Introduction J shaped sac Lies between esophagus and small intestine. Three parts Fundus , 2. Body, 3. Antrum Physiological Oral portion: first 2/3 rd of body Caudal: remainder of body + Antrum
Fundus – part lies above the esophageal opening. Body – middle part Smooth muscle layer – thin Antrum – lower part Heavy musculature Terminal part - pyloric sphincter – between stomach and duodenum
Functions of stomach Storage of food. Protein digestion initiated Production of HCl Chyme food mixed with gastric secretion, semifluid mixture
Gastric filling Volume of empty stomach – 50ml During meal – 1000-1500mL Little change in tension and little rise in intra gastric pressure Interior of stomach – fold – rugae Receptive relaxation mediated via Vagus
Gastric Storage Storage – in the body of the stomach Muscular layers – thin – fundus and body Peristaltic waves are weak From the body – Antrum Muscles are stronger Peristaltic contraction – stronger Mixing
Gastric Mixing Antral Mixing Chyme Strong peristaltic wave- Chyme – pyloric sphincter. Almost closed Each peristaltic wave– few mL of antral contents into duodenum
Gastric Emptying Antral peristalsis – driving force for gastric emptying. Influenced by signals Stomach Duodenum. Gastric and duodenal factors Increases excitability of SM Greater excitability – greater BER – more the peristaltic contraction
Gastric factors Amount of Chyme in stomach Distention – stretch on SM Intrinsic plexus Via Vagus nerve Gastrin – hormone Fluidity of the chyme Contents must be in fluid form to be evacuated.
Duodenal factors Largely controlled by duodenal factors Duodenum need to be ready Duodenal factors influencing Fat Acid Hyper tonicity Distention Decreases gastric emptying via neural/ hormonal response
Neural response is via Intrinsic nerve plexus Extrinsic nerve plexus Collectively called the Enterogastric reflex Activated By irritants and acid in chyme By break down products of protein digestion With in 30 sec
Hormonal response Hormones released from duodenal mucosa Collectively called enetrogastrones Inhibit antral contractions Reduce gastric emptying Secretin / CCK
Functions Prevent excessive chyme from entering the duodenum Reduces intestinal cell erosion by limiting inflow of gastric acid Increase duration of digestion of chyme
Vomiting/Emesis Forceful expulsion of gastric contents through the mouth Stomach, esophagus and associated sphincters – relaxed Force of expulsion Contraction of Diaphragm Abdominal muscles Vomiting center – medulla- coordinates
Begins with deep inspiration, closure of glottis Diaphragm contracts – descends Abdominal muscles – contracts Increases intra abdominal pressure Stomach – squeezed Gastric contents forced upwards via the relaxed sphincters and esophagus
Preceded by Sweating Profuse salivation Increase in HR Nausea Activation of ANS
Causes of Vomiting Gagging Irritation of the stomach/ duodenum Elevated intracranial pressure Rotation or acceleration of the head causing dizziness. Drugs – Emetics Acts on upper GI tract Stimulation Chemoreceptors – next to vomiting center Chemoreceptor trigger zone- area Postrema
Gastric Digestive Juice 2L/day Gastric Mucosal cells secrete Divided into two area Oxyntic mucosa- funds and body Pyloric gland area - antral Luminal surface – infoldings of the mucosa –Gastric pits – base – gastric glands
These invaginations are line by Exocrine cells Endocrine cells Paracrine cells
In the Oxyntic mucosa– 3 types of exocrine cells are found lining pits and glands Mucous cells –entrance of glands Thin watery Mucous Chief cells and parietal cells – lines deeper parts of the glands. Chief cells – pepsinogen Parietal cells – HCl/ Intrinsic factor Collective form the gastric digestive juice
Pyloric glands secrete Pepsinogen Mucous No acid is secreted
HYDROCHLORIC ACID SECRETION Parietal/Oxyntic cells secrete HCl Functions Activates the enzyme pepsinogen – pepsin Provides acidic medium optimum for pepsin action Breakdown of connective tissue and muscle fibers – breakdown of food. Denaturation of proteins Kills micro organisms
