L2 Stomach & Regulation of Gastric Secretion PDF

L2 Stomach & Regulation of Gastric Secretion GNT Physiology This lecture was presented by: Prof. Mohammed Alzoghaibi & Dr. Maha Saja Color Index: • Main text • Important • Female Slides • Male Slides • Notes • Extra Editing File Objectives ● Discuss the role of the stomach in digestion. ● Enumerate the functions of the stomach ● Discuss the secretory functions of the stomach: ○ ● What are the glands lining the stomach wall. ○ Discuss the cells lining the diﬀerent glands and their speciﬁc secretions. ○ Discuss the mechanism of HCl secretion by parietal cells. ○ Discuss control mechanisms of gastric secretions. ○ Enumerate and discuss the phases of gastric secretion. Resources Only GI chapters included Describe the diﬀerent motility patterns in the stomach and their role in digestion. ● Describe the mechanism of stomach emptying and discuss the factors controlling it. ● Discuss the role of the stomach in digesting the main food constituents. ● Discuss the pathophysiologic basis of peptic ulcer and gastritis. sherwood-human-physiology Click here for a helpful channel by the team! Summary of this Lecture will be in the channel soon.. This is prof sultan meo! ❝ِ‫َواذْ ﻛُر رﱠ ﺑﱠكَ ﻓِﻲ َﻧﻔْﺳِ كَ ﺗَﺿَ رﱡ ﻋًﺎ َوﺧِﯾ َﻔ ًﺔ َودُونَ اﻟْﺟَ ﮭْرِ ﻣِنَ ا ْﻟﻘ َْولِ ﺑِﺎ ْﻟ ُﻐدُوﱢ َو ْاﻵﺻَ ﺎل‬ (٢٠٥) َ‫َو َﻻ َﺗﻛُن ﻣﱢنَ اﻟْﻐَ ﺎ ِﻓﻠِﯾن‬ ،‫ ﺑذﻛر رﺑﮫ ﻓﻲ ﻧﻔﺳﮫ‬،‫ﷲ ﻋﺑده ورﺳوﻟﮫ ﻣﺣﻣدا أﺻﻼ وﻏﯾره ﺗﺑﻌﺎ‬ ّ ‫ ﻓﺄﻣر‬،‫ وھو أﻛﻣل أﻧواع اﻟذﻛر وأﺣواﻟﮫ‬،‫ وﯾﻛون ﺑﮭﻣﺎ‬،‫ وﯾﻛون ﺑﺎﻟﻠﺳﺎن‬،‫اﻟذﻛر ّ ﺗﻌﺎﻟﻰ ﯾﻛون ﺑﺎﻟﻘﻠب‬ ،‫ ﺧوﻓﺎ أن ﯾﻛون ﻋﻣﻠك ﻏﯾر ﻣﻘﺑول‬،‫ َو ِﺟ َل اﻟﻘﻠب ﻣﻧﮫ‬،‫ﷲ‬ ّ ‫ َوﺧِﯾ َﻔ ًﺔ ﻓﻲ ﻗﻠﺑك ﺑﺄن ﺗﻛون ﺧﺎﺋﻔﺎ ﻣن‬،‫ ﻣﻛررا ﻷﻧواع اﻟذﻛر‬،‫ ﻣﺗﺿرﻋﺎ ﺑﻠﺳﺎﻧك‬:‫ ﺗَﺿَ رﱡ ﻋًﺎ أي‬.‫ ﻣﺧﻠﺻﺎ ﺧﺎﻟﯾﺎ‬:‫أي‬ ‫ واﺑﺗﻎ ﺑﯾن‬،‫ وﻻ ﺗﺧﺎﻓت ﺑﮭﺎ‬،‫ ﻻ ﺗﺟﮭر ﺑﺻﻼﺗك‬،‫ ﻛن ﻣﺗوﺳطﺎ‬:‫ َودُونَ اﻟْﺟَ ﮭْرِ ﻣِنَ ا ْﻟﻘ َْولِ أي‬.‫ واﻟﻧﺻﺢ ﺑﮫ‬،‫وﻋﻼﻣﺔ اﻟﺧوف أن ﯾﺳﻌﻰ وﯾﺟﺗﮭد ﻓﻲ ﺗﻛﻣﯾل اﻟﻌﻣل وإﺻﻼﺣﮫ‬ ‫ ﻓﺈﻧﮭم‬،‫ﷲ ﻓﺄﻧﺳﺎھم أﻧﻔﺳﮭم‬ ّ ‫ َوﻻ َﺗﻛُنْ ﻣِنَ اﻟْﻐَ ﺎ ِﻓﻠِﯾنَ اﻟذﯾن ﻧﺳوا‬.‫ وھذان اﻟوﻗﺗﺎن ﻟذﻛر ﷲ ﻓﯾﮭﻣﺎ ﻣزﯾﺔ وﻓﺿﯾﻠﺔ ﻋﻠﻰ ﻏﯾرھﻣﺎ‬،‫ ﺑِﺎ ْﻟ ُﻐدُوﱢ أول اﻟﻧﮭﺎر َواﻵﺻَ ﺎلِ آﺧره‬.‫ذﻟك ﺳﺑﯾﻼ‬ .‫ﷲ ﻻ ﯾﺳﺗﺟﯾب دﻋﺎء ﻣن ﻗﻠب ﻏﺎﻓل ﻻه‬ ّ ‫ ﻓﺈن‬،‫ وأﻋرﺿوا ﻋﻣن ﻛل اﻟﺳﻌﺎدة واﻟﻔوز ﻓﻲ ذﻛره وﻋﺑودﯾﺗﮫ‬،‫ﺣرﻣوا ﺧﯾر اﻟدﻧﯾﺎ واﻵﺧرة‬ ‫ﺗﻔﺳﯾر اﻟﺳﻌدي‬- Introduction & Anatomy of stomach Stomach Physiologically [2] Anatomically [1] Fundus 2 functional parts Antrum Body Caudad (Antral Pump) antrum plus lower third of the body. Caudad :near legs Orad (Reservoir) fundus and upper two thirds of the body. Orad:near head Upper region Funds + upper ⅔ of body Thickening of sphincter Tonic contraction Phasic contraction Lower ⅓ of body + antrum + pylorus Caudal = ‫اﺳﻔل‬ Gastric Muscle Wall Female slides ❖ 1. 2. 3. Gastric muscle wall is made of 3 layers: Outer longitudinal Middle circular Inner oblique ❖ Thickness of muscle layer increases as we move from proximal to distal regions. Gastric pacemaker region is located at the upper part of body. This is where slow waves are generated. slow wave more toward ‫ﺗطﻠﻊ‬ threshold cause contraction Gastric mucosa Female slides Gastric mucosa is formed of columnar epithelium that is folded into “pits”. The pits are the opening of gastric glands. There are several types of gastric glands in the stomach and are distributed diﬀerentially in the stomach. ❖ ❖ ❖ Role of pylorus ❖ ❖ ❖ Female slides It is slightly tonically contracted almost all the time “pyloric sphincter”. It is usually open enough to allow water & ﬂuids to pass. It is controlled by nervous and hormonal reﬂexes from the stomach and duodenum. General motor Functions of the Stomach Our second stop in our journey with the burger is the stomach The burger that reached the stomach is no longer a burger It is called “food bolus” [5] Important 1 Storage of large quantities of food 2 Preparing the chyme for digestion in the small intestine 3 Absorption of water and lipid-soluble substances (alcohol and drugs) 4 Regulate emptying of the chyme from the stomach into the small intestine. 1: Upper part elevated after the junction of esophagus. 2: Cause of this division ? The function diﬀerent in the 2 parts 3: Thickness is more in antrum than fundus -> Contraction is strongest at antrum 4: Mucous layer extremely thick because the wall of stomach is folded —>it form gastric gland and there is a pit in the surface of stomach ‫ ﻣﺛل اﻟﺣﻔر‬this pit hide in the depth of gastric gland, this gland lined by all epithelial cell that will secrete secretion done by stomach 5: How stomach deal with this food bolus? Transform it into something that intestine can handle with it Gastric Glands Secretions Location - Mucus,HCO3 Cardia -Mucus (neck) cells -Peptic (Chief) cells -Parietal cells (Oxyntic cells) HCl ,Pepsinogen, IF, Mucus Body & fundus (above the notch) Many G cells Gastrin ,Mucus Antrum (below the notch) Cardiac glands Oxyntic (gastric or parietal) glands “upper ⅔of stomach, constituted 80% of gland in the stomach” ↓ ‫دﻛﺗور اﻟﻌﯾﺎل رﻛز ﻋﻠﻰ اﻟرﺳﻣﮫ ذي‬ Cell lining Pyloric glands Lower part Antrum + Pylorus constituted 20% of stomach gland Minly 2 type of cell but there is other cells -From previous table, we can conclude that Chief cells (peptic cells), they are available in oxyntic glands and few in pyloric glands. as well as , parietal cells. -Oxyntic glands are the most abundant gastric glands found in fundus and corpus (body). Types of cells present in the Gastric Glands Cell Oxyntic (parietal) cell Peptic (chief ) cell Mucus (neck) cells top part of the surface Enteroendocrine Or Enterochromaﬃn -like cells G cells D Cells (decreases HCl secretion) Secretions Location HCl & IF (intrinsic factor) Body (most distinctive cells in stomach) Pepsinogen Body Mucus, HCO3- antrum Histamine - Function:protection Gastrin (increases HCl secretion from Parietal cells) Somatostatin 1: Med442: Every gland has a neck and a base. Mucus cells are found in the neck region of glands. They neutralize acidity and protect the wall of stomach. Mucus is secreted throughout the whole stomach. 