This chapter should help you to:

· Name the parts of the digestive tract and the primary function of each.
· Describe the structure of the tongue.
· Describe the development of the teeth.
· Describe the layered structure of the teeth, the structures that hold them in place, and the composi- tion of the gingiva.
· Name the 4 layers that form the walls of the tubular organs of the digestive tract and the tissue types found in each layer.
· Compare the tubular organs of the digestive tract in terms of the structure of each of their layers and relate any structural variations to differences in organ function.
· Know the distinguishing structural features of the various regions of each of the tubular organs of the digestive tract.
· Name the secretory product(s), the distinguishing structural features, and (where appropriate) the staining properties for each type of secretory cell in the digestive tract mucosa.
· List the features of the small intestine that promote nutrient absorption and trace the steps in this process .
· Identify the organ, region, cell types present, and type of section tie, transverse or longitudinal) from a slide or photomicrograph of a section of any part of the digestive tract.

SYNOPSIS

I. GENERAL FEATURES OF THE DIGESTIVE TRACT

A. Components: The digestive tract is a series of organs forming a long muscular tube whose continuous lumen opens to the exterior at both ends. The organs include the oral cavity, oral pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (cecum and appendix; ascending, transverse, and descending colon), rectum, and anal canal.

B. General Structural Features: The walls of each organ consist of 4 concentric layers (Fig 15-1): the mucosa, submucosa, muscularis externa, and serosa or adveutitia, (To quickly master digestive tract histology, first learn the general composition and location of each layer and then focus on distinguishing features that characterize each organ; see Table 15-1.) Distin guishing structural features make more sense when considered in relation to the functions below

1. Mucosa, This layer borders the lumen and has 3 parts. The epithelium (mucous membrane) derives from endoderm. It is stratified squamous in the oral cavity, oral pharynx, esophagus, and anal canal; it is simple columnar in the stomach, intestines, and rectum. The lamiua propria is a layer of loose connective tissue beneath the endothelium; it contains small blood and lymphatic vessels. The muscularis mucosae is a thin layer of smooth muscle bordering the submucosa.
2. Submucosa, This dense, irregular connective tissue layer contains blood and lymphatic vessels and the submucosal (Meissner's) plexus of nerves. Some organs are characterized by glands and lymphoid nodules in this layer.
3. Muscularis externa, This consists of 2 layers of smooth muscle--an inner circular and an outer longitudinal-through most of the tract. Between them lies the myenteric (Auerbach's) plexus. The muscle around the oral cavity is skeletal; where it is absent leg, hard palate, gingiva) the submucosa binds tightly to bone. In the upper esophagus, this layer contains mainly skeletal muscle, which is replaced by smooth muscle in the lower portion. The stomach's muscularis externa has 3 layers: outer longitudinal, middle circular, and inner oblique. The colon's outer longitudinal layer is gathered into 3 bands, the taeniae coli. The smooth and skeletal muscles encircling the anal canal form involuntary and voluntary sphinc ters, respectively.
4. Serosa and adventitia. The tract's outer covering differs by location. The esophagus and rectum are surrounded and held in place by a connective tissue adventitia like that around blood vessels. Intraperitoneal organs (stomach, jejunum, ileum, transverse and sigmoid colon) are suspended by mesenteries and covered by a serosa composed of a thin layer of loose connective tissue covered by simple squamous epithelium (mesothelium). Retro peritoneal organs (duodenum, ascending and descending colon) are bound to the posterior abdominal wall by adventitia and covered on their free (anterior) surfaces by serosa.

C, General Functional Features: The main functions of the digestive tract are the absorption of nutrients and water and the excretion of wastes and toxins.

