I. General Features of the Digestive Tract
The digestive tract is a series of organs forming a long muscular tube whose continuous lumen opens at both ends to the exterior. The organs include the oral cavity, oral pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (cecum; appendix; ascending, transverse, descending, and sigmoid colon; rectum), and anal canal.
B. General Structural Features
Each organ's wall has four concentric layers (Fig. 15–1): the mucosa, submucosa, muscularis externa, and serosa or adventitia. (To master digestive tract histology, first learn the general composition and location of each layer and then focus on distinguishing features of each organ; Table 15–1.) Distinguishing structural features make more sense when considered in relation to organ functions (I.C).
Mucosa. This layer borders the lumen and has three parts. The epithelium derives from endoderm throughout the tract, except in the oral cavity and anal canal, where it derives from invaginating ectoderm. The epithelium is stratified squamous in the oral cavity, oral pharynx, esophagus, and anal canal; it is simple columnar in the stomach, intestines, and rectum. The lamina propria is the loose connective tissue layer containing blood and lymphatic vessels beneath the epithelium. The muscularis mucosae is a thin, smooth muscle layer bordering the submucosa.
Submucosa. This dense, irregular connective tissue layer contains blood and lymphatic vessels and the submucosal (Meissner's) nerve plexus. Some organs are characterized by glands and lymphoid nodules in this layer.
Muscularis externa. This comprises two smooth muscle layers (inner circular and 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 (e.g., hard palate, gingiva), the submucosa binds tightly to the bone. In the upper esophagus, this layer contains skeletal muscle, which is replaced by smooth muscle in the lower portion. The stomach's muscularis externa has three layers: outer longitudinal, middle circular, and inner oblique. The colon's outer longitudinal layer is gathered into three bands called the teniae coli. Smooth and skeletal muscles encircling the anal canal form involuntary and voluntary sphincters, respectively.
Serosa and adventitia. The tract's outer covering differs according to location. The esophagus and rectum are surrounded and held in place by a connective tissue adventitia similar to that around blood vessels. Intraperitoneal organs (stomach, jejunum, ileum, transverse and sigmoid colon) are suspended by mesenteries and covered by a serosa (i.e., a thin layer of loose connective tissue covered by simple squamous epithelium, or mesothelium). Retroperitoneal organs (duodenum, ascending and descending colon) are bound to the posterior abdominal wall by adventitia and are covered on their anterior surfaces by serosa.
C. General Functional Features
The primary functions of the digestive tract include the absorption of nutrients and water and the excretion of wastes and toxins.
Digestion. Enzymatic digestion of food is a prerequisite for absorption. Enzymes act mainly at food surfaces, and chewing exposes more surface area. Lip, cheek, and tongue muscles position food between the teeth. Saliva dissolves water-soluble particles and contains enzymes that attack carbohydrates (16.II.A and C). Taste buds (24.IV.A) check for contaminants, toxins, and nutrients. The tongue moves chewed food 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 aids the tongue in swallowing and moves food down the esophagus, 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 (HCl), 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. These enzymes hydrolyze nutrients to an absorbable form. Bile's detergent action disperses water-insoluble lipid into tiny droplets, increasing the surface area available to pancreatic lipases. The epithelial cells lining the small intestine (enterocytes) have additional enzymes on their luminal surfaces to complete nutrient hydrolysis.
Absorption. This primary function of the digestive tract occurs mainly in the intestines: the small intestines absorb nearly all the nutrients and most of the water and the large intestines absorb mainly water. To maximize the absorptive surface, the small intestine's lining has multiple permanent folds, including plicae circulares (VII.A) and villi (VII.B.1). Intestines are lined by columnar absorptive cells (enterocytes; VII.B.3) whose apical microvilli 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 processing. Enterocytes assemble chylomicrons from absorbed lipids and transfer them to lymphatic capillaries (lacteals) in the lamina propria. Here, lipids reach the blood through the lymphatic vascular system.