2: protect B12 by bind to it to go to terminal ileum where it go to be absorbed 3:Med442:The only cell that releases HCL in the body is the oxyntic cell. 4: play important role in regulate HCL secretion 5: should be released in circulation to be activated antrum There is a deep pit lining with epithelial cells but each epithelial cell speciﬁc and have certain function Gastric Glands 1 Structure of Oxyntic gland HCl is secreted across the parietal cell microvillar membrane and ﬂows out of the intracellular canaliculi into the oxyntic gland lumen. The surface mucous cells line the entire surface of the gastric mucosa and the openings of the cardiac, pyloric, and oxyntic glands. These cells secrete mucus and HCO - to protect the gastric surface from the acidic environment of the stomach. The distinguishing characteristic of a surface mucous cell is the presence of numerous mucus granules at its apex. Figure 1 Figure 2 ❖ ❖ ❖ ❖ 2 Structure of Pyloric gland Med442: There are no chief cells or parietal cells in the pyloric region. Med442: Mucus secreting cells are near the neck region. Med442: Deeper within the gland, there are G cells which secrete Figure 3 gastrin. ❖ ❖ ❖ 3 Structure of parietal cells ❖ ❖ ❖ Med442 :HCL is secreted by parietal cells into canaliculus, then it ﬂows into the lumen of the stomach through the opening. Canaliculus=( ‫) ﻗﻧﺎة‬ Female doctor : inactive cell the canaliculi system ‫ اﺧف‬hidden , when it got activated ‫ﯾزﯾد‬ Active parietal cell have : - Apical side: side that face lumen of stomach arrange into canaliculi Basolateral side: side that face blood Figure 4 Gastric pit Oxyntic gland Figure 2 Figure 1 Figure 4 Figure 3 Gastric juice is composed of: Male slides Mucus (mucus gel layer) Electrolytes HCL Pepsinogen Intrinsic Important Mechanism of HCl Secretion by Parietal Cells most important secretion in stomach Male slides ❖ Chloride ion is actively transported from the cytoplasm of the parietal cell into the lumen of the canaliculus, and sodium ions are actively transported out of the canaliculus into the cytoplasm of the parietal cell. ❖ Water becomes dissociated into hydrogen ions and hydroxyl ions in the cell cytoplasm. The hydrogen ions are then actively secreted into the canaliculus in exchange for potassium ions. ❖ Carbon dioxide, either formed during metabolism in the cell or entering the cell from the blood, combines under the inﬂuence of carbonic anhydrase with the hydroxyl ions to form bicarbonate ions. These then diﬀuse out of the cell cytoplasm into the extracellular ﬂuid in exchange for chloride ions that enter the cell. Basolateral side canali culi canalicu Explanation by female doctor : How does parietal cell secrete HCL ?? Parietal cell on the apical side of membrane have a “ H/K ATPase pump” it pump H out into lumen of stomach with exchange for K into the cell. Note : in physiology when ever I pump an ion 1- pump in opposite direction an ion in the same charge 2- or pimp in same direction an ion with negative charge From where come H: ● Blood ● Dissociation of HCO3 CO2+H2O Carbonic anhydrase H2CO3 HCO3+H From where come K : ● Because down concentration gradient by Na/K ATPase in because basolateral membrane with pump 3 Na out and 2 K in. - - HCO3 which come from dissociation of H2CO3 will be transformers into blood by exchanger protein “HCO3/Cl exchanger” when Cl go to the cell will go again to cl channel into the lumen of stomach Cl will bind in lumen of stomach to H Finalllllyyy HCL formed🤩🤩 In addition to HCL: 1- little KCl 2- very little NaCl Apical side li Explanation by med442 : Our body is made of water. CO2 is released by the cell as a product of metabolism by free diffusion. 1- When CO2 and water combine together in the presence of carbonic anhydrase enzyme they will form carbonic acid. The carbonic acid will dissociate into bicarbonate and hydrogen. 2- The hydrogen will be pumped out of the cell canaliculus (luminal side) by H+/K+ ATPase (primary active transport). It will pump H+ in exchange of K+. The movement of H+ outside parietal cell depends on: H+/K+ ATPase and amount of K+ found in lumen of the stomach Where did the K+ that will be pumped into cell come from? Inside of the cell. Na+/K+ ATPase is found on basolateral side of cell (blood side) The main function of Na+/K+ ATPase is to pump 3Na+ out and 2K+ onto the cell. This creates a high concentration of K+ inside the cell which will cause leakage of the potassium into the canaliculus side of cell through (potassium channels. In summary, the leaked potassium will be used in exchange for H+ and will enteral cell (recycled potassium). 