The Digestive System


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The Digestive System

  1. 1. The Digestive System
  2. 2. <ul><li>Motility : </li></ul><ul><ul><li>Movement of of food through the GI tract. </li></ul></ul><ul><ul><ul><li>Ingestion: </li></ul></ul></ul><ul><ul><ul><ul><li>Taking food into the mouth. </li></ul></ul></ul></ul><ul><ul><ul><li>Mastication: </li></ul></ul></ul><ul><ul><ul><ul><li>Chewing the food and mixing it with saliva. </li></ul></ul></ul></ul><ul><ul><ul><li>Deglutition: </li></ul></ul></ul><ul><ul><ul><ul><li>Swallowing the food. </li></ul></ul></ul></ul><ul><ul><ul><li>Peristalsis: </li></ul></ul></ul><ul><ul><ul><ul><li>Rhythmic wave-like contractions that move food through GI tract. </li></ul></ul></ul></ul>Functions of the GI Tract
  3. 3. <ul><li>Secretion: </li></ul><ul><ul><li>Includes both exocrine and endocrine secretions. </li></ul></ul><ul><ul><ul><li>Exocrine: </li></ul></ul></ul><ul><ul><ul><ul><li>HCl, H 2 0, HC0 3 - , bile, lipase, pepsin, amylase, trypsin, elastase, and histamine are secreted into the lumen of the GI tract. </li></ul></ul></ul></ul><ul><ul><ul><li>Endocrine: </li></ul></ul></ul><ul><ul><ul><ul><li>Stomach and small intestine secrete hormones to help regulate the GI system. </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and somatostatin. </li></ul></ul></ul></ul></ul>Functions of the GI Tract (continued)
  4. 4. <ul><li>Digestion: </li></ul><ul><ul><li>Breakdown of food particles into subunits (chemical structure change). </li></ul></ul><ul><li>Absorption: </li></ul><ul><ul><li>Process of the passage of digestion (chemical subunits) into the blood or lymph. </li></ul></ul><ul><li>Storage and elimination: </li></ul><ul><ul><li>Temporary storage and elimination of indigestible food. </li></ul></ul>Functions of the GI Tract (continued)
  5. 5. Digestive System (GI) <ul><li>GI tract divided into: </li></ul><ul><ul><li>Alimentary canal. </li></ul></ul><ul><ul><li>Accessory digestive organs. </li></ul></ul><ul><li>GI tract is 30 ft long and extends from mouth to anus. </li></ul>Insert fig. 18.2
  6. 6. Layers of GI Tract <ul><li>Composed of 4 tunics: </li></ul><ul><ul><li>Mucosa. </li></ul></ul><ul><ul><li>Submucosa. </li></ul></ul><ul><ul><li>Muscularis. </li></ul></ul><ul><ul><li>Serosa. </li></ul></ul>
  7. 7. <ul><li>Lines the lumen of GI tract. </li></ul><ul><ul><li>Consists of simple columnar epithelium. </li></ul></ul><ul><li>Lamina propria: </li></ul><ul><ul><li>Thin layer of connective tissue containing lymph nodules. </li></ul></ul><ul><li>Muscularis mucosae: </li></ul><ul><ul><li>Thin layer of smooth muscle responsible for the folds. </li></ul></ul><ul><ul><ul><li>Folds increase surface area for absorption. </li></ul></ul></ul><ul><li>Goblet cells: </li></ul><ul><ul><li>Secrete mucus. </li></ul></ul>Mucosa
  8. 8. <ul><li>Thick, highly vascular layer of connective tissue. </li></ul><ul><li>Absorbed molecules enter the blood and lymphatic vessels. </li></ul><ul><li>Submucosal plexus (Meissner’s plexus): </li></ul><ul><ul><li>Provide autonomic nerve supply to the muscularis mucosae. </li></ul></ul>Submucosa
  9. 9. <ul><li>Responsible for segmental contractions and peristaltic movement through the GI tract. </li></ul><ul><ul><li>Inner circular layer of smooth muscle. </li></ul></ul><ul><ul><li>Outer longitudinal layer of smooth muscle. </li></ul></ul><ul><li>Contractions of these layers move food through the tract; pulverize and mix the food. </li></ul><ul><li>Myenteric plexus located between the 2 muscle layers. </li></ul><ul><ul><li>Major nerve supply to GI tract. </li></ul></ul><ul><ul><ul><li>Fibers and ganglia from both sympathetic and parasympathetic nervous systems. </li></ul></ul></ul>Muscularis
