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Anatomy and Histology of the Digestive Tract☆
Anatomy and Histology of the Digestive Tract☆ HM Amerongen, University of Arizona, Tucson, AZ, USA ã 2015 Elsevier Inc. All rights reserved.
Introduction Architecture of the Digestive Tract Overview of Blood and Lymphatic Vessels Overview of Innervation Esophagus Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Stomach Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Small Intestine Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Large Intestine Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation References
Glossary Adventitia Loose connective tissue forming the outer layer of an organ and attaching the organ to adjacent structures. Chief cell (or peptic cell) Epithelial cell present in gastric glands responsible for secretion of pepsinogen – a precursor to the proteolytic enzyme, pepsin. Chylomicrons Protein-coated triglyceride particles produced in enterocytes from dietary lipids and delivered to underlying lymphatics for distribution to the body. Crypt of Lieberku¨hn Straight tubular gland characteristic of the mucosa of small and large intestines. Enterochromaffin-like cell (or ECL cell) Histaminesecreting enteroendocrine cell of the stomach epithelium involved in regulation of gastric acid secretion. Enterocyte (or absorptive cell) The main epithelial cell of the small and large intestines. Enterocytes are involved in digestion (brush border enzymes), absorption (various transport mechanisms), and immune defense (transepithelial transport of IgA). Goblet cell Goblet-shaped mucous-secreting cell present in epithelia lining small and large intestines and upper respiratory tract. M cell Cell present in epithelium overlying lymphoid follicles in the gut and the upper respiratory tract, involved in transferring antigenic material from the luminal surface to
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underling antigen-presenting cells so that an immune response can be generated when appropriate. Mesothelium Layer of squamous or cuboidal epithelial cells lining body cavities and secreting a lubricating fluid that allows organs within the cavity to slide against each other and against the wall of the cavity. Mucosa The inner lining of hollow organs such as the digestive, respiratory, and urogenital tracts, and comprised of an epithelium, a loose connective tissue lamina propria, and, in the case of the digestive tube, a small amount of smooth muscle, the muscularis mucosae. Muscularis propria Main musculature of the digestive tube, subdivided into circular and longitudinal layers and responsible for peristalsis. Paneth cells Epithelial cells present at the bases of crypts of Lieberkuhn in the small intestine and proximal large intestine. They secrete antibacterial glycoproteins, principally lysozyme. Parietal cell (or oxyntic cell) Epithelial cell in gastric glands with an elaborate apical membrane compartment carrying proton pumps that drive stomach acid production. Parietal cells also secrete intrinsic factor, a glycoprotein essential for vitamin B12 absorption. Peyer’s patch Cluster of lymphoid follicles associated with the ileal epithelium, involved in generating immune responses against gut pathogens. There are approximately 25 Peyer’s patches along the length of the ileum.
Change History: August 2014. HM Amerongen has updated references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.02118-8
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Serosa Smooth layer covering organs within body cavities and lining the walls of those cavities. A serosa is comprised
of a layer of simple squamous epithelium called mesothelium, with associated connective tissue.
Introduction The principal functions of the digestive system are mechanical and chemical digestion of food; absorption of nutrients, fluid, and electrolytes; and elimination of indigestible material in feces. In addition, since the lumen of the digestive tube is an extension of the outside world, its epithelial surface must serve as a barrier that allows maintenance of physiological conditions in body tissues distinct from conditions in the lumen. Moreover, in conflict with its absorptive function, the tube must prevent entry of potential pathogens, and hence it also has significant immunological functions. The digestive system is comprised of the digestive tube together with accessory organs, including the teeth, tongue, and salivary glands associated with the oral cavity, and the pancreas and liver whose secretions are delivered into the duodenum of the small intestine (Figure 1). This article presents the gross anatomy and histology (architecture and cytology) of the four major organs of the digestive tube: the esophagus, stomach, small intestine, and large intestine. Recommended texts for more detailed information are Moore et al. (2013) for gross anatomy, and Ross and Pawlina (2011) and Kierszenbaum (2011) for histology.
Architecture of the Digestive Tract The walls of the esophagus, stomach, small intestine, and large intestine have four major layers (Figure 2). From the outside and going toward the lumen, they are as follows: The outer layer is made up either of a serosa or an adventitia, depending on whether that portion of the tract lies within the abdominal cavity or not. Where the tract lies outside the body cavity, an adventitia of loose connective tissue that attaches the organ
Figure 1 Gross anatomy of the digestive system and its relationship to the respiratory system. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
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Figure 2 Layers of the digestive tube as they appear in (a) esophagus, (b) stomach, (c) small intestine (duodenum), and (d) colon. m, mucosa; o, outer layer; p, muscularis propria; sm, submucosa. Mucous glands are present in the submucosa of esophagus and duodenum. The outer layer in the regions shown is a serosa in all but the esophagus. In the stomach the serosa (indicated by an arrowhead) is barely visible because it is very thin.
to adjacent structures is present. Where the tract lies within the abdominal cavity (or peritoneal cavity) the outer layer is a serosa comprised of simple squamous epithelium overlying a thin layer of connective tissue. By means of its smooth mesothelium, a serosa allows each alimentary tract segment to slide past adjacent serosa-covered structures, especially when the smooth surfaces are lubricated with a thin coat of peritoneal fluid. Note that serosa is a generic term: all organs lying within body cavities are covered by serosa. The serosa of abdominal organs, including the gastrointestinal tract, is called peritoneum, specifically visceral peritoneum (as opposed to parietal peritoneum, which covers the wall of the abdominal cavity). The stomach, small intestine, and portions of the large intestine are suspended in the abdominal cavity by mesenteries, which are sheets of tissue connecting these organs to the body wall. Mesenteries are continuous with the serosa of parietal and visceral peritoneum, and they carry blood vessels, nerves, and lymphatics to serve the digestive tube. Mesenteries are also a common location for fat to deposit. The muscularis propria (or muscularis externa) is responsible for the peristaltic contractions that move food through the tract. It usually consists of an outer longitudinal layer and an inner circular layer of smooth muscle, although there can be variations in this pattern depending on the region (noted below). Lying between inner and outer muscle layers is the myenteric plexus (or Auerbach’s plexus) comprised of autonomic nerves including intrinsic enteric fibers, sympathetic and parasympathetic fibers, as well as parasympathetic nerve cell bodies. The submucosa is a layer of loose connective tissue that acts as a ‘service corridor,’ carrying arteries, veins, and larger lymphatics to supply the muscularis propria and the mucosa. There is a submucosal nerve plexus (or Meissner’s plexus), which, like the myenteric plexus, is composed of autonomic nervous tissue. The mucosa is itself made up of three layers: The muscularis mucosae is a thin layer of muscle, which, like the muscularis propria, is organized into inner circular and outer longitudinal fibers. The lamina propria is a layer of loose connective tissue containing capillaries and nerves that supply the epithelium. Diffuse lymphoid tissue and lymphoid follicles are common in this layer. The epithelium is the innermost layer of the mucosa, and its structure varies greatly in different regions of the digestive tract, as described below. Note that mucosa, like serosa, is a generic term: all of our tracts are lined by a mucosa (formerly called mucous membrane) comprised minimally of epithelium and lamina propria and, in some cases such as the digestive tract, also including a muscularis mucosae.
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Overview of Blood and Lymphatic Vessels The digestive tube receives a prodigious blood supply mainly from branches of the aorta. The esophagus receives numerous branches along its length from the thoracic aorta. But the entire stomach and small and large intestines are fed by three unpaired branches of the abdominal aorta: the celiac trunk, and the superior and inferior mesenteric arteries. When the draining veins leave the wall of the digestive tube, those in the abdominal cavity do not empty into the inferior vena cava located alongside the abdominal aorta. Instead, they join to form the hepatic portal vein, which drains directly into the liver. In this way, practically all absorbed materials come into contact with the liver before entering the systemic circulation. Lymphatic drainage of the digestive tube follows the arteries back to the abdominal aorta and then ascends through a series of lymph nodes to become confluent with the cisterna chyli, the dilated beginning of a large lymphatic channel, the thoracic duct. The thoracic duct then passes upward through the thorax alongside the vertebral column to empty into the left subclavian vein near the root of the neck. Thus, absorbed lipids in the form of chylomicrons that enter initial lymphatics in the wall of the digestive tube are transported to the blood via the thoracic duct. It is also possible for lipid-soluble toxicants to follow this route.
