Key concepts in Digestion. Indigestion module Overview of digestion or, gut reactions - to food Prof. Barry Campbell Gastroenterology Cellular & Molecular Physiology e-mail: bjcampbl@liv.ac.uk http://pcwww.liv.ac.uk/~bjcampbl
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
SCHEMATIC REPRESENTATION OF MAIN REGIONS OF THE GASTROINTESTINAL TRACT REGION: Oesophagus - Transit FUNCTION: Small intestine Stomach duodenum jejunum ileum - storage, H + /peptic digestion & intrinsic factor - fat, protein, carbohydrate digestion & absorption, Ca 2+ /Fe 2+ - water and electrolyte transport - bile salt & vit B12 transport Large intestine Colon - Storage - water and electrolyte transport rectum & anus - defaecation
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
Schematic: the gut wall
Intrinsic and extrinsic nerves of the digestive tract ABORAL e.g. secretory cell ORAL Submucosal plexus (Meissner s) e.g. Stretch & chemosensitive neurons INTRINSIC NERVES e.g. post-ganglionic nonadrenergic or cholinergic fibres Myenteric plexus (Auerbach s) EXTRINSIC NERVES Visceral afferents Parasympathetic efferents
Function & Dysfunction in the GI tract Physiology Growth/development secretion absorption motility & signalling to CNS surveillance (immuno/metabolic) co-ordination (neurons/hormones) - cancer Pathology - peptic ulcer, cystic fibrosis - malabsorption - irritable bowel, oesophagitis, gastroparesis & non-ulcer dyspepsia - ulcerative colitis, Crohn s disease, Coeliac disease
Regions of the stomach Pyloric sphincter Duodenum lower oesophageal sphincter Fundus Pacemaker zone - peristaltic contractions Antrum muscular pump Corpus acid-secreting
THE GASTRIC MUCOSA CORPUS Major cell types surface epithelial chief (zymogen) parietal enterochromaffinlike (ECL) Functions - mucus, HCO - 3 - pepsinogen - HCl, intrinsic factor - histamine ANTRUM surface epithelial chief (zymogen) G-cells D-cells - mucus, HCO - 3 - pepsinogen - gastrin - somatostatin
Cells of the gastric (corpus) gland Gland lumen Surface epithelial cells - protective role Proliferating cells H + Parietal cells - secrete acid to lumen Enterochromaffin-like cell (ECL) - secrete histamine Chief cells - secrete pepsinogen to lumen
Exocrine cells: Endocrine cells: Secrete into the lumen (secrete internally) Mucus cells chief (zymogen) cells parietal cells G-cells D-cells enterochromaffin -like (ECL) cells
The acid(hcl)-secreting parietal cell resting stimulated
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 H + K + Cl - Tubulovesicular system 1. 2. 3. Apical Carbonic anhydrase * H 2 O + CO 2 H 2 CO 3 Cl - 5. 4. K + 2. HCO 3- + H + Basolateral HCO 3 - Na + K +
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)
THE CONTROL OF ACID SECRETION Gland lumen ECL cell H + Parietal cell Chief cell - - + histamine + + somatostatin GASTRIN Ach D-cell + noradrenaline, CCK, VIP & CGRP
Control of G-cell function Protein/peptides/ amino acids H + + + Stomach (antrum) lumen G-cell D-cell Gastrin releasing peptide (GRP) + - GASTRIN somatostatin circulation Stomach body (corpus): ECL cell/ parietal cell
Acid inhibitory therapy H + K + inhibitors Proton pump reflux oesophagitis heart burn H + /K + ATPase (the proton pump) Parietal cell Omeprazole (Losec/Nexium) Peptic ulcer Histamine H 2 receptor H 2 receptor antagonists Tagamet, Zantac, Pepcid AC
Helicobacter pylori A class 1 biological carcinogen (IARC, 1994) 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
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