  10. 10. Serosa <ul><li>Binding and protective outer layer. </li></ul><ul><li>Consists of areolar connective tissue covered with simple squamous epithelium. </li></ul>
  11. 11. <ul><li>Extrinsic innervation: </li></ul><ul><ul><li>Parasympathetic nervous system: </li></ul></ul><ul><ul><ul><li>Vagus and spinal nerves: </li></ul></ul></ul><ul><ul><ul><ul><li>Stimulate motility and GI secretions. </li></ul></ul></ul></ul><ul><ul><li>Sympathetic nervous system: </li></ul></ul><ul><ul><ul><li>Postganglionic sympathetic fibers that pass through submucosal and myenteric plexuses and innervate GI tract: </li></ul></ul></ul><ul><ul><ul><ul><li>Reduce peristalsis and secretory activity. </li></ul></ul></ul></ul>Regulation of the GI Tract
  12. 12. <ul><li>Enteric nervous system: </li></ul><ul><ul><li>Sites where parasympathetic fibers synapse with postganglionic neurons that innervate smooth muscle. </li></ul></ul><ul><li>Submucosal and myenteric plexuses: </li></ul><ul><ul><li>Local regulation of the GI tract. </li></ul></ul><ul><li>Paracrine secretion: </li></ul><ul><ul><li>Molecules acting locally. </li></ul></ul><ul><li>Hormonal secretion: </li></ul><ul><ul><li>Secreted by the mucosa. </li></ul></ul>Regulation of the GI Tract (continued)
  13. 13. <ul><li>Mastication (chewing): </li></ul><ul><ul><li>Mixes food with saliva which contains salivary amylase. </li></ul></ul><ul><ul><ul><li>Enzyme that can catalyze the partial digestion of starch. </li></ul></ul></ul><ul><li>Deglutition (swallowing): </li></ul><ul><ul><li>Begins as a voluntary activity. </li></ul></ul><ul><ul><li>Involves 3 phases: </li></ul></ul><ul><ul><ul><li>Oral phase is voluntary. </li></ul></ul></ul><ul><ul><ul><li>Pharyngeal and esophageal phases are involuntary. </li></ul></ul></ul><ul><ul><ul><ul><li>Cannot be stopped. </li></ul></ul></ul></ul><ul><ul><li>Larynx is raised. </li></ul></ul><ul><ul><li>Epiglottis covers the entrance to respiratory tract. </li></ul></ul>From Mouth to Stomach
  14. 14. <ul><li>Involuntary muscular contractions and relaxations in the mouth, pharynx, larynx, and esophagus are coordinated by the swallowing center in the medulla. </li></ul><ul><li>Esophagus: </li></ul><ul><ul><li>Connects pharynx to the stomach. </li></ul></ul><ul><ul><ul><li>Upper third contains skeletal muscle. </li></ul></ul></ul><ul><ul><ul><li>Middle third contains a mixture of skeletal and smooth muscle. </li></ul></ul></ul><ul><ul><ul><li>Terminal portion contains only smooth muscle. </li></ul></ul></ul>From Mouth to Stomach (continued)
  15. 15. Esophagus <ul><li>Peristalsis: </li></ul><ul><ul><li>Produced by a series of localized reflexes in response to distention of wall by bolus. </li></ul></ul><ul><li>Wave-like muscular contractions: </li></ul><ul><ul><li>Circular smooth muscle contract behind, relaxes in front of the bolus. </li></ul></ul><ul><ul><li>Followed by longitudinal contraction (shortening) of smooth muscle. </li></ul></ul><ul><ul><ul><li>Rate of 2-4 cm/sec. </li></ul></ul></ul><ul><ul><li>After food passes into stomach, LES constricts. </li></ul></ul>Insert 18.4a
  16. 16. <ul><li>Most distensible part of GI tract. </li></ul><ul><ul><li>Empties into the duodenum. </li></ul></ul><ul><li>Functions of the stomach: </li></ul><ul><ul><li>Stores food. </li></ul></ul><ul><ul><li>Initiates digestion of proteins. </li></ul></ul><ul><ul><li>Kills bacteria. </li></ul></ul><ul><ul><li>Moves food (chyme) into intestine. </li></ul></ul>Stomach
  17. 17. Stomach (continued) <ul><li>Contractions of the stomach churn chyme. </li></ul><ul><ul><li>Mix chyme with gastric secretions. </li></ul></ul><ul><ul><li>Push food into intestine. </li></ul></ul>Insert fig. 18.5
