The Digestive System

1. The Digestive System • Mechanism for nourishing the body • Most nutrients in food require either degradation or release prior to absorption • Digestion occurs in GI Tract • Digestion • Mechanical • chewing and peristalsis • Chemical • enzymes, HCl

2. Overview of GI Tract • Upper GI Tract • Mouth and pharnyx provide entryway • Lead to Esophagus • Esophagus wall consists of same layers found in remainder of GI tract • epithelium (mucosa), submucosa, muscularis mucosa, circular and longitudinal muscles • Secretory glands found throughout GI except colon • Exocrine glands and Endocrine glands

3. Upper GI Tract Continued • Sphincters • circular muscles located throughout digestive tract • Lower Esophageal Sphincter • allows passage of food into stomach • Pyloric Sphincter • Controls release of chyme from stomach to duodenum • Stomach • J shaped organ • volume ranges from 50 to 1500 mL (2 -52 oz)

4. Lower GI tract and Accessory Organs • Small Intestine • duodenum, jejunum and ileum • main site for nutrient digestion and absorption • duodenum receives secretions from liver, gallbladder and pancreas • Liver • hepatocytes make bile from cholesterol • right and left hepatic bile ducts join to form common hepatic duct • unites with cystic duct leading to gallbladder

5. Lower GI tract and Accessory Organs • Gallbladder • capacity to hold 40-50 mL of bile • functions to concentrate and store bile • Pancreas • 2 types of active tissue • Acini or ducted exocrine tissue • produces digestive enzymes • secreted into small ducts within pancreas which leads to common hepatic bile duct • empties into duodenum • Ductless endocrine tissue • secretes hormones, glucagon and insulin

6. Structure of SI • Epithelial surface (mucosa) structured to maximize surface area • Large folds of mucosa (folds of Kerckring) • Villi • projections lined with 100s of absorptive cells • contain blood capillaries and central lacteal • Microvilla • extensions of plasma membrane of absorptive cells • possess surface coat of glycocalyx • forms brush border • most digestive enzymes produced by SI found here.

7. Structure of SI • Crypts of Lieberkuhn • pits located between villi • epithelial cells in these crypt migrate upward and out of crypts toward tips of villi • turnover every 3-5 days • Cells include • paneth cells secrete proteins with unknown function • globlet cells secrete mucus • Enterochromaffin cells with endocrine functions

8. Structure of SI • Lymphoid Tissues • mucosa and submucosa • Peyer’s Patches • T-lymphocytes and B-lymphocytes • provide defense against bacteria and foreign bodies • Ileocecal valve • allows unabsorbed materials to leave ileum and enter cecum

9. Colon • Cecum • Ascending, transverse and descending sections • Sigmoid sections • Haustra or pouches • created by contraction of 1 or 3 muscular strips (tenaie coli) along with contraction of circular muscles • Absorbs water and lytes

10. Regulation Of Digestive Process • Regulatory Peptides (GI hormones and neuropeptides) • Gastrin (hormone) • produced mainly by gastric cells • released upon entry of food into stomach • stimulates HCl release • gastric and intestinal motility • pepsinogen release • Cholecystokinin (CCK, hormone) • produced by SI cells • released upon entry of chyme into stomach • amino acids, fat • targets pancreas and gallbladder

11. Regulatory Peptides • Secretin • produced by cells of SI • secreted in response to chyme (acid) into duodenum • targets pancreas • may inhibit GI motility • Gastric Inhibitory Polypeptide (GIP) • produced by SI cells • Inhibits gastric secretions and motility • Simulates intestinal and insulin secretions

12. Regulatory Peptides • Somatostatin • Produced by pancreatic and SI cells • Paracrine • released by endocrine cells but diffuse through extracellular space to target tissue • Enters gastric juice • Inhibits gastrin secretion, as well as GIP and secretin • Inhibits gastric acid release, gastric motility, pancreatic exocrine secretions and gall bladder secretions

13. Neural Regulation • Enteric Nervous System • located in wall of GI tract • begins in esophagus and ends at anus • controls peristaltic activity • affected by parasympathetic and sympathetic nervous systems • Acetylcholine increase GI motility • Norepinephrine and epinephrine inhibit GI activity • Also influences GI secretions

14. Neurocrines (Regulatory Peptides) • Neurocrines • Peptides originating from nerves of gut • Vasoactive Intestinal Peptide (VIP) • stimulates intestinal secretions • relaxes GI sphincters • inhibits gastric acid secretion • stimulates bicarbonate release • Gastrin Releasing Peptide (GRP) • Stimulates release of HCl, gastrin and CCK • Neurotensin (Bombesin) • Mediates gastric emptying, gastric acid secretion and SI motility

15. Process of Digestion • Oral Cavity and Salivary Glands • mastication of food • mixed with salivary gland secretions • parotid glands • water, lytes and enzymes • submandibular and sublingual glands • water, lytes, enzymes and mucus • Enzymes • alpha amylase and lingual lipase

16. Process of Digestion • Esophagus • Entry of food results in peristalsis • acetylcholine • LES • LES pressure decreases upon swallowing • Neural and hormonal regulation • functions to prevent gastric reflux

17. Process of Digestion • Stomach • Body extends from LES to angular notch • includes fundus • serves as reservoir as well as producer of gastric juice • Antrum (Pyloric Portion) • extends from angular notch to duodenum • grinds and mixes food with digestive juice (chyme) • provides strong peristalsis

