1 Key concepts in Digestion. Indigestion module Overview of digestion or, gut reactions to food Prof. Barry Campbell Gastroenterology Cellular & Molecular Physiology email: bjcampbl@liv.ac.uk http://pcwww.liv.ac.uk/~bjcampbl 2 DIGESTION The progressive breakdown of food into a form suitable for absorption and the associated transport processes Digestion therefore also includes: The processes of secretion The processes of absorption Movement of the gut contents growth & differentiation The mechanisms protecting the gut from damage or attack, and the mechanisms controlling and integrating all of the above 3 SCHEMATIC REPRESENTATION OF MAIN REGIONS OF THE GASTROINTESTINAL TRACT REGION: FUNCTION: Oesophagus Transit Stomach storage, H /peptic digestion & intrinsic factor Small intestine duodenum jejunum fat, protein, carbohydrate digestion & absorption, Ca 2 /Fe 2 water and electrolyte transport Large intestine ileum Colon rectum & anus bile salt & vit B12 transport Storage water and electrolyte transport defaecation
4 SECRETIONS OF THE GUT Salivary glands synthesis/secretion: amylase, mucus. Water, electrolytes Exocrine pancreas synthesis/secretion: proteases,lipase,amylase. HCO 3, water Liver bile salt synthesis, bile secretion. Gall bladder storage and concentration of bile 5 Schematic: the gut wall 6 Intrinsic and extrinsic nerves of the digestive tract ABORAL e.g. secretory cell ORAL e.g. Stretch & chemosensitive Submucosal plexus (Meissner s) neurons INTRINSIC NERVES e.g. postganglionic nonadrenergic or cholinergic fibres Myenteric plexus (Auerbach s) EXTRINSIC NERVES Visceral afferents Parasympathetic efferents
7 Function & Dysfunction in the GI tract Physiology Growth/development secretion absorption motility & signalling to CNS surveillance (immuno/metabolic) coordination (neurons/hormones) cancer Pathology peptic ulcer, cystic fibrosis malabsorption irritable bowel, oesophagitis, gastroparesis & nonulcer dyspepsia ulcerative colitis, Crohn s disease, Coeliac disease 8 Regions of the stomach Pyloric sphincter Duodenum Antrum muscular pump lower oesophageal sphincter Fundus Corpus acidsecreting Pacemaker zone peristaltic contractions 9 CORPUS THE GASTRIC MUCOSA Major cell types surface epithelial chief (zymogen) parietal enterochromaffinlike (ECL) Functions mucus, HCO 3 pepsinogen HCl, intrinsic factor histamine ANTRUM surface epithelial chief (zymogen) Gcells Dcells mucus, HCO 3 pepsinogen gastrin somatostatin
10 Gland lumen H Cells of the gastric (corpus) gland Surface epithelial cells protective role Proliferating cells Parietal cells secrete acid to lumen Enterochromaffinlike cell (ECL) secrete histamine Chief cells secrete pepsinogen to lumen 11 Exocrine cells: Endocrine cells: Secrete into the lumen (secrete internally) Mucus cells Gcells chief (zymogen) cells parietal cells Dcells enterochromaffin like (ECL) cells 12 The acid(hcl)secreting parietal cell resting stimulated
13 Parietal cell transport processes for HCl secretion 1. Proton pump (H /K ATPase) 2. K channel 3. Cl channel 4. Sodium pump 5. Cl /HCO 3 exchanger Carbonic anhydrase * H 2 O CO 2 H 2 CO 3 HCO 3 H 5. Cl H K Cl Tubulovesicular system 1. 2. 3. 4. K 2. HCO 3 Na K Apical Basolateral 14 PHYSIOLOGICAL CONTROL SYSTEMS IN THE GASTROINTESTINAL TRACT Endocrine Paracrine Neural Intrinsic Gut hormones Local regulators Myenteric & submucosal nerve plexuses Extrinsic Afferent & efferent n. vagal & splanchnic trunks (autonomic nervous system) 15 Gland lumen THE CONTROL OF ACID SECRETION ECL cell H Parietal cell Chief cell histamine somatostatin GASTRIN Ach Dcell noradrenaline, CCK, VIP & CGRP
16 Control of Gcell function Protein/peptides/ amino acids H Stomach (antrum) lumen Gcell Dcell Gastrin releasing peptide (GRP) GASTRIN somatostatin circulation Stomach body (corpus): ECL cell/ parietal cell 17 reflux oesophagitis heart burn Acid inhibitory therapy H /K ATPase (the proton pump) Parietal cell H K inhibitors Proton pump Omeprazole (Losec/Nexium) Tagamet, Zantac, Pepcid AC Peptic ulcer Histamine H 2 receptor H 2 receptor antagonists 18 A class 1 biological carcinogen (IARC, 1994) Helicobacter pylori In antrum, associated with; somatostatin secretion gastrin (hypergastrinaemia) acid secretion duodenal and peptic ulcer disease In antrum and corpus, associated with Gastrin (hypergastrinaemia) acid secretion atrophic gastritis, gastric cancer
19 The Nobel Prize in Physiology or Medicine 2005 "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease" 3 October 2005 Barry J. Marshall J. Robin Warren http://nobelprize.org/medicine/laureates/2005/press.html