  18. 18. Stomach (continued) <ul><li>Gastric mucosa has gastric pits in the folds. </li></ul><ul><li>Cells that line the folds deeper in the mucosa, are gastric glands. </li></ul>Insert fig. 18.7
  19. 19. <ul><li>Secrete gastric juice: </li></ul><ul><ul><li>Goblet cells: mucus. </li></ul></ul><ul><ul><li>Parietal cells: HCl and intrinsic factor. </li></ul></ul><ul><ul><li>Chief cells: pepsinogen. </li></ul></ul><ul><ul><li>Enterochromaffin-like cells (ECL): histamine and serotonin. </li></ul></ul><ul><ul><li>G cells: gastrin. </li></ul></ul><ul><ul><li>D cells: somatostatin. </li></ul></ul><ul><ul><li>Stomach: ghrelin. </li></ul></ul>Gastric Glands
  20. 20. HCl Production <ul><li>Parietal cells secrete H + into gastric lumen by primary active transport, through H + / K + ATPase pump. </li></ul><ul><li>Parietal cell’s basolateral membrane takes in Cl - against its electrochemical gradient, by coupling its transport with HC0 3 - . </li></ul>Insert fig. 18.8
  21. 21. <ul><li>HCl production is stimulated: </li></ul><ul><ul><li>Indirectly by gastrin. </li></ul></ul><ul><ul><li>Indirectly by ACh. </li></ul></ul><ul><li>ACh and gastrin stimulate release of histamine. </li></ul><ul><ul><li>Histamine: </li></ul></ul><ul><ul><ul><li>Stimulates parietal cells to secrete HCl. </li></ul></ul></ul>HCl Production (continued)
  22. 22. HCl Functions <ul><li>Makes gastric juice very acidic. </li></ul><ul><ul><li>Denatures ingested proteins (alter tertiary structure) so become more digestible. </li></ul></ul><ul><li>Activates pepsinogen to pepsin. </li></ul><ul><ul><li>Pepsin is more active at pH of 2.0. </li></ul></ul>Insert fig. 18.9
  23. 23. Digestion and Absorption in the Stomach <ul><li>Proteins partially digested by pepsin. </li></ul><ul><li>Carbohydrate digestion by salivary amylase is soon inactivated by acidity. </li></ul><ul><li>Alcohol and aspirin are the only commonly ingested substances absorbed. </li></ul>
  24. 24. Gastric and Peptic Ulcers <ul><li>Peptic ulcers: </li></ul><ul><ul><li>Erosions of the mucous membranes of the stomach or duodenum produced by action of HCl. </li></ul></ul><ul><li>Zollinger-Ellison syndrome: </li></ul><ul><ul><li>Ulcers of the duodenum are produced by excessive gastric acid secretions. </li></ul></ul><ul><li>Helicobacter pylori: </li></ul><ul><ul><li>Bacterium that resides in GI tract that may produce ulcers. </li></ul></ul><ul><li>Acute gastritis: </li></ul><ul><ul><li>Histamine released by tissue damage and inflammation stimulate further acid secretion. </li></ul></ul>
  25. 25. <ul><li>Parietal and chief cells impermeable to HCl. </li></ul><ul><li>Alkaline mucus contains HC0 3 - . </li></ul><ul><li>Tight junctions between adjacent epithelial cells. </li></ul><ul><li>Rapid rate of cell division (entire epithelium replaced in 3 days). </li></ul><ul><li>Prostaglandins inhibit gastric secretions. </li></ul>Protective Mechanisms of Stomach
  26. 26. Small Intestine <ul><li>Each villus is a fold in the mucosa. </li></ul><ul><li>Covered with columnar epithelial cells interspersed with goblet cells. </li></ul><ul><li>Epithelial cells at the tips of villi are exfoliated and replaced by mitosis in crypt of Lieberkuhn. </li></ul><ul><li>Lamina propria contain lymphocytes, capillaries, and central lacteal. </li></ul>Insert fig. 18.12
  27. 27. <ul><li>Duodenum and jejunum: </li></ul><ul><ul><li>Carbohydrates, amino acids, lipids, iron, and Ca 2+ . </li></ul></ul><ul><li>Ileum: </li></ul><ul><ul><li>Bile salts, vitamin B 12 , electrolytes, and H 2 0. </li></ul></ul>Absorption in Small Intestine
