Digestion in stomach lect 3 .pdf

Digestion in the stomach Oleg Osadchiy 1 Learning objectives ✓ Overview the functions of the stomach in the process of digestion. ✓ Outline the structure of the stomach and the layers of the gastric wall. ✓ Describe the mechanisms that govern gastric motility. ✓ Explain the process of chemical diges...

Digestion in the stomach Oleg Osadchiy 1 Learning objectives ✓ Overview the functions of the stomach in the process of digestion. ✓ Outline the structure of the stomach and the layers of the gastric wall. ✓ Describe the mechanisms that govern gastric motility. ✓ Explain the process of chemical digestion in the stomach. ✓ Describe the structure and function of the gastric glands. 2 Learning objectives ✓ Explain the functions of the gastric acid in digestion and the mechanisms that regulate the gastric acid secretion. ✓ Explain the role of pepsin in digestion in the stomach. ✓ Describe the mechanisms that contribute to three phases of gastric secretion (cephalic, gastric, and intestinal). 3 Overview of GIT. Functions of stomach in digestion (i) Motor function – a) Acts as a temporary reservoir for the food. b) Mixing food with gastric secretions. c) Propels digested food to the duodenum. (ii) Secretory function – a) Secretion of gastric acid. b) Secretion of enzymes (pepsinogen and gastric lipase). c) Secretion of mucus and bicarbonates (to protect gastric mucosa from acidity). (iii) Source of humoral agents that regulate digestion – Gastrin, Histamine, Somatostatin. 5 Structure of the stomach. Structure of stomach ✓ Stomach three main regions – fundus, body, and antrum. ✓ Fundus is the upper portion of the stomach that is located above the lower esophageal sphincter. ✓ Below the fundus is a large, central portion of the stomach, called the body. ✓ Extending from the body is the antrum, the lower portion of stomach. ✓ The end of antrum communicates with duodenum via a pyloric sphincter (consists of smooth muscle). 7 Mucosa Submucosa Muscularis externa Serosa Four layers of the gastric wall. Stomach wall ✓ The stomach wall is composed of the same basic four layers as the rest of GIT – (i) Mucosa. (ii) Submucosa. (iii) Muscularis externa. (iv) Serosa. 9 Functions of stomach in digestion (i) Motor function. (ii) Secretory function. (iii) Source of humoral agents that regulate digestion. 10 Muscularis externa of the stomach contains three layers of muscle. Muscularis externa of the stomach ✓ The muscularis externa in the stomach has three layers of muscle (rather than only two layers of muscle found in esophagus and the intestine). (i) Outer longitudinal layer. (ii) Middle circular layer. (iii) Inner oblique layer. 12 Muscularis externa of the stomach ✓ The proximal part of the stomach (fundus and proximal part of the body) is thin-walled. ✓ The amount of muscle in the gastric wall is increasing in the distal direction, i.e. towards the antrum. ✓ The largest amount of smooth muscle in the wall is present in the antrum of stomach, so it generates most vigorous contractions. 13 Control of the gastric motility ✓ Parasympathetic stimulation and the hormone gastrin increase the force of gastric smooth muscle contractions. ✓ Sympathetic stimulation and the hormones secretin and cholecystokinin reduce the force of gastric smooth muscle contractions. 14 Contractile cells Autorhythmic cells Two types of smooth muscle cells in GIT. Where the stomach contractions originate from? Types of the muscle contractions in the stomach. Note different role of the proximal and distal part of the stomach in gastric motility. Factors that support the reservoir function of the proximal part of the stomach (i) Tonic contractions (sustained increase in muscle tension) is compressing the food, and reduces the intragastric volume it occupies. This releases some space inside the stomach, to accommodate additional amounts of food. (ii) Rugae (multiple folds) present in the stomach mucosa account for high distensibility of the stomach. (iii) Receptive relaxation of the stomach upon food entry from esophagus. 18 Tonic contraction generates a sustained compressive force that reduces the volume occupied by food. This releases an extra space upon subsequent muscle relaxation. The gastric mucosa contains large folds called rugae. As the stomach becomes distended with food and liquid, these folds flatten out. Thus, rugae allow the stomach to expand. Stomach is the most distensible part of GIT. Receptive relaxation of the smooth muscle is induced in the proximal part of stomach immediately upon entry of the food from esophagus. Receptive relaxation reduces intragastric pressure, and increases the stomach volume, so it can accommodate as much as 2 liters of food. Receptive relaxation is induced via the vagovagal reflex. Types of the smooth muscle contractions in the stomach. Types of phasic contractions in the stomach (i) Propulsion. (ii) Retropulsion. (iii) Gastric emptying. 