Digestive System 2 PDF

1 The Digestive System Learning outcomes Know and understand all of the terms in bold font. Know the four characteristic layers of the GI tract throughout its length. Understand how the mucosa, submucosa, muscularis externa of each organ of the G...

1 The Digestive System Learning outcomes Know and understand all of the terms in bold font. Know the four characteristic layers of the GI tract throughout its length. Understand how the mucosa, submucosa, muscularis externa of each organ of the GI tract is specialized. Know the names/histological features of these specializations. Know what the DNES, GALT, and enteric nervous system are. Describe the main components of the GALT. Understand the difference between a mucosal and a submucosal structure. Understand the difference between the mucosal cells of the gastric pits and goblet cells. Know where the crypts of Lieberkühn are located and what their main functions are.  2 Introduction The function of the digestive system is to obtain the metabolites necessary for the growth and energy needs of the body. Food is taken in through the mouth and digested into small molecules that can be absorbed through the lining of the gastrointestinal tract. The remainder is eliminated as faeces. Structurally the digestive system develops from a tube segmented into a succession of interconnected organs. Each segment is specialized for a particular stage in the digestive process. Two of these organs are accompanied by external glands - the mouth with its salivary glands and the duodenum with secretions from the liver (gallbladder) and pancreas. Organs of the digestive system Oral Cavity Esophagus Stomach Cardia Fundus (body) Pylorus Small Intestine Duodenum Jejunum Ileum Large Intestine Colon Rectum Anus From the esophagus to the rectum, Figure 1. Organs of the digestive system the wall of the alimentary canal has 4 layers 1. Mucosa surface epithelium lamina propria muscularis mucosa 2. Submucosa 3. Muscularis externa inner circular layer of smooth muscle outer longitudinal layer of smooth muscle 4. Serosa (or Adventitia) Figure 2. Layers of the alimentary canal  3 Functions of the layers of the GI tract Surface epithelium  Promote the absorption of the products of digestion.  Facilitate the transport of food.  Produce mucus.  Aid in digestion. Lamina Propria Protection. The lamina propria can be rich in lymphoid tissue. Plasma cells in the lamina propria produce IgA antibodies, which are transported across the epithelium into the gut lumen. Capillaries nourish the overlying epithelium and glands. Houses the mucosal glands. Muscularis mucosa Moves the mucosa locally to improve its contact with food. A muscle layer in a mucosa is very rare, and in humans always confirms that the mucosa belongs to the GI tract. Submucosa Provides a pathway for arteries, veins and nerves. This layer of loose connective tissue allows the mucosa and muscularis externa to move independently. Lymphocytes and lymphatic nodules abound in some places. Muscularis externa Mixes and propels the food in the digestive tract. Contraction of this muscle is co-ordinated by the myenteric and submucosal nerve plexuses. Adventitia The segments of the gut that are directly attached to surrounding tissues are covered with an adventitia. Elsewhere the adventitia is replaced with a serosa to allow the intestines and stomach to slide around freely during digestive contractions. Other components of the digestive system organs Each of the above layers is specialized in one organ of the digestive system or another. In addition, there are six other specializations of general importance. 1. Glands Glands are formed by a lining epithelium growing down into the underlying tissue. The small mucosal glands are simple tubular glands without ducts. They are confined to the lamina propria and may fill that layer. Larger glands that invade into the submucosa are compound. They produce mucus that drains to the surface through ducts. The very large extrinsic glands (liver, pancreas, major  4 salivary glands) burrow all the way through the organ wall during embryogenesis and remain attached only by a duct (which traces the path from the site of origin of the gland to its final location outside of the GI tract). The mucosal glands have two independent functions - secretion and cytogenesis. Mucus is a major secretory product but some also produce enzymes as well. Because of the harsh conditions inside the digestive tract the lining epithelium turns over rapidly. The stem cells for the epithelium are tucked away deep in mucosal glands. Here they maintain a pool of actively dividing progenitor cells. As these cells migrate/get pushed up the gland they differentiate. They are shed several days after spreading out on the surface. 