Digestive System Part 2: Gastric Secretion PDF

Digestive System Part 2: Gastric secretion Dr Seley Gharanei, Assistant Professor Cell and Tissue Biomedicine [email protected] MB ChB Phase I Block 1 Health, Metabolism and Learning outcomes of part2:  Describe the function and secretion...

Digestive System Part 2: Gastric secretion Dr Seley Gharanei, Assistant Professor Cell and Tissue Biomedicine [email protected] MB ChB Phase I Block 1 Health, Metabolism and Learning outcomes of part2:  Describe the function and secretion of gastric Juice  Identify the mechanisms of gastric acid secretion  Identify the regulation of gastric acid secretion  Identify the phases of gastric acid secretion  Describe how acid secretion is controlled  Outline the classes of drugs used to treat disorders of acid secretion Recap  Gastric Secretion The stomach secretes up to 3 litres of gastric juice per day. The main components are: 1. Hydrochloric acid (HCl) 2. enzymes: pepsinogens, gastric lipase 3. intrinsic factor 4. mucus Gastric juice is secreted from gastric glands of the gastric mucosa. Q1: How is the stomach protected from self-  Acid secretion  The concentration of H+ in the gastric lumen may reach 150mM  Produces a gastric luminal pH of between 1-2  Parietal Cell  Proton Pump (H+K+ ATPase) apical membrane  chloride channel on the apical membrane  Na+K+ ATPase on the basolateral membrane Gastrointestinal Physiology. Costanzo, Linda S., PhD, Physiology, Chapter 8, 339-393. Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All  bicarbonate/chloride exchanger rights reserved. P1 B0 CTB Plasma Membrane and Membrane Transport Catch-up Biology, Chapter 9  Hydrochloric Acid Production 1. CO2 from the blood into the parietal cell. 2. CO2 combines with H2O to form H2CO3 Carbonic acid in presence of CA. 3. H2CO3 dissociates into HCO3- and H +. 4. H + is pumped out into the stomach luman using the H+/K+ ATPase (proton pump) in exchange for a K+ 5. HCO3- leaves the cell via the HCO3-/ Cl- into the blood in exchange of Cl- 6. The Cl- ions move to the lumen by facilitated diffusion The McGraw Hill companies 7. H+ and Cl- form HCl in gastric lumen  Regulation of Gastric Secretion Parietal cells bear receptors for three stimulators of acid secretion. – Acetylcholine (muscarinic type receptor) – Gastrin – Histamine (H2 type receptor) Q2: What is chyme?  Regulation of Gastric Secretion  Gastric secretion is regulated by neural and hormonal mechanisms. Stimulatory and inhibitory events occur in 3 phases.  Cephalic, Gastric, and Intestinal. Cephalic (reflex) phase: prior to food entry Gastric phase: once food enters the stomach Intestinal phase: as partially digested food enters the duodenum  Cephalic (reflex) phase: prior to food entry Cephalic phase  The taste or smell of food, or even thoughts of food stimulate the medulla oblongata  leading to parasympathetic action potentials by the vagus nerves to the stomach.  Resulting in HCL and pepsin secretion by parietal and chief cells and stimulate the secretion of the hormone gastrin. The McGraw Hill companies  Gastrin is carried through the circulation back to the stomach where it stimulates further secretion of HCl and pepsin. Q3: What cells produce gastrin? Gastric phase Gastric phase: once food enters the stomach  Distention of the stomach activates a parasympathetic reflex.  Action potentials are carried by the vagus nerves to the medulla oblongata.  Medulla oblongata stimulates further secretions to the stomach.  Distention also stimulates local The McGraw Hill companies reflexes that amplify stomach secretions.  Intestinal phase  As partially digested food enters the duodenum.  Chyme in the duodenum with a pH less than 2 or containing lipids inhibits gastric secretions  By three mechanisms 1. Sensory input to the medulla from the duodenum inhibits the motor input from the medulla to the stomach. Stops secretion of pepsin and HCl. The McGraw Hill companies 2. Local reflexes inhibit gastric secretion 3. Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum inhibit gastric secretions in the stomach  Physiological Regulation of Gastric Acid Secretion Stimulated by: Inhibited by: gastrin somatostatin acetylcholine prostaglandins E2 and histamine I2 intestinal hormones Q4: What cells produce histamine?  