Mechanism Parietal cell HCl – isotonic solution Cl - : 150 mEq and H + :150 mEq/ L Parietal cells Apical membrane – gastric lumen Basolateral membrane – Interstitial fluid H + is actively transported against con gradient Cl - is transported by secondary active transport
In the parietal cell H 2 0 H + + OH - H + is secreted into the lumen by H + - K + ATPase. Pumps K + into the cell from lumen K+ diffuses back through leak channels
Co 2 enters the cell from plasma Combines with H 2 O forming Carbonic acid Co 2 + H 2 O H 2 Co 3 Catalyzed by carbonic anhydrase Carbonic acid splits to form H + and HCO 3 - H+ replaces the one which are secreted. H + + OH - H 2 O
HCO 3 - is moved into plasma via Cl - - HCO 3 - exchanger Increases Cl - concentration inside the parietal cells Concentration gradient and electrochemical gradient – Cl - diffuses out into the lumen
Acid secretion is stimulated by Histamine via H 2 receptor Acetylcholine via M 3 muscarinic receptor Gastrin acts via enterochromaffin like cells
Pepsinogen Major digestive constituent of digestive juice Produced in inactive form by chief cells Stored – zymogen granules Activated by HCl upon release into the lumen HCl cleaves a small fragment Autocatalytic Protein digestion
Mucus Gastric mucosa is covered by mucus Protective barrier Lubricating property: mechanical injury Self digestion form pepsin Pepsin gets inactivated on contact Alkaline pH: prevents injury by HCl
Intrinsic factor Glycoprotein secreted by Parietal cells Helps absorption of Vitamin B 12. Vitamin B 12 essential for red cell formation Absorbed only in combination Ileum- last part of small intestine Absence – Pernicious anemia
Regulation of Gastric Secretion Gastrin, Histamine, and Acetylcholine along with Somatostatin Ach, Gastrin, Histamine – stimulatory Increases HCl secretion Insertion of H + - K + ATPase Somatostatin inhibits – HCl Ach and gastrin also stimulates Pepsinogen secretion
Acetylcholine Neurotransmitter – intrinsic nerve plexus via vagus nerve Release stimulated by Vagus Short local reflex Stimulates Parietal cell Chief cell G cells ECL cells
Gastrin Secreted by G cells Release stimulated by Presence of proteins products Ach Stimulates Parietal cells Chief cell ECL cells Direct and indirect stimulation of HCl
Histamine Released from ECL Paracrine action Release is stimulated by Ach Gastrin Acts on parietal cells – HCl production
Somatostatin Released from D cells Stimulus – acid Negative feedback inhibition of secretions of Parietal cells G cells ECL cell
Strong co-operation between all these hormones Gastrin and Ach stimulate histamine Histamine binds to its receptor on oxyntic cell Potentiation of the stimulatory action of Ach and Gastrin upon the secretion of H+. Large proportion of H+ secretion caused by gastrin is mediated via histamine secretion
Increase in pH below 3 Depresses the secretion of Gastrin Inhibitory nervous reflex inhibiting gastrin
Phases of gastric Secretion Three phases of gastric secretion Cephalic Anticipation, sight, smell and taste Gastric Intestinal Presence of food in the stomach and Intestine
Cephalic Phase Increased secretion of gastric juice before the food reaches stomach Feed forward manner Activates Vagus
Sham Feeding Experiment
1. The taste or smell of food, tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata ( green arrow ). 2. Parasympathetic action potentials are carried by the vagus nerves to the stomach ( pink arrow ). 3. Preganglionic parasympathetic vagus nerve fibers stimulate postganglionic neurons in the enteric plexus of the stomach. 4. Postganglionic neurons stimulate secretion by parietal and chief cells and stimulate gastrin secretion by endocrine cells. 5. Gastrin is carried through the circulation back to the stomach ( purple arrow ), where it stimulates secretion by parietal and chief cells. Cephalic Phase Gastrin Circulation Secretions stimulated Taste or smell of food Tactile sensation in mouth Medulla oblongata Vagus nerves Stomach 1 2 3 5 4
