1. Digestive Physiology Digestive Physiology Physiological functions of the small intestine, liver & pancrease By: M.H.Dashti Lecture 5

2. Anatomy of the Small Intestine 20 feet long----1 inch in diameter Large surface area for majority of absorption 3 parts –duodenum---10 inches –jejunum---8 feet –ileum---12 feet  ends at ileocecal valve

3. Secretions of the small intestine many villi on surface of intestine : 2 types of glands 1- Brunner ’ s glands- compound mucus glands, Secreting Alkaline mucus -Stimulated by parasympathetic -Inhibited by sympathetic -?stress related ulceration 2- crypts/glands of Lieberkuhn between villi Exocrine from Enterocyte Endocrine: Secretin (S), cck ( I ),GIP ( K ),VIP ( v ),Motilin ( mo ) Digestive enzymes not secreted from small intestine except enterokinase secreted from duodenal mucosa

4. Crypt of Lieberkuhn Mucous cells (simple goblet cells) Enterocyte (absorptive cells with brush border) Villus Paneth cell (have Secretory granules of lysozyme) Endocrine cells (secrete hormones for control of gut function) under local nervous control some minor hormonal control (VIP,secretin, CCK )

5. Secretin Fat HCO 3 - H+H+ Secretin S cells stomach Bile S.I.

6. Cholecystokinin I cells CCK Peptides Amino acids, Enzymes Fat stomach pancreas duodenum Insulin Glucagon + Stomach Bile S.I.

7. Other intestinal hormones GIP (Gastric Inhibitory peptide ) from k cells –Stimulated by carbohydrates in duodenum –Stimulate insulin secretion VIP ( Vasoactive Intestinal Peptide ) –Stimulated by H + in duodenum –Inhibit gastric secretion & Stimulate intestinal secretion –VIPoma Motilin –Stimulated by H + in duodenum –Co-related to Migratory Myoelextric Complex ( MMC )

8. Small intestine motility Small intestine motility Weak peristalsis in comparison to the stomach---chyme remains for 3 to 5 hours Segmentation--- local mixing of chyme with intestinal juices---sloshing back & forth

9. Bile Production Components: water –Cholesterol, FA & Lecithin –bile salts = Na & K salts of bile acids –bile pigments (bilirubin) –Alkalinephosphatase Gall bladder concentrates bile by absorbing water & Na-cl 0.5-1 Lof bile/day is secreted yellow-green in color & pH 7.6 to 8.6

10. Bile production & enterohepatic circulation Bilirubin is produced by the metabolism of Heme& is transported to the liver by albumin

11. Gallstones Calcium - bilirobinate due to glucoronidase activity of bacteria Cholesterol stones due to increased Cholesterol/PL ratio

12. Pancreatic Secretions & their Regulation Both endo. & exocrine Secretions are under neural & hormonal control Regulated in 3 phases Secretin –increased sodium bicarbonate release from ducts CCK –increased digestive enzymes & hormones ( I & G ) release ( EGSF ) GIP –Stimulated by fatty acids & sugar in S.I. –causes increased insulin release (EISF )

13. Regulation of pancreatic acinar secretion Cholera toxin Delivers Inositol tri- phosphate Adenylate cyclase

14. Sites of pancreatic secretions Acinar fluid is isotonic & its ionic composition resembles the plasma Spontaneous secretion of interalobular ducts have greater K + & HCO 3 - than plasma Secretin stimulated secretion from the cells of extra lobular ducts are still more rich in HCO 3 -

15. Cellular mechanisms for HCO 3 - rich secretion by pancreatic acinar cells K+K+ H2OH2O H2OH2O

16. Cellular mechanisms for HCO 3 - rich secretion by pancreatic extra lobular ductal cells Stimulated by secretin, cck & Ach H2OH2O

17. Ionic concentration of pancreatic juice as a function of its flow rate

18. Pancreatic digestive Enzymes EnzymeActivatorSubstrateCatalytic Function or Products Trypsins (trypsinogens)Entero - peptidase Proteins and polypeptides Cleave peptide bonds adjacent to aromatic amino acids Chymotrypsins (chmo - trypsinogens) TrypsinProteins and polypeptides Cleave peptide bonds adjacent to arginine or lysine Elastase (proelastase)TrypsinElastine, some other proteins Cleave bonds adjacent to aliphatic amino acids Carboxypeptidase A (pro- carboxypeptidase A) TrypsinProteins and polypeptides Cleave carboxyl terminal amino acids that have aromatic or branched aliphatic side chains

20. EnzymeActivatorSubstrateCatalytic Function or Products Carboxypeptidase B (pro- carboxy peptidase B) TrypsinProteins and polypeptides Cleave carboxyl terminal amino acids that have basic side chains Colipase (procolipase) TrypsinFat dropletsBinds to bile salt-triglyceride –water interface, making anchor for lipase Pancreatic lipase…TriglyceridesMonoglycerides and fatty acids Cholesterol ester hydrolase …Cholesteryle esters Cholesterol and fatty acids Pancreatic α- amylase Cl - StarchSame as salivary α-amylase Ribonuclease…RNANucleotides Deoxyribonuclease…DNANucleotides Phospholipase A 2 (pro- phospholipase A 2 ) TrypsinPhospholipidsFatty acids, lysophospholipids Pancreatic digestive Enzymes (Continue) Pancreatic digestive Enzymes (Continue)