Overview of Innervation The alimentary tract receives both motor and sensory innervation. Motor innervation to the digestive tube arrives via efferent fibers from the sympathetic and parasympathetic divisions of the autonomic nervous system. Both types of fibers generally follow arterial branches from the aorta to produce a dense plexus around the arteries. In addition, the digestive tube contains its own intrinsic nervous system, whose function is modulated by central input. Sympathetic division fibers are postganglionic, arising from cell bodies located in the celiac ganglion and paravertebral chain ganglia. These fibers are primarily vasoactive and cause constriction of arterioles. Parasympathetic fibers within the alimentary tract wall are both pre- and postganglionic. Preganglionic fibers run in branches of the 10th cranial nerve (vagus) to innervate the stomach, small intestine, and ascending portion of the colon. The rest of the colon (transverse and descending) receives parasympathetic innervation via the pelvic splanchnic nerves whose preganglionic cell bodies are in sacral spinal cord segments 2, 3, and 4. Postganglionic parasympathetic fibers arise from cell bodies located in myenteric and submucosal plexuses (located in muscularis propria and submucosa, respectively, as described above). Short postganglionic axons from myenteric plexus neurons innervate the smooth muscle of the muscularis propria. Those from the submucosal plexus innervate the muscularis mucosae and are secretomotor to submucosal and mucosal glands. Sensory innervation consists of free nerve endings between epithelial cells and pressure receptors in the lamina propria. Cell bodies for these afferent fibers are found in the corresponding dorsal root ganglia.
Esophagus The esophagus is a lubricated muscular tube that carries the food bolus from the oral cavity to the stomach. It does not play any significant role in digestion or absorption.
Gross Anatomical Relationships The esophagus is about 25 cm long and extends from the inferior part of the laryngopharynx at the level of the sixth cervical vertebra, through the thorax to the diaphragm. It pierces the diaphragm via the esophageal hiatus at the level of the 10th thoracic vertebra and then extends a short distance (approximately 2.5 cm) into the abdomen before joining the stomach. Most of the esophagus is situated in the mediastinum, an area of the thorax bounded in front by the sternum, behind by the vertebral column, and on either side by the lungs. The posterior surface of the esophagus is in contact with the upper 10 thoracic vertebrae as it gently curves to the left in its descent to pierce the diaphragm. The anterior surface of the upper half of the esophagus is in contact with the trachea. At the level between the fourth and fifth thoracic vertebrae the trachea bifurcates into the right and left bronchi and from this point on, the lower front portion of the esophagus is in contact with the pericardium of the heart. The right side of the esophagus is in contact with the right lung (pleura intervening) and a portion of the thoracic duct. The left side contacts the left common carotid and left subclavian arteries along its upper one-third while its lower two-thirds are in relation to the aortic arch followed by the thoracic aorta.
Architecture and Cytology Where the esophagus lies outside any body cavity (i.e., for most of its length), its outer layer is an adventitia of loose connective tissue attaching it to adjacent structures. The short portion of the lower esophagus that lies within the abdominal cavity is covered by a serosa.
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Figure 3 Micrograph of the esophagus mucosa showing stratified squamous epithelium, lamina propria, and, at the bottom, part of the muscularis mucosae. There is interdigitation of the epithelium with the connective tissue of the lamina propria to increase the surface area for metabolic exchange (capillaries are present only in the connective tissue) and to firmly anchor the epithelium.
At the transition from pharynx to esophagus, the skeletal muscle of the lower pharyngeal constrictor is carried over into the two layers of the muscularis propria. Hence, in the upper one-quarter to one-third of the esophagus the muscularis propria is composed of skeletal muscle fibers, which are involved in the reflex act of swallowing. In the remainder of the esophagus the muscularis is made up of smooth muscle. The muscularis propria does not enlarge visibly to form sphincters. The upper esophageal sphincter is formed by the cricopharyngeus muscle, which is attached to the cricoid cartilage of the larynx. The lower esophageal sphincter consists of increased resting tone maintained by intrinsic myotonic properties as well as cholinergic regulation (Boron and Boulpaep, 2009). The submucosa of the esophagus, in addition to carrying nerves and vessels that serve the mucosa, contains occasional clusters of esophageal mucous glands whose product drains via ducts to the esophageal lumen, to provide lubrication for the tube. The mucosa of the esophagus has a nonkeratinized, stratified squamous epithelium that lies on a loose connective tissue lamina propria and is separated from the submucosa by a well-developed muscularis mucosa (Figure 3). Stratified squamous epithelia are relatively thick and are generally considered to provide a protective barrier without allowing for significant exchange across the epithelium.
Blood Supply and Innervation Esophageal blood supply is from inferior thyroid arteries in the neck, from bronchial and intercostal arteries and the aorta in the thorax, and from the inferior phrenic and left gastric arteries in the abdomen. Venous drainage is to the thyroid, azygos, and left gastric veins. Venous anastomoses in the submucosa of the lower esophagus permit blood to drain either toward the azygos veins and hence to the vena cava, or to the gastric veins and hence to the liver via the hepatic portal vein, depending on differential pressures in the caval (systemic) and portal circulations (Figure 4). This is significant because if hepatic flow is impaired, blood normally draining through the liver is forced into the azygos drainage and the venous anastomoses carrying this heavier flow become dilated. These dilations, known as esophageal varices, can rupture spontaneously causing life-threatening hemorrhage. Somatic (to skeletal muscle) and parasympathetic innervation to the esophagus, including upper and lower esophageal sphincters, is via the vagus nerve. Sympathetic innervation comes from thoracic spinal cord segments 1–10.
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Figure 4 Diagram showing organs draining via the hepatic portal vein through the liver, and locations of portal-caval anastomoses (1) in the lower esophagus, (2) in the midrectum, (3) in the anterior body wall, via umbilical veins, which may reopen under pressure, (4) where the liver connects to the diaphragm, and (5) where superficial veins of colon drain to the body wall. Under conditions of portal hypertension, varices may occur at all of these sites. Reproduced from Drake, R. L.; Vogl, W.; Mitchell, A. W. M. Gray’s Atlas of Anatomy; Churchill Livingstone: Philadelphia, PA, 2008, with permission from Churchill Livingstone.
Stomach The stomach is responsible for the mechanical and chemical breakdown of the food bolus into chyme. It also plays a significant role in sterilization of food. It does not play a major role in absorption, although lipid-soluble substances may be absorbed through the stomach wall.
Gross Anatomical Relationships The stomach begins at the lower end of the esophagus about 2 5 mm to the left of the midline at a level between the 10th and 11th thoracic vertebrae. It angles downward and to the right, across the midline, to end at the pylorus, which is to the right of the midline at a level between the first and second lumbar vertebrae. The stomach deviates from the shape of a tube by bulging out toward the left. Viewed from the front, the long convex outer edge of this bulge forms the greater curvature (Figure 5). The right border of the stomach forms a short concave edge called the lesser curvature. The rounded upper end of the greater curvature is especially prominent as a bulge called the fundus. The fundus is in contact with the overlying diaphragm and extends above the level of entrance of the esophagus. The area of stomach immediately surrounding the esophageal entrance is called the cardiac portion. Proceeding from the cardiac end to the pylorus, the posterior aspect of the stomach is in relationship to the diaphragm, spleen, left kidney, pancreas, and superior mesenteric artery and vein. Anterior relations of the stomach are the left lobe of the liver, transverse colon, diaphragm, and anterior abdominal wall. The cardiac portion and fundus are protected by the ribs whereas the remainder of the body of the stomach has only the soft tissues of the anterior abdominal wall over it. The distal portion of the stomach that narrows to join the duodenum is called the antrum or pyloric stomach. The opening of the stomach to the duodenum is the pylorus.