Excretion. Metabolic wastes are excreted by the liver as bile and emptied into the duodenal lumen by the bile duct. Smooth muscles in the small intestine's walls move undigested material and waste products to the large intestine (colon). Here, more mucus is added and the remaining water is extracted. This process concentrates and solidifies the intestinal contents, forming feces. This material is further dehydrated, stored in the rectum, and expelled through the anal canal.
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 secrete hormones and amines (e.g., 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.
Innervation. Distributed in and along the tract's walls are the myenteric (Auerbach's) and submucosal (Meissner's) autonomic nerve plexuses. These include postsynaptic sympathetic fibers, presynaptic and postsynaptic parasympathetic fibers, parasympathetic ganglion cell bodies, and some visceral sensory fibers. After voluntary swallowing, these autonomic plexuses coordinate peristalsis—wavelike contractions of the muscularis externa that propel ingested material through the tract. They also control the muscularis mucosa, which maintains contact between the mucosa and the tract's contents and helps empty mucosal glands. These plexuses also modulate the secretory activity of certain DNES-like cells. In general, sympathetic action inhibits, and parasympathetic action enhances, gut motility.
Blood supply. Superior and inferior mesenteric branches of the abdominal aorta ramify 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 sinusoids (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 (systemic) circulation.
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 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.
Simplified schematic diagram of the layers in the walls of the digestive tract.
Table 15–1. Distinguishing Features of the Walls of the Digestive Tract*. ||Download (.pdf)
Table 15–1. Distinguishing Features of the Walls of the Digestive Tract*.
The digestive tract's upper end 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.
The mucosa includes the lining epithelium and the underlying lamina propria. 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 similar to those in the dermis (18.I.B.2). The papillary capillaries nourish the epithelium. The oral cavity has no muscularis mucosae. The submucosa is more fibrous than the lamina propria; it contains many blood vessels and small salivary glands. The oral cavity also lacks a standard muscularis externa. Skeletal muscle underlies the submucosa in the lips, cheeks, tongue, floor of the mouth, oral pharynx, and soft palate, including its downward extension, the uvula. Bone underlies the thin submucosa of the hard palate and gums (gingiva).
Here, a transition occurs from nonkeratinized mucous membrane to the keratinized stratified squamous epithelium of the skin. The thin keratinized layer covering the lips’ vermilion 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 lip surface in tissue sections.
This component of the oral cavity is a mass of skeletal muscle covered by a mucosa. The mucosa is bound tightly to the muscle by the lamina propria, which penetrates the muscle. The tongue has little or no submucosa. The muscle is arranged in bundles of many sizes; these are separated by connective tissue and cross each other in three 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 are 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, which are mucosal projections. There are four types of papillae.
Filiform papillae are the most numerous. They are sharp, often partly keratinized, conical projections lacking taste buds.
Fungiform papillae resemble mushrooms. Each papilla 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 filiform papillae.
Foliate papillae occur along the tongue's lateral edges 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.
Circumvallate papillae are the largest and least numerous; only 7 to 12 occur near the V-shaped groove at the back of the tongue. Each is surrounded by a ringlike mucosal ridge from which it is separated by a circular furrow, with taste buds mainly on the papilla. As with the foliates, ducts from serous (von Ebner's) glands empty into the furrow and wash chemical stimuli from the taste buds, allowing new tastes to be sensed.
III. Teeth & Associated Structures
Note to medical and dental students: Although the teeth are the focus of dental histology, detailed coverage of tooth development and histology varies widely among medical school curricula. Few questions on teeth appear on the United States Medical Licensing Examination (USMLE). Thus, medical students may wish to restrict their review of this topic to the major headings and learn the meaning of the bold-faced words, leaving further study to their dental colleagues (for whom this book is also intended).
Humans have four types of teeth, each with a distinctive crown and root structure. The structure and location of each type suit 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 two 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 three 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.
