. react to stresses Periodontaldiseases includegingivitis, inflammationof The periodontal ligament is fibrous connective tis the gums,and periodontitis, which involves inflammation sue with bundled collagen fibers (Sharpey fibers) binding at deeper sites, both of which arecaused most commonly the cementum and the alveolarbone (Figure 15-11). Unlike by bacterial infections with poor oral hygiene. Chronic peri typical ligaments, it is highly cellular and has a rich supply of odontitis weakens the periodontal ligamentand can lead to blood vessels and nerves,giving the periodontal ligament sen loosening ofthe teeth. The depth of the gingival sulcus, mea sory and nutritive functions in addition to its role in support sured during clinical dental examinations,is an important ing the tooth.It permits limited movement ofthetooth within indicator of potential periodontal disease. the alveolus and helps protectthe alveolusfrom the recurrent pressure exerted during mastication. Its thickness(150-350 um) is fairly uniform along the root but decreases with aging. Periodontium The alveolar bone lacks the typical lamellarpattern of The periodontium comprises the structuresresponsible for adult bone but has osteoblasts and osteocytesengaging in con maintaining the teeth the maxillary and mandibular bones, in tinuous remodeling of the bony matrix. It is surrounded by and includesthe cementum,the periodontal ligament,and the periodontal ligament, which servesas its periosteum. Col the alveolar bonewith the associatedgingiva (Figure 15-6b; lagen fiber bundles of the periodontal ligament penetrate this Figure 15-11). bone, binding it to thecementum (Figure 15-1lc). Cementum covers the dentin of the root and resembles Around the peridontium the keratinized oral mucosa of bone, but it is avascular. It is thickest around the root tip where the gingiva is firmlybound to theperiosteum ofthe maxillary cementocytes reside in lacunae with processes in canaliculi, and mandibular bones (Figure 15-11). Between the enamel especially near the cementum surface.Although less labile and the gingival epithelium is the gingival sulcus, a groove 317/573 up to 3 mm deep surrounding theneck (Figure 15-1la). A spe and protect the mucosa (Figure 15-13a). Near the stomach cialized part of this epithelium,the junctional epithelium, the mucosa also contains groups of glands, the esophageal isbound to the tooth enamel by means of a cuticle, which cardiac glands,which secrete additionalmucus. resembles a thick basal lamina to which the epithelial cells are attached by numerous hemidesmosomes. >> MEDICAL APPLICATION The lubricating mucus produced in the esophagus offers > ESOPHAGUS little protection againstacid that may move there from the stomach. Such movement can produce heartburn or reflux The esophagus is a muscular tube, about 25-cm long in esophagitis.An incompetent inferior esophageal sphincter adults, which transportsswallowed material from the pharynx may result in chronicheartburn, which can lead to erosion of to the stomach. The fourlayers of the GI tract (Figure 15-12) the esophageal mucosa or gastroesophageal reflux disease become well-established and clearly seen in theesophagus. first (GERD). Untreated GERD can produce metaplastic changes The esophageal mucosa has nonkeratinized stratified squa in the stratified squamous epithelium of the esophageal mous epithelium, and the submucosa contains small mucus mucosa, a condition called Barrett esophagus. secreting glands, the esophageal glands, which lubricate 318/573  Swallowing begins with voluntary muscle action but fin Four major regions make up the stomach: the cardia, fun ishes with involuntary peristalsis. In approximately the upper dus, body, and pylorus (Figure 15-14a). The cardia is a nar one-third ofthe esophagus, the muscularis is exclusively skel row transitional zone, 1.5-3 cm wide, between the esophagus etal muscle like that of the tongue. The middle portion of the and the stomach; thepylorus is the funnel-shaped region that esophagus has a combination of skeletal and smooth muscle opens into the small intestine. Both these regions are primarily fibers (Figure 15-13b), and in the lower third the muscularis involved with mucus production and are similar histogically. is exclusively smooth muscle. Only the distal 1-2 cm of the The much larger fundus and body regions are identical in esophagus, in the peritoneal cavity, is covered by serosa; the microscopic structureand are the sites of gastric glands releas enclosed by theloose connective tissue of the adventitia, rest is ing acidic gastric juice. The mucosa and submucosa of the which blends into the surrounding tissue. empty stomach have large, longitudinallydirected folds called rugae, which flatten when the stomach fills with food. The > STOMACH wall in allregions of the stomach is made up of all four major layers (Figures 15-14c and 15-15). The stomach is a greatly dilated segment of the digestive tract whose main functions are: >> MEDICAL APPLICATION To continue the digestion of carbohydrates initiated by the amylase of