1. Digestion. Enzymatic degradation of foods is a prerequisite for absorption; enzymes act mainly at food surfaces. Chewing exposes more surface area. Lip, cheek, and tongue muscles help position food between the teeth. Saliva dissolves water-soluble particles and contains enzymes that attack carbohydrates (I6.II.A & C). Taste buds (24.IV.A) check for contaminantsl toxins, and nutrients. The tongue moves chewed food back into the oral pharynx and closes the epiglottis to protect the airway. Skeletal muscle in the walls of the oral pharynx and upper third of the esophagus aid the tongue in swallowing and move food down the esophagus to where smooth muscle takes over. The esophagus adds mucus to reduce friction, but mainly moves material to the stomach. Glands in the stomach wall add acid (HCI), a protease (pepsin), and mucus to the mixture (now called chyme). Smooth muscles in the stomach wall mix and pulverize the chyme and move it to the small intestine (duodenum), where pancreatic enzymes and bile are added. The enzymes hydrolyze nutrients to an absorbable form. The detergent action of bile disperses water-insoluble lipid into tiny droplets, increasing the surface area available to pancreatic lipases. The lining epithelial cells (enterocytes) of the small intestine have additional enzymes on their luminal surfaces to complete the hydrolysis of certain nutrients.
2. Absorption. This primary function of the digestive tract occurs mainly in the intestines: the small intestines absorb nutrients, and the large intestines absorb water. To maximize the absorptive surface, the small intestine's lining has multiple permanent folds including plicae circulares and villi. Intestines are lined by absorptive cells (enterocytes) whose apical micro villi further increase the surface area. These cells absorb and transfer amino acids and sugars to capillaries in the lamina propria, whose blood carries them to the liver for further process ing. Enterocytes assemble chylomicrons from absorbed lipids and transfer them to lymphatic capillaries (lacteals) in the lamina propria. From here, lipids reach the blood through the lymphatic vascular system.
3. Excretion. Metabolic wastes are excreted by the liver as bile and emptied into the duodenal lumen by the bile duct. Smooth muscles in the walls of the small intestine move undigested material and waste products to the large intestine (colon). Here, more mucus is added and most of the water is extracted. This concentrates and solidifies the intestinal contents, forming feces. This material is further dehydrated and stored in the rectum and finally expelled through the anal canal.
4. Endocrine function. Individual cells with characteristics of the diffuse neuroendocrine system (DNES) (4.VI.C.2) are scattered among the epithelial cells lining the tract's mucosal glands and crypts. These enteroendocrine cells were formerly called argentaffin, ar gyrophilic, and enterochromaffin cells because of their affinity for stains containing silver and chromium. They secrete hormones and amines leg, serotonin, secretin, gastrin, somatostatin, cholecystokinin, glucagon) that regulate such local gastrointestinal functions as gut motility and the secretion of acid, enzymes, and hormones by other cell types.
5. Innervation. Distributed along and in the walls of the tract are the myenteric (Auerbach's) and submucosal (Meissner's) autonomic nerve plexuses. These include postsynaptic sympathetic fibers, pre- and postsynaptic parasympathetic fibers, parasympathetic ganglion cell bodies, and some visceral sensory fibers. After voluntary swallowing, these autonomic plexuses coordinate peristaisis-wavelike contractions of the muscularis externa that propel ingested material through the tract. They also control the independent activity of the mus cularis mucosa, which maintains contact between the mucosa and the contents of the tract and help empty mucosal glands. These plexuses also modulate the secretory activity of certain DNES-like cells. In general, sympathetic action inhibits gut motility and parasym pathetic action has the opposite effect.
6. Blood supply. Mesenteric branches of the abdominal aorta branch further in the mesenteries to form a series of arcades. Small arteries penetrate the tract walls to feed capillaries of the lamina propria. Only small veins accompany branches of the mesenteric arteries. The larger veins draining these organs diverge from the arterial path and empty either directly or through tributaries into the hepatic portal vein, which branches within the liver to feed the hepatic sinnsoids (16.IV.C.3). Amino acids, sugars, small fatty acids, and any toxins absorbed in the intestine thus travel directly to the liver to be metabolized, stored, or detoxified before reaching the general circulation. 7. Protection. The extensive absorptive surface of the digestive tract increases the risk of infection. The risk is reduced by immunoreactive cells--including IgA-secreting plasma cells--in the lamina propria and submucosa. Other defenses include lysozyme secreted by Paneth's cells, digestive enzymes in the lumen, the layer of mucus covering the epithelium, and the tight junctions between absorptive cells. Toxic substances that do reach the blood are carried directly to the liver for detoxification in the SER of the hepatocytes.

II. ORAL CAVITY

The upper end of the digestive tract is bounded anteriorly by the teeth and lips, posteriorly by the oral pharynx, laterally by the teeth and cheeks, superiorly by the hard and soft palate, and inferiorly by the tongue and floor of the mouth.

A. Wall Structure: The mucosa includes the lining epithelium and the underlying lamina pro pria. Nonkeratinized stratified squamous epithelium (mucous membrane) covers all internal surfaces of the oral cavity and pharynx except the teeth. The lamina propria is a vascular connective tissue with papillae like those of the dermis (18.I.B.2). The papillae contain capil laries that nourish the epithelium. The oral cavity has no muscularis mucosae. The submucosa is a more fibrous connective tissue than the lamina propria; it contains many blood vessels and small salivary glands. The oral cavity lacks a standard muscularis externa. Skeletal muscle underlies the submucosa in the lips, cheeks, tongue, floor of the mouth, oral pharynx, soft palate, and its downward extension, the uvula. Bone underlies the thin submucosa of the hard palate and gums (gingiva).

B. Lips: Here, there is a transition from nonkeratinized mucous membrane to the keratinized stratified squamous epithelium of the skin. The thin keratinized layer covering the lips' ver million border allows the reddish color of blood in vessels of the lamina propria to show through. Hair follicles, keratin, and additional pigment help distinguish the outer lip surface from the inner in tissue sections.

