Control mechanisms how the gut keeps in touch

Control mechanisms. . . how the gut keeps in touch. . .

PHYSIOLOGICAL CONTROL SYSTEMS IN THE GASTROINTESTINAL TRACT • Endocrine • Paracrine • Neural - Gut hormones - Local regulators • Intrinsic - Myenteric & submucosal nerve plexuses - Afferent & efferent n. • Extrinsic vagal & splanchnic trunks (autonomic nervous system)

Regions of the stomach lower oesophageal sphincter Pyloric sphincter Duodenum Fundus “Pacemaker zone” - peristaltic contractions Corpus “acid-secreting” Antrum “muscular pump”

THE GASTRIC MUCOSA Major cell types Functions CORPUS • • surface epithelial chief (zymogen) parietal enterochromaffin-like (ECL) - 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 • G-cells • chief (zymogen) cells • D-cells • parietal 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 Apical 1. * H 2 CO 3 2. 3. Tubulovesicular system Carbonic anhydrase H 2 O + CO 2 K+ Cl- H+ Cl- 5. 4. 2. K+ HCO 3 - + H+ Basolateral HCO 3 - Na+ K+

THE CONTROL OF ACID SECRETION ECL cell + Gland lumen histamine H+ Parietal cell GASTRIN Ach + + - Chief cell D-cell somatostatin noradrenaline, + CCK, VIP & CGRP

Control of G-cell function Protein/peptides/ amino acids + G-cell Stomach (antrum) lumen H+ + D-cell Gastrin releasing peptide (GRP) + GASTRIN somatostatin Stomach body (corpus): circulation ECL cell/ parietal cell

Acid inhibitory therapy H+ H+/K+ ATPase (the proton pump) reflux oesophagitis “heart burn” K+ Proton pump inhibitors Omeprazole (Losec/Nexium) Parietal cell Tagamet, Zantac, Pepcid AC H 2 receptor Peptic ulcer Histamine H 2 receptor antagonists

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