  28. 28. <ul><li>Microvilli contain brush border enzymes that are not secreted into the lumen. </li></ul><ul><ul><li>Brush border enzymes remain attached to the cell membrane with their active sites exposed to the chyme. </li></ul></ul><ul><li>Absorption requires both brush border enzymes and pancreatic enzymes. </li></ul>Intestinal Enzymes
  29. 29. Intestinal Contractions and Motility <ul><li>2 major types of contractions occur in the small intestine: </li></ul><ul><ul><li>Peristalsis: </li></ul></ul><ul><ul><ul><li>Slow movement. </li></ul></ul></ul><ul><ul><ul><li>Pressure at the pyloric end of small intestine is greater than at the distal end. </li></ul></ul></ul><ul><ul><li>Segmentation: </li></ul></ul><ul><ul><ul><li>Major contractile activity of the small intestine. </li></ul></ul></ul><ul><ul><ul><li>Contraction of circular smooth muscle. </li></ul></ul></ul><ul><ul><ul><ul><li>Mix chyme. </li></ul></ul></ul></ul>Insert fig. 18.14
  30. 30. Contractions of Intestinal Smooth Muscles <ul><li>Occur automatically in response to endogenous pacemaker activity. </li></ul><ul><li>Rhythm of contractions is paced by graded depolarizations called slow waves. </li></ul><ul><ul><li>Slow waves produced by interstitial cells of Cajal. </li></ul></ul><ul><ul><li>Slow waves spread from 1 smooth muscle cell to another through nexuses. </li></ul></ul>Insert fig. 18.15
  31. 31. <ul><li>When slow waves above threshold, it triggers APs by opening of VG Ca 2+ channels. </li></ul><ul><li>Inward flow of Ca 2+ : </li></ul><ul><ul><li>Produces the upward depolarization phase. </li></ul></ul><ul><ul><li>Stimulates contraction of smooth muscle. </li></ul></ul><ul><li>Repolarization: </li></ul><ul><ul><li>VG K + channels open. </li></ul></ul><ul><ul><ul><li>Slow waves decrease in amplitude as they are conducted. </li></ul></ul></ul><ul><li>May stimulate contraction in proportion to the magnitude of depolarization. </li></ul>Contractions of Intestinal Smooth Muscles
  32. 32. Cells and Electrical Events in the Muscularis Insert fig. 18.16
  33. 33. <ul><li>Outer surface bulges outward to form haustra. </li></ul><ul><li>Little absorptive function. </li></ul><ul><ul><li>Absorbs H 2 0, electrolytes, several vitamin B complexes, vitamin K, and folic acid. </li></ul></ul><ul><ul><ul><li>Intestinal microbiota produce significant amounts of folic acid and vitamin K. </li></ul></ul></ul><ul><ul><ul><li>Bacteria ferment indigestible molecules to produce short-chain fatty acids. </li></ul></ul></ul><ul><ul><ul><ul><li>Does not contain villi. </li></ul></ul></ul></ul><ul><li>Secretes H 2 0, via active transport of NaCl into intestinal lumen. </li></ul><ul><ul><li>Guanylin stimulates secretion of Cl - and H 2 0, and inhibits absorption of Na + (minor pathway). </li></ul></ul><ul><ul><ul><ul><li>Membrane contains Na + /K + pumps. </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Minor pathway. </li></ul></ul></ul></ul></ul>Large Intestine
  34. 34. <ul><li>Small intestine: </li></ul><ul><ul><li>Most of the fluid and electrolytes are absorbed by small intestine. </li></ul></ul><ul><ul><ul><li>Absorbs about 90% of the remaining volume. </li></ul></ul></ul><ul><ul><li>Absorption of H 2 0 occurs passively as a result of the osmotic gradient created by active transport. </li></ul></ul><ul><ul><ul><li>Aldosterone stimulates NaCl and H 2 0 absorption in the ileum. </li></ul></ul></ul><ul><li>Large intestine: </li></ul><ul><ul><li>Absorbs about 90% of the remaining volume. </li></ul></ul><ul><ul><ul><li>Absorption of H 2 0 occurs passively as a result of the osmotic gradient created by active transport of Na + and Cl - . </li></ul></ul></ul>Fluid and Electrolyte Absorption in the Intestine