Stimulation of Gastric Acid Secretion Cholinergic ECL nerve Muscarinic cell Gastrin Blood vessel Receptor receptor + + ACh Histamine Gastrin + + + Muscarinic H2-receptor Gastrin Receptor receptor + Parietal cell ACh = acetylcholine H+ P proton pump Q5: What is the name of this H+ Image by Dr A proton pump and how does it Green  Physiological Regulation of Gastric Acid Secretion Stimulated by: Inhibited by: gastrin somatostatin acetylcholine prostaglandins E2 and histamine I2 intestinal hormones  Prostaglandins  prostaglandins (E2 and I2) A group of lipids (eicosanoids) derived from arachidonic acid.  Made at sites of tissue damage or infection.  Can be made in nearly all the organs in the body.  Involved in the healing process.  Control processes such as inflammation and bloodflow.  First step of prostaglandin synthesis is catalysed by a cyclooxygenase enzyme. http://www.yourhormones.info/hormones/prostaglan For more information dins.aspx on prostaglandins: CTB theme lectures on inflammation  Inhibition of Gastric Acid Secretion SSR - Somatostatin Cholinergic ECL nerve Muscarinic cell Gastrin Blood vessel Receptor receptor + + ACh Histamine Gastrin + + + Muscarinic H2-Receptor Gastrin - Receptor receptor PGE2 + SSR - Somatostatin PGE2 Receptor - Parietal cell PGE2 = H+ SSR = prostaglandin somatostat E2 AA = AA P proton pump in receptor Q6: What cells arachidonic produce acid H+ Image by Dr A Green  Drugs used to Treat Disorders of Acid Secretion Antacids and alginates: Antacids act by buffering gastric acid, thereby raising the gastric pH e.g. Calcium carbonate and magnesium carbonate (Rennie®) Alginates are anionic polysaccharides that form a viscous gel up on binding to water. Antacids + alginates (Gaviscon®) acid reflux Histamine H2-receptor antagonists: e.g. famotidine Decrease basal and stimulated acid secretion Proton pump inhibitors: Irreversibly inhibit the H+/K+-ATPase pump, the terminal step in the acid secretory pathway e.g. Omeprazole and Lansoprazole P1 B1 PPT Drugs to treat disorders of acid secretion  SSR - Somatostatin Cholinergic ECL nerve Muscarinic cell Gastrin Blood vessel Receptor Receptor + + ACh Histamine Gastrin H2-antagonists + - + + Muscarinic H2-Receptor Gastrin - Receptor Receptor + SSR - Somatostatin PGE2 PGE2-R - Parietal cell H+ Image by Dr A AA P Green proton pump - P1 B1 PPT Drugs to Proton pump inhibitors H + treat disorders of acid secretion  Summary  Gastric secretion  Mechanism of HCl production  Phases of gastric acid secretion  Regulation of acid secretion  The drugs to treat the disorders of acid secretion  Resources Clinical Key Student (https://www.clinicalkey.com/student): Physiology. Seventh Edition. Costanzo, L. S. 2022. Elsevier. Costanzo, Linda S., PhD, Physiology, Chapter 8, 339-393. Medical Sciences, Naish and Syndercombe Court, Chapter 15: The Alimentary System https://0-www-clinicalkey-com.pugwash.lib.warwick.ac.uk/student/content/book/3-s2.0- B9780702073373000158 Engevik AC, Kaji I, Goldenring JR. 2020. The Physiology of the Gastric Parietal Cell. Physiol Rev. Apr 1;100(2):573-602. PMID: 31670611; Schubert ML. 2017. Physiologic, pathophysiologic, and pharmacologic regulation of gastric acid secretion. Curr Opin Gastroenterol. Nov;33(6):430-438. PMID: 28787289. Waldum HL, Hauso Ø, Fossmark R. 2014. The regulation of gastric acid secretion - clinical perspectives. Acta Physiol (Oxf). Feb;210(2):239-56. PMID: 24279703. Video Gastric Acid Physiology  Answers to the questions Q1: How is the stomach protected from self-digestion The stomach is protected from self-digestion by the mucosal barrier. This barrier has several components. First, the stomach wall is covered by a thick coating of bicarbonate-rich mucus. This mucus forms a physical barrier, and its bicarbonate ions neutralize acid. Second, the epithelial cells of the stomach’s mucosa meet at tight junctions, which block gastric juice from penetrating the underlying tissue layers. Q2: what is chyme? Chyme is thick semi-liquid mass mixed with gastric secretions and enzymes. Q3: What cells produce gastrin? Gastrin is produced by G cells in the antrum of the stomach. Q4: What cells produce histamine? Histamine is produced by ECL cells in the gastric gland. Q5: What is the name of this proton pump and how does it function? This proton pump is called H+/K+ ATPase, that carries out active transport that uses energy from ATP hydrolysis. Q6: What cells produce Somatostatin? Somatostatin is produced by the D cells in gastric gland.