1. GASTROINTESTINAL PHYSIOLOGY Chapter-I (Gastrointestinal Secretions) Ass. Prof. Dr. Emre Hamurtekin EMU Faculty of Pharmacy

2. STRUCTURAL CONSIDERATIONS

3. The intestine has a very substantial surface area for absorption. Sphincters: – upper & lower esophageal sphincters – pylorus – ileocecal valve – inner & outer anal sphincters

4. STRUCTURAL CONSIDERATIONS Throughout the small intestine, it is folded up into fingerlike projections called villi. Crypts are the infoldings between the villi.

5. GASTROINTESTINAL SECRETIONS Salivary secretion Gastric secretion Pancreatic secretion Biliary secretion Intestinal fluid

6. SALIVARY SECRETION

7. Saliva is produced by 3 pairs of salivary glands: – Parotid gland – Submandibular gland – Sublingual gland Constituents: – Amylase (initiate digestion) – IgA, lysozyme (protect oral cavity from bacteria) – Mucin (lubricate the food) Saliva is hypotonic and alkaline Salivary secretion is almost entirely controlled by neural influences: – Parasympathetic*: most important role – Sympathetic: composition of saliva (little influence on volume)

8. SALIVARY SECRETION Functions of saliva: – Facilitates swallowing – Initiates digestion – Keep the mouth moist – Solvent for molecules that stimulate the taste buds – Aids speech – Keep the mouth and teeth clean (mechanical&antibacterial) Chewing Smelling/Seeing food Nausea Salivary secretion Sleep Fear Fatigue

9. GASTRIC SECRETION

10. ANATOMIC CONSIDERATIONS

11. ORIGIN & REGULATION Cephalic phase (before the meal is taken) Gastric phase (most significant) Intestinal phase (when the meal left the stomach) SECRETIONS: (fundus/body of stomach) Surface mucous cells: mucus, bicarbonate, trefoil peptide Parietal cells: hydrocholoric acid, intrinsic factor ECL cell: histamine secretion Chief cell: pepsinogen AND gastric lipase

12. ORIGIN & REGULATION There are 3 primary stimuli of gastric secretion: – Gastrin – Histamine – Acetylcholine GASTRIN: – Gastrin is a hormone released by G cells in the antrum of the stomach. – It is released in response to, a) GRP (bombesin) which is relesed from enteric nerve endings b) oligopeptides in the gastric lumen. – Carried to fundic glands by bloodstream – Binds to receptors on parietal, chief cells(?) to activate secretion and also ECL cells to activate histamine release HISTAMINE: – Binds to H2 receptors on parietal cells and activate parietal cell secretion. ACETYLCHOLINE: – Enteric nerve endings release acetylcholine – Stimulates parietal and chief cells

13. ORIGIN & REGULATION During the cephalic phase of gastric secretion, secretion is activated by vagal input originates from the brain region. Vagal outflow to the stomach releases acetylcholine and GRP initiating secretory function. Meal constituents trigger gastrin release + distension of stomach activates strech receptors which provoke vago-vagal and local reflexes that further amplify gastric secretion. Somatostatin (released from antral D cells) inhibits both G and ECL cells as well as parietal cell acid secretion.

14. GASTRIC PARIETAL CELLS

16. Basolateral membrane Acid secretion Stomach Lumen M3H2 CCK-B AchHistamine Gastrin Ca cAMP

17. PANCREATIC SECRETION

18. ANATOMIC STRUCTURE Exocrine pancreas is a compound alveolar gland. Duct cells : secrete bicarbonate – HCO3 is secreted in exchange for Cl (Cl / HCO3 exchanger) Exocrine cells : secrete enzymes Zymogen granules are formed in the cell and discharged by exocytosis. The small duct radicles pancreatic duct of Wirsung ampulla of Vater duodenal papilla (sphincter of Oddi) Duct of Santorini