  35. 35. Defecation <ul><li>Waste material passes to the rectum. </li></ul><ul><li>Occurs when rectal pressure rises and external anal sphincter relaxes. </li></ul><ul><li>Defecation reflex: </li></ul><ul><ul><li>Longitudinal rectal muscles contract to increase rectal pressure. </li></ul></ul><ul><ul><ul><li>Relaxation of internal anal sphincter. </li></ul></ul></ul><ul><ul><li>Excretion is aided by contractions of abdominal and pelvic skeletal muscles. </li></ul></ul><ul><ul><ul><li>Push feces from the rectum. </li></ul></ul></ul>
  36. 36. Structure of Liver <ul><li>Liver largest internal organ. </li></ul><ul><ul><li>Hepatocytes form hepatic plates that are 1–2 cells thick. </li></ul></ul><ul><ul><li>Arranged into functional units called lobules. </li></ul></ul><ul><li>Plates separated by sinusoids. </li></ul><ul><ul><li>More permeable than other capillaries. </li></ul></ul><ul><li>Contains phagocytic Kupffer cells. </li></ul><ul><li>Secretes bile into bile canaliculi, which are drained by bile ducts. </li></ul>
  37. 37. Structure of Liver (continued) Insert fig. 18.20
  38. 38. <ul><li>Products of digestion that are absorbed are delivered to the liver. </li></ul><ul><li>Capillaries drain into the hepatic portal vein, which carries blood to liver. </li></ul><ul><ul><li>¾ blood is deoxygenated. </li></ul></ul><ul><ul><li>Hepatic vein drains liver. </li></ul></ul>Hepatic Portal System
  39. 39. Enterohepatic Circulation <ul><li>Compounds that recirculate between liver and intestine. </li></ul><ul><ul><li>Many compounds can be absorbed through small intestine and enter hepatic portal blood. </li></ul></ul><ul><ul><li>Variety of exogenous compounds are secreted by the liver into the bile ducts. </li></ul></ul><ul><li>Can excrete these compounds into the intestine with the bile. </li></ul>Insert fig. 18.22
  40. 40. Major Categories of Liver Function
  41. 41. <ul><li>The liver produces and secretes 250–1500 ml of bile/day. </li></ul><ul><li>Bile pigment (bilirubin) is produced in spleen, bone marrow, and liver. </li></ul><ul><ul><li>Derivative of the heme groups (without iron) from hemoglobin. </li></ul></ul><ul><li>Free bilirubin combines with glucuronic acid and forms conjugated bilirubin. </li></ul><ul><ul><li>Secreted into bile. </li></ul></ul><ul><li>Converted by bacteria in intestine to urobilinogen. </li></ul><ul><ul><li>Urobilogen is absorbed by intestine and enters the hepatic vein. </li></ul></ul><ul><ul><ul><li>Recycled, or filtered by kidneys and excreted in urine. </li></ul></ul></ul>Bile Production and Secretion
  42. 42. Metabolism of Heme and Bilirubin Insert fig. 18.23
  43. 43. Bile Production and Secretion (continued) <ul><li>Bile acids are derivatives of cholesterol. </li></ul><ul><ul><li>Major pathway of cholesterol breakdown in the body. </li></ul></ul><ul><li>Principal bile acids are: </li></ul><ul><ul><li>Cholic acid. </li></ul></ul><ul><ul><li>Chenodeoxycholic acid. </li></ul></ul><ul><ul><ul><li>Combine with glycine or taurine to form bile salts. </li></ul></ul></ul><ul><ul><ul><ul><li>Bile salts aggregate as micelles. </li></ul></ul></ul></ul><ul><li>95% of bile acids are absorbed by ileum. </li></ul>Insert fig. 18.25
  44. 44. Detoxification of the Blood <ul><li>Liver can remove hormones, drugs, and other biologically active molecules from the blood by: </li></ul><ul><ul><li>Excretion into the bile. </li></ul></ul><ul><ul><li>Phagocytosis by Kupffer cells. </li></ul></ul><ul><ul><li>Chemical alteration of the molecules. </li></ul></ul><ul><ul><ul><li>Ammonia is produced by deamination of amino acids in the liver. </li></ul></ul></ul><ul><ul><ul><li>Liver converts it into urea. </li></ul></ul></ul><ul><ul><ul><ul><li>Excreted in urine. </li></ul></ul></ul></ul>