C. Tongue: This is a mass of skeletal muscle covered by a mucosa. The mucosa is bound tightly to the muscle by the lamina propria, which penetrates between the bundles of muscle fibers. There is little or no submucosa. The muscle is arranged in bundles of many sizes; these are separated by connective tissue and cross each other in 3 planes. This gives the tongue the flexibility required for speech, positioning food, chewing, and swallowing. The mucosa differs on the dorsal (upper) and ventral (lower) surfaces. The ventral surface has a thin nonkeratinized stratified squamous epithelium underlain by a lamina propria. The epithelium covering the dorsal surface is partly keratinized. The anterior two-thirds of the dorsal surface is separated from the posterior third by a V-shaped groove. Behind this, the epithelium invaginates to form the crypts of the lingual tonsils (14.IX). Cryptless patches of lymphoid tissue in the lamina propria cause surface bulges in this region. The anterior two-thirds of the dorsal surface has many papillae-projections of the mucosal surface. There are 4 types of papillae.

1. Filiform papillae are the most numerous. They are sharp, often partly keratinized, conical projections that lack taste buds.
2. Fungiform papillae resemble mushrooms. Each has taste buds (24.IV.A) on its expanded upper surface but not on its narrow stalk. Fungiform papillae occur singly and are scattered among the fiiiform papillae.
3. Foliate papillae are poorly developed in humans. They occur in rows separated by furrows into which serous glands in the lamina propria drain. The furrow walls (sides of the papillae) harbor many taste buds.
4. Circumvallate papillae are the largest and least numerous, with only 7-12 occurring near the V-shaped groove at the back of the tongue. Each is surrounded by a ringlike ridge of mucosa from which it is separated by a circular furrow, whose walls contain taste buds on both sides. As with the foliates, ducts from serous (von Ebner's) glands empty into the furrow and periodically wash the chemical stimuli from the taste buds, allowing new tastes to be sensed.

III. TEETH & ASSOCIATED STRUCTURES

A. Tooth shape: Humans have 4 types of teeth, each with a distinctive crown and root structure. The structure and location of each type suit it to its functions. Incisors are located directly behind the lips. Each has a single root and a chisel-shaped crown for cutting. Canines (cuspids) lie lateral to the incisors. Each has a single root and a conical crown for grasping and tearing. Premolars (bicuspids) lie posterolateral to the canines. Each has 2 roots and a squat ovoid crown with a flat upper surface for crushing. Their location near the front of the mouth allows them to aid in grasping. Molars (tricuspids) lie behind the premolars. Each has 3 roots and a rounded, boxlike crown with a flat upper surface for crushing and grinding. Their location near the angle of the jaw allows them to exert greater crushing force than the premolars.

B. Permanent and Deciduous Teeth: Human adults (barring loss to decay, trauma, or other causes) normally have 32 permanent teeth arranged in 2 arches (maxillary, or upper; mandibu lar, or lower). Each arch has 2 bilaterally symmetric quadrants. The 8 teeth in each quadrant define the adult "dental formula": 2 incisors, 1 canine, 2 premolars, and 3 molars. Deciduous (baby) teeth develop first and are normally replaced by permanent teeth. The arrangement of the 20 deciduous teeth is like that of the permanent teeth, but there are no molars. The dental formula for the 5 deciduous teeth in each quadrant is 2 incisors, 1 canine, and 2 premolars.

C, Tooth Structure: Each tooth has the following named parts (Fig 15-2), which lie above, at, or below the gum line:

