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GASTROINTESTINAL SYSTEM (GI Tract). I. General Organization, Esophagus and Stomach. Barry R. J. Rittman, Ph.D. Reading: Gartner and Hiatt Chapter 14, Klein and McKenzie PP219-237 Learning Objectives: Understand the organization of the four layers of the Gastrointestinal tract. Describe the 4 layers of the esophagus, with emphasis on the epithelium and the location of the gland types in the underlying layers. Describe unique features of the tunica muscularis of the esophagus and stomach. List histologic characteristics common to glands throughout the stomach. Name gland types in the different zones of the stomach. List their differences based on pit and gland length. gland shape, cell types, and function. List cell types, found in gastric glands, and know the functions of each. Key Words: Tunica mucosa, lamina propria, submucosa, muscularis, adventitia, serosa, Meissner’s plexus, Auerbach’s plexus, esophageal and mucosal glands, parietal cells and chief cells. General organization The gastrointestinal tract (=digestive tract), consists of a tube and associated glands and organs that have arisen from the epithelium of the primitive gut. The following notes refer only to the esophagus, stomach, small intestine, large intestine, appendix and anal canal. FOUR BASIC LAYERS: Tunica Mucosa Tunica Submucosa Tunica Muscularis Tunica Adventitia (or Serosa) It will be easier to study the specific regions if you remember that the basic composition of the each of the four layers is a reflection of the specialized function of each region. Tunica Mucosa. Composed of epithelium with basement membrane, lamina propria and muscularis mucosa. Epithelium and basement membrane. The type of epithelium varies according to the local functions. Esophagus is flexible – to accommodate fluids and solid food while protecting the underlying tissue from both temperature and abrasion from food. The stomach must be protected from its own acid. The intestines must have a high absorptive capacity. In many regions the epithelium gives rise to ducts and glands that reside deeper in the wall of the GI tract. Lamina propria. A loose connective tissue sometimes with large numbers of cells of the immunologic defense system; Rich vascular supply; Lymphatic vessels and glands may also be present. Muscularis mucosa. This is a very thin layer of smooth muscle usually close to the mucosa. It has an inner circular and outer longitudinal layer but these are usually difficult to delineate. Tunica Submucosa. This layer is under the mucosa and is loose connective tissue much less cellular than the mucosa. This layer contains larger blood vessels and lymphatics, often glands and an important network of nerves and ganglia belonging to Meissner's plexus. The submucosa act as padding for the mucosa and together they may throw the inner surface into permanent folds. Tunica Muscularis/ Muscularis Externa. This is the main bulk of muscle for the alimentary canal. With a few exceptions it consists of smooth muscle with inner circular and outer longitudinal layers. Between these layers is another network of nerves and ganglia known as Auerbach's plexus. The significance of Meissner's and Auerbach's plexuses will be considered later section dealing with the enteric nervous system. The muscularis is responsible for peristalsis of the alimentary canal. Tunica Adventitia or Serosa. Connective tissue always surrounds the muscularis, padding and protecting it. When facing the peritoneal cavity, i.e. distal esophagus, stomach, jejunum, ileum and parts of the large intestine, this connective tissue is encased with a thin layer of simple squamous epithelium known as the mesothelium. When mesothelium forms the outermost layer of the gut, the combined connective tissue and mesothelium is referred to as the serosa. The moist serosa performs an important function in allowing adjacent portions of the GI to come into contact and be able to slide over each with minimal abrasion. In non-peritonealized or retroperitoneal surfaces, such as thoracic esophagus, duodenum and ascending and descending colon there are some areas that are devoid of this mesothelial lining and only have connective tissue present. Here the outer tunic is referred to as the tunica adventitia or adventitia. The Enteric Nervous System (ENS). This consists of nerve cell bodies and their processes found in the wall of the gut. The neuron cell bodies are found singly or in groups in two major plexuses; Submucosal or Meissner's Plexus. In the submucosa in significant amounts mainly in the small and large intestines. Myenteric or Auerbach's plexus. Between the inner circular and outer longitudinal layers of the muscularis externa. The ENS controls peristaltic movement by contracting and relaxing the muscularis mucosa and the muscularis externa. It is considered to be a part of the autonomic nervous system; it is separate but is modulated by the sympathetic and parasympathetic systems. The ENS has as many neuron cell bodies here as there are in the spinal cord. Peristalsis has been shown in in vitro experiments to be maintained even without CNS connections. Enteroendocrine System: Various small cells are located in various parts of the G1 tract. These have a variety of names several names – neuroendocrine cells, APUD cells (Amine Precursor Uptake and Decarboxylation cells), chromaffin, argentaffin, and neuroendocrine cells. Dispersed among the epithelial cells lining the GI tract from the stomach distally. These are endocrine cells that secrete their products across the basement membrane into the underlying capillaries. Their placement in the columnar epithelium lining the gut lumen permits them to respond to stimuli in the luminal solutions, with the production of amines and