3- The bicarbonate will be transported into blood in exchange for Cl-. When the Cl- accumulates in the cell, it will escape through the luminal side of cell via Chloride channels. END RESULT= The hydrogen the is pumped into the canaliculus and the Cl- that escaped the canalicular side will combine and form HCL. Some K+ will combine with Cl and form KCL. Na will also combine with Cl- and form NaCl (very little amount) Summary of HCl secretion -Depends on H/K ATPase -Inhibited by: omeprazole used to treat: stomach peptic ulcer and gastric reﬂux -Alkaline tide -H/K pump depends on [K]out [HCl] drives water into gastric content to maintain osmolality During gastric acid secretion: amount of HCO3- in blood = amount of HCl being secreted , Alkaline tide Control of HCL secretion(M) ❖ Gastric acid secretion is mediated through neural (via Vagus nerve) and hormonal pathways (via histamine and gastrin). ❖ Parietal cells possess special histamine receptors, H2 receptors, whose stimulation results in increased acid secretion. they also get activated by distension ❖ Special neuroendocrine cells of the stomach, known as enterochromaﬃn like (ECL) cells, are believed to be the source of this histamine. They are located mostly in the acid-secreting regions of the stomach. The mechanisms that stimulate the ECL cells to release histamine are poorly understood. ❖ The eﬀectiveness of cimetidine, a H2 blocker, in reducing acid secretion has indirectly demonstrated the importance of histamine as an eﬀector of gastric acid secretion. H2 blockers are commonly used for the treatment of peptic ulcer disease or gastroesophageal reﬂux disease.(M) Important Neural via Vagus nerve Ach act on parietal cells → increases HCL secretion Direct Indirect Act on G cells by releasing Gastrin releasing peptide(GRP) → secrete gastrin which act on CCKB receptor 4 of parietal cells → increases HCL secretion Act on enterochromaﬃn like cells (ECL) which secrete histamine → act on H2 receptor of parietal cell → increases HCL secretion. Hormonal Gastrin (Endocrine secretion) Paracrine Histamine (M) — Histamine activate H2 receptor on parietal cells thus increase HCL secretion. H2 blockers are used for the treatment of peptic ulcer disease or gastroesophageal reﬂux disease. (e.g, Cimetidine) D cells in antrum & corpus If you like to read doctor’s Notes of these pictures, Your ﬁnger here please.. Eﬀects of vagal activation on gastric secretion Postganglionic ﬁbers of parasympathetic lie within ENS (found on wall of stomach). So activation of the parasympathetic system will stimulate the release of Ach -> which will act directly on chief cells, parietal cells and ECL cells. However, G cells are stimulated by GRP not Ach. Inhibition of Acid Secretion (Enterogastrones): ❖ ❖ ❖ Somatostatin (D-cells) in antrum. Secretin (S-cells) in duodenum. Glucose-dependent insulinotropic peptide (GIP) (K-cells) in duodenum. Agents stimulate and inhibit H+ secretion by gastric parietal cells . Mention them. Other Gastric Secretions 1-Mucus Mucus cells secrete large quantities of viscid thick mucus that coats the muscle mucosa. The mucus is alkaline. ❖ ❖ The epithelial cell layer of stomach have junction in between cell very tight to protect return anything from lumen of stomach into cell and damage it Which is rich in bicarbonate -> protects the stomach mucosa*.(if the surface get some erosion by gastric acid which inside lumen HCO3 can buﬀer acidity before it rich mucus and damage it and cause peptic ulcer ) 2-Pepsin Peptic (chief) cells secrete pepsinogen.. What is its role in digestion? Several types of pepsinogen secreted from chief cells. They are activated by HCl into pepsin and once activated, they can activate more pepsinogen. These amino acids. or peptides activate G cells to secrete Gastrin thus increasing HCL secretion. Peptic (chief) cells secrete pepsinogen. The optimum pH is (1.5-3.5) (1.8-3.5). pH > 5 inactivates pepsin. Pepsin breaks down proteins into peptones & polypeptides*. Pepsinogen secretion is stimulated by Ach, acid, gastrin, secretin & CCK. ❖ ❖ ❖ ❖ ❖ ❖ ❖ What controls the release of pepsinogen? 1- Ach secretion “direct eﬀect on chief cells 2- Acidity in stomach. Ex: HCL in stomach can stimulate chief cells to secrete pepsinogen. 1- Chief cells in the gastric mucosa secrete pepsinogen (inactive form of pepsin) protective mechanism because will digest the cell if it activated in it 2- Once pepsinogen reaches the lumen of the stomach, HCL will act on it. 3- HCL will activate pepsinogen -> pepsin (active enzyme) What’s the role of pepsin in digestion? It plays a role in protein digestion (breaks down proteins into smaller polypeptides” dietary proteins -> parietal digested protein. 15% of ingested protein is digested in stomach by pepsin. 2 stimulator for pepsin : 1-acidity of cell 2- parasympathetic ACh by vagus nerve A feature of active enzymes: once the active form is formed, it promotes conversion of inactive form to active ‫ﯾﺣﻔز ﻧﻔﺳﮫ‬ 3-Intrinsic Factor: ❖ ❖ ❖ ❖ In addition to HCl, parietal cells secrete IF. What is its importance? It is a glycoprotein secreted by parietal cells. It is the only essential function of stomach as it is essential for vitamin B12 absorption*. Atrophy of gastric mucosa leads to pernicious anemia. Parietal cells secrete IF along with HCL. The IF will hold onto B12 that entered the stomach with food, and protects it from being degraded by stomach acidity until they reach the terminal of the ileum “site of B12 absorption” -> IF will release vit. B12. Any damage to parietal cells will result in anemia (no IF). -> B12 can’t be absorbed -> eﬀect on RBC synthesis and eventually will result in megaloblastic anemia (pernicious anemia) The Rate of Secretion ❖ Male slides The Rate of Secretion Modify the Composition of Gastric Juice ❖ At a low secretion rate, gastric juice contains : 1-high concentrations of Na+ and Cl- and 2-low concentrations of K+ and H+. ❖ When the rate is increased: 1-Na+ concentration decreases. Na+ secretion once stomach is empty is high -> makes NaCl secretion in interdigestive period ( high ) 2-H+concentration increases signiﬁcantly. 