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Figure 5 Gross anatomy of the stomach as seen cut open longitudinally. The lesser curvature, from cardia to pylorus, is at the left; the greater curvature is at the right. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
Architecture and Cytology Because the stomach lies within the abdominal cavity, its outer layer is visceral peritoneum. This serosa is continuous with a mesentery, the lesser omentum, that suspends the stomach from the liver, which is in turn attached to the body wall. The muscularis propria of the stomach consists of outer longitudinal, middle circular, and inner oblique layers of smooth muscle. At the pyloric-duodenal junction, the circular layer is enlarged to form the pyloric sphincter. The mucosa has a simple columnar epithelium that is extensively invaginated into the lamina propria to form the stomach glands. The superficial segment of each tubular invagination is called a gastric pit. Each gastric pit branches at its base to form the deeper cardiac, gastric, and pyloric glands proper. Thus, the gastric pits can in a sense be regarded as ducts of the deeper glands. The pits themselves are also glandular, however, being lined by mucous cells. Undifferentiated stem cells are located at the bases of gastric pits. These cells undergo mitosis and provide replacements for surface mucous cells that are lost as well as for other cells in the deeper glands. Mucous cells at the stomach surface are replaced by stem cells approximately every 3 to 6 days. Parietal cells and chief cells have a much slower turnover rate. The cardiac glands of the stomach are situated near the junction with the esophagus. They are coiled tubular glands made up of mucous cells. The gastric (or fundic) glands are straight, branched tubular glands (Figure 6) made up of mucous cells (in the neck), parietal cells (or oxyntic cells; mainly in the neck, also in the base), chief cells (mainly in the base, also in the neck), and scattered enteroendocrine cells. Parietal cells secrete HCl, which creates an optimal pH for stomach enzymes and protects against many bacteria and viruses. They also produce intrinsic factor, a glycoprotein necessary for absorption of vitamin B12 by the ileal mucosa. They contain abundant mitochondria, and a membrane compartment that in active cells exists as deep microvillous-lined canaliculi of the apical membrane, and in inactive cells is mainly a tubulovesicular compartment in the apical cytoplasm. These membranes contain the proton pumps (H+K+-ATPase) that drive acid production. Chief cells (or peptic cells) secrete pepsinogens, which are converted to pepsins at low pH. Pepsins are a family of proteolytic enzymes that initiate protein digestion in the stomach. Chief cells contain abundant rough endoplasmic reticulum in the basal cytoplasm, a prominent Golgi apparatus, and prominent secretory granules in the apical cytoplasm, reflecting their function as regulated secretors of glycoprotein. Enteroendocrine cells secrete hormones that influence gut function. Some have a free apical surface while others do not contact the gut lumen. Their secretory granules are accumulated in the basal cytoplasm, since these cells exocytose their secretory product through the basal membrane. Gastrin, a hormone secreted by enteroendocrine cells in the stomach, stimulates stomach motility and HCl production by parietal cells. Enterochromaffin-like (ECL) cells are a subcategory of histamine-secreting enteroendocrine cells that affect acid secretion either via direct stimulation of parietal cells or indirectly by stimulation of gastrin-secreting cells (Boron and Boulpaep, 2009). The pyloric glands, like the cardiac glands, are coiled tubular glands. They are mainly made up of mucous cells but enteroendocrine cells are also present, and indeed are most numerous in this part of the stomach. Gastric pits are most prominent in the pyloric region, being conspicuously longer in this region than in the cardiac region and body of the stomach. The lining of the contracted stomach is thrown up into folds called rugae. They have a core of submucosa and flatten out when the stomach is full, thereby allowing a degree of distensibility.
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Figure 6 Micrograph of the stomach mucosa. At the top, the lumen of the stomach is covered by pale surface mucous cells, which also line the gastric pits that invaginate the mucosa for about one-quarter of its thickness. Gastric pits lead into tubular gastric glands lined in their upper half with pinkstaining parietal cells and in their lower half with purple-staining chief cells.
Figure 7 Blood supply of the stomach. The celiac trunk branches from the abdominal aorta. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
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Blood Supply and Innervation Blood supply to the stomach is from branches of the celiac trunk, itself a branch of the aorta at the level of the 12th thoracic vertebra (Figure 7). The lesser curvature is supplied by left and right gastric arteries, which anastomose within the curvature. The greater curvature receives blood from the left and right gastroepiploic (or gastroomental) arteries. Venous drainage of the stomach is by the splenic vein (greater curvature) and left and right gastric veins (lesser curvature), which join the inferior and superior mesenteric veins to form the portal vein. Parasympathetic innervation of the stomach is provided by the vagus nerve and sympathetic via the splanchnic nerves and the celiac ganglion, all of which pass to the stomach along its blood vessels.
Small Intestine The small intestine is responsible for the final chemical breakdown of food by digestive enzymes, and the absorption of nutrients, water, and electrolytes.
Gross Anatomical Relationships The small intestine has three regions. The duodenum is the initial C-shaped portion about 25 cm long that bends snugly around the head of the pancreas. It begins at the pylorus to the right of the midline, curves further to the right around the head of the pancreas, and then curves back across the midline at the level of the second lumbar vertebra to become continuous with the jejunum. The duodenum is attached to the posterior abdominal wall and therefore has no mesentery except where it turns forward to leave the abdominal wall and become the jejunum. The jejunum and ileum together are about 6 m long, with the jejunum comprising about two-fifths and the ileum three-fifths. They are suspended from the posterior abdominal wall by a mesentery that begins at the duodenum—jejunum junction and runs downward and to the right for 18–20 cm to end at the ileocecal junction where the ileum empties into the colon. The mesentery rapidly lengthens to accommodate the length of jejunum and ileum. Consequently, these portions of the small intestine are thrown into numerous loops.
Figure 8 Micrograph of the ileum showing part of a Peyer’s patch, which consists of multiple lymphoid follicles that extend through the mucosa and submucosa. M cells are present in the epithelium overlying each follicle.
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In addition to the solitary lymphoid follicles that can be present in the mucosa of any part of the digestive tube, the ileal wall contains about 20 distinctive clusters of follicles called Peyer’s patches (Figure 8). These span the mucosa and submucosa. Both solitary follicles as well as those in Peyer’s patches are overlain by a specialized follicle-associated epithelium characterized by the presence of M cells – epithelial cells that conduct transepithelial transport of antigen from the lumen into the underlying follicle (Amerongen et al., 1992).