B. Permanent and Deciduous Teeth
Human adults (barring loss from decay, trauma, or other causes) have 32 permanent teeth arranged in two arches (maxillary, or upper, and mandibular, or lower). Each arch has two bilaterally symmetric quadrants. The eight teeth in each quadrant define the adult “dental formula”: two incisors, one canine, two premolars, and three 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 five deciduous teeth in each quadrant is two incisors, one canine, and two premolars.
Each tooth has the following parts (Fig. 15–2), which lie above, at, or below the gum line:
Crown (corona). Projecting above the gum, this is the only part covered by enamel.
Root (radix). This part projects below the gum into the bony socket (alveolus) that anchors the tooth. A tooth can have one to three roots, which are covered by cementum. A small opening at the root's apex (apical foramen) provides access of vessels and nerves to the pulp cavity.
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.
Pulp cavity. This part lies at the tooth's core, mainly in the root but extending into the crown. It is filled with pulp, a loose, vascular connective tissue. Vessels and nerves enter by means of the apical foramen. Some nerve (pain) fibers lose their myelin after entering the cavity; they may extend for short distances into the dentinal tubules (III.C.5.b).
Dentin. A layer of bonelike tissue, dentin envelops the pulp in both the crown and root.
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.
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, 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 of dentin have a honeycomblike appearance (dentin forms the comb; Tomes’ fibers and tissue fluid form the honey). An unmyelinated nerve fiber often lies in the dentinal tubule.
Histogenesis. Dentin's organic matrix, termed predentin, is 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 minerals from the tissue fluid.
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.
Composition. Because mineral salts (mainly hydroxyapatite) make up 95% of enamel, it is the body's hardest substance. Unlike bone and dentin, its organic components (preenamel) do not include collagen, but rather two unique classes of proteins known as amelogenins and enamelins.
Organization. Enamel is arranged as tightly packed hydroxyapatite columns (enamel rods or prisms) bound together by interrod enamel.
Production. During tooth formation, enamel is produced by tall columnar cells called ameloblasts. Each has a basal nucleus, a well-developed Golgi complex, RER, and a short apical cell process (Tomes’ process). This process extends into the enamel matrix and contains secretory vesicles filled with preenamel. As the organic material is secreted from the ameloblast's apical surface, the cell recedes. Unlike the Tomes’ fibers of odontoblasts, the Tomes’ processes recede along with the ameloblasts, leaving behind a solid rod of organic preenamel. Calcification begins at each rod's periphery and proceeds toward its core. Ameloblasts do not accompany the tooth during eruption; instead, they degenerate. Enamel is thus irreplaceable.
Cementum. This bonelike tissue covering the dentin of the root is thicker at its apex than at its neck. It contains cementocytes that, like osteocytes, lie in lacunae, communicate through canaliculi, and produce the matrix. Cementum is an active tissue that can undergo either enhanced production or resorption, depending on the stresses to which it is subjected; thus, it helps keep the root in close contact with the socket wall.
Periodontal ligament. The collagen fibers of this dense connective tissue sling surround the tooth's root, inserting into both cementum and alveolar bone. This ligament serves as the alveolar periosteum, binds the root to the socket wall, 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.
Alveolar bone is simply the bone of the mandible and maxilla that lines the alveoli (sockets) and to which the teeth attach by periodontal ligaments. Even in adults it consists of primary (woven) bone (8.III.C.1).
Gingiva (gums). The oral mucosa covering the mandibular and maxillary arches in which the teeth are anchored consists of nonkeratinized stratified squamous epithelium. It includes an underlying lamina propria, whose long papillae interdigitate with epithelial ridges. The lamina propria binds tightly to the epithelium by hemidesmosomes and to the periosteum of the underlying bone by interwoven collagen fibers. The gingival epithelium forms a cuff around the crown's base and is separated from the tooth by a narrow gingival crevice. At the base of the crevice, the gingiva forms a basal laminalike thickening, the cuticle, that encircles the tooth and attaches to the enamel. This is the epithelial attachment of Gottlieb.