3-Cl-concentration increases. ❖ ❖ Gastric juice is derived from the secretions of two major sources: -Parietal cells: its secretion (HCl secretion) contributes mainly to the changes in electrolyte composition with higher secretion rates. -Non parietal cells: constant secretion, thus having little contribution to the electrolyte changes. Interdigestive period (i.e., between meals) : production of H+out of parietal cells is very low and Cl- is high, By eating -> H+ will increase and so as Cl- High secretion rate (after a meal)- high HCl. Always isotonic This means if we increase HCL production, that will not aﬀect the osmolarity of secretion inside the stomach. This because having more HCL production inside the stomach after getting a meal will also increase water secretion toward the stomach (that’s why we feel thirsty and we drink water after having a meal, in order to regulate osmolarity The Rate of Secretion (in summary) female slides -Low secretion rate —------->high NaCl. (Between meals) -High secretion rate —-------> high HCl. (After meal) -Always isotonic. Peptic ulcer disease ● What causes peptic ulcer disease ? -is the imbalance between damaging factors and protective factors. ● female slides What are they ? Damaging factors Protective factors HCL Alkaline mucus NSAIDS Somatostatin H.Pylori Prostaglandins ● What is Zollinger—Ellison syndrome ? -It’s a tumor that produce more gastrin hormone —-> ++ acidity secretions. **don’t worry , the whole paragraph has been explained in pathology** Phases of Gastric Secretion When does the stomach start secret this secretion -Gastric secretion starts even before food reaches the stomach and when food is in the stomach and continues even after food leaves stomach into duodenum. Sight/smell/.. will activate cerebral cortex -> parasympathetic system will ﬁre. Vagal stimulation through neuronal connections will stimulate stomach to start secreting its juices. -The stimulation of acid secretion resulting from the ingestion of food can be divided into 3 phases: Cephalic phase: Looking , smell food ❖ ❖ ❖ ❖ 1 30% of HCL is secreted in this phase. Before food arrives at stomach. Stimuli (Smelling, taste , Chewing and swallowing). Mechanism: ?(long reﬂex) vagus ◇ CNS send impulses via the vagus nerves,The nerve endings release ACh, which directly stimulates acid secretion from parietal cells. ◇ CNS send impulses via the vagus nerves ,nerves also release gastrin-releasing peptide (GRP), which stimulates G cells to release gastrin, indirectly stimulating parietal cell acid secretion. Gastric phase:Most important phase Stimulate by destination of stomach , chemical in food ❖ 60% of HCL is secreted in this phase. ❖ when food enters the stomach . ❖ Stimuli (distention , amino acid , small peptides). ❖ Mechanism : (long reﬂex vagus) (short reﬂex ENS) (hormonal) ➢ Distention of the stomach stimulates mechanoreceptors, which stimulate the parietal cells directly through short local (enteric) reﬂexes and by long vago-vagal reﬂexes. ➢ Digested proteins in the stomach are also potent stimulators of gastric acid secretion, an eﬀect mediated through gastrin release. Several other chemicals, such as alcohol and caﬀeine, stimulate gastric acid secretion through mechanisms that are not well understood. 2 intestinal phase: minimal eﬀect (mainly inhibit HCL more than stimulate it) ❖ ❖ ❖ ❖ 3 10% of HCL is secreted in this phase. when chyme enters duodenum. Stimuli (protein digestion products in the duodenum). Mechanism ◇ protein digestion products in the duodenum stimulate gastric acid secretion through the action of the circulating amino acids on the parietal cells. ◇ Distention of the small intestine, probably via the release of the hormone entero-oxyntin from intestinal endocrine cells, stimulates acid secretion. Very helpful Motor Function Of the Stomach 1-Storage of food: ❖ ❖ ❖ ❖ ❖ ❖ ❖ Mainly in the proximal portion Involves muscle relaxation When bolus of food in the esophagus approaches the stomach A wave of relaxation recedes it that relaxes the LES & the orad region of the stomach “Receptive relaxation”Peristaltic wave of esophagus is preceded by a relaxation wave -> which relaxes LES as well as the upper part of stomach wall. Distend upper part of stomach to allow accommodation Allow food to enter and the volume of stomach increases without an increase in intragastric pressure this is because the stomach is relaxing as food comes in -> accommodates food without signiﬁcance increase in pressure When the stomach is stretched by food, a vagovagal reﬂex is initiated from the stomach to the brain stem and back to the muscular wall of the stomach resulting in reduction in muscular wall tone which allows storage. Stomach can store 0.8-1.5 L of food. Gastric contents may remain unmixed for 1 hour in the corpus (body of stomach). The pressure in the stomach remains low until the volume reaches ~1.5 L of food. This function is regulated by Receptive Relaxation Reﬂex (vagovagal): Triggered by swallowing reﬂex.