1. Regulation of Gastric juice secretion M.I.Glad Mohesh, Assistant Professor, Department of Physiology, Shri Sathya Sai Medical College & RI, Ammapettai, Kancheepuram District, Tamilnadu state, India. gladmohesh@gmail.com

2. Specific learning objectives, At the end of this class you will be able to, 1.Describe how gastric juice secretion is regulated during digestive phase in stomach. 2.Describe the factors that stimulate secretion of gastric juice in stomach. 3.Describe the factors that inhibit secretion of gastric juice in stomach. 4.Explain the physiological basis of the action of Cimetidine.

3. Canis lupus familiaris Ivan Petrovich Pavlov (1849-1936) Russian Physiologist Nobel Prize for Physiology or Medicine in 1904

4. Secretions in the stomach

5. Gastric juice secretion is, *Accurately synchronized with the need for it. *Secretion persists since, food is about to enter the stomach and continues till food is present in the stomach. Digestive phase x Inter-Digestive phase. Secretion is regulated by, Neurocrine /endocrine/ paracrine methods.

6. Agents that stimulate parietal cells. 1.Acetylcholine. Post ganglionic parasympathetic fibres (vagus) Acetylcholine Parietal cellsG cells(gastrin) ECL cells (HCL) (histamine) Atropine-blocker.

8. 2.Gastrin : G cells in Antral mucosa Expt : gastric antral removal -- gastrin secretion. Vagal stimulation – Ach - gastrin Inhibited by – somatostatin Gastrin + Ach – more powerful ( potentiation) (A+B+C) > (A)+(B)+(C)

9. 3.Histamine: *very potent stimulator of gastric acid secretion (mast cells - ECL cells (enterochromaffin cells) Histamine H 2 receptors parietal cells Eg) Cimetidine –H 2 receptor antagonist – gastric secretions.

11. Agents that inhibit parietal cells 1.Acid Secreted acid--inhibits release of gastrin from G cells Negative feedback mechanism (prevents damage of gastric mucosa) Acidic chyme –enters duodenum-gastric secretion is further inhibited. (intramural neural reflex operating via pH sensitive duodenal receptors).

12. 2.Somatostatin D cells – inhibits {G cells + ECL cells} Stimulus-gastric acidity Negative feedback mechanism Others involved- gastrin, CCK-PZ, secretin and vasoactive intestinal peptide{VIP},prostaglandins Stimulus-entry of acid & food into the duodenum. 3.Food *Carbohydrates, lipids & high osmolar contents of the chyme entering the duodenum. GIP & CCK-PZ Inhibits gastric juice secretion

14. Substances that alter HCl secretion

15. Digestive phase regulation can be explained in terms of 3 arbitrary phases, 1.Cephalic phase; Sight/Smell or even thought of food—stomach starts secreting the gastric juice. Stimulus 1.Unconditioned reflex : food in mouth 2.Conditoned reflex : smell/ sight/ thought or awareness of food in the mouth. (psychic or appetite juice) 30% of total gastric juice secretion secreted.

16. Experimental evidence: 1.Sham feeding : Animal feels that it is eating whereas nothing really reaches its stomach. Oesophageal fistula Mediated by : Vagus nerve Proof: Vagotomised animal does not show any secretion. Vagus – Ach + GRP released on G cell – gastrin secretion- gastric juice secretion.

17. http://physiologyonline.physiology.org/content/19/6/326 Pavlov’s esophagostomy and sham-feeding experiments

20. 2.Gastric phase: Food is in the stomach *Secretion rate is increased. *60% of the gastric juice secretion during the digestive phase of stomach happens in this phase. Stimuli: 1.distension of the stomach 2.chemicals released due to distension 3.chemicals present in the food.

21. Expt: Infusing saline directly into the stomach. Proof: 20-50% of the peak acid output(PAO). Via Vagus nerve afferent convey the information to CNS Vagus efferent Motor nucleus of vagus gastric secretion Expt :Role of vagus nerve Sectioning of one of the two vagi leaving the other intact + stimulation of the central end of vagus - gastric secretion

22. Stretching of the gastric mucosa by the presence of food in stomach leads to secretion of acid and enzyme. 1.Long vagovagal reflex action –Ach secretion by vagus. 2.Local reflexes in the intrinsic neural plexus. stretch of mucosa causes activation of Meissner’s plexus which stimulates secretions. local reflex Stretch vagovagal reflex.

23. 2.Chemical stimuli Expt : 1) Watery meal infusion 60-70% of peak acid output 2) equivalent amount of saline Most important stimuli, a)Proteins b) partially digested proteins and aminoacids. Humoural mechanism Gastrin + Acetylcholine + Histamine

24. a)Gastrin G cells in the antrum stimuli – a) distension of the gastric mucosa by food in the stomach. b) chemicals released on digestion, 1) peptones + aminoacids Released gastrin increases gastric juice secretion By some hypothetical pathways. 1)incr.HCL + pepsin secretion 2)Incr. Histamine secretion from ECL cells.

25. b) Acetylcholine stimuli: distension of gastric mucosa Ach release from vagus—acts via M1 receptors – can be blocked by atropine. Ach – release of Histamine from ECL cells. c) Histamine ECL (mast cells) in gastric mucosa. distension of gastric mucosa. Ach & gastrin stimulates its secretion acts via H 2 receptors – Cimetidine and Ranitidine.

26. Intestinal Phase Presence of food in intestine-mechanical & chemical stimuli. Mechanism is unclear-how it regulates gastric secretion. presence of chyme in duodenum- Enterooxyntin contribution is very minimal Actually this phase has a major role in inhibition of gastric juice secretion. a) Acid / fat and hyper osmolar substances enters duodenum.

27. Duodenum and jejunum secretes, a) secretin, b) bulbogastrone, c)CCK PZ, d)GIP Inhibits gastrin release –gastric juice secretion. b) Enterogastric reflex. food distends duodenum- local plexus is activated- inhibits through sympathetic fibres-secretion & motility of the stomach is inhibited. Stimuli : Fat Cerebral cortex, hypothalamus and limbic system influences gastric secretion.

28. INTER DIGESTIVE Phase.(Resting Phase) No food in stomach – minimal secretion of Gastric juice Represents basal gastric secretion.

29. References 1.Textbook of Medical Physiology,11 th edition, Guyton & Hall, Arthur C Guyton, John E Hall. 2.Understanding Medical Physiology,4 th edition, Bijlani, Manjunatha.S. 3.Fundamentals of Medical Physiology,4 th edition, L Prakasam Reddy.