L2) Stomach & Regulation of Gastric Secretion.pdf

1-Storage of food: 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 ‫★اﻟﺟدول ﻣﮭم‬ Hormone ﬁll th 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 le He Stimuli for secretion Stimulates: G cells of the: - Antrum - Duodenum - Jejunum is tab - Phases of gastric secretion From us ( team 443 ) not from the doctors re 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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