24 Propulsion Retropulsion Types of peristaltic waves (phasic contractions) in the stomach. Contribute to churning and grinding the food, along with mixing it with gastric secretions. Propulsion and retropulsion ✓ The peristaltic waves are initiated by the gastric pacemaker, which is located on the greater curvature, in the middle of the body of stomach. ✓ The peristaltic waves intensify as they reach antrum. ✓ Each peristaltic wave moves gastric content from the body of the stomach down to its antrum. This process is called propulsion. ✓ Because most food particles in the stomach initially are too large to fit through the narrow pyloric sphincter, they are forced back into the body of the stomach. This process is called retropulsion. 26 Propulsion and retropulsion ✓ The cycles of propulsion and retropulsion are repeated many times, until the food is fully dispersed and mixed with a gastric juice, to form a soupy liquid called chyme. 27 Gastric emptying is a process by which the content of the stomach is moved to the duodenum. Gastric emptying ✓ Once the food particles in chyme are small enough, they can pass through the pyloric sphincter. ✓ Gastric emptying involves two events – (i) Phasic contraction of the smooth muscle in the stomach antrum (antral pump). (ii) Relaxation of the pyloric sphincter. 29 A B C Gastric content is moved to the duodenum in small portions. Gastric emptying ✓ Gastric emptying occurs within 2-4 hours after eating a meal. ✓ Gastric emptying is a slow process – only about 3 ml of chyme move through the pyloric sphincter at a time. ✓ Slow gastric emptying provides adequate time for the nutrients to be digested and absorbed in the duodenum. 31 Hormone Gastric acid Fatty acids Movement of a portion of chyme to the duodenum closes the pyloric sphincter and inhibits further gastric emptying by releasing hormones secretin and CCK. Regulation of gastric emptying ✓ Two major factors that inhibit gastric emptying are the presence of fat and the presence of gastric acid (low pH) in the duodenum. ✓ Fatty acids in the duodenum stimulate release of a hormone CCK, that inhibits gastric contractions. ✓ Low pH in the duodenum stimulates release of a hormone secretin, which inhibits gastric contractions. ✓ Low pH and stretch of the duodenum also intiates a reflex of the enteric nervous system (via the myenteric plexus) that inhibits gastric emptying. 33 Gastric emptying of different types of food ✓ Liquids are leaving the stomach more rapidly than solids. ✓ Isotonic contents are leaving more rapidly than hypotonic or hypertonic contents. ✓ Foods rich in carbohydrates empty more rapidly than protein-rich foods. ✓ The rate of gastric emptying is slowest for fats. 34 Gastric emptying of glucose is faster compared to protein. Functions of stomach in digestion (i) Motor function. (ii) Secretory function. (iii) Source of humoral agents that regulate digestion. 36 Chemical digestion in stomach ✓ Secretory function of stomach involves production of gastric juice, which contains hydrochloric acid, pepsin, and gastric lipase. ✓ On top of that, two enzymes present in the saliva (salivary amylase and lingual lipase) continue their action in the stomach, after saliva has been swallowed. 37 Salivary amylase and lingual lipase ✓ Foods remain in the fundus for about an hour without becoming mixed with gastric juice. During this time, digestion by salivary amylase continues. ✓ When the chyme is mixed with acidic gastric juice, the salivary amylase is inactivated. ✓ In the meantime, the gastric acid activates the lingual lipase, which starts to digest triglycerids. 38 Gastric juice ✓ About 2 liters of gastric juice (pH 1-2) are secreted daily. ✓ Gastric juice is secreted by gastric glands. ✓ Gastric juice contains five major components – (i) Hydrochloric acid (ii) Pepsinogen (iii) Mucus (iv) Gastric lipase (v) Intrinsic factor (required for absorption of vitamin B12 in the ileum). 39 Structure of the gastric gland. Gastric glands ✓ Secretions from the exocrine cells of the gastric gland are released into the glands`canaliculus, and then flow into the gastric lumen via the pits (openings of the glands into the lumen). ✓ The gastric glands contain three types of exocrine cells – (i) Mucuous cells that secrete mucus. (ii) Parietal cells that secrete hydrochloric acid and intrinsic factor (needed for absorption of vitamin B12). (iii) Chief cells that secrete pepsinogen and gastric lipase. 