Acid secretion

General surgery ppt - PG

1. Physiology of Gastric acid secretion And Its role in acid peptic disease

2. Stomach Main Functions Storage Preparing the chyme for digestion in the small intestine. Initiation for digestion. Absorption of water and lipid-soluble substances.

3. Anatomy of the Stomach

4. 18-Apr-17 gastric secretion 4 Gastric Secretion Gastric juice HCl Electrolytes (Na,K,Mg,HPO4,SO4) Mucus, Intrinsic factor Bicarbonate Pepsins,Lipases Ghrelin

5. 18-Apr-17 gastric secretion 5 Gastric Gland

6. 18-Apr-17 gastric secretion 6 Gastric Gland Surface epithelial cells (mucus cells) Alkaline mucus. Mucous neck cells ( neck chief cells ) Soluble mucus Pepsinogen Parietal cells ( oxyntic cells) Hydrochloric acid Intrinsic factor Chief [peptic] cells ( zymogen cells) Pepsinogen Enterochromaffin cells serotonin Histamine Specialized cells Vasoactive intestinal peptide (VIP) Substance P Glucagon

7. 18-Apr-17 gastric secretion 7 Parietal cell Produce a solution containing Approx. 160 mmol of HCl /l; pH 0.8 (H+ conc. = 3 to 4 million time that in plasma) Energy cost = 1500 calories/l of HCl Intrinsic factor ( vit . B12 - R factor binding macromolecule) Also produce Gastric lipase Gastric amylase Gelatinase

8. 18-Apr-17 gastric secretion 8 Chief cells Produce small volume of electrolyte similar to ECF. Contain Pepsinogen . Some individuals secrete ABO blood group antigen in their gastric juice.

9. Ghrelin :from specialized cells that line the stomach and the pancreas. Stomach, cells that secrete ghrelin include the   P/D1 cells  in the fundus  . ‘Hunger hormone' because it stimulates appetite, increases food intake and promotes fat storage. When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops. Acts on hypothalamic  brain cells both to increase: Hunger Gastric acid secretion Gastrointestinal motility to prepare the body for food intake.

10. 18-Apr-17 gastric secretion 10 Pyloric Gland Similar structure like the oxyntic gland. Contain few peptic (chief) cells No parietal cells Contain mucus cells Mucus and electrolytes Have G-cells G cells produce Gastrin Peptic cells produce pepsinogen G-cells Mucous neck cell Gastric lumen Columnar mucus cells Peptic cell From Physiology Book by H.T. Sherrief

11. Phases of Acid Secretion Cephalic phase(30%): Smelling, Chewing and swallowing Stimulates parietal G-Cells GRP Gastric phase (60%): Gastric distention Proteins Intestinal phase (10%): Digested proteins

12. Gastric secretion : arise from glands in the wall of the stomach ,drain into its lumen . Surface cells – secrets primarily mucus & bicarbonate. Mucous & HCO3 protects stomach mucosa “Most characteristic secretion from glands in the fundus or body of stomach.” Two distinct cells : Parietal cells : HCL ,Intrinsic factor Chief cells: Pepsinogen + gastric lipase HCL – Sterilize meal ,hydrolysis of dietary macromolecule. Intrinsic factor : absorption of B12 Pepsinogen precursor of pepsin – initiates protein digestion Lipase – fat digestion Physiology

13. Three primary stimulus: Gastrin – hormone released G cells in the antrum . Gastrin is secreted in response to : Gastrin releasing peptide( bombesin ) – neurotransmitter released from enteric nerve endings. Presence of oligopeptides in gastric lumen. Gastrin is carried by bloodstream to fundic glands  binds to receptors on parietal & enterochromaffin like cells.  causes release of histamine. Histamine is also a trigger for parietal cells via binding to H2 receptors. Parietal & chief cells also stimulated by acetlycholine ---released from nerve endings in fundus .

14. Cephalic Phase of gastric secretion Mainly by vagal input  originates from brain (dorsal vagal complex)  causes the release of GRP & acetylcholline  initiates secretory function. Physical appearance of meal in stomach  activates stretch receptors  causes vago vagal & local reflex  amplify secretion. Prolonged food in stomach  serve as feed back inhibitory signal for secretion. It also release somatostatin  inhibits both G & ECL cells.

