Gastrointestinal Physiology PDF

Gastrointestinal Physiology Jun Hee Lee, Ph.D [email protected] Dept. Molecular and Integrative Physiology 109 Zina Pitcher Pl., 3019 BSRB (734) 764-6789  GI Physiology Lectures Lecture 1 – GI system overview – Mouth, Pharynx, Salivary gland and Esop...

Gastrointestinal Physiology Jun Hee Lee, Ph.D [email protected] Dept. Molecular and Integrative Physiology 109 Zina Pitcher Pl., 3019 BSRB (734) 764-6789  GI Physiology Lectures Lecture 1 – GI system overview – Mouth, Pharynx, Salivary gland and Esophagus – Stomach Lecture 2 – Intestines – Pancreas – Liver and Gallbladders Lecture 3 – Digestion and absorption of carbohydrates – Digestion and absorption of proteins – Digestion and absorption of fat GI System Overview Overview of GI processes Motility Secretion Digestion Absorption  Oral Cavity and Motility Esophagus Secretion M Swallowing and chewing S Saliva (amylase and lipase) Digestion D Carbohydrates and fats (minimal) Absorption A None Stomach Food M Mixing & Peristalsis S HCl, pepsinogen, bicarbonate, Bolus mucus, gastric lipase, gastrin, and histamine Chyme D Protein and fats Feces A Lipid soluble substances (alcohol and aspirin) Small Intestine M Segmentation and Peristalsis Large Intestine S Mucus, CCK, secretin, GIP, and M Mass movement other hormones S Mucus D Carbohydrates, fats, polypeptides and nucleic acids D None A Peptides, amino acids, glucose, A Ions, water, minerals fructose, fats, water, mineral, and vitamins vitamins  Overview: GI Motility Mixing & Churning Propulsion (Segmentation contractions) (Peristalsis) Thoroughly mix the chyme in the lumen. Bring the chyme into close contact with the intestinal wall. Most of the contractions are mixing & churning; peristalsis and the downstream movement of materials  Overview: Secretion & Absorption Food Bolus Chyme Feces Overview: Digestion & Absorption GI tract anatomy (I)  GI tract anatomy (II) Stomach wall Intestinal wall GI general histology Absorptive cells  Lamina Propria and Blood/lymphatic vessels  Smooth Muscle & Enteric Nervous System (ENS)  Enteric Nervous System (ENS) - Neural network regulating the gut CNS submucosal and myenteric plexus - Signals can originate in the gut or the CNS ENS - ENS can function independent of the myenteric plexus CNS submucus plexus - Regulates motility, secretion and hormone release  Hormonal Regulation Activation Inhibition  Phases of GI regulation Origin of Stimuli Cephalic phase Head sight, smell, taste, emotions Gastric phase Stomach distension, nutrients, osmolarity, pH Intestinal phase Intestine distension, nutrients, osmolarity, pH  Regulation of GI Processes Signals that regulate digestion Neural Regulation Enteric Nervous System 1. Distension of wall 2. Osmolarity 3. Acidity Hormonal Regulation 4. Digestion products Secretin, 5. Hunger, sight, smell, Cholecystokinin (CCK) and emotions Gastrin Glucose insulinotropic peptide Motility Secretion Digestion Absorption Upper GI Tract/ Salivary Glands Motility chewing and swallowing Secretion saliva (amylase, lipase) Digestion carbs and fats Absorption none  Saliva Lubrication (mucins) Buffers and dilutes spicy and acidic foods Partial digestion of food: starch and fat (amylase and lipase) Clean teeth and soft tissues Medium for the taste buds (gustation) Antibacterial/Antifungal (lysozyme, histatin) Maintenance of teeth (Ca2+, buffering) - Acidity dissolves minerals from teeth. - Salivary calcium re-mineralizes teeth.  Salivary glands 1500 ml saliva/day* Parotid: 25% of secretions Submandibular: 70% secretions Sublingual: 5% secretions * The volume of saliva secreted per gram is the largest secretion of any of the body’s exocrine glands.  Salivary glands: Acinar/ductal structure Epithelial cell types: Ductal cells fluid secretion and ion modification Ductal cells Acinar cells Mucous (viscous fluid - mucus) or Serous (fluid with soluble proteins - enzymes)...... Acinar cells...........  