  45. 45. Detoxification of the Blood (continued) <ul><li>Inactivation of steroid hormones and drugs. </li></ul><ul><ul><li>Conjugation of steroid hormones and xenobiotics make them anionic. </li></ul></ul><ul><ul><ul><li>Can be transported into bile by multispecific organic anion transport carriers. </li></ul></ul></ul><ul><ul><li>Steroid and xenobiotic receptors stimulate production of cytochrome P450 enzymes. </li></ul></ul>
  46. 46. Secretion of Glucose, Triglycerides and Ketones <ul><li>Liver helps regulate blood glucose concentration by: </li></ul><ul><ul><li>Glycogenesis and lipogenesis. </li></ul></ul><ul><ul><li>Glycogenolysis and gluconeogenesis. </li></ul></ul><ul><li>Contains enzymes required to convert free fatty acids into ketone bodies. </li></ul>
  47. 47. Production of Plasma Proteins <ul><li>Albumin and most of the plasma globulins (except immunoglobulins) are produced by the liver. </li></ul><ul><li>Albumin: </li></ul><ul><ul><li>Constitutes 70% of the total plasma protein. </li></ul></ul><ul><ul><ul><li>Contributes most to the colloid osmotic pressure in the blood. </li></ul></ul></ul><ul><li>Globulins: </li></ul><ul><ul><li>Transport cholesterol and hormones. </li></ul></ul><ul><ul><li>Inhibit trypsin. </li></ul></ul><ul><ul><li>Produce blood clotting factors I, II, III, V, VII, IX, XI. </li></ul></ul>
  48. 48. <ul><li>Sac-like organ attached to the inferior surface of the liver. </li></ul><ul><li>Stores and concentrates bile. </li></ul><ul><li>When gallbladder fills with bile, it expands. </li></ul><ul><ul><li>Contraction of the muscularis layer of the gallbladder, ejects bile into the common bile duct into duodenum. </li></ul></ul><ul><li>When small intestine is empty, sphincter of Oddi closes. </li></ul><ul><ul><li>Bile is forced up to the cystic duct to gallbladder. </li></ul></ul>Gallbladder
  49. 49. Pancreas <ul><li>Exocrine: </li></ul><ul><ul><li>Acini: </li></ul></ul><ul><ul><ul><li>Secrete pancreatic juice. </li></ul></ul></ul><ul><li>Endocrine: </li></ul><ul><ul><li>Islets of Langerhans: </li></ul></ul><ul><ul><ul><li>Secrete insulin and glucagon. </li></ul></ul></ul>Insert fig. 18.26
  50. 50. <ul><li>Contains H 2 0, HC0 3 - and digestive enzymes. </li></ul>Pancreatic Juice
  51. 51. Pancreatic Juice <ul><li>Complete digestion of food requires action of both pancreatic and brush border enzymes. </li></ul><ul><ul><li>Most pancreatic enzymes are produced as zymogens. </li></ul></ul><ul><ul><li>Trypsin (when activated by enterokinase) triggers the activation of other pancreatic enzymes. </li></ul></ul><ul><li>Pancreatic trypsin inhibitor attaches to trypsin. </li></ul><ul><ul><li>Inhibits its activity in the pancreas. </li></ul></ul>Fig. 18.29
  52. 52. <ul><li>Neural and endocrine mechanisms modify the activity of the GI system. </li></ul><ul><li>GI tract is both an endocrine gland, and a target for the action of hormones. </li></ul>Neural and Endocrine Regulation
  53. 53. <ul><li>Gastric motility and secretion are automatic. </li></ul><ul><li>Waves of contraction are initiated spontaneously by pacesetter cells. </li></ul><ul><li>Extrinsic control of gastric function is divided into 3 phases: </li></ul><ul><ul><li>Cephalic phase. </li></ul></ul><ul><ul><li>Gastric phase. </li></ul></ul><ul><ul><li>Intestinal phase. </li></ul></ul>Regulation of Gastric Function
  54. 54. Cephalic Phase <ul><li>Stimulated by sight, smell, and taste of food. </li></ul><ul><li>Activation of vagus: </li></ul><ul><ul><li>Stimulates chief cells to secrete pepsinogen. </li></ul></ul><ul><ul><li>Directly stimulates G cells to secrete gastrin. </li></ul></ul><ul><ul><li>Directly stimulates ECL cells to secrete histamine. </li></ul></ul><ul><ul><li>Indirectly stimulates parietal cells to secrete HCl. </li></ul></ul><ul><li>Continues into the 1 st 30 min. of a meal. </li></ul>