The taste or smell of food, tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata ( green arrow ). Taste or smell of food Tactile sensation in mouth Medulla oblongata Cephalic Phase
Parasympathetic action potentials are carried by the vagus nerves to the stomach ( pink arrow ). Vagus nerves Cephalic Phase
Preganglionic parasympathetic vagus nerve fibers stimulate postganglionic neurons in the enteric plexus of the stomach. Vagus nerves Cephalic Phase
Cephalic Phase Postganglionic neurons stimulate secretion by parietal and chief cells and stimulate gastrin secretion by endocrine cells. Gastrin Stomach
Cephalic Phase Gastrin is carried through the circulation back to the stomach ( purple arrow ), where it stimulates secretion by parietal and chief cells. Gastrin Circulation Secretions stimulated
Gastric Phase Food is in the stomach Stimuli: Protein, Caffeine, Distention, Alcohol Protein –chemoreceptors-intrinsic nerve plexus- secretory cells Activates extrinsic vagal fibers Activates gastrin release directly
Stomach Local reflexes stimulated by stomach distention Distention Secretions stimulated Vagus nerves Medulla oblongata 1 . Distention of the stomach activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata ( green arrow ). 2 . The medulla oblongata stimulates stomach secretions ( pink arrow ). 3 . Distention of the stomach also activates local reflexes that increase stomach secretions ( purple arrow ). Gastric Phase 1 2 3
Local reflexes stimulated by stomach distention Distention Vagus nerves Medulla oblongata Distention of the stomach activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata ( green arrow ). Gastric Phase Stomach
Gastric Phase Local reflexes stimulated by stomach distention Distention of the stomach also activates local reflexes that increase stomach secretions ( purple arrow ). Stomach Distention
Intestinal Phase Involves factors from the small intestine Inhibitory phase Shuts down gastric juice flow Chyme enters the small intestine
Presence of protein is withdrawn pH falls very low – acid accumulation Somatostatin released Inhibits gastric secretion Fat, acid, hyper tonicity and distention of duodenum- inhibits Enterogastric reflex – suppress GI cells
1 . Chyme in the duodenum with a pH less than 2 or containing fat digestion products (lipids) inhibits gastric secretions by three mechanisms. 2 . Sensory vagal action potentials to the medulla oblongata ( green arrow ) inhibit motor action potentials from the medulla oblongata ( pink arrow ). 3 . Local reflexes inhibit gastric secretion ( orange arrows ). 4 . Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum ( brown arrows ) inhibit gastric secretions in the stomach. Intestinal Phase Secretin, gastric inhibitory peptide, cholecystokinin Circulation pH<2 or lipids Local reflexes Decreased gastric secretions Medulla oblongata Vagus nerves Vagus nerves 1 2 3 4
Interdigestive Phase Secretion continues Sleep and between meals Vagally mediated Composed mostly of mucous, little pepsin and no acid Emotional stimuli increases secretion
Applied physiology
Peptic Ulcer Why stomach does not get digested itself? Surface of the mucosa lined by cells that secrete alkaline mucous Protein content of the mucus and alkalinity neutralizes H + ions. Tight Junctions Repair of damaged cells
Protective mechanism – inadequate Erosion of gastric surface – ulcer Can happen in Lower part of esophagus Stomach duodenum
Breaking of mucosal barrier Exposing underlying tissue for action of acid and pepsin H. Pylori can also cause Bacterium
Proton Pump The parietal cells release H+ions (protons) during HCl production This process is called the “proton pump”
Proton Pump Inhibitors: Mechanism of Action Irreversibly bind to H + /K + ATPase enzyme Result: achlorhydria —ALL gastric acid secretion is blocked