Consequences of Decreased Saliva Production This case was caused by extended use of methamphetamine. Similar outcome can be produced by  Regulation of Salivary Secretion Essentially neuronal (no hormonal) Parasympathetic (major) and sympathetic are both stimulatory – increased blood flow into the glands. Low rate of secretion keeps the mouth moist Cephalic phase of secretion – Smell or sight of food. Conditioned reflex – Pavlov’s dogs Response to stimuli in the mouth - This reflex is initiated by chemoreceptors (e.g. acid fruit juices) and pressure receptors in the walls of the mouth and on the tongue.  Phases of GI regulation Origin of Stimuli Cephalic phase Head sight, smell, taste, emotions Gastric phase Stomach distension, nutrients, osmolarity, pH Intestinal phase Intestine distension, nutrients, osmolarity, pH  Swallowing Swallowing (deglutition) is a reflex that pushes food or liquid into the esophagus. Coordinates signals to pharynx, esophagus and respiratory muscles Three phases Oral phase (Step 1) Pharyngeal phase (Step 2) Esophageal phase (Step 3)  Step 1: Oral phase Tongue pushes bolus against soft palate and back of mouth, triggering swallowing reflex. Voluntary control.  Step 2: Pharyngeal phase (1) (2a) (2b) (2c) 2a. The soft palate elevates to prevent food from entering the nasal passages. 2b.Upper esophageal sphincter relaxes while epiglottis closes to keep swallowed material out of the airways. 2c. Food descends into the esophagus  Step 3: Esophageal phase Food moves downward into the esophagus, propelled by peristaltic waves and aided by gravity. The coordinated sequence of contraction and relaxation in the upper esophageal sphincter, the esophagus, and the lower esophageal sphincter is necessary to deliver swallowed food to the stomach.  Movement of food into the stomach Lower esophageal sphincter temporarily relaxes with contraction wave - normally firmly closed - failure can lead to acid reflux (known as heartburn).  Vomiting Controlled by vomiting center in the brain stem Response to various neural input - Extensive stomach distention - Emetics (vomiting-inducing chemicals, e.g. syrup of ipecac) - Gagging (induced by touching the soft palate or throat) - Motion sickness Series of muscle contractions to force contents of the stomach through the esophagus and mouth.  Excessive vomiting Loss of fluid can lead to dehydration Loss of H+ ions can put a heavy alkaline load in the blood Risk of aspiration Acid can damage tissues in the esophagus and mouth Stomach  Stomach - Functions Storage: stores food and regulates the passage into the intestine Digestion: mechanical and chemical digestion of food into small particles Protection: protects the body from bacteria entering from the outside environment (role of acid)  Anatomy Specialized cells in the stomach synthesize and secrete mucous fluid, enzyme precursors, hydrochloric acid, and hormones. The abundant smooth muscle in the stomach is responsible for gastric motility. Cells of the Stomach Gastric cells and their products Cell Type Location Secretion Destination Parietal Cell Body HCl and IF Lumen Chief Cell Body Pepsinogen Lumen Mucous Cell All Mucus Lumen ECL Cell Body Histamine Mucosa D cell Body & Antrum Somatostatin Mucosa G Cell Antrum Gastrin Blood Gastric cells and their products Cell Type Location Secretion Destination Parietal Cell Body HCl and IF Lumen Chief Cell Body Pepsinogen Lumen Mucous Cell All Mucus Lumen ECL Cell Body Histamine Mucosa D cell Body & Antrum Somatostatin Mucosa G Cell Antrum Gastrin Blood  Parietal Cell Mechanism of Acid Secretion Acid production by the parietal cells in the stomach depends on the generation of carbonic acid; subsequent movement of hydrogen ions into the gastric lumen results from primary active transport.  