(will be discussed in the next slides) Empty stomach 50 ml Full stomach 1000 ml 2-Mixing Propulsion of food: ❖ ❖ ❖ ❖ ❖ ❖ ❖ ❖ Churns food to transform it into a form that can pass through the pylorus and easy for intestine to deal with. Mixing of food in the stomach transforms it into a semiﬂuid mix called “chyme”. Major mixing activities take place in the antrum (antral pump region, phasic contraction). The Basic Electrical Rhythm of the Stomach Wall. The digestive gastric juices come in contact with the food lying against the mucosal surface of the stomach. The presence of food causes weak peristaltic constrictor waves called mixing/constrictor waves once every 15-20 seconds. These waves are initiated by the gut wall basic electrical rhythm of the slow spontaneous electrical waves.Note: If you remember, we said that slow waves can’t produce contractions, except in the stomach (mixing waves). If slow waves produce a contraction, It’s weak (like this one) These waves progress from the body to the antrum and become intense, forcing the chyme to mix and move under high pressure from the antrum toward the pylorus. Each time a peristaltic wave passes from the antrum to the pylorus, few millimeters of antral content move into the duodenum through the pyloric sphincter We can not depend on weak peristaltic constrictor waves in mixing/digesting/pushing food to duodenum. Once slow waves reach threshold, they will generate enough AP. Every single AP in this area can last 5 sec “Very long” (normal 10-20 msec). When food arrives at stomach it causes distention. Distention of the stomach causes the slow wave potential to reach the threshold -> generation of AP -> contraction of stomach wall (contraction stats at mid. region of body). A peristaltic wave will cause another constrictor wave. When this wave reaches the pyloric sphincter it will be tonically contracted. In order for food to leave the stomach via the pyloric sphincter, it’s size should be less than 2mm. Whatever is bigger than 2mm will tumbled back in to antrum and goes through the same process until it's small enough to pass through pyloric sphincter. Motor Function Of the Stomach (cont-) 3-Regulate emptying of the chyme from the stomach into the small Intestine (duodenum): ❖ ❖ ❖ ❖ ❖ ❖ Emptying of modiﬁed gastric contents “chyme” into duodenum If particles are < 2mm they will squeezed through the tight pyloric sphincter and get emptied into duodenum “Pyloric pump” If particles are > 2mm they will pump into the tight pyloric sphincter and tumble back into antrum “retropulsion” ‫ﻣﺛل ھرس‬ ‫اﻟطﻌﺎم‬ To binch more food ‫ ﺗﻛون اﻋﻠﻰ‬wave ‫اذا ﻓﺿت اﻟﻣﻌده ﺗﺑدأ ال‬ ❖ Chyme: Is a murky semi-ﬂuid or paste composed of food that is thoroughly mixed with gastric secretions. Movement of chyme into duodenum is achieved by “Pyloric pump” Each time a peristaltic wave passes from the antrum to the pylorus, few millimeters of antral content move into the duodenum through the pyloric sphincter. That’s why once you have food between 2 contractions -> you want to mix it with digestive juices. The leading contraction will start and squeeze food down. If food particles are larger than 2mm, they will go back for further degradation which is done by contraction of pyloric sphincter (the leading contraction will squeeze sphincter and the trailing contraction will push food back and expose food to HCL to mix and digest “retropulsion”). Another AP will be generated to push the food down. Size of food is determined by stretch receptors that are located on pyloric sphincters. It will determine whether food will pass through sphincter or will go back. 4-The main functions of the upper part of the Stomach (Reservoir part): ❖ ❖ ❖ ❖ To maintain a continuous compression. To accommodate the received food without signiﬁcant gastric wall distention or pressure (Storage of food). Upper part of stomach: storage+relaxes Lowe part : mixing + grinding 5-Hunger Contraction: ❖ ❖ ❖ ❖ Male slides Male slides Hunger contractions occur when the stomach has been empty for several hours These are rhythmical peristaltic contractions that can become very strong and fuse to form a continuing tetanic contraction lasting sometimes 2-3 minutes. Hunger contractions are intense in young healthy people and increase by low blood glucose levels. Hunger pain can begin after 12-24 hr of last food ingestion. 