saliva, Gastric and duodenal ulcers are painful erosive lesions of To add an acidicfluid the ingested food and mixing its to the mucosa that may extend to deeper layers. Such ulcers contents into a viscous mass called chyme by the churn can occur anywhere between the lower esophagus and the ing activity ofthe muscularis, jejunum, and their causes includebacterial infections with To begin digestion oftriglycerides by a secreted lipase Helicobacter pylori, effects of nonsteroidal anti-inflammatory To promote the initial digestionof proteinswith the drugs,overproductionof HClor pepsin, and lowered produc enzyme pepsin. tion or secretion of mucus or bicarbonate. >MEDICAL APPLICATION Mucosa For various reasons, including autoimmunity, parietal cells may be damaged to the extent that insufficient quantities of Changing abruptly at the esophagogastric junction intrinsic factorare secretedand vitamin B,, is not absorbed (Figures15-14b), the mucosal surface of thestomach is a sim adequately.This vitaminis a cofactor required for DNA syn ple columnar epithelium that invaginatesdeeply into the lam thesis; low levels ofvitamin B,, can reduce proliferation of ina propria. The invaginations form millionsof gastric pits, each with an opening to the stomach lumen (seeFigure 15-14; erythroblasts, producing pernicious anemia. Figure 15-16). The surface mucous cells that line the lumen  Stomach FIGURE 15-15 Wall of the stomach with rugae. FIGURE 15-16 Gastric pits and glands. M CHAPTER 15 V Digestive P Tract SM Stomach ME A low-magnification micrograph of the stomach wall at the fundus shows the relative thickness of the four major layers: the mucosa (M), the submucosa (SM), the muscularis externa (ME), and the serosa (S).Two rugae (folds) cut transversely and consisting of mucosa and submucosa are included. The mucosa is packed with branched tubular glands penetrating the full thickness of the lamina propria so that this sublayer cannot be distinguished The muscularis mucosae at this magnification. (arrows), immediately beneath the basal ends of the gastric glands, is shown. The submucosa is largely loose connective tis sue, with blood vessels (V) and lymphatics. (X12; H&E) b and gastric pits secrete a thick, adherent, and highly viscous mucous layer that is rich in bicarbonate ions and protectsthe (a) SEM of the stomach lining cleared of its mucous layer mucosa from both abrasive effects of intraluminal food and reveals closely placed gastric pits (P) surroundedby polygonal the corrosive effects of stomach acid. apical ends of surface mucous cells. (X600) The gastric pits lead to long, branched, tubular glands that (b) A section of the same lining shows that these surface extend through the full thickness of the lamina propria. Stem mucous cells are part of a simple columnar epithelium continu cells for the epithelium that lines the glands,pits, and stomach ous with the lining of the pits (P). Each pit extends into the lumen are found in a narrow segment (isthmus) between each lamina propria and then branches into several tubular glands. These glands coil and fill most of the mucosa.Around the vari gastric pit and the gastric glands. The pluripotent stem cells ous cells of the closely-packed gastric glands are cells, capil divide asymmetrically, producing progenitor cells for all the laries, and small lymphatics of the connective tissue lamina other epithelial cells. Some of these move upward to replace propria. (X200; H&E) surface mucous cells, which have a turnover time of 4-7 days. 322/573 310 CHAPTER 15 Digestive Tract Other progenitor cells migrate more deeply and differentiate These cells are of four major types and important propertiesof into the secretory cells of the glands thatturn over much more each are as follows: slowly than the surface mucous cells. Mucous neck cells are present in clusters or as single The vascularized lamina propria that surrounds and among the other cells in the necks of gastric glands cells supports the gastric pits and glands contains smooth muscle and include many progenitor and immature surface fibers,lymphoid cells, capillaries, and lymphatics. Separat mucous cells (Figure 15-17). Less columnar than the ing the mucosa from the underlying submucosa is a layer of surface mucous cells lining the gastric pits, mucous neck smooth muscle, the muscularis mucosae (Figure 15-15). are often distorted by neighboring cells, but they cells In the fundus and body the gastric glands themselves have round nuclei and apical secretorygranules.Their fill most of the mucosa, with several such glands formed by mucus secretionis less alkaline than that of the surface branching at the isthmus or neck of each gastric pit. Secretory epithelial mucous cells. epithelial cells of the gastric glands are distributed unevenly Parietal (oxyntic) cells produce hydrochloric acid and release products that are key to the stomach's functions. (HCI) and are present among the mucous neck cells  Stomach 311 and throughout deeper parts of the gland. They are striking ultrastructuralfeature of an active parietal cell large