1. Crown (corona), This is the part of the tooth that projects above the gingiva (gum) and is the only part covered by enamel.
2. Root (radix). This projects below the gum into the bony socket (alveolus) that anchors the tooth. A tooth can have 1-3 roots, which are covered by cementum, A small opening at the root's apex (apical foramen) provides vessels and nerves access to the pulp cavity.
3. Neck (cervix), Lying at the crown-root junction at or just below the gum line, this is defined as the point where the enamel and cementum meet.
4. Pulp Cavity. This is found at the core of the tooth and lies mainly in the root, but extends into the crown. It is filled with pulp, a loose, vascular connective tissue. Vessels and nerves enter through the apical foramen. Some nerve (pain) fibers lose their myelin after entering the cavity; they may extend for short distances into the dentinal tubules.
5. Dentin, A relatively thick layer of bonelike calcified tissue, dentin surrounds the pulp cavity in both the crown and root. a. Composition. Hydroxyapatite crystals (8.III.A.2.b) make up 70% of dentin's dry weight, placing it between bone and enamel in hardness. Organic components include type I collagen and glycosaminoglycans. b. Organization. The dentin and pulp cavity are separated by a single layer of columnar cells called odontoblasts, These have basal nuclei, a well-developed Golgi complex, an RER, and many ribosomes. A long, branched, tapered odontoblast process (Tomes' fiber) extends from each cell's apical (dentinal) surface and penetrates the dentin's width in a dentinal tubule. Transverse sections through the dentin have a honeycomblike ap pearance (dentin forms the comb; Tomes' fibers and surrounding tissue fluid represent the honey). An unmyelinated nerve fiber often lies in the dentinal tubule. c. Histogenesis. The organic matrix components of dentin, together termed predentin, are secreted by odontoblasts from their apices. As the predentin is deposited and the dentin layer thickens, the cells retreat, leaving in place a thin cell process that gradually elongates to form a Tomes' fiber. Mineralization begins when the cells release into the predentin membrane-limited matrix vesicles containing fine hydroxyapatite crystals. The crystals act as nucleation sites for further mineral deposition. The crystals grow by accruing more mineral from the tissue fluid.
6. Enamel. A thick layer of calcified material covering the dentin of the crown, enamel is not a true tissue when mature, because it lacks cells or cell processes. a. Composition. Mineral salts (mainly hydroxyapatite) make up 95% of enamel, making it the hardest substance in the body. Unlike bone and dentin, its organic components do not include collagen. They do, however, include 2 unique classes of proteins-amelogenins and enamelins--whose role in organizing the mineral components is not yet clear. b. Organization. Enamel is arranged as tightly packed columns of hydroxyapatite. These enamel rods (prisms) are bound together by interrod enamel. c. Production. During tooth formation, enamel is produced by tall columnar cells, amel oblasts. Each has a basal nucleus, a well-developed Golgi complex, an RER, and a short apical cell process (Tomes' process). This process extends into the enamel matrix; it contains secretory vesicles filled with the glycoproteins that will constitute the organic portion of enamel. As the organic material is secreted from the ameloblast's apical surface, the cell recedes. Unlike the Tomes' fibers of the odontoblasts, Tomes' processes of ameloblasts recede along with the cell, leaving behind a solid rod of organic pre enamel. Calcification begins at the periphery of each rod and proceeds toward its core. Ameloblasts do not accompany the tooth during eruption; instead they degenerate. Once worn away or destroyed by bacteria, therefore, enamel is irreplaceable.
7. Cementum. This bonelike tissue covering the dentin of the roots is thicker at the apex of the root than near the neck of the tooth. It contains cementocytes, which, like osteocytes, lie in lacunae, communicate through canaliculi, and produce the surrounding matrix. Cementum is an active tissue that can undergo either enhanced production or resorption, depending upon the stresses to which it is subjected. It thus helps keep the roots in close contact with the walls of the alveoli.

D. Associated Structures:

1. Periodontal ligament. The collagen fibers of this dense connective tissue sling around the root of the tooth insert into both cementum and alveolar bone. This ligament serves as the alveolar periosteum, binds the root to the walls of the socket (alveolus), suspends the tooth, and permits slight movement. Its pressure-sensitive nerve endings warn against biting too hard and prevent the resorption of alveolar bone that would otherwise accompany direct transmission of pressure to the socket walls. Because its matrix undergoes rapid and continual turnover, it contains soluble collagen and glycosaminoglycans and is particularly susceptible to nutritional deficiencies. Vitamin C or protein deficiencies may cause it to degenerate, resulting in the loosening or loss of teeth.
2. Alveolar bone is simply the bone of the mandible and maxilla that lines the alveoli (sockets) and to which the teeth attach by the periodontal ligaments. Even in adults it consists of primary (woven) bone (8.III.C.1).
3. Gingiva (gums), The oral mucosa covering the mandibular and maxillary arches in which the teeth are anchored, the gingiva is composed of nonkeratinized stratified squamous epithelium. There is an underlying lamina propria, whose long papillae interdigitate with ridges of the overlying epithelium. The lamina propria is bound tightly to the epithelium by hemidesmosomes and to the periosteum of the underlying bone by intenvoven collagen fibers. The gingival epithelium forms a cuff around the base of the crown, separated from the tooth by a narrow gingival crevice. At the base of the crevice, the gingiva forms a basal lamina-like thickening, the cuticle, that encircles the tooth and attaches to the enamel. This is the epithelial attachment of Gottlieb.

E. Tooth Development: Beginning during the sixth week of gestation, tooth development in volves a cascade of epitheliomesenchymal interactions and proceeds through a series of mor phologic stages. This complex process can be more easily understood by monitoring the changes in epithelium and mesenchyme that occur during each stage and by focusing on the specific tooth components formed by each tissue. The epithelium is the oral epithelium. It derives from oral ectoderm and gives rise to the ameloblasts that form the enamel. The mesenchyme is the ectomesenchyme that underlies the oral epithelium. This embryonic connective tissue derives from the neural crest and gives rise to the odontoblasts and cementoblasts, which form dentin and cementum, respectively. It also forms the dental pulp. Mesenchyme surrounding the devel oping teeth forms the periodontal ligament and alveolar bone.