Architecture and Cytology The outer layer of the small intestine is a serosa, except where the duodenum attaches to the posterior abdominal wall via an adventitia of loose connective tissue. The muscularis propria is made up of outer longitudinal and inner circular layers. The inner circular layer forms a sphincter at the ileocecal valve. The submucosa of the duodenum (but not the jejunum or ileum) contains glands (Brunner’s glands) that secrete a bicarbonaterich mucus that helps protect the small intestine from the acidic stomach contents. The mucosa has a simple columnar epithelium that is invaginated to form the crypts of Lieberkuhn, and evaginated to form villi (Figure 9). Submucosa and mucosa of the small intestine are thrown into circular folds, the plicae circulares (valves of Kerkring), which are most prominent in the jejunum. These are permanent folds (they do not disappear when the lumen is full) and together with mucosal villi they increase the surface area for processing of luminal content. Goblet cells secrete mucin and are distributed throughout the epithelium of the small intestine, increasing in number distally, such that lubrication increases as fluid content in the lumen is reduced due to absorption. Paneth cells, located in a tight cluster at the bottom of each crypt, secrete antibacterial enzymes, principally lysozyme. As in the stomach, enteroendocrine cells are scattered throughout the epithelium. Enterocytes (or absorptive cells) are the main cell type in the mucosal epithelium. They are tall columnar cells with a prominent brush border (dense and regular microvilli) at the apical surface, a well-developed smooth endoplasmic reticulum compartment in the apical cytoplasm, a prominent Golgi apparatus, lots of mitochondria, and an extensively folded basolateral membrane. They are multifunctional cells involved in digestion, absorption, and immune defense. Enterocytes produce brush border enzymes, which are integral membrane proteins that populate the microvillar membrane at the enterocyte surface. One of these, enteropeptidase, cleaves the pancreatic enzyme precursor, trypsinogen, to its active form, trypsin. Trypsin then goes on to activate other digestive enzyme precursors secreted from the pancreas. The activated pancreatic
Figure 9 Micrograph of the jejunum mucosa. Paddle-shaped villi covered with enterocytes and goblet cells project into the lumen. Invaginations of epithelium at the base of the villi form straight tubular glands called crypts of Lieberkuhn. These are also lined by enterocytes and goblet cells. In addition, pink-staining Paneth cells are present in a cluster at the base of each crypt, and stem cells are present in the epithelium above the level of Paneth cells.
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enzymes digest fats and convert proteins to oligopeptides and carbohydrates to oligosaccharides. The remaining brush border enzymes then digest oligopeptides to amino acids and oligosaccharides to monosaccharides. Enterocytes absorb monosaccharides and amino acids by active transport and/or facilitated diffusion. These nutrients then diffuse down a concentration gradient out of the cell at the basolateral surface, and into fenestrated capillaries of the lamina propria. Monoglycerides and fatty acids diffuse across the apical membrane of enterocytes into a smooth endoplasmic reticulum compartment where they are resynthesized into triglycerides. A protein coat is added to the triglyceride and the resulting particles, called chylomicrons, are transported in vesicles to the basolateral membrane and exocytosed. Chylomicrons are then absorbed into a lacteal – a large lymphatic capillary present in each villus. Na+ ions enter enterocytes by facilitated diffusion through the apical membrane and are actively pumped out of the cell at the basolateral membrane, through the action of Na+K+-ATPase. The basal and lateral membranes of enterocytes are highly folded to increase the surface area for Na+K+-ATPase, and there are many mitochondria present near the membrane to supply ATP for active transport. The pumping out of sodium maintains a high salt concentration in the intercellular space near the base of the cell, and water is drawn out of the lumen down an osmotic gradient and enters lymphatic and blood capillaries. Tight junctions between enterocytes regulate absorption via the para-cellular route (Salama et al., 2006). Enterocytes also conduct transepithelial transport of the polymeric antibodies immunoglobulin A (IgA) and IgM, from the lamina propria where it is deposited by plasma cells, into the intestinal lumen. This process is mediated by the poly-Ig receptor, a glycoprotein expressed at the basolateral surface of enterocytes (Wines and Hogarth, 2006). Undifferentiated epithelial stem cells are located in the crypts just above the Paneth cells. These cells provide progeny to replace those that are sloughed off regularly as a part of normal epithelial cell turnover.
Blood Supply and Innervation The duodenum receives its blood supply from branches of the hepatic artery and the superior mesenteric artery, a branch of the aorta near the level of the first lumbar vertebra (Figure 10). The superior mesenteric artery passes in front of the duodenum, as it crosses the midline, and enters the mesentery to form multiple arcades that anastomose and supply the jejunum and ileum as well as nearly the first two-thirds of the colon. Draining veins accompany the arteries to form the superior mesenteric vein, which joins the splenic vein behind the pancreas to form the hepatic portal vein. Parasympathetic preganglionic fibers arrive at the small intestine via the vagus nerve, and sympathetic postganglionic nerve fibers arrive via the celiac and superior mesenteric plexuses.
Figure 10 Blood supply of the small intestine and colon from the superior mesenteric artery. Most of the jejunum and the ileum are cut away. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from LippincottRaven.
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Large Intestine The large intestine completes the absorption of nutrients, water, and electrolytes and forms the fecal mass.
Gross Anatomical Relationships The colon begins in the lower right abdominal cavity where it receives the contents of the ileum (Figure 1). The ileocecal junction forms a T, with the cecum and appendix descending inferiorly a short distance, and the ascending colon extending superiorly as far as the undersurface of the liver. At the hepatic (right colic) flexure, the large intestine then crosses the abdominal cavity draped slightly below the greater curvature of the stomach as the transverse colon. To the left of the stomach it bends inferiorly at the left colic flexure. It travels down the left side as the descending colon then turns toward the midline as the sigmoid colon, which ends near the midline in the rectum and anal canal. The ascending and descending colon are attached to the posterior abdominal wall. The transverse and sigmoid portions of the colon are suspended by mesenteries from the posterior body wall.
Architecture and Cytology The outer layer of the large intestine is a serosa over the colon except where it attaches to the posterior abdominal wall. It is covered by adventitia at these locations as well as over the rectum, which lies in the pelvis outside the abdominal cavity. The muscularis propria in the colon has the longitudinal muscle layer arranged into three longitudinal bands, the teniae coli. At the rectoanal junction, the circular layer of the muscularis forms an internal anal sphincter (smooth muscle) and an external anal sphincter (skeletal muscle). The submucosa contains the hemorrhoidal plexus of veins at the rectoanal junction. The mucosa has a simple columnar epithelium composed of the same cell types as are found in the small intestine, except that Paneth cells are present only in the proximal part of the large intestine, goblet cells are more numerous, and absorptive cells are correspondingly fewer. The epithelium is invaginated to form crypts of Lieberkuhn, but unlike in the small intestine, there are no villi (Figure 11). At the rectoanal junction, there is an abrupt transition from simple columnar to stratified squamous epithelium. At a variable distance along the anal canal, the stratified squamous epithelium changes from nonkeratinized to keratinized. Lymphoid follicles are common, especially in the distal colon and the rectum.
Figure 11 Micrograph showing straight tubular glands of the colon mucosa. Like the small intestine, the epithelium consists of enterocytes and goblet cells (the latter are more numerous in the colon), as well as stem cells in the walls of each crypt near the base. Paneth cells are absent except in the proximal colon.
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Figure 12 Blood supply of the colon from the superior and inferior mesenteric arteries. Reproduced from Hollinshead, W. H. Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
Blood Supply and Innervation Blood supply to the ascending and transverse colon is via the superior mesenteric artery. The descending colon, sigmoid colon, and superior rectum receive their blood from the inferior mesenteric artery, which arises from the aorta at the level of the third lumbar vertebra (Figure 12). Blood drains from these organs via the inferior mesenteric vein, which ends in the splenic vein before it joins the superior mesenteric vein to form the hepatic portal vein. The middle and inferior rectums drain via middle and inferior rectal arteries, which empty directly into the systemic circulation. As in the lower esophagus, portal systemic anastomoses are present in the rectal wall, and varicosities can develop in these vessels under conditions of portal hypertension. The proximal colon to approximately the left colic flexure is supplied with parasympathetic fibers via the vagus nerve, and with sympathetic fibers derived from spinal segments T10 to L1. From left colic flexure to rectum, parasympathetic innervation is from sacral spinal segments 2–4, and sympathetic innervation is from lumbar segments 1 and 2.
References Amerongen HM, Weltzin R, Mack JA, Winner LS, Michetti P, Apter FM, Kraehenbuhl JP, and Neutra MR (1992) Annals of the New York Academy of Sciences 664: 18–26. Boron WF and Boulpaep EL (2009) Medical physiology, 2nd ed. Philadelphia, PA: Saunders/Elsevier. Kierszenbaum AL (2011) Histology and cell biology: An introduction to pathology, 3rd ed. St. Louis, MO: Mosby. Moore KL, Dalley AF, and Agur AMR (2013) Clinically oriented anatomy, 7th ed. Philadelphia, PA: Lippincott, Williams and Wilkins. Ross MH and Pawlina W (2011) Histology: A text and atlas: With correlated cell and molecular biology, 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins. Salama NN, Eddington ND, and Fasano A (2006) Advanced Drug Delivery Reviews 58: 15–28. Wines BD and Hogarth PM (2006) Tissue Antigens 68: 103–114.
