Our gut reactions to food or, gut reactions - to food
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1 Key concepts in Digestion. Our gut reactions to food or, gut reactions to food Prof. Barry Campbell Cellular & Molecular Physiology
2 Swallowing (deglutition) Phase I ORAL VOLUNTARY Phase II PHARYNGEAL INVOLUNTARY Phase III OESOPHAGEAL INVOLUNTARY Food bolus formed by mastication Tongue moves up and backwards Pharynx Soft palate rises Epiglottis closes Pharynx contracts UOS relaxes Pharynx UOS UOS contracts Bolus moved by peristalsis LOS relaxes Tactile/distention receptors BRAIN STEM UOS relaxes Oesophageal body Striated muscle Smooth muscle LOS
3 Entry of food into the stomach LOS = lower oesophageal sphincter Ach = acetylcholine VIP = vasoactive intestinal polypeptide NO = nitric oxide Vagal afferent fibre BRAIN STEM Crural diaphragm Ach Phrenic nerve VIF (VIP/NO) VEF (Ach) LOS pressure LOS Vagal efferent fibres
4 Regions of the stomach Pyloric sphincter Duodenum lower oesophageal sphincter Fundus Pacemaker zone peristaltic contractions Antrum muscular pump Corpus acidsecreting = retropulsion
5 How do we accommodate a large meal? Receptive relaxation of the body of the stomach (corpus) Vagal afferent fibre Satiety effects nodose ganglion + BRAIN STEM Vagal efferent fibres DISTENSION Ach VIP/NO Ach Ach Relaxation of corpus to accommodate food Ach = acetylcholine VIP = vasoactive intestinal polypeptide NO = nitric oxide
6 When have we had enough? CCK = cholecystokinin Lowers appetite & food intake Vagal afferent fibre Satiety effects nodose ganglion CCK receptors Satiety effects + BRAIN STEM Vagal efferent fibres CCK Ach Ach Relaxation of corpus VIP/NO Ach Fatty meals delay gastric emptying by releasing CCK from the duodenum
7 Gastric emptying Liquids empty more rapidly than solids Also. Fatrich, hypertonic and acidic meals, and meals with high viscosity all delay gastric emptying Rate of emptying is controlled by duodenum
8 THE GASTRIC MUCOSA Major cell types Functions FUNDUS surface epithelial mucus, HCO 3 CORPUS surface epithelial chief (zymogen) parietal enterochromaffinlike (ECL) gastric lipase mucus, HCO 3 pepsinogen HCl, intrinsic factor histamine ANTRUM surface epithelial chief (zymogen) Gcells Dcells mucus, HCO 3 pepsinogen gastrin somatostatin
9 Cells of the gastric (corpus) gland Gland lumen Surface epithelial cells protective role Proliferating cells H + Parietal cells secrete acid to lumen Enterochromaffinlike cell (ECL) secrete histamine Chief cells secrete pepsinogen to lumen
10 The acid(hcl)secreting parietal cell resting stimulated
11 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 Apical Carbonic anhydrase * H 2 O + CO 2 H 2 CO 3 Cl K + 2. HCO 3 + H + Basolateral HCO 3 Na + K +
12 Gastric acid output Classical Phases of Gastric Acid Secretion Cephalic Thought, sight, smell, taste Ach, GRP (NEURAL) Ach histamine GRP Gastrin (PARACRINE) (ENDOCRINE) Time after feeding (hours)
13 Gastric acid output Classical Phases of Gastric Acid Secretion Cephalic Gastric Distension/Food in stomach Ach (NEURAL) Gastrin (ENDOCRINE) Ach histamine (PARACRINE) Gastrin histamine (PARACRINE) Time after feeding (hours)
14 Gastric acid output Classical Phases of Gastric Acid Secretion Cephalic Distension/Food in duodenum Ach (NEURAL) Gastrin (from duodenal G cells) (ENDOCRINE) Ach histamine (PARACRINE) Gastrin histamine (PARACRINE) Gastric Intestinal Time after feeding (hours)
15 Gastric acid output Classical Phases of Gastric Acid Secretion Cephalic Gastric Intestinal Time after feeding (hours)
16 THE CONTROL OF ACID SECRETION Gland lumen ECL cell H + Parietal cell Chief cell + histamine + + somatostatin GASTRIN Ach Stomach body (corpus): Dcell + noradrenaline, CCK, VIP & CGRP
17 Control of antral 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
18 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
19 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
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