1. Crown development. This process (Fig 15-3) is completed shortly before eruption. It begins in oral ectodermal ridges called dental laminae with the formation of epithelial tooth buds. Proceeding through a series of stages, the buds form a cap that envelops a papilla of ectomesenchyme. A wave of interactions between the epithelial cap and papillary mes enchyme begins at the top of the crown and progresses toward the cervical loop (Fig 15-3). Briefly stated, neuroectodermal mesenchyme clusters induce epithelial tooth buds in the dental lamina, inducing the proliferation and condensation of the papiilary mesenchyme. This, in turn, induces formation of the inner enamel epithelium (Fig 15-3), causing the papillary mesenchyme cells to become odontoblasts. The inner enamel epithelial cells are induced to become ameloblasts, which cause the odontoblasts to produce predentin. On calcification, this induces the ameloblasts to produce enamel. See the legend to Figure 15-3 for a detailed description of the process.
2. Root development. Once the crown is formed, the cervical loop grows rootward, enclosing the dental papilla. The inner and outer enamel epithelia fuse around the root, forming Hertwig's root sheath, whose inner layer induces odontoblast differentiation in the adjacent papillary mesenchyme. Once the predentin around the root calcifies, the root sheath degener ates. This brings surrounding mesenchymal cells into contact with the dentin, which induces them to become cementoblasts. Cementum secreted by these cells onto the root surface traps the ends of fibers produced by nearby fibroblasts. The fibroblasts remodel these fibers to form the periodontal ligament.
3. Eruption. As the root elongates, newly formed alveolar bone limits its downward growth, forcing the crown upward. Tissue between the crown and gingival surface degenerates, allowing the crown to erupt into the oral cavity. Ameloblasts covering the crown degenerate. No new enamel forms after eruption.
4. Development of permanent teeth. In the late cap stage, a secondary (permanent) tooth bud arises from the labial (lip) surface of each dental lamina stalk (Fig 15-3). Dental lamina tissue from each second premolar burrows backward, successively budding off 3 permanent molar buds. Permanent tooth buds remain dormant until activated after birth; they then undergo the same developmental steps as deciduous teeth. As each developing permanent tooth enlarges, it induces osteoclast-mediated resorption of the alveolar bone that separates the bony crypt in which it lies and the baby tooth's socket. Continued growth of the permanent tooth leads to resorption of the baby tooth's root until only the crown is left, held in place only by its epithelial attachment to the gingiva. Once this is lost, the permanent tooth erupts into the oral cavity.

IV. PHARYNX

A short, broad, muscular tube that lies behind the tongue and soft palate, the pharynx is shared by the respiratory and digestive tracts. Its superior portion, the respiratory pharynx, lies above the soft palate; it communicates with the nasal cavity and is lined by respiratory epithelium. The inferior portion, the oral pharynx (oropharynx), lies below the level of the soft palate. It communicates with the oral cavity and is lined by nonkeratinized stratified squamous epithelium. Its walls, whose structure resembles that of the oral cavity, contain the palatine and pharyngeal tonsils (14.IX), many small subepithelial mucous glands, and skeletal muscle arranged as circular pharyngeal constrictors and longitudinal pharyngeal muscles. The pharynx also communicates with both the esophagus and the larynx. During swallowing, the back of the tongue helps close the epiglottis (17.V.A) to direct food away from the larynx and into the esophagus.

V. ESOPHAGUS

This long, narrow, muscular tube transports food from the pharynx to the stomach. Its mucosa includes nonkeratinized stratified squamous epithelium, a lamina propria that interdigitates with the scalloped basal border of the epithelium, and a muscularis mucosae. The mucus-secreting esophageal glands that characterize its submucosa help distinguish the esophagus from the vagina (23.IX) in histologic sections. The muscularis extema of the esophagus is composed of skeletal muscle in the upper third, a mixture of skeletal and smooth muscle in the middle third, and smooth muscle in the lower third. The outer surface is covered by adventitia, except for the short serosacovered segment in the abdominal cavity between the diaphragm and stomach. Mucus-secreting esophageal cardiac glands are found in the lamina propria of the region near the stomach.

VI. STOMACH

This dilated portion of the digestive tract temporarily holds ingested food, adding mucus, acid, and the digestive enzyme pepsin, Muscular contractions of the stomach blend these components into a viscous mixture called chyme, The chyme is then divided into parcels for further digestion and absorption by the intestines.

A. General Structure: The stomach wall has the same layers as the rest of the tract. The complex mucosa contains numerous gastric glands, a 2-3-layer muscularis mucosae that helps empty the glands, and an intervening lamina propria. When the stomach is empty and con tracted, the mucosa and underlying submucosa are thrown into irregular, temporary folds called rugae, that flatten when it is full. The smooth muscle of the muscularis externa is arranged in 3 layers: outer longitudinal, middle circular, and inner oblique. The stomach has 4 major regions: cardia, fundus, body, and pylorus (Fig 15-4).

