GIT Changes Associated with Altered Secretion, Absorption & Motility (PDF)

Changes associated with altered GIT secretion, absorption and motility Dr. Samy Youssef, MD, MSc, Ph.D. Associate Professor of Physiology November 2024  Competency areas 1. 4.1.47 Determine changes in stomach acid secretion mechanisms leading to...

Changes associated with altered GIT secretion, absorption and motility Dr. Samy Youssef, MD, MSc, Ph.D. Associate Professor of Physiology November 2024  Competency areas 1. 4.1.47 Determine changes in stomach acid secretion mechanisms leading to peptic ulcer 2. 4.2.1 Define the cellular mechanisms in gastric acid secretion and associated bicarbonate tide. 3. 4.2.2 Describe the gastric biochemical protective defense mechanism against the stomach acidity 4. 4.1.55 Define the factors that govern gastric emptying and the disturbances associated with the gastroesophageal reflux disease (GERD) 5. 4.2.3 Identify the cellular mechanisms responsible for nutrient absorption and secretion 6. 4.1.56 Describe the mechanism of vomiting 7. 4.1.59 Describe the physiological mechanisms responsible for diarrhea and constipation Mrs. Sorya, a 45-year-old, works in stressful conditions. She complained of chest pain and visited many doctors with different diagnoses. The last physician only asked for CBC. Her Hb was 7 mg/dl. The doctor asked for stool analysis for occult blood. No frank blood in stool or urine. Q. Could GIT be related to this lady’s condition? Examination and US detected a slightly enlarged spleen.  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer 2. Stomach anatomical structure and food digestion  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer  List cellular mechanisms in gastric acid Gastric acid is primarily produced by parietal cells in the stomach through several cellular mechanisms: 1.Proton Pump (H+/K+ ATPase): This enzyme exchanges potassium ions from the gastric lumen with protons from the parietal cell cytoplasm, actively pumping hydrogen ions into the stomach, leading to acid secretion. 2.Carbonic Anhydrase: This enzyme catalyzes the conversion of CO2 and water into carbonic acid, which dissociates into bicarbonate and protons, contributing to hydrogen ion availability for acid production. 3.Chloride Channels: The Cl- ions are secreted into the gastric lumen through chloride channels, which combine with H+ to form hydrochloric acid (HCl). 4.Stimulation by Hormones and Neurotransmitters: Gastrin, histamine, and acetylcholine stimulate acid secretion by increasing the activity of the proton pump and other cellular signaling pathways.  List cellular mechanisms against PUD The gastric biochemical protective defense mechanisms against stomach acidity include: 1.Mucus Production: The stomach lining secretes a thick layer of mucus that coats the epithelial cells, providing a barrier against acidic gastric juice. 2.Bicarbonate Secretion: Bicarbonate ions neutralize stomach acid, helping to maintain a balanced pH in the stomach’s lumen. 3.Epithelial Cell Renewal: The stomach lining has a high turnover rate for its epithelial cells, which helps to replace damaged cells and maintain the barrier function quickly. 4.Tight Junctions: These structures between epithelial cells prevent gastric acid from leaking into the underlying tissues. 5.Prostaglandins: These compounds stimulate mucus and bicarbonate secretion and promote blood flow to the gastric mucosa, enhancing its protective capabilities  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer Acid is secreted by parietal cells in the stomach's proximal two-thirds (body). Gastric acid aids in creating optimal pH for pepsin. Acid secretion is initiated by food: by vagal stimulation of the gastrin-secreting G cells located in the distal one-third (antrum) of the stomach. Gastrin triggers the release of histamine from enterochromaffin-like cells in the body of the stomach. Histamine stimulates the parietal cells via their H2 receptors. The parietal cells secrete acid, and the resulting drop in pH causes the antral D cells to release somatostatin, which inhibits gastrin release (negative feedback control). Acid output declines in older patients who develop chronic gastritis, but it is otherwise maintained throughout life.  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer Usually, the gastrointestinal mucosa is protected by several distinct mechanisms: 1-Mucosal production of mucus and HCO3 creates a pH gradient from the gastric lumen (low pH) to the mucosa (neutral pH). The mucus serves as a barrier to the diffusion of acid and pepsin. 2-Epithelial cells remove excess hydrogen ions (H+) via membrane transport systems and have tight junctions, which prevent the diffusion of H+ ions. 3-Mucosal blood flow removes excess acid that has diffused across the epithelial layer. 4-Several growth factors (eg, epidermal growth factor, insulin-like growth factor I) and prostaglandins have been linked to mucosal repair and maintenance of mucosal integrity. 