Parietal Cell Regulation of Acid Secretion Gastric cells and their products Cell Type Location Secretion Destination Parietal Cell Body HCl and IF Lumen Chief Cell Body Pepsinogen Lumen Mucous Cell All Mucus Lumen ECL Cell Body Histamine Mucosa D cell Body & Antrum Somatostatin Mucosa G Cell Antrum Gastrin Blood  Chief Cell Regulation of Pepsin Activity Pepsin is NOT Essential for Protein digestion but facilitates it. Accounts for 20% of protein digestive activity. Critical for digestion of collagen (connective tissue matrix of meat).  Chief Cell Activation of Pepsin in Stomach Lumen Gastric cells and their products Cell Type Location Secretion Destination Parietal Cell Body HCl and IF Lumen Chief Cell Body Pepsinogen Lumen Mucous Cell All Mucus Lumen ECL Cell Body Histamine Mucosa D cell Body & Antrum Somatostatin Mucosa G Cell Antrum Gastrin Blood Gastric Mucosal Barrier (1) Protection against acid and pepsin Gastric Mucosal Barrier (2) Protection against acid and pepsin 1) A compact epithelial cell lining (tight junctions between cells) 2) An insoluble mucus (protective gel-like coating) 3) Bicarbonate ions neutralizing acids 4) Replacement of damaged epithelial cells The barrier is abrogated by chronic use of NSAID (e.g. aspirin) or H. pylori infection. Gastric cells and their products Cell Type Location Secretion Destination Parietal Cell Body HCl and IF Lumen Chief Cell Body Pepsinogen Lumen Mucous Cell All Mucus Lumen ECL Cell Body Histamine Mucosa D cell Body & Antrum Somatostatin Mucosa G Cell Antrum Gastrin Blood Hormonal Regulation The gastrin-gastric secretion and negative feedback mechanism G cells ECL cells D cells  Acid blockers Antacids Mylanta, Tums Histamine 2 (H2) receptor antagonist Tagamet (Cimetidine) Pepcid AC (Famotidine) Zantac (Ranitidine) Proton pump inhibitor Prilosec (omeprazole) Prevacid (lansoprazole)  Stomach Motility (1) Overview Stomach relaxes to increase volume – “receptive relaxation” – 50 ml (resting) 1500 ml (relaxed) Stomach Motility (2) Receptive Relaxation  Stomach Motility (3) Peristalsis 1. Grinding & Mixing 2. Regulated Exit  Stomach Motility (4) Regulation of Gastric Motility AJP - Gastrointestinal and Liver Physiology Vol. 299 no. 3, G585- G592  Stomach Motility (5) Intestinal-phase pathways inhibiting gastric emptying CCK, Secretin, GIP, etc. Summary (1) - Cephalic Phase - Summary (2) - Gastric Phase - Summary (3) - Intestinal Phase - Stomach Pathophysiology Peptic Ulcers Early 20th century gastric acid was thought the main cause of peptic ulcers. Antacids were the main treatment option. Recurrence rates were very high.  Helicobacter pylori 1983 Marshall and Warren isolated H. pylori from a patient with chronic gastritis Robert Warren Barry Marshall H. pylori is a bacteria present in the Barry Marshall/Robin Warren awarded stomachs of a majority of patients Nobel Prize for Physiology & Medicine 200 Helicobacter pylori Ulcer Recurrence rates 0% Antibiotics 50% Placebo Weeks after treatment Helicobacter pylori Produces Urease  Breaks down Urea into Ammonia and CO2  Ammonia neutralizes HCl  Dissolves and disintegrates mucin gel Ammonia, bacterial toxins  epithelial cell death and Inflammation  NSAID Induced Peptic Ulcers 10% of all peptic ulcers are caused by chronic aspirin administration Non-steroidal anti-inflammatory drugs (NSAIDs) have a multifactorial effect: Decreasing: cyclooxygenase-1 (COX-1) prostaglandin E2 (PGE2) bicarbonate mucus Increasing: Gastric acid  Summary Points OVERVIEW Four major processes performed by the GI tract Histological structures accommodating the functions Neuronal/hormonal regulation of GI functions UPPER GI TRACT Functions of saliva Regulation of salivary secretion Swallowing/vomiting processes STOMACH Different cell types in gastric epithelia The mechanism of gastric barrier protection Regulation of acid secretion by the gastrin-mediated negative feedback mechanism Pathophysiology of stomach (Helicobacter pylori) THANK YOU!