B. Gastric Mucosa: The stomach lining of simple columnar epithelium is perforated by nu merous small holes called foveolae gastricae, The foveolae are the openings of epithelial invaginations, the gastric pits, which penetrate the lamina propria to various depths. The pits serve as ducts for the branched tubular gastric glands, Each gland has 3 regions: an isthmus at the bottom of the pit, a straight neck that penetrates deeper into the lamina propria (perpendicu lar to the surface), and a coiled base that penetrates deeper still and ends blindly just above the muscularis mucosae. The mucosa is characterized by the following epithelial cell types.

1. Surface mucous cells. These form the simple columnar epithelium lining the stomach, the gastric pits, and much of the isthmus of each gastric gland. They secrete a neutral mucus that protects the stomach's surface from the acidity of the gastric fluid.
2. Undifferentiated cells. Low columnar cells with basal ovoid nuclei are found scattered in the neck of the gastric glands. Some divide in the neck and move upward to replace pit and surface mucous cells. Others move deeper into the glands and differentiate into the other cell types listed below. Surface mucous cells turn over more rapidly than do the other cell types.
3. Mucous neck cells occur singly or in clusters between the parietal cells in the neck of the gland. They differ from the surface mucous cells by secreting acidic mucus.
4. Parietal(oxyntic) cells secrete HCI and intrinsic factor. a. Structure and location. These cells are found mainly between mucous neck cells in the neck of the gland; they are present, but scarce, in the base. They are large, pale, and round to pyramidal. They have one or 2 central nuclei and an acidophilic cytoplasm. The many mitochondria indicate that their secretory activity is energy-dependent. Each cell has a circular invagination of its apical plasma membrane that is visible only with the electron microscope. When the cells are stimulated to produce HCI, the many tu bulovesicles in the apical cytoplasm fuse with the invaginated plasma membrane to form a deeper, more highly branched invagination termed the intracellular canaliculus. b. Function. HCI production involves active transport of H+ and C1- ions across canalicu lar membranes into the lumen. The C1- derives from blood-borne chloride. H+ forma tion involves a 2-step process in which CO, is converted by carbonic anhydrase to carbonic acid. This dissociates into H+ and bicarbonate. Intrinsic factor is a glycopro tein that is required for absorption of vitamin B,,. B,, deficiency leads to a disorder of erythropoiesis called pernicious anemia. Parietal cell secretion is stimulated by cholinergic nerve endings. Acid production is greatly enhanced by histamine and gastrin produced by enteroendocrine cells in gastric glands (and elsewhere).
5. Chief (zymogenic) cells secrete pepsinogen and some iipase. a. Structure and location. These cells, which predominate in the base of gastric glands, are smaller than parietal cells. They are basophilic owing to the ribosomes associated with their RER. They also contain membrane-limited pepsinogen-filled zymogen gran- ules. b. Function. The RER synthesizes pepsinogen and lipase, which are packaged in granules by the Golgi complex and stored in the cytoplasm for secretion. Pepsinogen is an inactive proenzyme or zymogen that is converted to the active protease pepsin when exposed to the acidic environment of the stomach lumen. Gastric lipase has only weak lipolytic activity.
6. Enteroendocrine cells. In the stomach, these cells (I.C.4) occur mainly in the base of gastric glands. They produce various endocrine and paracrine amines leg, histamine, serotonin) and peptide hormones leg, gastrin). They are considered components of the DNES.

C. Regional Differences:

1. Cardia. A narrow collarlike region, the cardia surrounds the point of entry of the esophagus. Here, the lamina propria contains simple or branched tubular cardiac glands like those in the terminal part of the esophagus. The basal portions of these glands are often coiled, with wide lumens. Although they produce mainly mucus and lysozyme, some parietal cells may be present.
2. Fundus and body. The glands in these regions are similar in structure and function. The body is the stomach's largest region, extending from the cardia to the pylorus. The fundus is a smaller, roughly hemispheric region that extends above the cardia. Gastric glands--termed fundic glands in both regions--are characterized by shallow pits and long glands. The pits extend about a third of the distance from the mucosal surface to the base of the glands. Fundic glands contain abundant parietal and chief cells. Parietal cells are concentrated in the neck and upper part of the base, while chief cells predominate in the lower portion. Serotonin (5-hydroxytryptamine)-secreting cells are typically found at the bases of these glands.
3. Pylorus. This makes up the distal 4-5 cm of the stomach, leading to the small intestine. Pyloric glands are characterized by deep pits and short glands (mnemonic: P for both pylorus and pits). The pits extend half to two-thirds of the distance from the mucosal surface to the base of the glands. Although all glandular cell types may be present, large pale staining mucus-secreting cells with basal nuclei predominate (these are hard to distinguish from mucous neck cells in H&E-stained sections) and parietal cells are rare. Chief cells are especially scarce in this region. Gastrin-secreting cells (G cells) are typical of the bases of these glands. At the pylorus-small intestine junction, a thickened band of the middle circular layer of the muscularis externa, the pyloric sphincter, controls the passage of chyme.