Introduction Architecture of the Digestive Tract Overview of Blood and Lymphatic Vessels Overview of Innervation Esophagus Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Stomach Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Small Intestine Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation Large Intestine Gross Anatomical Relationships Architecture and Cytology Blood Supply and Innervation References
Glossary Adventitia Loose connective tissue forming the outer layer of an organ and attaching the organ to adjacent structures. Chief cell (or peptic cell) Epithelial cell present in gastric glands responsible for secretion of pepsinogen – a precursor to the proteolytic enzyme, pepsin. Chylomicrons Protein-coated triglyceride particles produced in enterocytes from dietary lipids and delivered to underlying lymphatics for distribution to the body. Crypt of Lieberku¨hn Straight tubular gland characteristic of the mucosa of small and large intestines. Enterochromaffin-like cell (or ECL cell) Histaminesecreting enteroendocrine cell of the stomach epithelium involved in regulation of gastric acid secretion. Enterocyte (or absorptive cell) The main epithelial cell of the small and large intestines. Enterocytes are involved in digestion (brush border enzymes), absorption (various transport mechanisms), and immune defense (transepithelial transport of IgA). Goblet cell Goblet-shaped mucous-secreting cell present in epithelia lining small and large intestines and upper respiratory tract. M cell Cell present in epithelium overlying lymphoid follicles in the gut and the upper respiratory tract, involved in transferring antigenic material from the luminal surface to
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underling antigen-presenting cells so that an immune response can be generated when appropriate. Mesothelium Layer of squamous or cuboidal epithelial cells lining body cavities and secreting a lubricating fluid that allows organs within the cavity to slide against each other and against the wall of the cavity. Mucosa The inner lining of hollow organs such as the digestive, respiratory, and urogenital tracts, and comprised of an epithelium, a loose connective tissue lamina propria, and, in the case of the digestive tube, a small amount of smooth muscle, the muscularis mucosae. Muscularis propria Main musculature of the digestive tube, subdivided into circular and longitudinal layers and responsible for peristalsis. Paneth cells Epithelial cells present at the bases of crypts of Lieberkuhn in the small intestine and proximal large intestine. They secrete antibacterial glycoproteins, principally lysozyme. Parietal cell (or oxyntic cell) Epithelial cell in gastric glands with an elaborate apical membrane compartment carrying proton pumps that drive stomach acid production. Parietal cells also secrete intrinsic factor, a glycoprotein essential for vitamin B12 absorption. Peyer’s patch Cluster of lymphoid follicles associated with the ileal epithelium, involved in generating immune responses against gut pathogens. There are approximately 25 Peyer’s patches along the length of the ileum.
Change History: August 2014. HM Amerongen has updated references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.02118-8
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Anatomy and Histology of the Digestive Tract
Serosa Smooth layer covering organs within body cavities and lining the walls of those cavities. A serosa is comprised
of a layer of simple squamous epithelium called mesothelium, with associated connective tissue.
Introduction The principal functions of the digestive system are mechanical and chemical digestion of food; absorption of nutrients, fluid, and electrolytes; and elimination of indigestible material in feces. In addition, since the lumen of the digestive tube is an extension of the outside world, its epithelial surface must serve as a barrier that allows maintenance of physiological conditions in body tissues distinct from conditions in the lumen. Moreover, in conflict with its absorptive function, the tube must prevent entry of potential pathogens, and hence it also has significant immunological functions. The digestive system is comprised of the digestive tube together with accessory organs, including the teeth, tongue, and salivary glands associated with the oral cavity, and the pancreas and liver whose secretions are delivered into the duodenum of the small intestine (Figure 1). This article presents the gross anatomy and histology (architecture and cytology) of the four major organs of the digestive tube: the esophagus, stomach, small intestine, and large intestine. Recommended texts for more detailed information are Moore et al. (2013) for gross anatomy, and Ross and Pawlina (2011) and Kierszenbaum (2011) for histology.
Architecture of the Digestive Tract The walls of the esophagus, stomach, small intestine, and large intestine have four major layers (Figure 2). From the outside and going toward the lumen, they are as follows: The outer layer is made up either of a serosa or an adventitia, depending on whether that portion of the tract lies within the abdominal cavity or not. Where the tract lies outside the body cavity, an adventitia of loose connective tissue that attaches the organ
Figure 1 Gross anatomy of the digestive system and its relationship to the respiratory system. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
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Figure 2 Layers of the digestive tube as they appear in (a) esophagus, (b) stomach, (c) small intestine (duodenum), and (d) colon. m, mucosa; o, outer layer; p, muscularis propria; sm, submucosa. Mucous glands are present in the submucosa of esophagus and duodenum. The outer layer in the regions shown is a serosa in all but the esophagus. In the stomach the serosa (indicated by an arrowhead) is barely visible because it is very thin.
to adjacent structures is present. Where the tract lies within the abdominal cavity (or peritoneal cavity) the outer layer is a serosa comprised of simple squamous epithelium overlying a thin layer of connective tissue. By means of its smooth mesothelium, a serosa allows each alimentary tract segment to slide past adjacent serosa-covered structures, especially when the smooth surfaces are lubricated with a thin coat of peritoneal fluid. Note that serosa is a generic term: all organs lying within body cavities are covered by serosa. The serosa of abdominal organs, including the gastrointestinal tract, is called peritoneum, specifically visceral peritoneum (as opposed to parietal peritoneum, which covers the wall of the abdominal cavity). The stomach, small intestine, and portions of the large intestine are suspended in the abdominal cavity by mesenteries, which are sheets of tissue connecting these organs to the body wall. Mesenteries are continuous with the serosa of parietal and visceral peritoneum, and they carry blood vessels, nerves, and lymphatics to serve the digestive tube. Mesenteries are also a common location for fat to deposit. The muscularis propria (or muscularis externa) is responsible for the peristaltic contractions that move food through the tract. It usually consists of an outer longitudinal layer and an inner circular layer of smooth muscle, although there can be variations in this pattern depending on the region (noted below). Lying between inner and outer muscle layers is the myenteric plexus (or Auerbach’s plexus) comprised of autonomic nerves including intrinsic enteric fibers, sympathetic and parasympathetic fibers, as well as parasympathetic nerve cell bodies. The submucosa is a layer of loose connective tissue that acts as a ‘service corridor,’ carrying arteries, veins, and larger lymphatics to supply the muscularis propria and the mucosa. There is a submucosal nerve plexus (or Meissner’s plexus), which, like the myenteric plexus, is composed of autonomic nervous tissue. The mucosa is itself made up of three layers: The muscularis mucosae is a thin layer of muscle, which, like the muscularis propria, is organized into inner circular and outer longitudinal fibers. The lamina propria is a layer of loose connective tissue containing capillaries and nerves that supply the epithelium. Diffuse lymphoid tissue and lymphoid follicles are common in this layer. The epithelium is the innermost layer of the mucosa, and its structure varies greatly in different regions of the digestive tract, as described below. Note that mucosa, like serosa, is a generic term: all of our tracts are lined by a mucosa (formerly called mucous membrane) comprised minimally of epithelium and lamina propria and, in some cases such as the digestive tract, also including a muscularis mucosae.