  55. 55. <ul><li>Arrival of food in stomach stimulates the gastric phase. </li></ul><ul><li>Gastric secretion stimulated by: </li></ul><ul><ul><li>Distension. </li></ul></ul><ul><ul><li>Chemical nature of chyme (amino acids and short polypeptides). </li></ul></ul><ul><ul><ul><li>Stimulates G cells to secrete gastrin. </li></ul></ul></ul><ul><ul><ul><li>Stimulates chief cells to secrete pepsinogen. </li></ul></ul></ul><ul><ul><ul><li>Stimulates ECL cells to secrete histamine. </li></ul></ul></ul><ul><ul><ul><ul><li>Histamine stimulates secretin of HCl. </li></ul></ul></ul></ul><ul><ul><li>Positive feedback effect. </li></ul></ul><ul><ul><ul><li>As more HCl and pepsinogen are secreted, more polypeptides and amino acids are released. </li></ul></ul></ul>Gastric Phase
  56. 56. Gastric Phase (continued) <ul><li>Secretion of HCl is also regulated by a negative feedback effect: </li></ul><ul><ul><li>HCl secretion decreases if pH < 2.5. </li></ul></ul><ul><ul><li>At pH of 1.0, gastrin secretion ceases. </li></ul></ul><ul><ul><ul><li>D cells stimulate secretion of somatostatin. </li></ul></ul></ul><ul><ul><ul><ul><li>Paracrine regulator to inhibit secretion of gastrin. </li></ul></ul></ul></ul>Insert. Fig. 18.30
  57. 57. <ul><li>Inhibits gastric activity when chyme enters the small intestine. </li></ul><ul><li>Arrival of chyme increases osmolality and distension. </li></ul><ul><ul><li>Activates sensory neurons of vagus and produces an inhibitory neural reflex: </li></ul></ul><ul><ul><ul><li>Inhibits gastric motility and secretion. </li></ul></ul></ul><ul><ul><ul><li>In the presence of fat, enterogasterone inhibits gastric motility and secretion. </li></ul></ul></ul><ul><li>Hormone secretion: </li></ul><ul><ul><li>Inhibit gastric activity: </li></ul></ul><ul><ul><ul><li>Somatostatin, CCK, and GLP-1. </li></ul></ul></ul>Intestinal Phase
  58. 58. <ul><li>Submucosal and myenteric plexuses contain 100 million neurons. </li></ul><ul><li>Include preganglionic parasympathetic axons, ganglion cell bodies, postganglionic sympathetic axons; and afferent intrinsic and extrinsic sensory neurons. </li></ul>Enteric Nervous System
  59. 59. Enteric Nervous System (continued) <ul><li>Peristalsis: </li></ul><ul><li>ACh and substance P stimulate smooth muscle contraction above the bolus. </li></ul><ul><li>NO, VIP, and ATP stimulate smooth muscle relaxation below the bolus. </li></ul>Insert fig. 18.31
  60. 60. Paracrine Regulators of the Intestine <ul><li>Serotonin (5-HT): </li></ul><ul><ul><li>Stimulates intrinsic afferents, which send impulses into intrinsic nervous system; and activates motor neurons. </li></ul></ul><ul><li>Motilin: </li></ul><ul><ul><li>Stimulates contraction of the duodenum and stomach antrum. </li></ul></ul><ul><li>Guanylin: </li></ul><ul><ul><li>Activates guanylate cyclase, stimulating the production of cGMP. </li></ul></ul><ul><ul><ul><li>cGMP stimulates the intestinal cells to secrete Cl - and H 2 0. </li></ul></ul></ul><ul><ul><ul><ul><li>Inhibits the absorption of Na + . </li></ul></ul></ul></ul><ul><li>Uroguanylin: </li></ul><ul><ul><li>May stimulate kidneys to secrete salt in urine. </li></ul></ul>
  61. 61. Intestinal Reflexes <ul><li>Intrinsic and extrinsic regulation controlled by intrinsic and paracrine regulators. </li></ul><ul><li>Gastroileal reflex: </li></ul><ul><ul><li>Increased gastric activity causes increased motility of ileum and movement of chyme through ileocecal sphincter. </li></ul></ul><ul><li>Ileogastric reflex: </li></ul><ul><ul><li>Distension of ileum, decreases gastric motility. </li></ul></ul><ul><li>Intestino-intestinal reflex: </li></ul><ul><ul><li>Overdistension in 1 segment, causes relaxation throughout the rest of intestine. </li></ul></ul>
