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Gastrointestinal system

Gastrointestinal system. Xiang-Yao LI, PhD Department of Physiology Zhejiang University School of Medicine Email: lixiangy@zju.edu.cn. Digestion in the stomach. Specialized cells in the stomach synthesize and secrete mucous fluid, enzyme precursors, hydrochloric acid, and hormones.

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Gastrointestinal system

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  1. Gastrointestinal system Xiang-Yao LI, PhD Department of Physiology Zhejiang University School of Medicine Email: lixiangy@zju.edu.cn

  2. Digestion in the stomach

  3. Specialized cells in the stomach synthesize and secrete mucous fluid, enzyme precursors, hydrochloric acid, and hormones. The abundant smooth muscle in the stomach is responsible for gastric motility.

  4. Gastric juice • Properties • pH 0.9~1.5 • 1.5~2.5 L/day • Major components • Hydrochloric acid (>150mM, parietal cells) • Pepsinogen • Mucus • Intrinsic factor • Role of HCl • Acid sterilization • Activation of pepsinogen • Promotion of secretin secretion • Assisted effect of iron and calcium absorption

  5. Mechanism of HCl secretion • Active transport • Huge H+ gradient (3 million) active transport

  6. One inhibitory and three stimulatory signals that alter acid secretion by parietal cells in the stomach.

  7. Pepsinogen • MW: 42,500 • Secreted by the chief cells as an inactive precursor of pepsin • Activated in the stomach, initially by H+ ions and then by active pepsin, autocatalytic activation • Active pepsin (MW: 35,000) an endopeptidase, which attacks peptide bonds in the interior of large protein molecules

  8. The acidity in the gastric lumen converts the protease precursor pepsinogen to pepsin; subsequent conversions occur quickly as a result of pepsin’s protease activity.

  9. Mucus Gastric pit • Secreted by the epithelial cells • Role • Lubrication of the mucosal surface • Protection of the tissue from mechanical damage by food particles

  10. Mucus-HCO3- barrier

  11. Intrinsic factor • A high molecular weight glycoprotein, synthesized and secreted by the parietal cells • The intrinsic factor binds to Vit B12 and facilitates its absorption Secretion of other enzymes • Gastric lipase • Gastric amylase • Gelatinase

  12. Regulation of gastric secretion • Basic factors that stimulate gastric secretion • Acetylcholine (+ all secretory cells) • Gastrin (+ parietal cells) • Histamine (+ parietal cells)

  13. Regulation of gastric secretion • Nervous regulation • ‘Short’ reflex pathways • ‘Short’ excitatory reflexes: mediated by cholinergic neurons in the plexuses • ‘Short’ inhibitory reflexes: mediated by non-adrenergic non-cholinergic (NANC) neurons • Long’ autonomic pathways • ‘Long’ excitatory reflexes: parasympathetic • ‘Long’ inhibitory pathways: sympathetic

  14. Regulation of gastric secretion • Humoral regulation Excitatory ACh Histamine Gastrin Inhibitory Somatostatin Secretin 5-hydroxytryptamine (5-HT) Prostaglandin

  15. Phases of gastric secretion • Cephalic phase • Gastric phase • Intestinal phase

  16. Factors: Distension, acidity, AA, peptides Factors: Distension, Acidity, Osmolarity, digestive products

  17. Inhibition of gastric secretion The functional purpose of the inhibition of gastric secretion by intestinal factors is presumably to slow the release of chyme from the stomach when the small intestine is already filled or overactive

  18. Inhibition of gastric secretion • Reverse enterogastric reflex: initiated by the presence of food in the small intestine • Secretin secretion: stimulated by the presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factors in the upper small intestine

  19. Delivery of acid and nutrients into the small intestine initiates signaling that slows gastric motility and secretion which allows adequate time for digestion and absorption in the duodenum.

  20. Motor function of the stomach Proximal stomach cardia fundus corpus (body) Distal stomach antrum pylorus pyloric sphincter

  21. Waves of smooth muscle contraction mix and propel the ingested contents of the gastric lumen, but only a small amount of the material enters the small intestine (duodenum) as a result of each wave cycle.

  22. Motor function of the stomach • Receptive relaxation • Storage function (1.0~1.5 L) • Vago-vagal reflex • Peristalsis • BER in the stomach

  23. Contractions in the empty stomach • Migrating Motor Complex (MMC) • Periodic waves of contraction, which move along the gastrointestinal tract from stomach to colon • Purpose of this activity: to ‘sweep’ debris out of the digestive tract during the interdigestive period • MMCs can lead to hunger contractions, which are associated with discomfort, referred to as ‘hunger pains’

  24. Emptying of the stomach • Emptying rate • Fluid > viscous • Small particle > large particle • Isosmotic > hyper- & hypo-osmotic • Carbohydrates > Protein > Fat • Regular meal 4~6 hrs

  25. Regulation of stomach emptying • Gastric factors that promote emptying • Gastric food volume • Gastrin • Duodenal factors that inhibit stomach emptying • Enterogastric nervous reflexes • Fat • Cholecystokinin

  26. PANCREATIC SECRETION

  27. Pancreatic juice • pH 7.8~8.4 • ~1500 ml/day • Isosmotic • Components: • Pancreatic digestive enzymes: secreted by pancreatic acini • Sodium bicarbonate: secreted by small ductules and larger ducts

  28. At low magnification At higher magnification

  29. Secretion of bicarbonate ions • Secreted by the epithelial cells of the ductules and ducts that lead from acini • Up to 145mmol/L in pancreatic juice (5 times that in the plasma) • Neutralizing acid entering the duodenum from the stomach

  30. PANCREATIC ACINAR CELL SECRETORY PRODUCTS

  31. Secretion of pancreatic digestive enzymes Carbohydrates -- Pancreatic amylase Pancreatic lipase Fat Cholesterol esterase Phospholipase Trypsinogen Proteins Chymotrypsinogen Procarboxypolypeptidase Proelastase

  32. Trypsin Inhibitor • Inhibits the activity of trypsin and thus guards against the possible activation of trypsin and the subsequent autodigestion of the pancreas

  33. REGULATION OF PANCREATIC SECRETION • Basic stimuli that cause pancreatic secretion • Ach • Cholecystokinin: • Secreted by I cells • Stimulates the acinar cells to secrete large amounts of enzymes • Secretin: • Released by S cells • Acts primarily on the duct cells to stimulate the secretion of a large volume of solution with a high HCO3- concentration

  34. REGULATION OF PANCREATIC SECRETION • Phases of pancreatic secretion: A meal triggers cephalic, gastric, and intestinal phases of pancreatic secretion • Cephalic Phase • Gastric Phase • Intestinal Phase

  35. THE THREE PHASES OF PANCREATIC SECRETION

  36. MECHANISMS THAT PROTECT THE ACINAR CELL FROM AUTODIGESTION

  37. ACUTE PANCREATITIS • Acute pancreatitis is sudden swelling and inflammation of the pancreas • The symptomatology and complications of acute pancreatitis are caused by autodigestion (resulting from the leakage of pancreatic enzymes) of the pancreas and surrounding tissue • It is commonly due to biliary tract disease, complications of heavy alcohol use, or idiopathic causes • Mortality rates range from below 10% to more than 50%, depending on severity

  38. BILE SECRETION

  39. Bile is stored and concentrated in the gall bladder during the interdigestive period

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