6-Absorption of water and a few highly-lipid soluble substances (alcohol and Aspirin): Female slides ❖ Stomach is a poor absorptive area of GIT: ➢ It lacks the villous type of absorptive membrane. ➢ It has tight junctions between epithelial cells. Three Kinds of Relaxation Occur in the Gastric Reservoir (orad): 1-Receptive Relaxation Reﬂex: ❖ Triggered by: swallowing reﬂex. ❖ When the esophageal peristaltic waves reach the stomach, the stomach relaxes through inhibition of myenteric neurons which prepares the stomach to receive the food that is propelled into the esophagus during swallowing. ❖ 3-Adaptive relaxation: 2-Feedback Relaxation: ❖ ❖ ❖ Gastric fundus dilates when food passes down the pharynx and esophagus ❖ Triggered by: presence of nutrients in the small intestine. It can involve both local reﬂex connections between receptors in the small intestine and the gastric ENS (Enteric nervous system). or hormones that are released from endocrine cells in the small intestinal mucosa and transported by the blood to signal the gastric ENS and stimulate ﬁring in vagal aﬀerent terminals in the stomach Feedback relaxation signiﬁcance is delaying gastric emptying Most important ❖ Triggered by: stretch receptors (vago-vagal reﬂex). ❖ Stomach dilates when ﬁlled, accommodating greater and greater quantities of food up to a limit (0.8 to 1.5 L). Gastric stretch receptors → Vagal aﬀerents → brain stem (medulla oblongata) → Vagal eﬀerents → enteric nervous system → inhibitory motor neurons → Muscle Relaxation Adaptive relaxation is lost in patients undergone a vagotomy. Following a vagotomy, increased tone in the musculature of the reservoir decreases the wall compliance, which in turn aﬀects the responses of gastric stretch receptors to distention of the reservoir. Pressure–volume curves obtained before and after vagotomy reﬂect the decrease in compliance of the gastric wall. The loss of adaptive relaxation after a vagotomy is associated with a lowered threshold for sensations of fullness and pain. ❖ ❖ ❖ ❖ Activation of vomiting center Retropulsion Phenomena 2 1 As the trailing contraction (explained later) approaches the closed pylorus, the gastric contents are forced into an antral compartment of ever-decreasing volume and progressively increasing pressure. This will Result in jet-like retropulsion through the oriﬁce formed by the trailing contraction. Repetition at 3 cycles/min reduces particle size to the 1-mm to 7-mm range that is necessary before a particle can be emptied into the duodenum. These intense peristaltic contractions that cause emptying increase the pressure in the stomach to 50-70 cm of H2O (compared to a pressure of ~10 cm of H2O during the mixing peristaltic contractions). Motor Behavior of the Antral Pumps Is Initiated by a Dominant Pacemaker (Motility in the Antrum): Male slides Gastric action potentials determine the duration and strength of the phasic contractions of the antral pump. They are initiated by a dominant pacemaker (ICC) (interstitial cells of Cajal). ❖ ❖ The action potentials (AP) propagate rapidly around the gastric circumference and trigger a ring-like contraction 1 2 The AP and associated ring-like contraction then travel more slowly toward the gastroduodenal junction. ❖ Electrical syncytial properties of the gastric musculature account for propagation of the action potentials from the pacemaker site to the gastroduodenal junction. ❖ The pacemaker region in humans generates AP and associated antral contractions at a frequency of three per minute. “Slow waves” ❖ The gastric action potential lasts about 5 seconds, it has: ◇ Rising phase (depolarization) ◇ Plateau phase ◇ Falling phase (repolarization) ❖ Electrical action potentials in gastrointestinal muscles occur in four phases, determined by speciﬁc ionic mechanisms: Phase 1: Ca+2 inﬂux Rising phase (upstroke depolarization) Activation of voltage-gated calcium channels and voltage-gated potassium channels Phase 0: Resting membrane potential; outward potassium current Phase 2: Initial repolarization. K+ eﬄux Phase 3: Balance between K+ eﬄux and Ca+2 inﬂux Plateau phase; balance of inward calcium current and outward potassium current. Phase 4: Falling phase (repolarization); inactivation of voltage-gated calcium channels and activation of calcium-gated potassium channels. There are two phases of Ca+2 inﬂux = 2 contractions 1- Leading contraction (due to depolarization) 2- Trailing contraction (due to plateau) long period of Ca+2 inﬂux. The Gastric Action Potential Triggers Two Kinds of Contractions ❖ The gastric action potential is responsible for two components of the propulsive contractile behavior in the antral pump: Contraction Trailing Contraction It has a relatively constant amplitude Variable amplitude Associated with the rising phase of the action potential. Associated with the plateau phase. Male slides The two contractions happen because of the extremely long duration of the Action Potential ❖ The leading contractions have negligible amplitude as they propagate to the pylorus. As the rising phase reaches the terminal antrum and spreads into the pylorus, contraction of the pyloric muscle closes the oriﬁce between the stomach and duodenum. ❖ The trailing contraction follows the leading contraction by a few seconds. Stomach emptying ❖ Stomach emptying is the result of intense peristaltic antral contractions against resistance to passage of chyme at the pylorus. ❖ ❖ Role of the Pylorus in Controlling Stomach Emptying. The distal opening is the pylorus The pyloric sphincter is characterized by strong circular muscle (as compared to the antrum) and remains slightly tonically contracted most of the time. However, during pyloric constriction, it is usually open enough to allow watery chyme and ﬂuids to still pass through the pylorus into the duodenum, but not food particles. ❖ Pyloric constriction is determined by (both are from the duodenum and stomach): ◇ Nervous reﬂex signals ◇ Humoral reﬂex signals ❖ What is the purpose of gastric emptying? ◇ To deliver chyme to the intestine to continue its digestion and absorption. ◇ The rate at which chyme is delivered matters! ❖ The rate of