18. Stomach • Gastric Juices • produced by 3 different gastric glands • Cardiac glands (fundus) • mucus cells (HCO3 and mucus) and endocrine cells • no parietal (oxyntic cells) • Parietal glands (body) • mucus cells, oxyntic cells (secrete HCl and IF), chief cells secrete pepsinogen upon stimulation by acetylcholine • Pyloric glands (antrum) • both mucus and oxyntic cells • endocrine G cells that produce gastrin • Acetylcholine stimulates chief, oxyntic and other gastric cells

19. Gastric Juices • HCl • activates inactive zymogen pepsinogen to active pepsin • denatures proteins • serves as bactericide • Mucus • lubricates and protects gastric lining • Intrinsic Factor (IF) • necessary for vitamin B12 absorption

20. HCl • Release from oxyntic cells stimulated by • acetylcholine, gastrin, CCK, histamine • Histamine • secreted from mast cells • paracrine that binds to H2 receptors on parietal cells to stimulate HCl release • mechanism used in drug therapy to lower acid • drugs prevent histamine from binding to H2 receptors • decreases acid release

21. Gastric Emptying • GI hormones and neuropeptides affect a pacemaker • determines frequency and rate of contractions • 1-5 mL chyme allowed to enter duodenum every 30 seconds • Fat appears to slow gastric emptying • Inhibitors • Secretin, GIP, Somatostatin, CCK

22. Small Intestine • Chyme has low pH • SI protected by pancreatic secretions and secretions from Brunner’s glands • Secretin and CCK • Digestive juices • Glands within crypts of Lieberkuhn • Pancreas • Responsible for enzymes that digest 50% CHO, 50% protein, 90% lipids

23. Digestive Juice • Pancreatic Proteases • trypsinogen, chymotrypsinogen, procarboxypeptidases, proelastase, collagenase • secreted in vesicles • must be activated • trypinsogen converted to trypsin by enteropeptidase (enterokinase) and by free trypsin • hydrolyze peptide bonds either internally or from ends • mono, di and some tri can be absorbed • Brush border aminopeptidases to hydrolyze further

24. Digestive Juice • CHO • Pancreatic alpha amylase • hydrolyzes alpha 1-4 bonds • Alpha dextrinase to hydrolyze 1-6 branches • Brush border enzymes (maltase, sucrase, lactase) • Lipids • Pancreatic lipase hydrolyzes TG to yield MG, FFA and glycerol • Bile required

25. Bile Synthesis • Made in liver cells from cholesterol • cholesterol oxidized • chenodeoxycholic acid and cholic acid • conjugated to glycine or taurine • glycocholic acid and taurocholic acid • conjugation of bile acids with amino acids improves its ability to form micelles • cholesterol and PLs secreted into bile • bile acid dependent frx • Water, Lytes and bilirubin secreted in bile

26. Bile Storage • Gallbladder • Concentrates bile by removing 90% of water • Stores bile • Stimulated to release bile by CCK • CCK secreted in response to amino acids and lipids • Bile is secreted into duodenum

27. Function of Bile • Digestion • Bile acids are amphipathic • Decrease surface tension of fat • Permits emulsification of fat • Increases exposure of area of lipids • Allow digestive enzymes (lipase) to get close to fat • Absorption • Micelle Formation

28. Micelles • Bile acid monomers from simple micelles • Hydrophobic centers, hydrophilic periphery • Fatty acids and MAGs enter micelles • Mixed Micelles • Micelles travel to brush border • MAGs and fatty acids diffuse through unstirred water layer and into enterocytes • Bile acids released for reuse

29. Enterohepatic Circulation • > 90% of bile acids secreted in duodenum are reabsorbed into ileum • Enters portal vein for transport via blood back to liver • Reabsorbed bile acids are secreted in bile along with newly made bile acids • New bile mixed with recirculated bile is sent via cystic duct for storage in gallbladder • Pool of bile (2-4 g) may recycle 1-2 times/meal

30. Secondary Bile Acids • Bile acids not reabsorbed in ileum may be deconjugated by bacteria in colon • deconjugated bile acids form secondary bile acids • cholic acid is converted to deoxycholic acid which may be reabsorbed • chenodeoxycholic acid is converted to lithocholic acid which is excreted in feces • ~ 0.5 g of bile salts are lost in feces daily

31. Decreasing Blood Cholesterol • Only route of cholesterol excretion is in feces • By increasing excretion of bile in feces, one can lower blood cholesterol levels • necessitates use of body cholesterol for synthesis of new bile acids • drugs (powdered resins) bind bile and enhance excretion from body • soluble fiber behaves like resins

32. Role of Intestinal Brush Borderin Digestion • CHO Digestion • Isomaltase • 1-6 bonds in oligosaccharides and dextrins • Sucrase • alpha 1-4 bonds in sucrose and maltose • Glucoamylase, glucosidase, maltase • alpha 1-4 bonds in oligosaccharides, maltotriose and maltose • Maltase, Lactase and Sucrase

33. Role of Intestinal Brush Borderin Digestion • Protein Digestion • Aminopeptidases hydrolyze N terminal amino acids from oligopeptides, tripeptides and dipeptides • Tripeptidases • Dipeptidases

34. Absorption • Begins in duodenum • Continues throughout jejunum and ileum • May be accomplished by • simple diffusion • facilitated diffusion • active transport • pinocytosis or endocytosis • paracellular absorption • Mechanism depends on • nutrient solubility; electrical gradient; size

35. Colon • Greater absorption of sodium, chloride and water • Secretion of bicarbonate into colon • neutralize acids produced by colonic anaerobic bacteria via action on CHO • also synthesize vitamin K, biotin and folate • Acids produced in colon include short chain fatty acids • acetate, butyrate, propionate • may be absorbed by colonocyte • Progressive dehydration of unabsorbed materials • 1 L of chyme reduced to < 200 mL of defecated material