Beginning during week 6 of gestation, tooth development involves a cascade of epithelial–mesenchymal interactions and proceeds through a series of morphologic stages. This complex process is more easily understood by monitoring the changes in epithelium and mesenchyme that occur during each stage and by focusing on the tooth components formed by each tissue. The oral epithelium derives from oral ectoderm and gives rise to the ameloblasts that form the enamel. The mesenchyme is the ectomesenchyme underlying the oral epithelium. This embryonic connective tissue derives from the neural crest and gives rise to the odontoblasts and cementoblasts that form dentin and cementum, respectively. It also forms the dental pulp. Mesenchyme around the developing tooth forms the periodontal ligament and alveolar bone.
Crown development (Fig. 15–3) is completed shortly before eruption. It begins in oral ectodermal ridges called dental laminae with the formation of epithelial tooth buds. The buds form a cap that envelops a papilla of ectomesenchyme. A wave of interactions between the epithelial cap and papillary mesenchyme begins at the top of the crown and progresses toward the cervical loop (see Fig. 15–3). Briefly stated, ectomesenchymal clusters induce epithelial tooth buds in the dental lamina, prompting the proliferation and condensation of the papillary mesenchyme. This process, in turn, induces formation of the inner enamel epithelium (see 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. Calcified predentin induces the ameloblasts to produce enamel. (See Figure 15–3 for a detailed description of the process.)
Root development. Once the crown forms, 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 degenerates. This brings surrounding mesenchymal cells into contact with the dentin, inducing 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.
Eruption. As the root elongates, 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 enamel forms after eruption.
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 (see Fig. 15–3). Dental lamina tissue from each second premolar burrows backward, successively budding off three permanent molar buds. Permanent tooth buds remain dormant until activated after birth; subsequently, they undergo the same developmental steps as deciduous teeth. As each permanent tooth enlarges, it induces osteoclast-mediated resorption of the alveolar bone that separates the bony crypt in which it lies from 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 only by its cuticle to the gingiva. After this is lost, the permanent tooth erupts into the oral cavity.
Schematic diagram of an incisor. Labeled components include the crown (A), enamel (B), dentin (C), pulp (D), alveolar bone (E), periodontal ligament (F), gingiva (G), cementum (H), and apical foramen (I). (Revised, with permission, from Leeson TS, Leeson CR. Histology. 5th ed., Philadelphia, PA: WB Saunders; 1985.)
Stages in crown development. A. Dental lamina stage. Localized bands of proliferating cells in the basal layer of the stratified oral epithelium, peripheral to the developing tongue, form two (one per jaw) horseshoe-shaped epithelial ridges, or dental laminae, over the mesenchyme of the future mandibular and maxillary arches. B. Bud stage. Stimulated by local clusters of neural crest–derived mesenchyme cells, proliferation increases in the base of each dental lamina at the 10 sites of future deciduous teeth. These epithelial tooth buds enlarge and bulge into the underlying mesenchyme. C. Early cap stage. With further proliferation, the deep bud surfaces invaginate and widen to form solid caps over mesenchymal clusters. In the cap's core, the cell density decreases as internal cells become stellate and the interstices accumulate tissue fluid. The peripheral cells, which contact the basal lamina, form a simple epithelial shell and continue to divide, increasing the cap's size. A stalk of dental lamina connects each cap to the oral epithelium. The mesenchyme under the cap proliferates and condenses, indenting the cap's base. D. Late cap stage. Mesenchyme within the indentation forms the dental papilla, further indenting the cap's base. The epithelial cells over the papilla (inner enamel epithelium) become columnar, whereas those forming the rest of the shell (outer enamel epithelium) remain low cuboidal. The stellate cells and fluid inside the shell make up the stellate reticulum. Between the stellate reticulum and the inner enamel epithelium lies a layer of epithelial cells called the stratum intermedium. Together, the inner and outer epithelia, stratum intermedium, and stellate reticulum constitute the enamel organ. The outer enamel epithelium is continuous with the narrowing stalk of the dental lamina; this gives rise to another tooth bud that will subsequently form a permanent tooth (IV.F). E. Bell stage. As the cap grows, the indentation deepens, the inner enamel epithelium expands around the enlarging papilla, and the developing tooth becomes bell-shaped. Mesenchyme cells near the inner enamel epithelium condense, differentiate into a layer of columnar odontoblasts, and begin forming predentin. Mesenchyme in the papilla's core forms the dental pulp. Columnar cells of the inner enamel epithelium differentiate into ameloblasts and begin producing enamel soon after the dentin begins to calcify. After the enamel layer is complete, the ameloblasts shorten and become inactive. The ringlike junction of the inner and outer enamel epithelium at the rim of the bell is termed the cervical loop. Capillaries indent the outer enamel epithelium, and it loses its connection with the oral epithelium as the dental lamina degenerates. (Revised and redrawn, with permission, from Warshawsky H. The teeth. In: Weiss L, ed. Histology: Cell and Tissue Biology. 6th ed. New York: Elsevier; 1988.)