19. PANCREATIC JUICE Pancreatic juice is alkaline and has a high bicarbonate content. Most of the digestive enzymes in the pancreatic juice are released in inactive forms. Trypsin is main the activator of most of the pro-enzymes. Acute pancreatitis !!! Secretion of pancreatic juice is primarily under hormonal control: – Secretin - rich in HCO3 and poor in enzymes – CCK (cholecystokinin) – rich in enzymes but low in volume The effect of secretin is mediated by cAMP The effect of CCK is mediated by phospholipase C Neuronal control: – Acetylcholine - cause discharge of zymogen granules (mediated by phospholipase C)

20. BILIARY SECRETION

22. INTRODUCTION FUNCTIONS: Digestion and absorption of fats (bile acids) Excretory fluid by which the body disposes of  lipid soluble end products of metabolism  lipid soluble xenobiotics  cholesterol (native or as bile acids)

23. BILE Bile is made up of bile acids, bile pigments, and other substances dissolved in alkaline solution. Bilirubin and biliverdin pigments are responsible for the color of the bile. Bile acids is the most important component in bile for the digestion and absorption function of the biliary secretion. 4 major bile acids in humans: – Cholic acid primary (principle) – Chenodeoxycholic acid bile acids – Deoxycholic acid – Lithocholic acid

24. BILE Cholic acid Deoxycholic acid Colonic bacteria Chenodeoxycholic acid Colonic bacteria Lithocholic acid Ursodeoxycholic acid Colonic bacteria Seconder bile acids: Deoxycholic acid Lithocholic acid Ursodeoxycholic acid

25. BILE Bile acids reduce surface tension. Bile acids are responsible for emulsification of fat preparatory to its digestion and absorption in the small intestine (form micelles).

26. BILE 90-95% of the bile acids are absorbed from small intestine. – Simple diffusion – Na-bile salt co-transport system (terminal ileum) 5-10% are enter the colon and converted to deoxycholic acid (absorbed back) and lithocholic acid (mostly excreted in the stool) Absorbed bile acids are transported back to the liver (enterohepatic circulation) and excreted again in the bile.

27. Daily water turnover (ml) in GI tract INGESTED2000 ENDOGENOUS SECRETIONS * Salivary glands1500 * Stomach2500 * Bile500 * Pancreas1500 * Intestine1000 7000 TOTAL INPUT2000 + 7000 = 9000 REABSORBED * Jejunum5500 * Ileum2000 * Colon1300 8800 BALANCE IN STOOL9000 - 8800 = 200

28. INTESTINAL FLUID In the small intestine, secondary active transport of Na is important in bringing about absorption of glucose, amino acids and bile acids. Presence of glucose in the intestinal lumen facilitates Na reabsorption. Between meals, Na and Cl are absorbed together by coupled activity of Na / H exchanger and Cl / HCO3 exchanger.

29. ELECTRONEUTRAL NaCl ABSORPTION IN THE SMALL INTESTINE and COLON 2K 3Na Na, K ATPase NHE Na H CLD HCO3 Cl ApicalBasal Cl 3Na Modified from Ganong’s Physiology

30. ELECTROGENIC Na ABSORPTION IN THE COLON Na Na, K ATPase 2K 3Na 2K Na K Epithelial Na channel Apical Basal Distal colon epithelium Modified from Ganong’s Physiology

31. Daily water turnover (ml) in GI tract INGESTED2000 ENDOGENOUS SECRETIONS * Salivary glands1500 * Stomach2500 * Bile500 * Pancreas1500 * Intestine1000 7000 TOTAL INPUT2000 + 7000 = 9000 REABSORBED * Jejunum5500 * Ileum2000 * Colon1300 8800 BALANCE IN STOOL9000 - 8800 = 200

32. Cl SECRETION IN SMALL INTESTINE and COLON Cl 2Cl K CFTR Lumen Modified from Ganong’s Physiology K Na-K-2Cl Na, K ATPase Na K

33. THE END