41 Gastric mucosa with numerous gastric pits (electron micrograph). 42 Gastrin ✓ In addition, the gastric glands contain the endocrine cells, the G cells, which are mostly found in the antrum. ✓ G cells secrete a hormone gastrin into the bloodstream. ✓ Gastrin stimulates the parietal cells to secrete the hydrochloric acid. ✓ Gastrin secretion is increased by vagal stimulation, and by the presence of amino acids in the gastric content. ✓ Gastrin secretion is reduced when a high amount of hydrochloric acid is present in the stomach (negative feedback mechanism). 43 Pyloric glands (gastric antrum) Oxyntic glands (gastric body) Two types of glands in the stomach. Chemical digestion by the gastric juice (i) Gastric acid (ii) Pepsin (iii) Gastric lipase 45 Gastric acid is secreted by the parietal cells. Gastric lumen Luminal membrane Basolateral membrane Secretion of hydrochloric acid. Secretion of hydrochloric acid ✓ Parietal cells are rich with an enzyme carbonic anhydrase, which catalyzes formation of carbonic acid from H2O and CO2. ✓ Carbonic acid then dissociates to H+ and HCO3- ions. ✓ The proton pump (H+/K+ ATPase), which is present at the luminal membrane, actively transports H+ into the stomach lumen, while bringing K+ ions into the cell. ✓ This increases K+ concentration inside the parietal cell, which causes K+ to diffuse back to the gastric lumen via the K+ channel present at the luminal membrane. 48 Secretion of hydrochloric acid ✓ HCO3- ions exit the parietal cell in exchange for Cl- ions through the Cl-/HCO3- antiporter present at the basolateral membrane. ✓ Bicarbonate ions then diffuse from interstitial fluid into the blood. ✓ The action of the Cl-/HCO3- antiporter contributes to an increased concentration of Cl- in the parietal cell, which causes Cl- to diffuse from the cell to the gastric lumen, via the Cl- channel present in the luminal membrane. 49 Ionic concentrations in gastric juice compared to plasma. Ionic concentrations in gastric juice compared to blood plasma ✓ K+, Cl-, and H+ concentrations in gastric juice are higher than in plasma. ✓ Na+ concentration in gastric juice is lower than in plasma. ✓ Gastric juice is isotonic to plasma. ✓ The rate of gastric acid secretion varies with the time of the day, being lower in the morning and higher in the afternoon and evening. 51 Control of the gastric acid secretion ✓ In the GIT, there are seven hormones and paracrine agents that regulate gastric acid secretion. ✓ Five agents are produced in the stomach (gastrin, histamine, acetylcholine, somatostatin, and prostaglandin E2). ✓ Two agents are produced in the duodenum (secretin and cholecystokinin). 52 Prostaglandin E2 Regulation of secretion of hydrochloric acid. Secretion of hydrochloric acid ✓ HCl secretion is stimulated by ACh released from the parasympathetic nerves, gastrin secreted by G-cells, and histamine released by mast cells in the lamina propria. ✓ HCl secretion is inhibited by somatostatin and prostaglandin E2. ✓ The receptors for all five agents are present at the basolateral membrane of parietal cells, which is facing the blood. ✓ These agents stimulate or inhibit translocation of the vesicles that contain proton pumps, from the cytosol to the luminal membrane of the parietal cell. 54 Secretion of gastric acid by parietal cells is inhibited by hormones secretin and cholecystokinin produced by endocrine cells in the duodenum. Stimulation of gastric acid secretion by gastrin and histamine. Inhibition of gastric acid secretion by somatostatin. Role of hydrochloric acid ✓ HCl kills microbes present in the food. ✓ HCl denatures proteins in food, facilitating their subsequent digestion by pepsin. ✓ Converts pepsinogen to the active enzyme, pepsin. ✓ Creates optimum pH for proteolytic activity of pepsin. ✓ In duodenum, HCl stimulates a release of enteric hormones which increase pancreatic secretion and the flow of bile (secretin and cholecystokinin). 