A short, broad, muscular tube 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, communicates with the nasal cavity, and is lined by respiratory epithelium. The inferior portion, the oral pharynx, lies below the level of the soft palate. It communicates with the oral cavity and is lined by nonkeratinized stratified squamous epithelium. Its walls 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.
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. Mucus-secreting esophageal glands characterize its submucosa and help distinguish esophagus from vagina (23.VIII) in histologic sections. The muscularis externa of the esophagus comprises 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 serosa-covered 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.
This dilated portion of the digestive tract temporarily holds ingested food, adding mucus, acid, and the digestive enzyme pepsin. Its contractions blend these components into a viscous mixture called chyme, which is subsequently divided into parcels for further digestion and absorption by the intestines.
The stomach wall has the same layers as the rest of the tract. The complex mucosa contains numerous gastric glands, a two- or three-layered muscularis mucosae that helps empty the glands, and an intervening lamina propria. When the stomach is empty and contracted, 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 comprises three layers: outer longitudinal, middle circular, and inner oblique. The stomach has four major regions: cardia, fundus, body, and pylorus (Fig. 15–4).
The stomach's simple columnar epithelial lining is perforated by many small holes called foveolae gastricae. The foveolae open into 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 three regions: an isthmus at the bottom of the pit, a straight neck that penetrates deeper into the lamina propria (perpendicular 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.
Surface mucous cells form the simple columnar epithelium lining the stomach lumen, 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 acidic gastric fluid.
Undifferentiated cells are low columnar cells with basal ovoid nuclei scattered in the neck of the gastric glands. After dividing in the neck, some 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.
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.
Parietal (oxyntic) cells secrete HCl and intrinsic factor.
Structure and location. These cells lie mainly between mucous neck cells in the neck of the gland. They are large, and round to pyramidal, with one or two central nuclei and a pale, acidophilic cytoplasm. The presence of many mitochondria reflects the energy dependence of their secretory activity. 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 HCl, the many tubulovesicles in the apical cytoplasm fuse with the invaginated plasma membrane to form a deeper, more highly branched invagination termed the intracellular canaliculus.
Function. HCl production involves the active transport of H+ and Cl− ions across canalicular membranes into the lumen. The Cl− derives from blood-borne chloride. H+ formation involves a two-step process in which CO2 is converted by carbonic anhydrase to carbonic acid, which dissociates into H+ and bicarbonate. Acid production is enhanced by histamine and gastrin produced by enteroendocrine cells in gastric glands (and elsewhere). Intrinsic factor is a glycoprotein required for vitamin B12 absorption. B12 deficiency leads to a disorder of erythropoiesis called pernicious anemia. Parietal cell secretion is stimulated by cholinergic nerve endings.
Chief (zymogenic) cells secrete pepsinogen and gastric lipase.
Structure and location. These low columnar cells predominate in the base of gastric glands and are smaller than parietal cells. They are basophilic owing to the RER's ribosomes. They also contain membrane-limited pepsinogen-filled zymogen granules.