15. Gastric parietal cells—secreting concentrated acid Cells packed with mitochodria  supply energy  function H+K ATPase  drives H+ ion out against concentration gradient. H+ & CL- concentration increases ----HCL HCL Secretion Secreted by parietal cells Fundus Body

16. HCL Secretion Mechanism of HCl production: H/K ATPase Inhibited by: omeprazole [ HCl ] drives water into gastric content to maintain iso-osmolality During gastric acid secretion: amount of HCO 3 - in blood = amount of HCl being secreted Alkaline tide

17. Neural & Hormonal Control of Gastric Secretion Vagus nerve (neural effector ) Gastrin (hormonal effector ) Enterochromaffin -like cells  Histamine H2 receptor (parietal cells)  acid secretion Cimetidine (H 2 receptor blocker)

18. Inhibition of Acid Secretion Inhibitory hormones ( Enterogastrones ): Secretin (S-cells) in duodenum Somatostatin (D-cells) in antrum Glucose-dependent insulinotropic peptide (GIP) in duodenum.

19. Acid Peptic Disease Acid peptic diseases  :due to overlapping pathogenic mechanisms leading to either- excessive  acid  secretion diminished mucosal defense.  Mucosal lesion of Stomach (gastric ulcer) Duodenum (duodenal ulcer) Gastric acid & pepsin Play major pathogenic role Helicobacter pylori infection Play a major role as well Stress Ingestion of drugs: Aspirin, NSAIDS Gastrin producing tumours: Zollinger – Ellison syndrome

20. 18-Apr-17 gastric secretion 23 Thought to result from imbalance between Aggressive factors Protective factors Aggressive factors Protective factors Acid & pepsin H . pylori Irritation aspirin, NSAIDS Gastric mucus Bicarbonate Prostaglandins blood supply

21. 18-Apr-17 gastric secretion 24 Helicobacter Pylori Infection occurs in about 95% of patients with duodenal ulcers 75% to 85% of patients with gastric ulcers The infection is also found in: 25% of people without peptic ulcers Thus other factors Must be present to trigger ulcer formation.

22. 18-Apr-17 gastric secretion 25 Thrives in highly acid environment Produces urease enzyme For ammonia formation Neutralize the acid Produces a number of toxins Cause inflammation & damage to epithelium Produces proteases & phospholipases Degrade the glyco -lipid complex of mucus gel  The thickness of mucus gel Stimulate chronic gastritis associated with Depletion of somatostatin from d-cells Gastrin release from G-cells Stimulate acid production

23. 18-Apr-17 gastric secretion 26 Other Pathogenic Factors Some patients have True G cell hyperplasia G cell hyperfunction or Increased sensitivity of parietal cells to stimulation Increased capacity to secrete acid and pepsin Some patients secrete normal amount of acid. Secrete abnormal mucus Failure of protective barrier

24. 18-Apr-17 gastric secretion 27 Gastric emptying Accelerated More acid is being delivered to duodenal bulb than in normal. Stress Emotions and anger increase GASTRIC ACID and PEPSIN secretion Smoking. Zollinger – Ellison syndrome Excessive production of Gastrin from islet cell tumor ( Gastrinoma ).

25. 18-Apr-17 gastric secretion 28 Basis of Treatment Antacids Majority of drugs based on Combinations with Calcium, aluminium , magnesium salts Side effects Calcium compound Cause constipation Magnesium compounds Cause diarrhoea Aluminium compounds Block absorption of other drugs Digoxin , tetracycline

26. 18-Apr-17 gastric secretion 29 Proton pump “H + /K + ATPase ” inhibitor Irreversible inhibition of “H + /K + ATPase ” pump in the parietal cell  Gastric acid production Most powerful inhibitor of  Gastric acid secretion. Histamine – H 2 receptor antagonists Competitive inhibition of histamine at H 2 receptor on parietal cell Cimetidine , ranitidine

27. 18-Apr-17 gastric secretion 30 Helicobacter pylori eradication Successfully prevents relapses Treatment regiment include Proton pump inhibitor Taken together with 2 antibiotics

28. T riple therapy for the destruction HP Pantoprazole 40 mg in the morning and 40 mg at night + A moxicillin 500 mg 4 times a day + Clarithromycin 250 mg 2timesaday. Course : 7 days, E radication of HP 95%. Pantoprazole 40 mg in the morning and 40 mg at night + Clarithromycin 250 mg 2 times daily + M etronidazole 400 mg 2 times a day . Course : 7 days, E radication of HP 95-97%. Omeprazole 20 mg 2 times a day + Clarithromycin 250 mg 2 times a day + Metronidazole 400 mg 2 times a day.

29. Thank you!!!!