58 Pepsin What is the protein denaturation? Chemical digestion by the gastric juice (i) Gastric acid (ii) Pepsin (iii) Gastric lipase 60 Structure of the gastric gland. Pepsin ✓ The chief cells in gastic mucosa secrete pepsinogen, which is converted to pepsin via effects of HCl. ✓ Pepsin is proteolytic enzyme acting as endopeptidase. It is acting on the peptide bonds in the inner parts of the peptide chain, so a long polypeptide is splitted into several smaller fragments (oligopeptides). ✓ Pepsin is active in the presence of acidic pH (pH 2.0). It becomes inactivated at a higher pH. 63 Pepsin shows maximum proteolytic activity in acidic pH. Stimulation of pepsinogen production in chief cells by various hormones and paracrine agents. Activation of pepsinogen by hydrochloric acid and pepsin. Chemical digestion by the gastric juice (i) Gastric acid (ii) Pepsin (iii) Gastric lipase 67 Gastric lipase ✓ In addition to pepsin, the chief cells in the stomach are producing a gastric lipase. ✓ Gastric lipase spits triglycerids into fatty acids and glycerol. ✓ This enzyme operates best at a pH of 5-6, which is higher than the pH (1-2) of the gastric juice in an adult person. ✓ Gastric lipase, nevertheless, plays a role in the fat digestion in newborn infants, in whom the gastric acid secretion has not been fully established yet. ✓ In neonates, the pancreatic lipase is not fully active yet, so the digestion of fat in the stomach is important. 68 Gastric lipase ✓ Upon emptying of the content of the stomach to duodenum, gastric lipase is inactivated through the action of pancreatic proteases. ✓ However, in patients with pancreatic insufficiency, the lack of pancreatic proteases in the duodenum may permit the continued action of gastric lipase after the gastric content is propelled into the duodenum. ✓ In this setting, gastric lipase may partly compensate for the impaired digestion of fat resulting from the pancreatic disease. 69 Secretion Motility Food reservoir Oxyntic glands Tonic contractions Gastric emptying Pyloric glands Gastrin (hormone) Phasic Contractions Summary: differences in secretory and motor function between the proximal and distal parts of the stomach. Absorption in stomach ✓ Only a small amount of nutrients is absorbed in stomach because its epithelial cells are impermeable to most materials. ✓ However, mucous cells of the stomach absorb some water, ions, certain drugs (e.g. aspirin) and alcohol. 71 Phases of gastric secretion. Phases of gastric secretion (i) Cephalic phase (30% of the total amount of gastric acid secreted in response to a meal) (ii) Gastric phase (60% of gastric acid) (iii) Intestinal phase (10% of gastric acid) 73 Food Acid Experiment of sham feeding. Note that food is not allowed to enter the stomach, as it is collected through a fistula introduced into the cut esophagus. Gastric juice is collected from the stomach through a cannula during the process of eating. Cephalic phase of the gastric acid secretion. Cephalic phase of the gastric secretion ✓ Sight, smell, and taste of food cause stimulation of the vagal nuclei in the brain. ✓ Vagus nerve stimulates gastric secretion either directly via effect on the parietal cells, or indirectly by inducing a release of gastrin from G-cells. ✓ Neural mechanisms (vagus nerve) play the most important role in the cephalic phase of the gastric secretion. 76 Gastric phase of the gastric acid secretion. Gastric phase of the gastric secretion ✓ When the food is swallowed and enters the stomach, it produces mechanical and chemical stimulation of gastric mucosa. ✓ Mechanical stimulation is caused by stretch. Chemical stimulation is caused by amino acids present in the food. ✓ These stimulations activate the vagus nerve, as well as induce a release of gastrin and histamine from the endocrine cells of gastric mucosa. ✓ Thus, both neural and hormonal mechanisms play an important role in the gastric phase of gastric secretion. 78 Intestinal phase of the gastric acid secretion. Mechanical and chemical stimulation Secretin, CCK Intestinal phase of the gastric secretion ✓ When the chyme is evacuated from the stomach to duodenum, it produces mechanical and chemical stimulation of the duodenal mucosa. ✓ Mechanical stimulation is caused by stretch. Chemical stimulation is caused by acidity, hyperosmolarity, and fatty acids. ✓ These stimulations activate a neural reflex reflex that inhibits gastric activity. In addition, the endocrine cells of duodenal mucosa release hormones secretin and CCK, which inhibit gastric motility and acid secretion. ✓ Thus, both neural and hormonal mechanisms play an important role in the intestinal phase of gastric secretion. 80 Phases of gastric secretion. After this lecture you are able to ✓ Describe the structure and function of the stomach. ✓ Describe the types of the gastric motility, including the role of the stomach as food reservoir. ✓ Explain the mechanism for emptying of the gastric content to duodenum. ✓ Explain chemical digestion in the stomach, including the action of gastric acid, pepsin, and gastric lipase. ✓ Describe the mechanisms that contribute to three phases of gastric secretion (cephalic, gastric, and intestinal). 82