1. Copyright © 2006 by Elsevier, Inc. Types of Secretory Glands Single Cell - mucous cells or goblet cells Simple - indentations in epithelium (crypts of Lieberkühn) Tubular - acid secreting oxyntic gland Complex - salivary, pancreas

2. Copyright © 2006 by Elsevier, Inc. Control of Secretions Local - tactile, distention, irritation Reflex - nervous input Hormonal - G.I. hormones Parasympathetic Stim. -  rate of secretion Sympathetic Stim. -  or  rate of secretion

3. Copyright © 2006 by Elsevier, Inc. Digestive Enzymes Salivary glands  -amylase ptyalin lingual lipase Stomach pepsin Intestinal Mucosa enterokinase sucrase maltase lactase  -dextrinase (isomaltase) amino- oligopeptidase dipeptidase Pancreas amylase trypsin chymotrypsin carboxypeptidase elastase lipase-colipase phospholipase A 2 cholesterol esterase

4. Copyright © 2006 by Elsevier, Inc. Daily Secretion of Intestinal Juices Saliva Gastric secretion Pancreatic secretion Bile Small intestinal secretion Brunner’s gland secretion Large intestinal secretion Total Daily Volume (ml) 1000 1500 1000 1800 200 6700 pH 6.0-7.0 1.0-3.5 8.0-8.3 7.8 7.5-8.0 8.0-8.9 7.5-8.0

5. Copyright © 2006 by Elsevier, Inc. Saliva Two types of secretion - - Serous - watery secretion, contains an  -amylase (and ptyalin) - Mucous - contains mucin - lubrication Secrete 800-1500 ml/day of saliva Maximum rate of secretion: 4 ml/min

6. Copyright © 2006 by Elsevier, Inc. Salivary Glands Type of % of total Gland saliva Secreted Parotid Serous Submandibular Mucous/ Serous Sublingual Mucous/ 10% Serous Buccal Mucous <1% 90%

7. Copyright © 2006 by Elsevier, Inc. Figure 64-2; Guyton & Hall

8. Copyright © 2006 by Elsevier, Inc. Oxyntic gland from the body of the stomach Figure 64-4; Guyton & Hall

9. Copyright © 2006 by Elsevier, Inc. Oxyntic gland from the body of the stomach Figure 64-5; Guyton & Hall

10. Copyright © 2006 by Elsevier, Inc. Downloaded from: StudentConsult (on 19 February 2010 04:59 PM) © 2005 Elsevier

11. Copyright © 2006 by Elsevier, Inc. Gastric Acid Three major functions - -Bacteriostatic -Converts pepsinogen to pepsin -Begins protein digestion (with pepsin)

12. Copyright © 2006 by Elsevier, Inc. Pepsinogen Pepsinogen is an inactive, secreted form of pepsin -  Acid converts pepsinogen to pepsin  Pepsin (35 kDa) converts more pepsinogen to pepsin - proteolytic enzyme - optimal pH 1.8 - 3.5 - reversibly inactivated > pH 5.0 - irreversibly inactivated > pH 7-8

13. Copyright © 2006 by Elsevier, Inc.

14. Peptic Ulcers Peptic ulcers occur when damaging effects of acid and pepsin overcome ability of mucosa to protect itself  Gastric ulcers - main problem is decreased ability of mucosa to protect itself  Duodenal ulcers - main problem is exposure to increased amounts of acid and pepsin

15. Copyright © 2006 by Elsevier, Inc. Treatment of Peptic Ulcers Antacids H 2 receptor blockers- Rantidine (Zantac) - Cimetidine (Tagamet) Proton pump inhibitors- Omeparazole (Prilosec) Antibiotics Surgical (rare) - vagotomy - antrectomy

16. Copyright © 2006 by Elsevier, Inc. Figure 65-7; Guyton & Hall

17. Copyright © 2006 by Elsevier, Inc. Pancreas As chyme floods into small intestine two things must happen:  Acid must be neutralized to prevent damage to duodenal mucosa  Macromolecular nutrients - proteins, fats and starch must be broken down much further so their constituents can be absorbed

18. Copyright © 2006 by Elsevier, Inc. Pancreas Pancreas plays vital role in accomplishing both objectives  Digestive enzymes for all food types  Bicarbonate solution to neutralize acid chyme

19. Copyright © 2006 by Elsevier, Inc. Internal Structure of Pancreas Compound gland with structure similar to salivary gland Acini - grape-like clusters of cells that store and secrete digestive enzymes Ducts - secrete bicarbonate  Intercalated ducts - receive secretions from acini  Intralobular ducts - receive fluid from intercalated ducts

20. Copyright © 2006 by Elsevier, Inc. Enzymes for Protein Digestion Proteolytic enzymes - Trypsin - Chymotrypsin - Carboxypeptidase Cleaves proteins to polypeptides Cleaves polypeptides to AA

21. Copyright © 2006 by Elsevier, Inc. Enzymes for Carbohydrate Digestion Pancreatic amylase - starches - glycogen to disaccharides

22. Copyright © 2006 by Elsevier, Inc. Enzymes for Fat Digestion Pancreatic lipase -  fat  fatty acids +monoglycerides Phospholipase -  phospholipids  fatty acid Cholesterol esterase -  cholesterol esters  fatty acid