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 acid in the stomach lumen. Gastric lipase has only weak lipolytic activity.
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 (e.g., histamine, serotonin) and peptide hormones (e.g., gastrin). They are considered DNES components.
Cardia. A narrow collarlike region, the cardia, surrounds the entry of the esophagus. Here, the lamina propria contains simple or branched tubular cardiac glands similar to those in the terminal esophagus. These glands have shallow crypts and coiled bases with wide lumens. Although they produce mainly mucus and lysozyme, some parietal cells may be present.
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 hemispherical region extending above the cardia. Gastric glands—termed fundic glands in both regions—are characterized by shallow pits and long glands. The pits extend approximately one-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 base; chief cells predominate in the lower base. Serotonin (5-hydroxytryptamine) secreting enteroendocrine cells are found at the base.
Pylorus. This region comprises the distal 4 to 5 cm of the stomach leading to the small intestine. Pyloric glands have deep pits and short glands (mnemonic: P for both pylorus and pits). The pits extend one-half to two-thirds of the distance from the mucosal surface to the base of the glands. Large pale-staining mucus-secreting cells with basal nuclei predominate. Parietal cells and especially chief cells are scarce here. Gastrin-secreting enteroendocrine cells (G cells) lie in bases of these glands. At the pylorus–small intestine junction, a thickened band of the muscularis externa's middle circular layer, the pyloric sphincter, controls the passage of chyme.
Regions of the stomach and their histologic structure. (Reproduced, with permission, from Junqueira LC, Carneiro J, Basic Histology: Text & Atlas. 11th ed. New York: McGraw-Hill, Inc.; 2005. Fig. 15–10.)
The small intestine includes the duodenum, jejunum, and ileum. It receives chyme from the stomach, bile from the liver, and digestive enzymes from the pancreas. Here, nutrients are hydrolyzed to an absorbable form; they are absorbed along with most of the water and transferred to blood and lymphatic capillaries. Undigested material is moved to the large intestine by peristalsis. The word “small” refers to diameter: the small intestine is longer and narrower than the large intestine.
The small intestine's walls have the same layers as the rest of the tract (I.B; Fig. 15–1). The two-layered muscularis externa (I.B.3) exhibits typical organization, as does the submucosa (I.B.2), except in the duodenum, where distinctive submucosal (Brunner's) glands (VII.C.1) are present. A series of permanent folds, the plicae circulares, composed of submucosa and mucosa extend into the lumen and increase the surface area approximately threefold. The main distinguishing microscopic features of the small intestine are the composition and organization of the mucosa.
B. Mucosa of the Small Intestine
This is a simple columnar epithelium with goblet cells, underlain by a lamina propria and separated from the submucosa by a muscularis mucosae.
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 (5.III.A.1) and contains a central, blind-ended lymphatic capillary (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 nutrients in the blood and lymphatic capillaries to the general circulation. The villi increase the mucosal surface area approximately 10-fold and thus enhance absorption; their shape and abundance differ by region (VII.C).
Intestinal glands (crypts of Lieberkühn). These simple (often coiled) tubular glands extend into the lamina propria below the bases of the villi. They are lined by absorptive, goblet, Paneth, enteroendocrine, and undifferentiated cells. Their secretions enter the lumen by means of small openings between the villi. Similar glands are seen in the large intestine, where they contain many more goblet cells.
Enterocytes (absorptive cells). These are the predominant cells covering the villi and they occur in small numbers in the crypts. These tall columnar cells with basal nuclei have densely packed, glycocalyx-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 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 functions.
Digestion. Disaccharidases and dipeptidases bind to the luminal surface of the microvilli and complete the hydrolysis of nutrients begun by pancreatic enzymes in the lumen. The resulting monosaccharides and amino acids are more readily absorbed.
Absorption. Apical microvilli increase the absorptive surface area approximately 20-fold and thus enhance absorption. Amino acids and monosaccharides cross the apical plasma membrane by facilitated diffusion, whereas 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. Water absorption from the intestinal contents is facilitated by the abundant microvilli and is a key function of the small intestine.