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Anatomy and Histology of the Digestive Tract
Overview of Blood and Lymphatic Vessels The digestive tube receives a prodigious blood supply mainly from branches of the aorta. The esophagus receives numerous branches along its length from the thoracic aorta. But the entire stomach and small and large intestines are fed by three unpaired branches of the abdominal aorta: the celiac trunk, and the superior and inferior mesenteric arteries. When the draining veins leave the wall of the digestive tube, those in the abdominal cavity do not empty into the inferior vena cava located alongside the abdominal aorta. Instead, they join to form the hepatic portal vein, which drains directly into the liver. In this way, practically all absorbed materials come into contact with the liver before entering the systemic circulation. Lymphatic drainage of the digestive tube follows the arteries back to the abdominal aorta and then ascends through a series of lymph nodes to become confluent with the cisterna chyli, the dilated beginning of a large lymphatic channel, the thoracic duct. The thoracic duct then passes upward through the thorax alongside the vertebral column to empty into the left subclavian vein near the root of the neck. Thus, absorbed lipids in the form of chylomicrons that enter initial lymphatics in the wall of the digestive tube are transported to the blood via the thoracic duct. It is also possible for lipid-soluble toxicants to follow this route.
Overview of Innervation The alimentary tract receives both motor and sensory innervation. Motor innervation to the digestive tube arrives via efferent fibers from the sympathetic and parasympathetic divisions of the autonomic nervous system. Both types of fibers generally follow arterial branches from the aorta to produce a dense plexus around the arteries. In addition, the digestive tube contains its own intrinsic nervous system, whose function is modulated by central input. Sympathetic division fibers are postganglionic, arising from cell bodies located in the celiac ganglion and paravertebral chain ganglia. These fibers are primarily vasoactive and cause constriction of arterioles. Parasympathetic fibers within the alimentary tract wall are both pre- and postganglionic. Preganglionic fibers run in branches of the 10th cranial nerve (vagus) to innervate the stomach, small intestine, and ascending portion of the colon. The rest of the colon (transverse and descending) receives parasympathetic innervation via the pelvic splanchnic nerves whose preganglionic cell bodies are in sacral spinal cord segments 2, 3, and 4. Postganglionic parasympathetic fibers arise from cell bodies located in myenteric and submucosal plexuses (located in muscularis propria and submucosa, respectively, as described above). Short postganglionic axons from myenteric plexus neurons innervate the smooth muscle of the muscularis propria. Those from the submucosal plexus innervate the muscularis mucosae and are secretomotor to submucosal and mucosal glands. Sensory innervation consists of free nerve endings between epithelial cells and pressure receptors in the lamina propria. Cell bodies for these afferent fibers are found in the corresponding dorsal root ganglia.
Esophagus The esophagus is a lubricated muscular tube that carries the food bolus from the oral cavity to the stomach. It does not play any significant role in digestion or absorption.
Gross Anatomical Relationships The esophagus is about 25 cm long and extends from the inferior part of the laryngopharynx at the level of the sixth cervical vertebra, through the thorax to the diaphragm. It pierces the diaphragm via the esophageal hiatus at the level of the 10th thoracic vertebra and then extends a short distance (approximately 2.5 cm) into the abdomen before joining the stomach. Most of the esophagus is situated in the mediastinum, an area of the thorax bounded in front by the sternum, behind by the vertebral column, and on either side by the lungs. The posterior surface of the esophagus is in contact with the upper 10 thoracic vertebrae as it gently curves to the left in its descent to pierce the diaphragm. The anterior surface of the upper half of the esophagus is in contact with the trachea. At the level between the fourth and fifth thoracic vertebrae the trachea bifurcates into the right and left bronchi and from this point on, the lower front portion of the esophagus is in contact with the pericardium of the heart. The right side of the esophagus is in contact with the right lung (pleura intervening) and a portion of the thoracic duct. The left side contacts the left common carotid and left subclavian arteries along its upper one-third while its lower two-thirds are in relation to the aortic arch followed by the thoracic aorta.
Architecture and Cytology Where the esophagus lies outside any body cavity (i.e., for most of its length), its outer layer is an adventitia of loose connective tissue attaching it to adjacent structures. The short portion of the lower esophagus that lies within the abdominal cavity is covered by a serosa.
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Figure 3 Micrograph of the esophagus mucosa showing stratified squamous epithelium, lamina propria, and, at the bottom, part of the muscularis mucosae. There is interdigitation of the epithelium with the connective tissue of the lamina propria to increase the surface area for metabolic exchange (capillaries are present only in the connective tissue) and to firmly anchor the epithelium.
At the transition from pharynx to esophagus, the skeletal muscle of the lower pharyngeal constrictor is carried over into the two layers of the muscularis propria. Hence, in the upper one-quarter to one-third of the esophagus the muscularis propria is composed of skeletal muscle fibers, which are involved in the reflex act of swallowing. In the remainder of the esophagus the muscularis is made up of smooth muscle. The muscularis propria does not enlarge visibly to form sphincters. The upper esophageal sphincter is formed by the cricopharyngeus muscle, which is attached to the cricoid cartilage of the larynx. The lower esophageal sphincter consists of increased resting tone maintained by intrinsic myotonic properties as well as cholinergic regulation (Boron and Boulpaep, 2009). The submucosa of the esophagus, in addition to carrying nerves and vessels that serve the mucosa, contains occasional clusters of esophageal mucous glands whose product drains via ducts to the esophageal lumen, to provide lubrication for the tube. The mucosa of the esophagus has a nonkeratinized, stratified squamous epithelium that lies on a loose connective tissue lamina propria and is separated from the submucosa by a well-developed muscularis mucosa (Figure 3). Stratified squamous epithelia are relatively thick and are generally considered to provide a protective barrier without allowing for significant exchange across the epithelium.
Blood Supply and Innervation Esophageal blood supply is from inferior thyroid arteries in the neck, from bronchial and intercostal arteries and the aorta in the thorax, and from the inferior phrenic and left gastric arteries in the abdomen. Venous drainage is to the thyroid, azygos, and left gastric veins. Venous anastomoses in the submucosa of the lower esophagus permit blood to drain either toward the azygos veins and hence to the vena cava, or to the gastric veins and hence to the liver via the hepatic portal vein, depending on differential pressures in the caval (systemic) and portal circulations (Figure 4). This is significant because if hepatic flow is impaired, blood normally draining through the liver is forced into the azygos drainage and the venous anastomoses carrying this heavier flow become dilated. These dilations, known as esophageal varices, can rupture spontaneously causing life-threatening hemorrhage. Somatic (to skeletal muscle) and parasympathetic innervation to the esophagus, including upper and lower esophageal sphincters, is via the vagus nerve. Sympathetic innervation comes from thoracic spinal cord segments 1–10.
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Figure 4 Diagram showing organs draining via the hepatic portal vein through the liver, and locations of portal-caval anastomoses (1) in the lower esophagus, (2) in the midrectum, (3) in the anterior body wall, via umbilical veins, which may reopen under pressure, (4) where the liver connects to the diaphragm, and (5) where superficial veins of colon drain to the body wall. Under conditions of portal hypertension, varices may occur at all of these sites. Reproduced from Drake, R. L.; Vogl, W.; Mitchell, A. W. M. Gray’s Atlas of Anatomy; Churchill Livingstone: Philadelphia, PA, 2008, with permission from Churchill Livingstone.
Stomach The stomach is responsible for the mechanical and chemical breakdown of the food bolus into chyme. It also plays a significant role in sterilization of food. It does not play a major role in absorption, although lipid-soluble substances may be absorbed through the stomach wall.
Gross Anatomical Relationships The stomach begins at the lower end of the esophagus about 2 5 mm to the left of the midline at a level between the 10th and 11th thoracic vertebrae. It angles downward and to the right, across the midline, to end at the pylorus, which is to the right of the midline at a level between the first and second lumbar vertebrae. The stomach deviates from the shape of a tube by bulging out toward the left. Viewed from the front, the long convex outer edge of this bulge forms the greater curvature (Figure 5). The right border of the stomach forms a short concave edge called the lesser curvature. The rounded upper end of the greater curvature is especially prominent as a bulge called the fundus. The fundus is in contact with the overlying diaphragm and extends above the level of entrance of the esophagus. The area of stomach immediately surrounding the esophageal entrance is called the cardiac portion. Proceeding from the cardiac end to the pylorus, the posterior aspect of the stomach is in relationship to the diaphragm, spleen, left kidney, pancreas, and superior mesenteric artery and vein. Anterior relations of the stomach are the left lobe of the liver, transverse colon, diaphragm, and anterior abdominal wall. The cardiac portion and fundus are protected by the ribs whereas the remainder of the body of the stomach has only the soft tissues of the anterior abdominal wall over it. The distal portion of the stomach that narrows to join the duodenum is called the antrum or pyloric stomach. The opening of the stomach to the duodenum is the pylorus.