VII. SMALL INTESTINE

The small intestine, which includes the dnodenum, jejunum, and ilenm, receives chyme from the stomach, bile from the liver, and digestive enzymes from the pancreas. Here, nutrients are hydrolyzed into an absorbable form; they are absorbed and transferred to blood and lymphatic capillaries. Undigested material is moved to the large intestine by peristalsis. The word small refers to diameter, not length: the small intestine is longer and narrower than the large intestine.

A. General Structure: The walls of the small intestine have the same layers as do the rest of the tract (I.B). The 2-layered muscularis externa (I.B.3) exhibits archetypal organization, as does the submucosa (I.B.2), except in the duodenum, where distinctive submucosal (Brunner's) glands (VII.C.I) are present. A series of permanent folds, the plicae circulares (valves of Kerckring), composed of both submucosa and mucosa, extend into the lumen and increase the surface area about 3-fold. The main distinguishing features of the small intestine (as viewed through the microscope) are in the composition and organization of the mucosa.

B. Mucosa of the Small Intestine: This consists of simple columnar epithelium with goblet cells, underlain by a lamina propria and separated from the submucosa by a muscularis mucosae.

1. Villi. The presence of these epithelium-covered fingerlike mucosal projections into the lumen is the most diagnostic feature of small intestine structure. The lamina propria core of each consists of loose connective tissue (S.III.A.I) and contains a central, blind-ending lymphatic capillary (often called a lacteal), as well as blood capillaries. Smooth muscle fibers run lengthwise in the villus core; however, the muscularis mucosae per se does not extend into the villi. Rhythmic contractions (shortening) of the villi speed up during digestion and help propel the nutrients in blood and lymphatic capillaries to the general circulation. The villi increase the mucosal surface area about I0-fold and thus enhance absorption; their shape and abundance differ according to the region where they are located (VI.C).
2. Intestinal glands (crypts of Lieberkuhn), These simple tubular glands (often coiled) extend into the lamina propria below the bases of the villi. They are lined by absorptive, goblet, Paneth's, enteroendocrine, and undifferentiated cells. Their secretions enter the lumen via small openings between the villi. Similar glands are seen in the large intestine, where they contain many more goblet cells.
3. Enterocytes (absorptive cells). These are the predominant cell type covering the villi. They occur in small numbers in the crypts. These tall columnar cells with basal nuclei have densely packed, g]ycocalyx-covered microvilli extending from their apical surfaces into the lumen. The approximately 3000 microvilli per cell give the cell-lumen border a striped appearance, referred to as a striated border. Enterocytes attach laterally to neighboring cells by junctional complexes (4.IV.B), including tight junctions near the lumen. Although their structure is comparatively simple, these cells perform several complex and important func tions. a. Digestion. Disaccharidases and dipeptidases are associated with the luminal surfaces of the microvilli. These enzymes complete the hydrolysis of nutrients that was begun by pancreatic enzymes in the lumen. The resulting monosaccharides and amino acids are more readily absorbed. b, Absorption. Apical microvilli increase the absorptive surface area about 20-fold and thus enhance absorption. Amino acids and monosaccharides are actively transported across the apical plasma membrane, while the products of lipid hydrolysis (fatty acids and monoglycerides) cross passively. Larger molecules may enter through pinocytotic vesicles (caveolae) that form at the bases of the microvilli. c, Lipid processing and chylomicron assembly. Absorbed monoglycerides and fatty acids collect in the SER, where they are resynthesized into triglycerides and then assembled into chylomicrons--small lipid spheres with a thin surface coat of protein. Chylomicrons are packed in vesicles by the Golgi complex and move to the basolateral plasma mem brane for exocytosis; from here, most enter the lymphatic capillaries. d, Transport of smaller nutrients, Amino acids, monosaccharides, and short-chain fatty acids cross the cytoplasm and then the basolateral cell membrane to reach the lamina propria, where they enter the blood and lymphatic capillaries.
4. Goblet cells. These lie between the absorptive cells, with more in the surface epithelium than in the crypts. They gradually increase in number from the duodenum to the ileum. The acid glycoprotein (mucus) they secrete onto the mucosal surface lubricates the digestive tract's walls, protecting them from pancreatic enzymes and impeding bacterial invasion (see 4.VI.C.3 for details of mucus-secreting cell structure).
5. M cells. These membranous epithelial cells are flat cells overlying solitary lymphoid noduies and Peyer's patches (14.V) of the intestinal lamina propria. Their apical (luminal) surfaces have small folds rather than microvilli. The cells help initiate immune responses by endo cytosing antigens from the lumen and passing them to lymphoid cells in underlying nodules.
6. Paneth's cells. Lying in the bases of the crypts, these cells synthesize a protein polysaccharide complex. In addition to RER and Golgi complexes, they have many large acidophilic secretory granules that contain lysozyme, an antibacterial enzyme that may help control the intestinal flora.
7. Enteroendocrine cells. Most known types of enteroendocrine cells (I.C.4) are found in the crypts of the small intestine. Those that occur mainly in this area produce hormones and amines such as secretin, which increases pancreatic and biliary bicarbonate and water secre tion; cholecystokinin, which increases pancreatic enzyme secretion and gallbladder contrac tion; gastric inhibitory peptide, which decreases gastric acid production; and motilin, which increases gut motility.
8. Undifferentiated cells. Mucosal epithelial cells undergo continual turnover. Replacement occurs through the mitosis of undifferentiated (stem) cells located near the base of the crypts. Products of these divisions differentiate into all the cell types described above; by a mecha nism that is still unclear, they move toward the crypt base or toward the tips of the villi, from which they are finally sloughed into the lumen.