Lipid processing and chylomicron assembly. Absorbed monoglycerides and fatty acids collect in the SER, where they are resynthesized into triglycerides and subsequently assembled into chylomicrons—small lipid spheres with a thin protein coat. Chylomicrons are packed in vesicles by the Golgi complex and move to the basolateral plasma membrane for exocytosis; from here, most enter the lymphatic capillaries (lacteals, VII.B).
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.
Goblet cells. These cells lie between the absorptive cells, gradually increasing in number from duodenum to ileum. They have a broad apex filled with large pale-staining granules and a narrow stem containing a flattened nucleus that attaches to the basal lamina. The granules contain acidic glycoproteins (mucus) that they secrete onto the mucosal surface. The mucus lubricates the digestive tract's walls and protects them from pancreatic enzymes and bacterial invasion.
M cells. These flat membranous epithelial cells overlie solitary lymphoid nodules 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 endocytosing antigens from the lumen and passing them to lymphoid cells in underlying nodules.
Paneth's cells. These cells lie in the bases of the crypts and produce a protein–polysaccharide complex. In addition to RER and Golgi complexes, they have large acidophilic secretory granules containing lysozyme, an antibacterial enzyme that helps control intestinal flora. They are more abundant in the crypts of the ileum.
Enteroendocrine cells. Many enteroendocrine cell types (I.C.4) are found in the crypts of the small intestine. Here they produce hormones and amines such as secretin, which increases pancreatic and biliary bicarbonate and water secretion; cholecystokinin, which increases pancreatic enzyme secretion and gallbladder contraction; and gastric inhibitory peptide, which decreases gastric acid production; and motilin, which increases gut motility.
Undifferentiated cells. Mucosal epithelial cells undergo continual turnover. Replacement occurs through the mitosis of undifferentiated (stem) cells located near the base of the crypts. Evidence of this mitotic activity includes the presence of highly condensed, dark-staining chromosomes (i.e., mitotic figures) in the walls of the crypts. Products of these divisions differentiate into all of the cell types described above; by a mechanism 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.
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. It protects the duodenal lining from the acidity of the chyme and raises the luminal pH to optimize pancreatic enzyme activity. Unlike the jejunum and ileum, most of the duodenum is retroperitoneal (I.B.4). It is also the entry point for the bile and pancreatic ducts, which penetrate the full thickness of the duodenal wall. It typically has fingerlike or leaflike villi and relatively few goblet cells. Because the duodenum cradles the pancreas in situ, some pancreatic tissue may accompany duodenal sections, providing another clue for identification.
Jejunum. The jejunum, an intraperitoneal organ, has long, leaflike villi, many plicae circulares, 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.
Ileum. This intraperitoneal organ has fewer villi, which are short and broad-tipped (clublike), and 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)
The large intestine comprises 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 and wider than the small intestine. Its walls differ from the small intestine at both the gross and microscopic levels.
The colon's lining has no folds, except in the rectum, where vertical folds, called the rectal columns (of Morgagni), occur at the rectoanal junction. No villi are present. The epithelium is simple columnar with abundant 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, containing many 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.
This layer 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, coupled with the great abdominal pressure changes to which they are subjected (e.g., during coughing and straining), often causes these veins to become varicosed, resulting in the formation of hemorrhoids.
In the colon, this component is unique in that the outer longitudinal layer of smooth muscle is gathered into three thick longitudinal bands called teniae coli. A thin layer of longitudinal smooth muscle often exists between the bands. The inner circular muscle layer resembles that of the small intestine.
The outer covering on the various parts of the colon varies, depending on whether they are intraperitoneal (cecum, transverse, sigmoid) or retroperitoneal (ascending, descending) (I.B.4; see 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.
In humans, this canal is approximately 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 (18.VIII.B). 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, which is composed of skeletal muscle from the pelvic diaphragm.