Physiologie de la Scrtion Acide GastriqueAndr BADObado@bichat.inserm.fr E-02 Physiologie digestiveCentre de Recherche Biomdicale Bichat Beaujon (CRB3) INSERM U773, Paris

Histo-anatomie de lestomac

Scrtion acide est un processus rgulJuin 1822 Alexis St Martin survit mais avec fistule gastrique ( Dr Beaumont Williams)Scrtion acide est un processus discontinu.Emotions, stress, SNC, SNE, hormones etc

Scrtion Acide Gastrique: Initiation centrale

Scrtion Acide Gastrique

Golgi en 1893 postule: La scrtion acide gastrique provient des canalicules des cellules paritales Claude Bernard postule lexistence dun prcurseur de la production dacide avec leau comme prcurseur potentiel de la production de H+, OH- Elle est initialement trs concentre : 1/1.000.000 H+Mcanisme capable de fournir cette nergie:ATPase stimule par lion K+ dans les somes de muqueuse de porcATPase transporte le K+ comme contre-ion H+ ATPase H+/K+ATPase appartient une famille des ATPases de type P (Na+/K+; Ca++)

Scrtion est initialement trs concentre : 1/1.000.000 H+

ATPase H+,K+ gastrique ou pompe protonsDcouverte en 1973 dune ATPase stimule par K+ dans somes de muqueuse gastriqueATPase caractristique de la cellule paritale pouvant transporter H+ en utilisant K+ contre-ionFamille des P-ATPases dont le fonctionnement repose sur un mcanisme de phosphorylationdeux sous-units associes: Gene localis sur chr 19 Gene localis chr 13

ATPase H+,K+ sur la membrane gastriqueLumiregastriquCytosol de la Cellule paritaleIPPATP

Stimulation of Gastric Acid Secretion

Stimulation of Gastric Acid Secretion

Endoscopic photograph of an NSAID-induced gastric ulcer - 1

Scrtion est initialement trs concentre : 1/1.000.000 H+

Stratgie dinhibition de laciditPrix Nobel 1974

Activation de lOMEPRAZOLE

Distribution tissulaire de lOMEPRAZOLE1 mm16 h(B.Wallmark)

Adhrence

Rle de llot cag et de la protine CagA(daprs Covacci et Rappuoli, 2000)Cellule pithliale gastriqueSystme de scrtion type IVCagACagAPPolymrisation de lactinenoyau?H. pyloriInduction IL-8rarrangements du cytosqueletteProtines cellulairesP

Helicobacter Pylori et Muqueuse Antrale Humaine

Prix Nobel de Mdecine 2005 Barry J. Marshall et J. Robin Warren

Physiologie de la Scrtion Acide GastriqueAndr BADObado@bichat.inserm.fr E-02 Physiologie digestiveCentre de Recherche Biomdicale Bichat Beaujon (CRB3) INSERM U773, Paris

Cholcystokinine et Scrtine : deux hormones cls de la digestion

Figure 1-8. Stimulation of acid secretion. The H,K,ATPase is the enzyme responsible for elaboration of hydrochloric acid. It is a member of the P-type ATPase ion-motive ATPase family. It exchanges H for K, the K being supplied to the luminal surface of the pump as a function of activation of the parietal cell. Phosphorylation of the pump is part of the enzyme cycle, with luminal K stimulating the dephosphorylation of the protein. The gastric-acid pump is present in smooth-surfaced tubules (tubulovesicles) in the resting cell, whereas it is present in microvilli lining the secretory canaliculus in the acid-secreting cell. When isolated from resting cells, the pump membrane does not conduct KCl. When isolated from stimulated cells, a KCl transport pathway is present. Stimulation of the parietal cell alters morphology and activates a KCl transport pathway in the pump membrane. All stimuli therefore converge in terms of activation of the acid pump, the final step of acid secretion. This figure shows a model for stimulation of the parietal cell. Ach-acetylcholine; cAMPcyclic AMP.Figure 1-8. Stimulation of acid secretion. The H,K,ATPase is the enzyme responsible for elaboration of hydrochloric acid. It is a member of the P-type ATPase ion-motive ATPase family. It exchanges H for K, the K being supplied to the luminal surface of the pump as a function of activation of the parietal cell. Phosphorylation of the pump is part of the enzyme cycle, with luminal K stimulating the dephosphorylation of the protein. The gastric-acid pump is present in smooth-surfaced tubules (tubulovesicles) in the resting cell, whereas it is present in microvilli lining the secretory canaliculus in the acid-secreting cell. When isolated from resting cells, the pump membrane does not conduct KCl. When isolated from stimulated cells, a KCl transport pathway is present. Stimulation of the parietal cell alters morphology and activates a KCl transport pathway in the pump membrane. All stimuli therefore converge in terms of activation of the acid pump, the final step of acid secretion. This figure shows a model for stimulation of the parietal cell. Ach-acetylcholine; cAMPcyclic AMP.Figure 7-32. Endoscopic photograph of an NSAID-induced gastric ulcer. NSAIDnonsteroidal anti-inflammatory drugs. Rcemment on a pu confirmer que llot cag code1) Un systme de scrtion de type IV2) Le systme de type IV injecte la protine CagA dans les cellules pithliales gastriques3) CagA est phosphoryle par une kinase cellulaire inconnue4) La protine CagA phosphoryle entrane la phosphorylation/dphosphorylation des protines cellulaires 5) Il suivent la polymrisation de lactine et des rarrangements du cytosquelette (formation des pidestaux)6) Le systme IV injecte probablement une molcule de nature inconnue (?) qui induit la scrtion dinterleukine 8 entranant linflammation de la muqueuse gastrique

Figure 2-8. Cholecystokinin (CCK) and secretin are of major importance in the regulation of digestive function. Secretin released into the blood binds to secretin receptors on pancreatic ducts and stimulates bicarbonate (HCO3) secretion. Secreted bicarbonate neutralizes gastric acid, and intraluminal pH increases from 1 to 2 in the duodenal bulb to 6 to 7 in the distal duodenum. Release of CCK causes gallbladder contraction directly and through activation of vagal efferents, and stimulates pancreatic enzyme secretion by binding to CCK receptors on pancreatic nerves and acini [11]. The arriving gastric chyme is thus bathed in gallbladder bile with a high bile-acid concentration, and pancreatic secretion with a high bicarbonate concentration and more than 20 different lytic enzymes. Therefore, the actions of CCK and secretin generate optimal conditions for continued macronutrient digestion in the proximal small intestine. AAamino acids; BAbile acids; ENZenzymes; FAfatty acids.

References:[11]. Pandol SJ, Pancreatic physiology. In Gastrointestinal Disease. Edited by Sleisenger MH, Fordtran JS. Philadelphia: WB Saunders; 1993 1585-1600