C. Regional Differences:

1. Duodenum. The major distinguishing feature of this C-shaped first part of the small intestine is the presence of duodenal (Brunner's) glands in the submucosa. The mucous cells of these glands produce an alkaline secretion (pH 8.1-9.3) that enters the lumen through the crypts of Lieberkuhn. It protects the duodenal lining from the acidity of the chyme and raises the luminal pH to the optimum level for pancreatic enzyme activity. Unlike the jejunum and ileum, the duodenum is mostly a retroperitoneal organ (I.B.4). It is also the point of entry for the bile and pancreatic ducts, which penetrate the full thickness of the duodenal wall. It typically exhibits fingerlike or leaflike villi and relatively few goblet cells. Since the arms of the C cradle the head of the pancreas in situ, small pieces of pancreatic tissue often accom pany duodenal sections, providing another clue for identification.
2. Jejunum. An intraperitoneal organ, the jejunum has long leaflike vilii, many plicae cir culares, and an intermediate number of goblet cells. The key to its identification, however, is that although it has villi (and is thus part of the small intestine), it contains neither Brunner's glands nor Peyer's patches.
3. Ileum. This intraperitoneal organ has fewer villi, which are short and broad-tipped (clublike), and relatively abundant goblet cells. Its lamina propria typically contains many lymphoid nodule clusters (Peyer's patches; 14.V). These may be large enough to produce a visible bulge on the luminal surface and extend into the submucosa.

VIII. LARGE INTESTINE (COLON)

This includes the cecum; the ascending, transverse, descending, and sigmoid colon; and the rectum. It converts undigested material received from the small intestine into feces by removing water and adding mucus. The colon is shorter than the small intestine and has a wider lumen. Its walls have features that distinguish it from the small intestine at both the gross and microscopic levels.

A. Mucosa: The colon's lining has no folds, except in the rectum, where many vertical folds, called the rectal columns (of Morgagni), occur at the rectoanaljunction. No villi are present. The epithelium is simple columnar with a great abundance of goblet cells. The interposed absorptive cells have irregular short microvilli. Water absorption by these cells is passive; it follows the active transport of sodium out of their basal surfaces. The mucosa has many deep crypts of Leiberkuhn, containing abundant goblet cells and few enteroendocrine cells. The lamina propria has more lymphoid cells and nodules than does that of the small intestine. Nodules may extend into the submucosa.

B. Submucosa: This is generally unremarkable except in the lower rectum, where it contains portions of the hemorrhoidal plexus of veins, which extends into the lamina propria. The absence of valves in the veins within and draining the plexus, added to the great abdominal pressure changes they are subjected to during straining, etc, often causes these veins to become varicosed, resulting in the formation of hemorrhoids.

C. Muscularis Externa: In the colon, this component is unique in that the outer longitudinal layer of smooth muscle is gathered into 3 thick longitudinal bands called teniae coil. A thin layer of longitudinal smooth muscle often exists between the bands. The inner circular muscle layer resembles that of the small intestine.

D. Adventitia and Serosa: The outer covering on the various parts of the colon depends on whether they are intraperitoneal (cecum, transverse, sigmoid) or retroperitoneal (ascending, descending) (I.B.4; Table 15-1). The rectum passes vertically through the pelvis, surrounded by adventitia. The colon's serosa is characterized by the presence of many teardrop-shaped adipose-filled outpocketings termed appendices epiploicae.

IX. APPENDIX (VERMIFORM APPENDIX)

This is a narrow fingerlike evagination of the inferior end of the cecum. Histologically, it resembles the colon except that it has a smaller lumen, fewer and shorter crypts, many more lymphoid nodules, and no teniae coli.

X. ANAL CANAL

In humans, this canal is about 4 cm long and connects the rectum and the anal opening. The mucosa of the first 2 cm has typical colonic epithelium with very short crypts. This is replaced by stratified squamous epithelium, which continues to the anal opening. The lamina propria contains extensions of the hemorrhoidal plexus, and the submucosa under the stratified epithelium contains sebaceous glands and large circumanal apocrine sweat glands (Chapter 18). The muscularis in this region has a thickened inner circular layer of smooth muscle that forms the involuntary internal anal sphincter. Distal to this, the canal is encircled by the voluntary external anal sphincter, composed of skeletal muscle from the pelvic diaphragm.

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