stomach emptying is controlled by signals from the stomach and duodenum (will be discussed in the next slides), with the latter being far stronger and controls emptying of the chyme at a rate that allows the proper digestion and absorption in the small intestines. Stomach emptying Male slides Important Factors that Regulate Gastric Emptying Gastric Factors that Promote Emptying (usually are gastric factor) increase motility Distension Gastrin Powerful Duodenal Factors that Inhibit Emptying(usually are duodenal factor) decrease motility Distension Fat Acid Hypertonicity Trigger Neural or Hormonal Responses 1-Gastric Factors that Promote Stomach Emptying: Note: The ﬁrst 2 detailed boxes are in the males slides only. Alternatively, you can ﬁnd the females doctors’ simple explanation in the 3rd box. A-Eﬀect of Gastric Food Volume on Rate of Stomach Emptying: ↑ food volume -> pressure on pyloric sphincter = ↑ gastric emptying ❖ Increased gastric food volume → increased stretch in the stomach wall (which elicits local myenteric reﬂexes) →increased pyloric pump activity & the tonic contraction of the pyloric sphincter gets inhibited, leading to increased stomach emptying. B-Eﬀect of the Hormone Gastrin on Stomach Emptying: Gastric activates oxyntic cells to secrete GCL, ot also ↑ activity and motility of pyloric pump & Antrapump region = promote emptying. ❖ ❖ ❖ Gastrin is released from the antral mucosa in response to the presence of digestive products of meat. It promotes the secretion of acidic gastric juices (e.g. HCl) by the stomach gastric glands (or oxyntic glands) located on the inside surface of the body and fundus of the stomach; (i.e. proximal 80% of the stomach). It also enhances the activity of the pyloric pump and motor stomach function (moderate eﬀect) and probably promotes stomach emptying. Females Doctor: The presence of food in the stomach causes: 1. Distension of the stomach, which will trigger neural response by the Vagus nerve and the Enteric Nervous System.(long reﬂex vgus) 2. The proteins in the food stimulate G cell to release of Gastrin. Both of these factors increase the motility of the stomach. Gastric Factors that Promote Emptying Distension Proteins stimulate release of Gastrin Neural Increase motility of the stomach Stomach emptying Male slides 2-Powerful Duodenal Factors That Inhibit Stomach Emptying: Note: The ﬁrst 2 detailed boxes are in the males slides only. Alternatively, you can ﬁnd the females doctors’ simple explanation in the 3rd box in the next slide. A-Inhibitory Eﬀect of Enterogastric Nervous Reﬂexes from the Duodenum: ❖ ❖ ❖ ❖ When food enters the duodenum, multiple nervous reﬂexes are initiated from the duodenal wall and pass back to the stomach to regulate stomach emptying depending on the volume of chyme in the duodenum. These duodenal reﬂexes are mediated by three routes: goal: delay or reduce stomach emptying ◇ Directly from the duodenum to stomach through the ENS (enteric nervous system) in the gut wall. ◇ Through extrinsic nerves that go to the prevertebral sympathetic ganglia and then back through inhibitory sympathetic nerve ﬁbers to the stomach. ◇ Through the vagus nerves reﬂex (to a slight extent) → the brain stem → inhibit the normal excitatory signals that are transmitted to the stomach through the vagus nerves. These reﬂexes inhibit the pyloric pump and increase the tone of the pyloric sphincter thus decreasing stomach emptying. The duodenal factors that can initiate the enterogastric inhibitory reﬂexes include: Factors that activate 3 diﬀerent routes ◇ ◇ ◇ ◇ ◇ Duodenal distension. Duodenal irritation. Duodenal acidity. Osmolality of the chyme in the duodenum. Protein (and may be fat) content of the chyme in the duodenum. Fat is mediated by CKK, which is secreted when fatty acids arrive in duodenum. CKK slows gastric emptying, ensuring that gastric contents are delivered slowly to duodenum and provide adequate time for fat to be digested and absorbed. Very Important: The Inhibitory Eﬀect of Enterogastric Nervous Reﬂexes from the Duodenum is what causes the Feedback Relaxation (Mentioned earlier). B-Hormonal Feedback from the Duodenum Inhibits Gastric Emptying – Role of Fats and the Hormone Cholecystokinin: ❖ ❖ Fat entering the duodenum or acidity of chyme or excess quantities of chyme causes (probably a receptor mediated mechanism) the release of: ◇ Cholecystokinin (CCK) , acts as an inhibitor to block increased stomach motility caused by gastrin. ◇ Other inhibitory hormones such as secretin and gastric inhibitory peptide (GIP) from the epithelium of the duodenum and jejunum. Release of CCK (and probably secretin, and GIP) circulate and inhibit the pyloric pump and increase the tone of the pyloric sphincter, thus decreasing stomach emptying. Female slides Stomach emptying Powerful Duodenal Factors that Inhibit Emptying Distension Reflex from intestine to stomach (long reflex) Enterogastric Reﬂex GIP Main function : stimulate by present of carb it send signal to pancreas to release insulin insulin ‫ ﺗﻣﺗص اﻟﺟﻠوﻛوز ﯾﺑدأ ال‬intestine ‫ﻋﺷﺎن ﻟﻣﺎ ﺗﺑدأ ال‬ ‫ﯾﺗﻌﺎﻣل ﻣﻌﮭﺎ‬ Gastrin inhibitory peptide or glucose-dependent insulinotropic polypeptide Fat Acid I Cells S Cells Secretin CCK It act on gallbladder secrete billing secretion to help in fat digestion Hypertonicity Go to pancreas to secrete bicarb-richfield To neutralize acidity come from stomach Decrease Motility of the Stomach Females Doctor: Chyme in the duodenum causes: 1. Distension of duodenum, which will trigger the Enterogastric reﬂex. 