peptides that have profound effects on GI function, as you will find in your physiology course next semester. (You are NOT required to memorize these products or the cell distributions as listed below for this course) Digestive tract enteroendocrine system in general: Serotonin and substance P – increase gut motility. Vasoactive Intestinal polypeptide. – ion and water secretion, increase gut motility. Stomach: Rennin – aspartic proteinase (curdles milk). Gastrin - stimulates production of hydrochloric acid Histamine – stimulates HCl secretion. Gut: Somatostatin – inhibition of endocrine and exocrine secretions. Small Intestine - Pyloric segment of small intestine: Gastrin – stimulates production of hydrochloric acid Somatostatin – inhibits release of gastrin when duodenal contents become acidified. Gastric Inhibitory polypeptide (Urogastrone from K cells) - Released in response to glucose, amino acids and fatty acids in the gut lumen. Stimulates insulin secretion from pancreatic islets. Lysozyme - bactericide Tumor necrosis factor – α (TNF-α). Proinflammatory factor. Defensins. Increase permeability of bacteria and parasites by forming ion channels. Small intestine all: Gastrin - stimulates gastric acid secretion, gastric mucosal growth Secretin – alkaline pancreatic and biliary water secretion. Cholecystokinin – duodenum and jejunum – triggered by small peptides, amino acids and fat in the small intestine – stimulates gall bladder contraction and secretion from pancreatic acinar cells. Motilin – stimulates gastrointestinal motility. Glucagon like peptide (L cells). Released in response to glucose, amino acids and fatty acids in the gut lumen. Stimulates insulin secretion and inhibits glucagon secretion. ESOPHAGUS. GENERAL STRUCTURE. A thick muscular tube with numerous folds that allow distension for the passage of fluid and solid food to the stomach. Mucous glands and muscular coats aid the passage of the food. ESOPHAGUS (Cross section) A muscular organ between pharynx and stomach mostly intrathoracic. The empty esophagus is collapsed and thrown into longitudinal folds. It has the same basic structure GI structure but some important differences. Esophagus Mucosa: Epithelium - Thick stratified squamous non-keratinizing epithelium able to withstand abrasion but also flexible to accommodate food boli of different sizes. Lamina propria - A very thin layer of loose connective tissue often with clusters of lymphocytes. At the distal junction with the stomach, mucus-secreting glands known as mucosal or cardiac glands are found. Muscularis mucosa - Mostly of longitudinally-oriented smooth muscle bundles. Submucosa - Mucus secreting glands may be found in the submucosa and are known as submucosal glands or esophageal glands proper. Unlike the mucosal glands, they are distributed throughout all levels of the esophagus. In the distal 8 cm of the esophagus veins anastomose with the portal vein. Muscularis - The proximal one third to one quarter is skeletal muscle but gradually changes to smooth muscle. The distal one third of the esophagus is usually smooth muscle. There is a question of whether there is an anatomic correlate to the lower esophageal sphincter. There is not although the inner circular muscle layer of the distal esophagus is tonically contracted, preventing reflux of gastric contents into the esophagus, when a bolus of food enters the esophagus or during vomiting. Adventitia/serosa - The outermost layer of the thoracic esophagus is a loose connective tissue that blends into the surrounding tissues and is therefore classified as an adventitia. After passing through the diaphragm, mesothelium covers this connective tissue and this CT plus mesothelium layer is then known as a serosa. At the junction with the stomach is the lower esophageal sphincter controlling passage of material from esophagus into the stomach. THE STOMACH. GENERAL FEATURES. The major function of the stomach is food storage, mixing, and acidic breakdown for production of a semisolid paste known as chyme. Anatomically subdivided into four zones – cardia (C), fundus (F), body (B), and pylorus (P). Mucosa comprised of: Epithelium Gastric glands Lamina propria Muscularis mucosae Submucosa comprised of: Loose connective tissue. Rich vascular supply. Tunica Mucosa. Stomach mucosa is very complex with differences seen in different zones. The underlying submucosa throws stomach into folds (rugae). Surface is covered with a thick protective layer of mucus. Gastric pits and long gastric glands packed together making this tunic very thick and complex to study. Epithelium The epithelium lining the surface pits and plus cells in the glands are renewed by undifferentiated stem cells in the neck of each gland. Neck cells secrete alkaline mucus for protecting the mucosa from the high acidity of the stomach contents. The gastric pits branch into 5-8 tubular glands. Lamina propria Difficult to delineate as the branching of the gland, crowding of the cells and the complexity of the glands tends to obscure lamina propria. Muscularis mucosa. This layer is found at the bottom of the glands. Tunica Submucosa. This is a characteristic loose connective tissue with coarse collagen bundles. The increased thickening of this layer is responsible for the rugae of the mucosa. Nerve supply including Meissner’s plexus Muscularis externa: Three layers of smooth muscle. 1. Inner oblique. 2. Middle circular. 