5-Interfere with these mucosal defenses (particularly nonsteroidal anti-inflammatory drugs [NSAIDs] and Helicobacter pylori infection) predisposes to gastritis and peptic ulcer disease.  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer 6-NSAIDs promote mucosal inflammation and ulcer formation (sometimes with gastrointestinal bleeding) both topically and systemically. By inhibiting prostaglandin production via blockage of the enzyme cyclooxygenase (COX), NSAIDs reduce gastric blood flow, reduce mucus and HCO3 secretion, and decrease cell repair and replication. Also, because NSAIDs are weak acids and are nonionized at gastric pH, they diffuse freely across the mucus barrier into gastric epithelial cells, where H+ ions are liberated, leading to cellular damage.  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer Post-gastrectomy gastritis is gastric inflammation developing after partial or subtotal gastrectomy. Chronic inflammation may lead to atrophy. Metaplasia of the remaining corpus mucosa is common. The degree of gastritis is usually most significant at the lines of anastomosis. Several mechanisms are responsible: Bile reflux, common after such surgery, damages the gastric mucosa. Loss of antral gastrin decreases stimulation of parietal and peptic cells, causing atrophy. Vagotomy may result in a loss of vagal trophic action. There are no specific symptoms of gastritis. Postgastrectomy gastritis often progresses to severe atrophy and achlorhydria. Production of intrinsic factor may cease with resultant vitamin B12 deficiency (which may be worsened by bacterial overgrowth in the afferent loop). The relative risk of gastric adenocarcinoma seems to increase 15 to 20 years after partial gastrectomy; Describe the role of the stomach in preventing pernicious anemia  Changes in stomach 1. Determine changes in stomach acid secretion mechanisms leading to peptic ulcer Bariatric surgery leads to significant physiological changes, including reduced stomach size, hormonal alterations impacting appetite and metabolism, and enhanced glucose regulation. These changes contribute to weight loss, improvements in obesity-related conditions such as type 2 diabetes, and alterations in nutrient absorption. Bariatric surgery can lead to several undesired physiological changes, including nutritional deficiencies (like vitamin B12, iron, and calcium), gastrointestinal issues (such as dumping syndrome, nausea, vomiting, and diarrhea), changes in bowel habits, These changes can arise from the alterations in the digestive system and how nutrient absorption is handled post-surgery.  Changes in stomach 1. Define the factors that govern gastric emptying and the disturbances associated with the gastroesophageal reflux disease (GERD) Gastric emptying is influenced by several factors including: 1.Composition of the Meal: Fats slow down gastric emptying, while carbohydrates and proteins have intermediate effects. 2.Volume of Food: Larger volumes tend to result in faster gastric emptying initially, though the rate may slow as the stomach fills. 3.Gastric Motility: The strength and rhythm of gastric contractions directly impact how quickly contents are pushed into the small intestine. 4.Hormonal Regulation: Hormones like gastric inhibitory peptide (GIP) and cholecystokinin (CCK) can slow gastric emptying, while others like ghrelin may stimulate it. 5.Physiological Factors: Conditions such as stress, anxiety, diabetes, and various gastrointestinal disorders can affect gastric emptying rates.  Changes in stomach 1. Define the factors that govern gastric emptying and the disturbances associated with the gastroesophageal reflux disease (GERD) Gastroesophageal reflux disease (GERD) can be caused by several factors, including: Lower esophageal sphincter (LES) dysfunction: Weakness or relaxation of the LES allows stomach acid to flow back into the esophagus. Obesity: Increased abdominal pressure can push stomach contents up into the esophagus. Hiatal hernia: Part of the stomach pushes through the diaphragm into the chest cavity, which can disrupt normal esophageal function. Dietary choices: Foods like chocolate, caffeine, spicy foods, and fatty meals can trigger reflux. Lifestyle factors: Smoking, alcohol consumption, and certain medications may aggravate GERD symptoms. Pregnancy: Hormonal changes and increased abdominal pressure can contribute to reflux.  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion * Lecture on digestion and absorption*  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion Iron absorption primarily occurs in the duodenum and the upper part of the jejunum of the small intestine.  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion Glucose, fats, and proteins are absorbed in the gastrointestinal (GI) tract through distinct cellular mechanisms: 1.Glucose Absorption: Primarily occurs in the small intestine using sodium-glucose transport proteins (SGLTs) in the brush border of enterocytes. Glucose is co-transported with sodium ions against its concentration gradient, utilizing the sodium gradient established by the Na+/K+ ATPase pump on the basolateral membrane. 