2. Projections into the lumen The surface epithelium can bulge into the lumen due to thickening of the lamina propria (forming a “mucosal projection”), or of the submucosa (a “submucosal projection”) or even the circular layer of the muscularis externa (e.g. a sphincter). The layers overlying that bulge maintain their normal thickness and disposition. (Think of a rug that is humped up by a wrinkle in the underlying pad). Smooth muscle. Figure 4. Mucosal projection Submucosal projection Sphincter Sphincters are found between each of the adjacent organs of the GI tract to regulate the passage of material from one to another. Most are a simple thickening of the circular muscle layer of the muscularis externa. Tonic contraction of the smooth muscle keeps the sphincter closed. The two epithelia of adjacent organs typically form a sharp transition at the sphincter but in some cases the mucosa is somewhat atypical right over the sphincter. 3. GALT (Gut Associated Lymphatic Tissue) A large amount of lymphatic tissue is dedicated to protecting the digestive tract from antigens and infectious agents traversing the lining epithelium. In fact, most of the lymphocytes of the body are in the GALT. Moreover, the lymphocytes of the gut are a different population from those of the lymphatic organs. If one removes the lymphocytes of the tonsil, which is part of the GALT, labels them and reinjects them back into an animal, most will relocate to the GALT instead of the lymph nodes or spleen. In terms of amounts of lymphatic tissues, the immune system is foremost a defence for the digestive system. This GALT includes the tonsils, Peyer’s patches, appendix,  5 lymph nodes plus local deposits of lymphocytes and nodules scattered all along the GI tract. 4. DNES (Diffuse NeuroEndocrine System) The mucosa of the GI tract contains an assortment of DNES cells which produce chemical messengers. Such cells are found in the epithelium of most visceral organs but are especially prominent in the digestive system. Various segments of the GI tract are distinguished by the particular DNES chemical messengers that they produce. Most of these messengers have paracrine activities, while some also function as true hormones. They allow the digestive system to coordinate its activities both locally and across organs. Examples are secretin which stimulates secretion by the pancreas and cholecystokinin (CCK), which acts hormonally on both the pancreas and gall bladder. The DNES chemical messengers are polypeptides and most also function in the CNS, as neurotransmitter/neuromodulators. Thus, CCK is also found in the brain and acts on an appetite centre in the hypothalamus, to produce sensations of satiation (cessation of hunger). 5. Enteric nervous system Two extensive plexuses of autonomic ganglia innervate the organs of the digestive system. The myenteric plexus is a network of interconnected ganglia located between the inner circular and outer longitudinal layers of the muscularis externa. It shows up in sections as lens-shaped groups of neurons and supporting cells along the interface between the two muscle layers. A less extensive submucosal plexus controls the smooth muscle and DNES cells of the mucosa. Together these two components of the enteric nervous system contain more neurons than does the spinal cord! Elsewhere in the body, autonomic ganglia in organs are only small simple groups of parasympathetic postganglionic neurons directly controlled by preganglionic neurons from the brain. In contrast, the enteric ganglia have sensory neurons, interneurons, glial cells and sympathetic input in addition to parasympathetic neurons. This allows the GI tract to initiate and control its own activities intrinsically instead of being a slave of the CNS. If one severs all nerve connections from the brain to the GI tract, the smooth muscle of the intestines can still generate peristaltic waves of contraction in response to stimuli. Figure 5. Enteroendocrine cells along the GI tract  6 Figure 6. Plexus of autonomic ganglia located between the two muscle layers of the muscularis externa. Specializations of the individual organs of the GI tract Esophagus The esophagus is a muscular tube with a relatively simple function of conducting food from the mouth to the stomach. It is lined with a non-keratinized stratified squamous epithelium. This is a more resistant epithelium than the simple columnar variety that lines the rest of the GI tract. Compound mucous glands are scattered in the submucosa to lubricate the tube, especially in the lower part. Mucosal glands are absent. The stem cells for the epithelium are in the basal layer of the epithelium. The muscularis externa of the esophagus is interestingly specialized. The upper third consists of skeletal muscle; the middle third is a combination of skeletal and smooth muscle fibres and the lower third contains only smooth muscle. Thus, the initial act of swallowing is voluntary but finishes with involuntary peristalsis. The cardiac sphincter (all smooth muscle) controls the passage of food into the stomach.  