An_Overview_of_Gastrointestinal_Tract_Function.pdf

1 Overview of Gastrointestinal Tract (GIT) Function Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Learning Outcomes Recall the basic structure of the Gastrointestinal tract Recall the innervation of the Gastrointestinal tract Co...

1 Overview of Gastrointestinal Tract (GIT) Function Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Learning Outcomes Recall the basic structure of the Gastrointestinal tract Recall the innervation of the Gastrointestinal tract Compare and contrast the organisation and roles of the extrinsic and intrinsic (enteric) nervous system Describe the different types of Gastrointestinal tract motility and their functions Describe the electrophysiological properties of Gastrointestinal tract smooth muscle cells Describe the neural and endocrine regulation of Gastrointestinal tract motility General Organisation Of The Gastrointestinal Tract Gastrointestinal Tract consists of: Mouth Oesophagus Stomach Small intestine Large intestine Appendix Rectum Anus Accessory organs Gut separated into ‘sections’ by Sphincters Overview Ingestion of food – Mastication – Swallowing Motor functions of the stomach – Storage – Mixing/propulsion of food – Stomach emptying & its regulation Movements of the small intestine – Mixing contractions – Propulsive movements – Prevention of backflow Movements of the large intestine – Mixing/propulsive movements – Defecation Splanchnic Circulation Blood from gut, spleen & pancreas flows to the liver via portal vein Blood filtered by liver sinuses before leaving via hepatic vein into vena cava Allows removal of bacteria/particulate matter (by recticuloendothelial cells) that might enter the blood from the GI tract Prevents direct transport of potentially harmful agents into body Anatomy of Gastrointestinal Blood Supply Nervous Control of GIT Blood Flow Parasympathetic stimulation – stomach & lower colon – increases blood flow & glandular secretion Sympathetic stimulation – vasoconstriction of arterioles – happens during exercise – Circulatory shock Overview of Anatomy of the Gastrointestinal Tract - Revisited = Adventitia Schematic diagram showing the general organisation of the GIT wall All parts of the GIT except the oesophagus and the distal rectum have this general organisation The oesophagus and the distal rectum lack the serosa and mesentery Submucosal plexus found in small and large intestine Myenteric plexus present throughout GIT Neural Control of GIT Function Extrinsic – neural and hormonal – Ach excites – Noradrenaline / adrenaline inhibits Intrinsic – myogenic, neural and chemical All GIT motilities do not require external nerve supply Generated by the enteric nervous system and extrinsic factors only modify them Enteric Nervous System Approx. same number of neurons as the spinal cord (~100 million)! Consists of sensory, inter and motor neurons Receives input from the ANS, but can function independently from it Myenteric plexus lies between circular and longitudinal smooth muscle layers and innervates both muscle layers Mainly concerned with motor control of the GIT Submucosal plexus lies between the circular smooth muscle layer and the mucosa Innervates glandular epithelium, endocrine glands and blood vessels – controls GIT secretion & local blood flow Extrinsic Nervous System Sympathetic and parasympathetic branches of the autonomic nervous system Parasympathetic neurones are branches of the vagus, pelvic and splanchic nerves Innervate neurones in the myenteric plexus Main function is to stimulate GIT motility and secretion Sympathetic nerves originate from the celiac, superior and inferior mesenteric and hypogastric plexuses Terminate on the enteric nerves, the smooth muscles and the mucosa Main function is to inhibit GIT motility and secretion Gastrointestinal Tract Smooth Muscle Syncytium Revisit smooth muscle contraction from MD2002 Muscle fibres connected by gap junctions and focal adhesions (adherens junctions) Actin and myosin filaments aligned diagonally along long axis of cells Filaments anchored at dense bodies (α-actinin-rich) scattered throughout sarcoplasm Contractile arrays anchored to sarcolemma by dense plaques Electrical Activity of Gastrointestinal Smooth Muscle GI smooth muscle stimulated by continual slow, intrinsic electrical activity Initiated in stomach by Interstitial Cells of Cajal (ICC) Two types of electrical activity: – Slow waves (basal electrical rhythm (BER); pacesetter