2. Fat stimulates I cells to secrete CCK. 3. Acid damages the duodenum, so it will: a. Stimulates S cells to secrete Secretin. b. Stimulates the pancreas to release Bicarbonate to neutralize the acidity. (Will be discussed in the next lecture) 4. Hypertonicity All of these factors decrease the motility of the stomach. #med442 Both images were Skipped Digestion in the Stomach Carbohydrates Fat Protein Carbs in diet include; ● Cellulose. ● Starch. ● Disaccharides. Stomach digests 30-40% of consumed starch to maltose by action of salivary amylase. Fat in diet include; ● TGs. ● Cholesterol Stomach digests <10% of consumed TGs by action of lingual lipase. - Initiates protein digestion. - By action of pepsin. - Stomach digests 10-20% of consumed proteins transforming them into polypeptides, peptones. Summaries These summaries are written in the boys’ slides, they are not extra eﬀort from us Phases of Gastric Secretion: 1. 2. 3. Cephalic phase(30%): Smelling, Chewing and swallowing Stimulate parietal G-Cells (via GRP). Gastric phase (60%): gastric distention proteins Intestinal phase (10%): digested proteins Regulation of Stomach Emptying: 1. ● Gastric Factors That Promote Emptying: Food Volume: Increased food volume in the stomach promotes emptying from the stomach (inhibits the pylorus). Gastrin hormone: enhances the activity of the pyloric pump. Thus, it, too, probably promotes stomach emptying. ● 1. Powerful Duodenal Factors That Inhibit Stomach Emptying: ○ At the presence of food in the duodenum, multiple nervous reﬂexes are initiated from the duodenal wall that pass back to the stomach to slow or even stop stomach emptying via one of the following routes: ○ Directly through ENS ○ Through extrinsic nerves that go to the prevertebral sympathetic ganglia and then back through inhibitory sympathetic nerve ﬁbers to the stomach. ○ Through the vagus nerves. 1. ● ● ● The types of factors that can initiate enterogastric inhibitory reﬂexes include the following: The distention of the duodenum. Acidity of the duodenum activates S cells to release Secretin which constricts the antrum. Fat (monoglycerides) in the duodenum activates diﬀerent cells to produce CCK and GIP that delay gastric emptying. Hyperosmotic or hypoosmotic solutions delay gastric emptying. Amino acids elicit inhibitory enterogastric reﬂexes; by slowing the rate of stomach emptying. ● ● Constriction of Pyloric Sphincter: 1. 2. 3. - Hormones promote constriction of pyloric sphincter and inhibit stomach emptying: Cholecystokinin (CCK) Secretin Glucose-dependent insulinotropic peptide (GIP) Sympathetic innervation Summaries You c an ﬁ ll ‫★اﻟﺟدول ﻣﮭم‬ Hormone Actions Site of secretion Gastrin(M) Cholecystokinin (CKK) I cells of the: - Duodenum - Jejunum - Ileum Secretin S cells of the: - Duodenum - Jejunum p - Ileum (Acid inhibit its release) - Protein - Distention of the stomach - Vagal stimulation - (GRP) - Gastric H+ secretion - Growth of gastric mucosa - Protein - Fatty acids - Acids - Pancreatic enzyme secretion - Pancreatic HCO-3 secretion - Gallbladder contraction - Growth of the exocrine pancreas - Relaxation of sphincter of Oddi - Acids & fat in the duodenum - Pepsin secretion - Pancreatic HCO-3 secretion - Biliary HCO-3 - Growth of the exocrine pancreas Inhibits: - Gastric emptying Gastric H+ secretion GlucoseDependent Insulinotropic Peptide (GIP) K cells of the: - Duodenum - Jejunum - Protein - Fatty acids - Oral glucose - Insulin secretion from pancreatic β cells Motilin M cells of the: - Duodenum - Jejunum - Fat - Acid - Nerve - Gastric motility - Intestinal motility ‫ھو ﻧﻔﺳﮫ ﺣق اﻟﻣﺣﺎﺿرة اﻻوﻟﻰ‬ table Stimuli for secretion Stimulates: G cells of the: - Antrum - Duodenum - Jejunum this - Phases of gastric secretion From us ( team 443 ) not from the doctors Here TEST YOURSELF ! MCQ: Q1) Receptive relaxation reﬂex triggers by? A) stretch receptor B) swallowing reﬂex C)presence of nutrients in small intestine D) all of them Q2) Atrophy of gastric mucosa leads to? A) protein Malabsorption B) jaundice C) pernicious anemia D) diarrhea C) Somatostain D) HCL Q3) Pepsinogen is converted to pepsin by? A) Secretin B) CCK Q4) Which one of the following is “Hormone acts as inhibitor to block increased stomach motility caused by Gastrin” ? A) Gastrin B) Secretin C) Motilin D) CCK Answers: Q1:B | Q2:C | Q3:D | Q4:D SAQ: Q1) What are the three types of relaxation occur in gastric reservoir? 1. Receptive relaxation 2. Adaptive relaxation 3. Feedback relaxation Q2) Mention factors that promote stomach emptying? ● ● Increased gastric food volume Gastrin promotes the secretion of acidic gastric juices, and enhances the activity of the pyloric pump and motor stomach function Here.. for you! After studying this lecture. Team Leaders Rafan Alhazzani Fahad Almughaiseeb Ghaida Aldossary Faisal Alzuhairy Team Members Sarah Alshahrani Hamad Alziyadi mansour Alotaibi Melaf Alotaibi Nazmi A Alqutub Layan aldosary Raghad Almuslih Nazmi M Alqutub Norah alhazzani Layla Alfrhan khalid Alanezi Jouri Almaymoni Lama Almutairi Abdulaziz abahussain Salma Alkhlassi Remas mohammed Yousof Badoghaish Shoug Alkhalifa

L2 Stomach & Regulation of Gastric Secretion PDF

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