3. Outer longitudinal Auerbach’s plexus is between the outer 2 layers. Serosa. GASTRIC MUCOSA. Very complex with differences seen in different gastric zones. Glands invaginate from surface deep into the lamina propria. Surface mucous cells produce protective layer of mucous and bicarbonate ions to protect the surface. GASTRIC GLANDS. Neck Region - The top (luminal) portion of every gland opens into a gastric pit; this junction is known as the neck of the gland. This is the beginning of the gastric gland and is characterized by having a mixed population of columnar mucous neck cells and stem cells. Cell Types. Stem Cells: Undifferentiated cells that will give rise to the other cell types in the glands and the gastric pits every 5-7 days. Mucous neck cells. Secrete mucous. Parietal cells (Oxyntic cells). Secrete the following: Hydrochloric acid into gland lumen. Action of carbonic anhydrase and Na+ K+ ATPase for H+ and Cl- secreted at the same time. HCO3- into blood stream. Causing a rise in pH. Gastric intrinsic factor. Essential for absorption of vitamin B12. Chief Cells. Secrete inactive pepsinogen that becomes pepsin when in the acidic environment of the stomach lumen. Enteroendocrine cells. G cells. In response to meals secrete gastrin. Gastrin stimulates parietal cells to secrete hydrochloric acid. EC cells. Secrete serotonin and histamine. Serotonin increases gut motility. Histamine stimulates HCl secretion. D cells. Secrete somatostatin that inhibits secretion of enteroendocrine cells in the region. A cells. Secrete glucagon that stimulates glycogen degradation in the liver and increases blood glucose levels. _____________________________________________________________________________________ DIGESTIVE SYSTEM I LABORATORY. You will be studying the tunics of the esophagus and stomach from the inside lumen to the outside. Always begin by examining your slides with the naked eye; holding them against a white background will enable you to see gross differences. Then use low power to determine whether you have a complete cross section surrounding the lumen or merely a piece of the wall. The innermost mucosal layer will usually appear thicker and more basophilic than the outermost layer, and will frequently be thrown into folds. Be able to identify every structure that is in bold font. THE ESOPHAGUS. Proximal Esophagus Slide 8. Cross section- Identify the four basic layers Tunica Mucosa - stratified squamous non-keratinized epithelium, lamina propria, and muscularis mucosa. The function of protection against mechanical damage dictates that the epithelium is thick. This makes it an unsuitable epithelium for massive migration of lymphocytes. Some lymphocytes and other cells of the immune system may be found within the epithelium but generally these are far fewer in number than in many other parts of the GI tract. The majority of cells in the lamina propria are fibroblasts. The muscularis mucosa usually appears not as a continuous layer but as discrete bundles of longitudinally oriented smooth muscle of varying thickness. The submucosa is a loose connective tissue with numerous medium-sized blood vessels and collagen bundles. Mucus secreting esophageal glands are found here and you should be able to distinguish the glands from their ducts, which are lined with simple or stratified cuboidal epithelium. These ducts can sometimes be seen merging with the surface epithelium so that the mucous contents can be emptied onto the surface. Meissner's plexus can occasionally be seen here. Occasional lymphatic nodules may also be found in this layer. The muscularis externa is completely striated muscle to allow for rapid passage of the food through this portion of the esophagus. This feature indicates that this is the proximal one quarter to one third of the esophagus. In some animals such the dog, the muscularis of the entire esophagus is striated muscle, allowing rapid movement of food into the stomach. Look for Auerbach's plexus between the inner and outer layers The outermost layer is an adventitia. Distal Esophagus - Esophageal-Cardiac Junction Slide 68 This has the same basic feature as the previous slide, but has some important differences. Look for the thick stratified squamous non-keratinized epithelium of the esophagus to stop abruptly at the junction with the stomach. Can you recognize the ducts of the submucosal glands in the lamina propria? Look for prominent veins to the submucosa and lamina propria. See if, you can find cardiac glands in the lamina propria. In some slides they appear in continuity with, and are indistinguishable from, the mucus secreting cardiac glands of the stomach. The muscularis mucosa is very thick. Verify the smooth muscle composition of the inner circular and outer longitudinal layers of the muscularis externa. Although there should be a serosa covering this portion of the esophagus but in many slides the thin mesothelium has been lost during preparation of the section. THE STOMACH. Cardiac Stomach Slide 68. Despite the clear distinctions in the zones of the stomach described in the lecture, post-mortem artifacts, staining problems and pathologic features have changed the picture that you see on this section. The surface mucous cells are generally ripped off and externally the mesothelium is missing. Red blood cells can be found free in the lamina propria. Try to find only the following: Surface epithelium of surface mucous cells. Long pits, going at least halfway down the mucosa and frequently seen to be branching. Coiled, mucous-secreting pyloric glands. Do not try to find stem cells or mucous neck cells. Lamina propria containing numerous plasma cells. Well defined muscularis mucosa. Thick open submucosa of loose connective tissue. Inner oblique, middle circular, outer longitudinal layers of the muscularis externa. Auerbach's plexus. Serosa with an intact mesothelial lining. Fundus/ Body of Stomach Slide 69. Surface epithelium of surface mucous cells. Long pits, going at least halfway down the mucosa. and frequently seen branching. Lamina propria containing numerous plasma cells. Well defined muscularis mucosa. Thick open submucosa of loose connective tissue.