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Figure 5 Gross anatomy of the stomach as seen cut open longitudinally. The lesser curvature, from cardia to pylorus, is at the left; the greater curvature is at the right. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
Architecture and Cytology Because the stomach lies within the abdominal cavity, its outer layer is visceral peritoneum. This serosa is continuous with a mesentery, the lesser omentum, that suspends the stomach from the liver, which is in turn attached to the body wall. The muscularis propria of the stomach consists of outer longitudinal, middle circular, and inner oblique layers of smooth muscle. At the pyloric-duodenal junction, the circular layer is enlarged to form the pyloric sphincter. The mucosa has a simple columnar epithelium that is extensively invaginated into the lamina propria to form the stomach glands. The superficial segment of each tubular invagination is called a gastric pit. Each gastric pit branches at its base to form the deeper cardiac, gastric, and pyloric glands proper. Thus, the gastric pits can in a sense be regarded as ducts of the deeper glands. The pits themselves are also glandular, however, being lined by mucous cells. Undifferentiated stem cells are located at the bases of gastric pits. These cells undergo mitosis and provide replacements for surface mucous cells that are lost as well as for other cells in the deeper glands. Mucous cells at the stomach surface are replaced by stem cells approximately every 3 to 6 days. Parietal cells and chief cells have a much slower turnover rate. The cardiac glands of the stomach are situated near the junction with the esophagus. They are coiled tubular glands made up of mucous cells. The gastric (or fundic) glands are straight, branched tubular glands (Figure 6) made up of mucous cells (in the neck), parietal cells (or oxyntic cells; mainly in the neck, also in the base), chief cells (mainly in the base, also in the neck), and scattered enteroendocrine cells. Parietal cells secrete HCl, which creates an optimal pH for stomach enzymes and protects against many bacteria and viruses. They also produce intrinsic factor, a glycoprotein necessary for absorption of vitamin B12 by the ileal mucosa. They contain abundant mitochondria, and a membrane compartment that in active cells exists as deep microvillous-lined canaliculi of the apical membrane, and in inactive cells is mainly a tubulovesicular compartment in the apical cytoplasm. These membranes contain the proton pumps (H+K+-ATPase) that drive acid production. Chief cells (or peptic cells) secrete pepsinogens, which are converted to pepsins at low pH. Pepsins are a family of proteolytic enzymes that initiate protein digestion in the stomach. Chief cells contain abundant rough endoplasmic reticulum in the basal cytoplasm, a prominent Golgi apparatus, and prominent secretory granules in the apical cytoplasm, reflecting their function as regulated secretors of glycoprotein. Enteroendocrine cells secrete hormones that influence gut function. Some have a free apical surface while others do not contact the gut lumen. Their secretory granules are accumulated in the basal cytoplasm, since these cells exocytose their secretory product through the basal membrane. Gastrin, a hormone secreted by enteroendocrine cells in the stomach, stimulates stomach motility and HCl production by parietal cells. Enterochromaffin-like (ECL) cells are a subcategory of histamine-secreting enteroendocrine cells that affect acid secretion either via direct stimulation of parietal cells or indirectly by stimulation of gastrin-secreting cells (Boron and Boulpaep, 2009). The pyloric glands, like the cardiac glands, are coiled tubular glands. They are mainly made up of mucous cells but enteroendocrine cells are also present, and indeed are most numerous in this part of the stomach. Gastric pits are most prominent in the pyloric region, being conspicuously longer in this region than in the cardiac region and body of the stomach. The lining of the contracted stomach is thrown up into folds called rugae. They have a core of submucosa and flatten out when the stomach is full, thereby allowing a degree of distensibility.
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Anatomy and Histology of the Digestive Tract
Figure 6 Micrograph of the stomach mucosa. At the top, the lumen of the stomach is covered by pale surface mucous cells, which also line the gastric pits that invaginate the mucosa for about one-quarter of its thickness. Gastric pits lead into tubular gastric glands lined in their upper half with pinkstaining parietal cells and in their lower half with purple-staining chief cells.
Figure 7 Blood supply of the stomach. The celiac trunk branches from the abdominal aorta. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
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Blood Supply and Innervation Blood supply to the stomach is from branches of the celiac trunk, itself a branch of the aorta at the level of the 12th thoracic vertebra (Figure 7). The lesser curvature is supplied by left and right gastric arteries, which anastomose within the curvature. The greater curvature receives blood from the left and right gastroepiploic (or gastroomental) arteries. Venous drainage of the stomach is by the splenic vein (greater curvature) and left and right gastric veins (lesser curvature), which join the inferior and superior mesenteric veins to form the portal vein. Parasympathetic innervation of the stomach is provided by the vagus nerve and sympathetic via the splanchnic nerves and the celiac ganglion, all of which pass to the stomach along its blood vessels.
Small Intestine The small intestine is responsible for the final chemical breakdown of food by digestive enzymes, and the absorption of nutrients, water, and electrolytes.
Gross Anatomical Relationships The small intestine has three regions. The duodenum is the initial C-shaped portion about 25 cm long that bends snugly around the head of the pancreas. It begins at the pylorus to the right of the midline, curves further to the right around the head of the pancreas, and then curves back across the midline at the level of the second lumbar vertebra to become continuous with the jejunum. The duodenum is attached to the posterior abdominal wall and therefore has no mesentery except where it turns forward to leave the abdominal wall and become the jejunum. The jejunum and ileum together are about 6 m long, with the jejunum comprising about two-fifths and the ileum three-fifths. They are suspended from the posterior abdominal wall by a mesentery that begins at the duodenum—jejunum junction and runs downward and to the right for 18–20 cm to end at the ileocecal junction where the ileum empties into the colon. The mesentery rapidly lengthens to accommodate the length of jejunum and ileum. Consequently, these portions of the small intestine are thrown into numerous loops.
Figure 8 Micrograph of the ileum showing part of a Peyer’s patch, which consists of multiple lymphoid follicles that extend through the mucosa and submucosa. M cells are present in the epithelium overlying each follicle.
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Anatomy and Histology of the Digestive Tract
In addition to the solitary lymphoid follicles that can be present in the mucosa of any part of the digestive tube, the ileal wall contains about 20 distinctive clusters of follicles called Peyer’s patches (Figure 8). These span the mucosa and submucosa. Both solitary follicles as well as those in Peyer’s patches are overlain by a specialized follicle-associated epithelium characterized by the presence of M cells – epithelial cells that conduct transepithelial transport of antigen from the lumen into the underlying follicle (Amerongen et al., 1992).