cells, usually appearing rounded or pyrami is a deep, of the apical plasma circular invagination dal, each with one (sometimes two) central round membrane to form an intracellular canaliculus with nucleus. The cytoplasm is intenselyeosinophilic due a large surface area produced by thousands of micro to the high density of mitochondria (Figure 15-17). A villi (Figure 15-18). As shown in Figure 15-19, CHAPTER 312 CHAPTER 15 Digestive Tract FIGURE 15-19 synthesis of HCI by parietal cells. Blood capillary HCI CI Ci 3 CO2 HCOg HCO, OHP LH -H HK pump H,0 Junctional complex (1) Water (H,0)within the parietal cell is split into a hydrogen ion (H*) and hydroxide ion (OH). (2)H* is pumped into the lumen of the gastric gland by an H+/K* pump. 3)OH bonds with carbon dioxide (CO,)to form bicarbonate ion (HCO,). (4) An exchange occurs as HCO, is transported out of the parietal cell (HCO3then enters the blood), while chloride ion (CI)is transported into the parietal cell; C then enters the lumen of the gastric gland. 5)Within the lumen of the gastric gland, CI combines with H* to form hydrochloric acid (HCI). The main steps in the synthesis of HCl at parietal cells are indi into the canaliculi and combine with protons in the lumen of the cated here. Conversion of H,0 and CO, to HCO, (bicarbonate gastric gland to form HCI. ion) and H* (a proton)is by the enzyme carbonic catalyzed Basally released bicarbonate ions enter the local interstitial anhydrase. Active used to pump H into canaliculi in transport is fluidand microvasculature, helping to maintain the neutral pH of exchange for K* and to discharge HCO, by an antiport at the basal the mucosa.Other HCO, is taken up by surface mucous cells and cell domain in exchange for Ct.The CI ions diffuse from the cell used to raise the pH of mucus. carbonic anhydrasecatalyzes the conversion of cyto histamine and the polypeptide gastrin from enteroendocrine plasmic water and CO, into HCO,and H. The HCO, cells. is transported from the basal side of the cell and H' is Chief (zymogenic) cells predominate in the lower pumped from the cell apically, along with Cl. In the regions of the gastric glands (Figure15-17) and have all lumen the H' and CI ions combine to form HCI. While the characteristics of active protein-secreting cells. Ultra the gastric secretion becomes highly acidic, the mucosa structurally chief show abundant RER and numerous cells itself remains at a more neutral pH partly because ofthe apical secretory granules (Figure15-20). The granules bicarbonate released into the lamina propria. The albun contain inactive enzyme pepsinogens, precursors which dant mitochondria provide energy primarilyfor operat are converted in the acid environment of the stomach ing the cells' ion pumps. into active pepsins (Gr.peptein, to digest). Pepsins are Parietal cells also secrete intrinsic factor,a glycoprotein endoproteinases with broad specificity and maximal required for uptake of vitamin B,, in the small intestine. activity at a pH between 1.8 and 3.5. Pepsins initiate the Parietal cell secretory activity is stimulated both by hydrolysis of ingested protein in the stomach. Chief cells parasympathetic innervation and by paracrine release of also produce gastric lipase, which digests many lipids. 325/573  Stomach 313 FIGURE 15-20 Ultrastructureof parietal, chief, and enteroendocrine cells. CH A PTER 5 Digestive Tract Stomach C TEM of a transversely sectioned gastric gland shows the ultra granules near the lumen (L). An enteroendocrine cell (E) shows structure of three major cell types. Parietal cells (P) contain abun dense basal secretory granules and is a closed-type enteroen dant mitochondria and intracellular canaliculi (IC).Also shown are docrine cell; that is, it has no contact with the gland's lumen and chief cells (C), which have extensive rough ER and apical secretory secretes product in an endocrine/paracrine manner.(X1200) Enteroendocrine cells are scattered epithelial cells in >> MEDICAL APPLICATION the gastric mucosa with endocrine or paracrine func Tumors called carcinoids, which arise from enteroendocrine tions. In the fundus small enteroendocrine cells secreting EC cells, are responsible for the clinical symptoms caused by serotonin (5-hydroxytryptamine) are found at the basal overproduction of serotonin. Serotonin increases gut motil lamina of the gastric glands (Figure 15-20).In the pylo ity, and chronic high levels of this hormone/neurotransmitter rus other enteroendocrine cells are located in contact can produce mucosal vasoconstriction and tissue damage. with the glandular lumens, including G cells producing the peptide gastrin. Various enteroendocrine cells secreting different hor Upon stimulation, these cells release their hormone prod mones, usually peptides, are also found in the intestinal ucts that then exert paracrine (local) or endocrine (systemic) mucosa and are of major importance for function of the diges effects via the vasculature. Cells of the digestive tract DNES tive tract. Important examples are summarized in Table 15-1. fall into two classes: a "closed"type, in which the cellular apex Seldom seen by routine light microscopy, these cells can be is covered by neighboring epithelial cells (Figure 15-20),and visualized by TEM tissue treatment with chromium or silver an "open" type, in which the constricted apical end of the cell salts. This provided the alternative names enterochromaffin contacts the lumen and bears chemoreceptors that sample (EC) cells and argentaffin cells, respectively. Now usually the lumen's contents. Effects of the hormones include regu visualized immunohistochemically using antibodies against lation of peristalsis and tract motility; secretion of digestive their product, they are named with the initial letter of the enzymes, water, and electrolytes; and the sense of being sati main hormonethey produce (Table 15-1), Most of these cells ated after eating. process amines and are also collectively called APUD cells for In the cardia and pylorus regions of the stomach, the their "amine precursor uptake and decarboxylation' activity. mucosa also contains tubular glands, with long pits, branch All such cells are more generally considered part of the diffuse ing into coiled secretory portions, called cardiac glands and neuroendocrine system (DNES), which is discussed further pyloric glands (Figure 15-21). These glands lack both pari in Chapter 20. etal and chief cells, primarilysecreting abundant mucus. 326/573 314 CHAPTER 15 Digestive Tract TABLE 15-1 Principalenteroendocrine cells in the gastrointestinal tract. Major Action Cell Type Major Location Hormone Produced Promotes Inhibits D cells Pylorus, duodenum, and Somatostatin Secretion from other DNES pancreatic islets cells nearby EC cells Stomach, small and large Serotonin and substance P Increased gut motility intestines G cells Pylorus Gastrin Gastric acid secretion I cells Small intestine Cholecystokinin (CCK) Pancreatic enzyme secretion, Gastric acid secretion gallbladder contraction K cells Duodenum andjejunum Gastric inhibitory Gastric acid secretion polypeptide (GIP) L cells lleum and colon Glucagon-like peptide Insulin secretion Gastric acid secretion Sense (GLP-1) of hunger L cells lleum and colon Peptide YY H,0 and electrolyte absorption Gastric acid secretion in large intestine Mo cells Small intestine Motilin Increased gut motility N cells Ileum Neurotensin Gastric acid secretion S cells Small intestine Secretin Pancreatic and biliary Gastric acid secretion bicarbonate and water secretion Stomach emptying other Layers Mucosa The other major layers of the stomach wall are summarized in Viewed macroscopically, the lining of the small intestine Figures 15-14 and 15-15.In all stomach regions the submucosa shows a series of permanent circular or semilunar folds is composed of connective tissue with large blood and lymph (plicae circulares), consisting of mucosa and submucosa and many lymphoid cells, macrophages, and mast cells. vessels (Figures 15-22a and 15-23), which are best developed in the The muscularis has three poorly defined layers of smooth jejunum. Densely covering the entire mucosa of the small muscle: an outer longitudinal layer, a middle circular layer, intestine are short (0.5-1.5 mm) mucosal outgrowths called and an innermost oblique layer. Rhythmic contractions of villi that project into the lumen (Figure 15-22). These fin the muscularisthoroughly mix ingested food and chyme with ger- or leaflike projections are covered by a simple columnar mucus, HCI, and digestive enzymes from the gastric mucosa. epithelium of absorptive cells called enterocytes, with many At the pylorus the middle layer is greatly thickenedto form the interspersed goblet cells. Each villus has a core of loose pyloricsphincter. The stomach is coveredby a thin serosa. connective tissue that extends from the lamina propria and contains fibroblasts, smooth muscle fibers, lymphocytes and plasma cells, fenestrated capillaries, and a central lymphatic > SMALL INTESTINE called a lacteal. The small intestine is the site where the digestive processes are >> MEDICAL APPLICATION completed and where the nutrients (products of digestion) are absorbedby cells ofthe epithelial lining. The small intestine is rel Celiac disease (celiac sprue) is a disorder of the small intes long-approximately5m--and consists of three segments: atively tine mucosa that causes malabsorption and can lead to the duodenum,jejunum, and ileum. These segments have damage or destruction of the villi. The cause of celiac disease most histologic features in common and are discussed together. is an immunereaction against gluten or other proteins in wheat and certain other types of grain. The resulting inflam >> MEDICAL APPLICATION mation affects the enterocytes, leading to reduced nutrient absorption. Leiomyomas, benign tumors of smooth muscle cells, are the most commontype of tumor in the stomach and small intes tine and may become large. Autopsy records suggest that the Between the villi are the openings of short tubular glands muscularis of the stomach may include leiomyomas in up to called glands orcrypts (orcrypts of Lieberkühn)