  62. 62. <ul><li>Secretion of pancreatic juice and bile is stimulated by: </li></ul><ul><li>Secretin: </li></ul><ul><ul><li>Occurs in response to duodenal pH < 4.5. </li></ul></ul><ul><ul><li>Stimulates production of HC0 3 - by pancreas. </li></ul></ul><ul><ul><li>Stimulates the liver to secrete HC0 3 - into the bile. </li></ul></ul><ul><li>CCK: </li></ul><ul><ul><li>Occurs in response to fat and protein content of chyme in duodenum. </li></ul></ul><ul><ul><li>Stimulates the production of pancreatic enzymes. </li></ul></ul><ul><ul><li>Enhances secretin. </li></ul></ul><ul><ul><li>Stimulates contraction of the sphincter of Oddi. </li></ul></ul>Secretion of Pancreatic Juice
  63. 63. Digestion and Absorption of Carbohydrates <ul><li>Salivary amylase: </li></ul><ul><ul><li>Begins starch digestion. </li></ul></ul><ul><li>Pancreatic amylase: </li></ul><ul><ul><li>Digests starch to oligosaccharides. </li></ul></ul><ul><ul><li>Oligosaccharides hydrolyzed by brush border enzymes. </li></ul></ul><ul><li>Glucose is transported by secondary active transport with Na + into the capillaries. </li></ul>Insert fig. 18.32
  64. 64. <ul><li>Digestion begins in the stomach when pepsin digests proteins to form polypeptides. </li></ul><ul><li>In the duodenum and jejunum: </li></ul><ul><ul><li>Endopeptidases cleave peptide bonds in the interior of the polypeptide: </li></ul></ul><ul><ul><ul><li>Trypsin. </li></ul></ul></ul><ul><ul><ul><li>Chymotrypsin. </li></ul></ul></ul><ul><ul><ul><li>Elastase. </li></ul></ul></ul><ul><ul><li>Exopeptidases cleave peptide bonds from the ends of the polypeptide: </li></ul></ul><ul><ul><ul><li>Carboxypeptidase. </li></ul></ul></ul><ul><ul><ul><li>Aminopeptidase. </li></ul></ul></ul>Digestion and Absorption of Protein
  65. 65. Digestion and Absorption of Protein (continued) <ul><li>Free amino acids absorbed by cotransport with Na + . </li></ul><ul><li>Dipeptides and tripeptides transported by secondary active transport using a H + gradient to transport them into the cytoplasm. </li></ul><ul><li>Hydrolyzed into free amino acids and then secreted into the blood. </li></ul>Insert fig. 18.33
  66. 66. <ul><li>Arrival of lipids in the duodenum serves as a stimulus for secretion of bile. </li></ul><ul><li>Emulsification: </li></ul><ul><ul><li>Bile salt micelles are secreted into duodenum to break up fat droplets. </li></ul></ul><ul><li>Pancreatic lipase and colipase hydrolyze triglycerides to free fatty acids and monglycerides. </li></ul><ul><ul><li>Colipase coats the emulsification droplets and anchors the lipase enzyme to them. </li></ul></ul><ul><ul><li>Form micelles and move to brush border. </li></ul></ul>Digestion and Absorption of Lipids
  67. 67. <ul><li>Free fatty acids, monoglycerides, and lysolecithin leave micelles and enter into epithelial cells. </li></ul><ul><ul><li>Resynthesize triglycerides and phospholipids within cell. </li></ul></ul><ul><ul><ul><li>Combine with a protein to form chylomicrons. </li></ul></ul></ul><ul><li>Secreted into central lacteals. </li></ul>Digestion and Absorption of Lipids (continued)
  68. 68. <ul><li>In blood, lipoprotein lipase hydrolyzes triglycerides to free fatty acids and glycerol for use in cells. </li></ul><ul><li>Remnants containing cholesterol are taken to the liver. </li></ul><ul><ul><li>Form VLDLs which take triglycerides to cells. </li></ul></ul><ul><ul><li>Once triglycerides are removed, VLDLs are converted to LDLs. </li></ul></ul><ul><ul><ul><li>LDLs transport cholesterol to organs and blood vessels. </li></ul></ul></ul><ul><li>HDLs transport excess cholesterol back to liver. </li></ul>Transport of Lipids
  69. 69. Absorption of Fat Insert fig. 18.36