Architecture and Cytology The outer layer of the small intestine is a serosa, except where the duodenum attaches to the posterior abdominal wall via an adventitia of loose connective tissue. The muscularis propria is made up of outer longitudinal and inner circular layers. The inner circular layer forms a sphincter at the ileocecal valve. The submucosa of the duodenum (but not the jejunum or ileum) contains glands (Brunner’s glands) that secrete a bicarbonaterich mucus that helps protect the small intestine from the acidic stomach contents. The mucosa has a simple columnar epithelium that is invaginated to form the crypts of Lieberkuhn, and evaginated to form villi (Figure 9). Submucosa and mucosa of the small intestine are thrown into circular folds, the plicae circulares (valves of Kerkring), which are most prominent in the jejunum. These are permanent folds (they do not disappear when the lumen is full) and together with mucosal villi they increase the surface area for processing of luminal content. Goblet cells secrete mucin and are distributed throughout the epithelium of the small intestine, increasing in number distally, such that lubrication increases as fluid content in the lumen is reduced due to absorption. Paneth cells, located in a tight cluster at the bottom of each crypt, secrete antibacterial enzymes, principally lysozyme. As in the stomach, enteroendocrine cells are scattered throughout the epithelium. Enterocytes (or absorptive cells) are the main cell type in the mucosal epithelium. They are tall columnar cells with a prominent brush border (dense and regular microvilli) at the apical surface, a well-developed smooth endoplasmic reticulum compartment in the apical cytoplasm, a prominent Golgi apparatus, lots of mitochondria, and an extensively folded basolateral membrane. They are multifunctional cells involved in digestion, absorption, and immune defense. Enterocytes produce brush border enzymes, which are integral membrane proteins that populate the microvillar membrane at the enterocyte surface. One of these, enteropeptidase, cleaves the pancreatic enzyme precursor, trypsinogen, to its active form, trypsin. Trypsin then goes on to activate other digestive enzyme precursors secreted from the pancreas. The activated pancreatic
Figure 9 Micrograph of the jejunum mucosa. Paddle-shaped villi covered with enterocytes and goblet cells project into the lumen. Invaginations of epithelium at the base of the villi form straight tubular glands called crypts of Lieberkuhn. These are also lined by enterocytes and goblet cells. In addition, pink-staining Paneth cells are present in a cluster at the base of each crypt, and stem cells are present in the epithelium above the level of Paneth cells.
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enzymes digest fats and convert proteins to oligopeptides and carbohydrates to oligosaccharides. The remaining brush border enzymes then digest oligopeptides to amino acids and oligosaccharides to monosaccharides. Enterocytes absorb monosaccharides and amino acids by active transport and/or facilitated diffusion. These nutrients then diffuse down a concentration gradient out of the cell at the basolateral surface, and into fenestrated capillaries of the lamina propria. Monoglycerides and fatty acids diffuse across the apical membrane of enterocytes into a smooth endoplasmic reticulum compartment where they are resynthesized into triglycerides. A protein coat is added to the triglyceride and the resulting particles, called chylomicrons, are transported in vesicles to the basolateral membrane and exocytosed. Chylomicrons are then absorbed into a lacteal – a large lymphatic capillary present in each villus. Na+ ions enter enterocytes by facilitated diffusion through the apical membrane and are actively pumped out of the cell at the basolateral membrane, through the action of Na+K+-ATPase. The basal and lateral membranes of enterocytes are highly folded to increase the surface area for Na+K+-ATPase, and there are many mitochondria present near the membrane to supply ATP for active transport. The pumping out of sodium maintains a high salt concentration in the intercellular space near the base of the cell, and water is drawn out of the lumen down an osmotic gradient and enters lymphatic and blood capillaries. Tight junctions between enterocytes regulate absorption via the para-cellular route (Salama et al., 2006). Enterocytes also conduct transepithelial transport of the polymeric antibodies immunoglobulin A (IgA) and IgM, from the lamina propria where it is deposited by plasma cells, into the intestinal lumen. This process is mediated by the poly-Ig receptor, a glycoprotein expressed at the basolateral surface of enterocytes (Wines and Hogarth, 2006). Undifferentiated epithelial stem cells are located in the crypts just above the Paneth cells. These cells provide progeny to replace those that are sloughed off regularly as a part of normal epithelial cell turnover.
Blood Supply and Innervation The duodenum receives its blood supply from branches of the hepatic artery and the superior mesenteric artery, a branch of the aorta near the level of the first lumbar vertebra (Figure 10). The superior mesenteric artery passes in front of the duodenum, as it crosses the midline, and enters the mesentery to form multiple arcades that anastomose and supply the jejunum and ileum as well as nearly the first two-thirds of the colon. Draining veins accompany the arteries to form the superior mesenteric vein, which joins the splenic vein behind the pancreas to form the hepatic portal vein. Parasympathetic preganglionic fibers arrive at the small intestine via the vagus nerve, and sympathetic postganglionic nerve fibers arrive via the celiac and superior mesenteric plexuses.
Figure 10 Blood supply of the small intestine and colon from the superior mesenteric artery. Most of the jejunum and the ileum are cut away. Reproduced from Hollinshead, W. H.; Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from LippincottRaven.
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Large Intestine The large intestine completes the absorption of nutrients, water, and electrolytes and forms the fecal mass.
Gross Anatomical Relationships The colon begins in the lower right abdominal cavity where it receives the contents of the ileum (Figure 1). The ileocecal junction forms a T, with the cecum and appendix descending inferiorly a short distance, and the ascending colon extending superiorly as far as the undersurface of the liver. At the hepatic (right colic) flexure, the large intestine then crosses the abdominal cavity draped slightly below the greater curvature of the stomach as the transverse colon. To the left of the stomach it bends inferiorly at the left colic flexure. It travels down the left side as the descending colon then turns toward the midline as the sigmoid colon, which ends near the midline in the rectum and anal canal. The ascending and descending colon are attached to the posterior abdominal wall. The transverse and sigmoid portions of the colon are suspended by mesenteries from the posterior body wall.
Architecture and Cytology The outer layer of the large intestine is a serosa over the colon except where it attaches to the posterior abdominal wall. It is covered by adventitia at these locations as well as over the rectum, which lies in the pelvis outside the abdominal cavity. The muscularis propria in the colon has the longitudinal muscle layer arranged into three longitudinal bands, the teniae coli. At the rectoanal junction, the circular layer of the muscularis forms an internal anal sphincter (smooth muscle) and an external anal sphincter (skeletal muscle). The submucosa contains the hemorrhoidal plexus of veins at the rectoanal junction. The mucosa has a simple columnar epithelium composed of the same cell types as are found in the small intestine, except that Paneth cells are present only in the proximal part of the large intestine, goblet cells are more numerous, and absorptive cells are correspondingly fewer. The epithelium is invaginated to form crypts of Lieberkuhn, but unlike in the small intestine, there are no villi (Figure 11). At the rectoanal junction, there is an abrupt transition from simple columnar to stratified squamous epithelium. At a variable distance along the anal canal, the stratified squamous epithelium changes from nonkeratinized to keratinized. Lymphoid follicles are common, especially in the distal colon and the rectum.
Figure 11 Micrograph showing straight tubular glands of the colon mucosa. Like the small intestine, the epithelium consists of enterocytes and goblet cells (the latter are more numerous in the colon), as well as stem cells in the walls of each crypt near the base. Paneth cells are absent except in the proximal colon.
Anatomy and Histology of the Digestive Tract
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Figure 12 Blood supply of the colon from the superior and inferior mesenteric arteries. Reproduced from Hollinshead, W. H. Rosse, C. Textbook of Anatomy, 4th ed.; Harper & Row: Philadelphia, PA, 1985, with permission from Lippincott-Raven.
Blood Supply and Innervation Blood supply to the ascending and transverse colon is via the superior mesenteric artery. The descending colon, sigmoid colon, and superior rectum receive their blood from the inferior mesenteric artery, which arises from the aorta at the level of the third lumbar vertebra (Figure 12). Blood drains from these organs via the inferior mesenteric vein, which ends in the splenic vein before it joins the superior mesenteric vein to form the hepatic portal vein. The middle and inferior rectums drain via middle and inferior rectal arteries, which empty directly into the systemic circulation. As in the lower esophagus, portal systemic anastomoses are present in the rectal wall, and varicosities can develop in these vessels under conditions of portal hypertension. The proximal colon to approximately the left colic flexure is supplied with parasympathetic fibers via the vagus nerve, and with sympathetic fibers derived from spinal segments T10 to L1. From left colic flexure to rectum, parasympathetic innervation is from sacral spinal segments 2–4, and sympathetic innervation is from lumbar segments 1 and 2.
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