7 Figure 7. Layers of the esophagus Figure 8. Muscle types Except when swallowing the submucosa is thrown into large longitudinal folds to close the lumen. Stomach The stomach mixes masticated food with digestive juices and churns them into a pulp called chyme. Important digestion takes place in its acidic mileau, especially the breakdown of proteins. Only limited absorption takes place here. The inner wall of the stomach is thrown into large submucosal folds called rugae and is covered with mucosa. Rugae allow the stomach to expand considerably when filled with food. Figure 9. Rugae of the stomach – gross and microscopic levels The mucosal surface is thrown into tiny mucosal ridges between which are small creases (~1mm deep) called gastric pits. Specialized surface mucous cells line  8 the pits and the free surface of the stomach. The mucous that they produce is special in that it remains slippery at low pH (acid conditions precipitate ordinary mucous). This mucous fills the apical two thirds of the cell, protecting the underlying part of the cell giving the epithelium a distinctive appearance. Figure 10. Regions of the stomach The muscularis externa is especially well suited to “churning the chyme”. It has a third, “oblique” muscle layer added to it. The stomach’s unusual shape with an outpocketed fundus also aids in this function. With the pyloric and cardiac sphincters closed, chyme is vigorous propelled back and forth between the fundus and pylorus of the stomach. This gurgling action continues until hormones released from the duodenal mucosa, as well as nervous reflex control, cause relaxation of the pyloric sphincter, and the chyme is passed into the duodenum.  9 Figure 11. Gastric pits and glands Figure 12. Cells of the stomach Gastric glands extend from the bottom of the pits down to the muscularis mucosa. They are simple, branched tubular glands and empty into the base of the pits without ducts. The glands contain four major types of secretory cells: Mucous neck cells are located high up in the glands, near the opening into the gastric pits. They will mature into surface mucous cells by the time they have migrated out of the glands. Parietal cells occupy the middle of the glands. They secrete 0.16 M HCl by actively transporting both H+ and Cl- across their cell membrane. Parietal cells have an exquisite architecture with a large canaliculus lined with microvilli that can be opened up to secrete ions into the duct of the gland. Their cytoplasm is intensely eosinophilic, due to large numbers of mitochondria needed to fuel the ion pumps. As a minor extra, parietal cells also synthesize and secrete intrinsic factor, which is required for the absorption of vitamin B 12 in the small intestine. Figure 13. Parietal cell ultrastructure  10 Chief cells are easily recognized at the base of the glands. They secrete all of the digestive enzymes for the stomach. These enzymes are released as inactive precursors called zymogens. The most important is pepsinogen which is activated by the acidic conditions of the stomach to pepsin. Pepsin is a powerful protease in acidic conditions. Histologically, chief cells are strongly basophilic, as befits cells actively synthesizing proteins and they accumulate secretory granules at their apical ends. DNES cells secrete a variety of peptide hormones. The most notable are gastrin and somatostatin as shown in figure 5. In addition to the above, the glands contain stem cells and rapidly dividing progenitors of the secretory cells. This is important because the surface mucous cells turn over every few days. The gastric glands simplify at the two ends of the stomach, the cardia and pylorus. Chief and parietal cells are absent so that if small amounts of gastric fluid leak through the sphincters (gastric reflux) the concentrations of acid and digestive enzymes will be low. Figure 14. Distribution of gastric glands The small intestine The processes of digestion are completed in the small intestine and the digestive products are absorbed. The small intestine is some six metres long, permitting prolonged contact between the food, digestive enzymes, and the absorptive cells of the epithelial lining. This organ of the digestive tract consists of 3 segments, the duodenum, jejunum and ileum. However, these individual segments have more characteristics in common with each other than in distinction and the differences need not concern us here. The inner surface of the small intestine has three specializations, of the submucosa (plicae circulares), the mucosa (villi) and the epithelium (brush border) respectively, to increase the surface area available for absorption. Plicae circulares are permanent ridges of submucosa 1-2 cm tall, covered with mucosa. They increase the surface area about 3 fold. Being circularly arranged they also promote mixing of the chyme as it is churned by peristalsis.  