2.Fat Absorption: Dietary fats are emulsified by bile salts and digested by pancreatic lipases into fatty acids and monoglycerides. These products are absorbed passively through the lipid bilayer of enterocytes and then reassembled into triglycerides, packaged into chylomicrons, and released into the lymphatic system. 3.Protein Absorption: Proteins are broken down into amino acids and peptides by gastric and pancreatic enzymes. Amino acids are absorbed through specific transport systems, including sodium-dependent and sodium-independent transporters, in the brush border membrane of enterocytes. Larger peptides can also be absorbed via endocytosis. *See lecture on digestion and absorption*  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion  Changes in intestine 1. cellular mechanisms responsible for nutrient absorption and secretion Summary of secretion and their control of GT https://www.studocu.com/row/document/tanta-university/medical- endocrinology-and-physiology/git-secretions-endocrinology/49140638 Intestinal juice: Succus entericus is a digestive fluid produced by the intestinal mucosa that contains enzymes and other substances essential for the digestion and absorption of nutrients in the small intestine. It includes various enzymes, electrolytes, and mucus that aid in the digestion of food. Secretions in the gastrointestinal tract (GIT) include saliva, gastric juice, bile, pancreatic juice, and intestinal secretions. Saliva begins the digestion process in the mouth, gastric juice helps digest food in the stomach, bile aids in fat emulsification in the small intestine, and pancreatic juice contains enzymes that digest carbohydrates, proteins, and fats. Additionally, the intestinal lining produces mucus to protect and assist in the absorption of nutrients.  Changes in intestine 1. Describe the mechanism of vomiting Vomiting, or emesis, is a complex physiological process that involves the 1.The mechanism of vomiting involves the coordinated actions of the following steps12:Nausea: At the onset, nausea is gastrointestinal system and the central experienced, followed by excess salivation. nervous system. The mechanism is 2.Glottis becomes closed and the nasopharynx is primarily initiated by the vomiting also shut off by raising the soft palate. center in the brainstem, which 3.The body of the stomach, the cardiac sphincter, receives signals from various sources, and the esophagus relax. including the digestive tract, vestibular 4.Intra-abdominal pressure sharply rises. system (inner ear), and higher brain 5.The process continues until the stomach is empty. centers. When the brain perceives a The whole mechanism is guided and controlled by trigger (such as toxins, motion, or the brain and its vomiting center irritation), it activates the vomiting center, which leads to a series of muscle contractions: the diaphragm and abdominal muscles contract while the esophagus relaxes, allowing the contents of the stomach to be forcefully expelled through the mouth.  Changes in intestine 1. Describe the physiological mechanisms responsible for diarrhea and constipation 1-Diarrhea results from increased gastrointestinal motility and secretion, Diarrhea is typically caused by several leading to shorter transit time and 1-physiological mechanisms, including increased inadequate absorption of water. It can intestinal motility, secretion of electrolytes and be caused by infections, inflammatory water into the gut, and altered absorption. conditions, or dietary factors. 2-Infections (viral, bacterial, or parasitic) can trigger inflammation in the intestinal lining, 2- Conversely, constipation occurs due leading to increased permeability and fluid to decreased motility, leading to secretion. prolonged transit time, excessive 3-Additionally, certain hormones or irritants can water absorption, and hard stools. stimulate excessive intestinal secretions, while conditions like irritable bowel syndrome can This may stem from inadequate fiber increase motility, preventing proper absorption of intake, dehydration, or medical fluids and nutrients. conditions impacting gut function.. Hormones that can influence diarrhea include serotonin and vasoactive intestinal peptide (VIP). Serotonin, which is found in the gastrointestinal tract, can stimulate bowel movements and alter gut motility. Increased levels of serotonin can lead to more frequent bowel movements and diarrhea. VIP is another hormone that can promote intestinal fluid secretion and increase intestinal motility. GIT Food Nutrients Absorption (Important) Where iron is absorbed? A 45 years old man is found to have a condition in which the parietal cells of his stomach have been destroyed by an autoimmune mechanism. This condition is often associated with which of the following?: a.Prenicious anaemia. b.Gastric ulcerarion c.Steatorrhea. d.Protein deficiency Thank you