gastric acidity: pathophysiology and therapy · gastric acidity: pathophysiologie and therapy 20...

Master Course Gastroenterology Gastric acidity: pathophysiology and therapy

Prof. Dr. med. Radu Tutuian Leitender Arzt Gastroenterologie Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM) Inselspital, Universität Bern e-mail: [email protected]

Gastric acidity: pathophysiologie and therapy 2

Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM)

Topics

• Physiology of gastric acid secretion

• Abnormal gastric acid secretion

• Therapy – acid suppressive therapy



Parietal cell – at rest



Parietal cell – stimulated



Acid secretion by parietal cells



Phases of gastric secretion

Cephalic (30%) Gastric (50-65%) Intestinal (5-20%)



Phases of gastric acid secretion



Cephalic phase • Stimuli:

– Smelling, tasting, chewing and swallowing • Pathways, mediators

– vagus – acetylcholine (Ach), gastrin, gastrin-release peptide (GRP), histamine

• Experiments – Vagotomy – Sham feeding – Pharmacologic stimulation of CNS (insulin, tolbutamide)

– Pharmacologic inhibition of mediators (atropine)



ECL cell

ACh

Gastrin Vagal nerve

Blood

H+

Ca2+ IP3

PLC cAMP

AC

ACh Gastrin Histamine

H+ H+

H+

H+ H+

Active proton pump

Inactive proton pump

G cell GRP



Cephalic phase • Key points

– Self-selected meals produce higher response compared to bland meals

– Vagotomy blocks the efferent pathway of the cephalic phase

– Gastric phase composes 30% of total response to meal

– Direct vagal stimulation of parietal cell is more important than vagal stimulation via G-cells (gastrin)



Gastric phase • Stimuli:

– Antral pH, amino acids / peptides, distension • Pathways, mediators

– Local reflexes, long reflexes – acetylcholine (ACh), gastrin, gastrin-release peptide (GRP), histamine

• Experiments – Stomach distension

• Vagus mediated reflexes • Pyloro-pyloric reflexes • Pyloro-oxyntic reflexes

– Chemical stimulation (pH solutions, solutions of aminoacids and peptides, caffeine, alcohol)



Protein digestion

Peptides Amino acids H+ acetylcholine

gastrin Vago- vagal reflex

GRP

local reflex

ACh Stomach distention

Gastric phase



Intestinal phase • Stimuli:

– Duodenal pH, amino acids / peptides

• Pathways, mediators – Local reflexes – gastrin, enterooxyntin

• Experiments – Intravenous infusion of aminoacids



Absorbed amino acids

Intestinal phase

Intestinal Endocrine

Cell

Entero- oxyntin

Protein Digestion products

H+

Intestinal G Cell Gastrin



Gastric secretion regulation



Inhibition of gastric secretion

• Stimuli – Drop in intragastric pH

• Inhibits gastrin secretion • Stimulates somatostatin secretion

– Duodenal nutrients (decrease gastric secretion and inhibit gastric motility)

• Gastric inhibitory peptide (GIP) • Secretin • Colecystokinin (CCK) • Enterogastrones



Inhibition of gastric acid secretion



Topics






Peptic ulcer disease

Esophagitis Gastric ulcer

Duodenal ulcer



Peptic ulcer disease

• Common causes – H. pylori infection – NSAR / ASA – Stress ulcera (burns, head trauma, ?psychologic)

• Rare causes – Inflamatory bowel disease (IBD) – M. Crohn – Ischemic – Hypersecretory states (Zollinger-Elison syndrome)



Zollinger-Elison syndrom

• Autonomous gastrin secretion – Gastrin >1000 pg/ml

• Confirmation: secretin test

• Location of tumor: – Endosonography –  Octreoscan (somatostatin receptor)



Topics






H2-receptor antagonists

• Introduced in early 1970’ies – cimetidine – Tagamet®

– ranitidine – Zantac®

– nizatidine – Axid®

– famotidine – Pepcid®

• Block H2-receptors on parietal cells • Decrease maximal acid production • Treatment

– Duodenal/gastric ulcers – GERD



Proton pump inhibitors (PPIs)

• Introduced mid 1980’ies – Omeprazole – Antra®

– Lansoprazole - Agopton® – Pantoprazole – Zurcal®, Pantozol® – Rabeprazole - Aciphex® – Esomeprazole – Nexium®

• Block ATP-dependent H+/K+ pump



0

1

2

3

4

5

6

7

08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00 02:00 04:00 06:00

Time

Intra

gast

ric p

H

Baseline Ome 20 Lanso 30 Panto 40 Rabe 20

24-h intragastric pH profile on PPI qd

Nocturnal acid breakthrough between 21:00-22:00



Summary • Gastric acid secretion

– Active process, using ATP – 3 phases: cephalic, gastric, duodenal

• Abnormal gastric acid secretion – Erosions and ulcera – Gastrin producing tumors: Zollinger-Ellison Syndrome

• Acid suppressive therapy – Highly efficient – PPI and/or H2RA

gastric acidity: pathophysiology and therapy · gastric acidity: pathophysiologie and therapy 20...

Documents