11 Villi are finger-like columns of lamina propria about 1mm tall, projecting from the plicae and covered by epithelium. The epithelium consists of absorptive cells (enterocytes) and goblet cells. The connective tissue core of the villi contains capillaries, lacteal vessels (lymph vessels), nerves and smooth muscle fibers. They increase the surface area a further 10 fold. Microvilli form a brush border over the apical surfaces of the enterocytes covering the villi. They increase the surface area about 20 fold. Taken together, these specializations increase the surface area available for digestion and absorption about 600 fold for a total effective area of 200 m2. Plicae Plicae Plicae covered with villi Figure 15. Surface specializations of the small intestine Figure 16. Epithelial cells of the small intestine  12 Enterocytes predominate in the surface epithelium accompanied by goblet cells and a variable numbers of invading lymphocytes. Mucosal glands. The mucosal glands of the small intestine are called intestinal crypts (crypts of Lieberkuhn). They are small, simple tubular glands, much smaller than the glands of the stomach. This is because the pancreas secretes most of the digestive enzymes for the small intestine, whereas all of the gastric enzymes come from mucosal glands. The intestinal crypts contain several types of cells; stem cells, developing enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. New enterocytes are continually produced by mitosis in the glands and migrate out of the glands and up the villi, where they are shed at the tips after about 5 days. Paneth cells at the base of the glands secrete lysozyme, and perhaps other antibacterial substances, to prevent bacteria from colonizing the glands. Enteroendocrine (DNES) cells secrete a variety of hormones to control various functions of the intestinal tract. Figure 17. Villi and intestinal crypts (Crypts of Lieberkühn) Three regional specializations of the small intestine should be noted: Figure 18. Duodenal (Brunner’s) glands  13 Compound mucous glands called duodenal glands (Brunner's glands) extend along the first 10 cm or so of the duodenum. They fill the submucosa and, in humans, spill over into the lamina propria of the mucosa as well. These glands produce an alkaline mucous, with a pH between 8-9, to neutralize the acidity of the chyme as it enters the duodenum from the stomach since pancreatic digestive enzymes require an alkaline pH for optimal activity. An alkaline secretion from the pancreas also helps. Neutralization is essential to protect the delicate enterocytes from the low pH of the chyme. Duodenal glands also release the hormone urogastrone, to inhibit HCl secretion by the parietal cells of the stomach. Peyer's patches are regions of permanent lymphatic nodules in the mucosa and submucosa of the ileum. The ileocolic sphincter guards the distal end of the small intestine. It reflexively contracts when the proximal colon fills up, thereby controlling release of contents of the small intestine. The Large Intestine The large intestine consists of the colon (ascending, transverse, descending), the appendix, and the rectum. None of these has plicae or villi, although temporary submucosal folds may form when the large intestine is empty. Figure 19. Mucosa of the large intestine The lumenal surface is smooth and lined with columnar absorptive cells and goblet cells. The absorptive cells do not have brush borders. The goblet cells become increasingly abundant as one progresses down the large intestine. Intestinal glands (also called crypts of Lieberkuhn, as in the small intestine) extend into the lamina propria to furnish epithelial cells and mucous. The functions of the large intestine are to absorb water and form the indigestibles of the food into faeces.  14 Figure 20. Large intestine Figure 21. Taenia coli (tc) of colon The one radical specialization of the large intestine is of the muscularis externa. The smooth muscle cells of its outer longitudinal layer are clustered into 3 pronounced bands, visible at the gross level. Contraction of these taenia coli folds the intestinal wall up like an accordion. This billows out the wall as a series of bulges called “valves”, greatly decreasing the overall length of the large intestine in the body cavity. Appendix A main component of the GALT of the large intestine is the appendix. This structure is a blind, finger-like projection from the caecum (the very first part of the large intestine). Its wall is similar in structure to that of the rest of the large intestine except that the lamina propria and much of its submucosa are filled with dense diffuse lymphatic tissue and lymphatic nodules. Since the appendix is a blind pouch, it is prone to the accumulation of faecal material. This provides a rich source of local antigens but makes it a frequent site of serious infection (appendicitis). Rectum The rectum extends through the body wall to the beginning of the anal canal. It resembles the colon, but with an even greater number of goblet cells. Figure 22. Anal canal  15 Anal canal. At the junction between the rectum and anal canal, the epithelium changes abruptly from simple columnar to stratified squamous (non-keratinized), indicative of the increased abrasion put on this part of the GI tract during defecation. The submucosa contains a plexus of enlarged hemorrhoidal veins, which can become inflamed and painful. The inner circular muscle layer at the upper end of the anal canal is thickened to form the internal anal sphincter comprised of smooth muscle and is under autonomic control. Farther down the anal canal, the outer longitudinal muscle changes from smooth to skeletal muscle to form the external anal sphincter, which (fortunately) is under voluntary control. Finally, the lower portion of the anal canal becomes keratinised and merges with the external skin. End of Descriptive Text – Digestive System