23. Copyright © 2006 by Elsevier, Inc. Why Doesn’t the Pancreas Digest Itself? Pancreatic proteolytic enzymes are stored and secreted in an inactive form - (also, a trypsin inhibitor is present in cells)  trypsinogen  trypsin  chymotrypsinogen  chymotrypsin  procarboxypeptidase  carboxypeptidase

24. Copyright © 2006 by Elsevier, Inc. Activation of Proteolytic Enzymes Trypsinogen Trypsin Enterokinase - located on intestinal mucosal cells Trypsin - autocatalytic activation - activates - chymotrypsinogen, - procarboxypeptidase - trypsinogen enterokinase

25. Copyright © 2006 by Elsevier, Inc. Trypsin Inhibitor Enzyme precursors stored in cells along with trypsin inhibitor -  Trypsin inhibitor prevents formation of trypsin - - in acini - in ducts  Acute pancreatitis - - a primary lack of trypsin inhibitor - not enough trypsin inhibitor is present

26. Copyright © 2006 by Elsevier, Inc. Bicarbonate Neutralizes Acid Chyme Secretin induced bicarbonate secretion neutralizes acid chyme creating optimal conditions (pH = 7-8) for digestive enzymes - HCl + NaHCO 3 NaCl + H 2 CO 3 CO 2 H2OH2O Secretin is nature’s antiacid

27. Copyright © 2006 by Elsevier, Inc. Model of Bicarbonate Secretion 1. CO 2 combines with H 2 O in presence of C.A. in cell 2. Carbonic acid dissociates into HCO 3 - and H + ions 3. H + ions are transported through apical membrane by secondary transport mechanism that requires Na + gradient. Na + gradient is established by usual Na + -K + ATPase pump. 4. HCO 3 - moves out of cell in exchange for Cl -.

28. Copyright © 2006 by Elsevier, Inc. LUMEN Cl - HCO 3 - CO 2 H+H+ H + + HCO 3 - Na + K+K+ C.A. S S P H2OH2O BLOOD DUCT CELL Na +, H 2 O K+K+ K+K+ H2OH2O HCO 3 - + 6 4 3 2 1

29. Copyright © 2006 by Elsevier, Inc. Model of Bicarbonate Secretion (cont’d) 5. Rate of HCO 3 - secretion is dependent upon luminal Cl - concentration. 6. Na + moves down electrochemical gradient. Water moves into lumen establishing osmotic equilibrium. (Pancreatic juice is always isotonic.) Secretin - acts to open Cl - channels and thus increase secretion of bicarbonate.

30. Copyright © 2006 by Elsevier, Inc. Effect of Secretion Rate on Ionic Composition of Pancreatic Juice Low secretion rates -  bicarbonate concentration is low  chloride concentration is high High secretion rates -  bicarbonate concentration is high  chloride concentration is low Sodium and potassium concentrations always same as plasma

31. Copyright © 2006 by Elsevier, Inc. Regulation of pancreatic secretion Figure 64-10; Guyton & Hall

32. Copyright © 2006 by Elsevier, Inc. Regulation of Pancreatic Secretion Secretion of fluid and HCO 3 - is mainly dependent upon amount of acid entering duodenum Secretion of enzymes is mainly dependent upon amount of fat and protein entering duodenum  Acetylcholine - vagovagal reflexes  Cholecystokinin - fat and protein  Secretin - acid Mainly enzymes Fluid / HCO 3 -

33. Copyright © 2006 by Elsevier, Inc. Phases of Pancreatic Secretion Cephalic (20%) Gastric (5-10%) Intestinal (70-80%)  acid  secretin  HCO 3 - /H 2 O  fat/protein  CCK  enzymes  acid/fat/protein  vagovagal Ach  enzymes CCK and acetylcholine both potentiate the effects of secretin on water and bicarbonate secretion. Both phases mediated by vagus - low volume, high enzyme secretion

34. Copyright © 2006 by Elsevier, Inc. Pancreatic HCO 3 - Output (Secretin) Response to Duodenal Acidification Secretin released when pH < 4.5. Below pH = 3, secretin release is maximal in segment of duodenum. Further release of secretin depends upon area of small intestine affected. (Maximal bicarbonate response is 30 mEq/hr) During meal pH rarely < 3.5 or 4.0.

35. Copyright © 2006 by Elsevier, Inc. Distribution of GI Hormones Digestive products are equally effective in releasing secretin when applied to any part of duodenum or jejunum. Secretin Fundus Antrum Duo Jejun Ileum Colon

36. Copyright © 2006 by Elsevier, Inc. Pancreatic Failure Digestion is abnormal when pancreas fails to secrete normal amounts of enzymes.  Pancreatitis  Removal of pancreatic head - malignancy Without pancreatic enzymes -  60% fat not absorbed (steatorrhea)  30-40% protein and carbohydrates not absorbed

37. Copyright © 2006 by Elsevier, Inc. Pancreatitis Pancreatitis means inflammation of pancreas. Autodigestion theory can explain condition. Chronic pancreatitis - (multiple shared causes)  alcohol - most common cause in adults  cystic fibrosis - most common cause in children Acute pancreatitis - (multiple shared causes)  gallstones - most common cause

38. Copyright © 2006 by Elsevier, Inc. Secretion Failure in Cystic Fibrosis CF patients lack chloride transporter at apical membrane. Watery ductal secretion decreases which concentrates acinar secretions in ducts. Precipitation of proteinaceous secretions block ducts and can destroy gland by autodigestion.

39. Copyright © 2006 by Elsevier, Inc.