potentials) – Spike potentials RMP can vary in different regions Interstitial Cells of Cajal (ICC) Figure from Sanders GASTROENTEROLOGY 1996; 111: 492–515 Electrical activity of GI Smooth muscle Slow waves Slow waves are not action potentials but slow undulating changes in resting membrane potential Slow waves do not themselves cause muscle contraction (except may be in the stomach) Excite appearance of spike potentials Intensity varies - 5 and 15mV Frequency ranges - 3-12 per min Electrical activity of GI Smooth muscle - Spike potentials True action potentials Occur automatically when resting membrane potential > ~40mV The higher the slow wave potential -> greater frequency of spike potentials Spike potentials last 10-40x as long in gastrointestinal muscle as action potentials in large nerve fibers each GI spike lasts 10 to 20ms Baseline membrane potential can also vary Depolarisation leads to increased excitability Hyperpolarisation leads to decreased excitability Electrical Activity of Smooth Muscle Cells K+ efflux Ca2+ influx Spontaneously fluctuates between -65 and -45mV Initiated in pacemaker cells known as interstitial cells of Cajal (ICC) Mainly due to the opening of calcium ion channels leading to the influx of Ca2+ into the cells. Terminated by Ca-dependent K+ efflux. Types of Gastrointestinal Motility Two main types of GIT motility: 1. Fed state – Peristalsis and mixing movements – Accounts for functions 1-3 in previous slide 2. Interdigestive state – Also known as the migrating motor complexes (MMCs) – Responsible for function 4 in previous slide Peristalsis Peristalsis - automatic reflex (peristaltic reflex) in response to stretch of the GIT wall Occurs during fed state in all parts of the GIT from the oesophagus to rectum Always moves in an oral to rectal direction at ~2 to 25 cm/s Under pathological conditions can be reversed leading to conditions such as vomiting Need an active myenteric plexus The stretch initiates the circular muscles behind (oral) it to contract (ascending excitatory reflex) and the circular muscles in front (anal) of it to relax (descending inhibitory reflex) Segmentation Function is to mix digested food Contractions of circular muscle layer at short intervals along GIT Contractions start as in 1 opposite Contractions then move forward to now contract in original relaxed area (2 opposite) Migrating Motor Complexes (MMC) Occur during periods of fasting / between meals Function to clear stomach and small intestine of debris and bacteria Consists of 4 phases – Phase I (45-60 mins) - quiescent period with slow waves – Phase II (30-35 mins) - action potential activity on slow waves but sporadic contractions of circular muscle – Phase III (2-12 mins) - action potential activity on slow waves but regular contractions of circular muscle – Phase IV – period in which action potential activity and contraction reduce and merge into phase I Peristalsis Endocrine Control of Gastrointestinal Tract Motility Hormone Source Target Organ Action Cholecystokinin (CCK) I cells duodenum Stomach Gall Bladder ↓ gastric emptying ↑ contraction Calcitonin gene related peptide (CGRP) Enteric neurons Blood vessels ↑ vasodilation Glucagon like peptides (GLP-1 and 2) L cells in ileum, colon and rectum Stomach GIT mucosa ↓ gastric emptying Ghrelin Gr or X/A cells in stomach stomach ↑ motility and gastric emptying Motilin Endocrine cells upper GIT Oesophageal sphincter Stomach Duodenum ↑ smooth muscle contraction MMC Neurotensin N cells throughout the GIT GIT smooth muscle Relaxation of LOS ↓ antral motility Pituitary adenylate cyclase activating peptide (PACAP) Enteric neurones GIT smooth muscle Relaxation Somatostatin D cells of stomach & duodenum δ cells pancreatic islets Stomach Intestine ↑ smooth muscle contraction Tachykinins (e.g. substance P) Sensorimotor neurones; Enteric neurones Longitudinal and circular layer of smooth muscle ↑ contraction Vasoactive Intestinal Peptide (VIP) Enteric neurones GIT smooth muscle ↑ relaxation Summary We have revisit the basic structure of the Gastrointestinal tract We have compared and contrasted the organisation and roles of the extrinsic and intrinsic (enteric) nervous system We have described the different types of Gastrointestinal tract motility and their functions (expanded on, in next lecture) We have described the electrophysiological properties of Gastrointestinal tract smooth muscle cells We have described the neural and endocrine regulation of Gastrointestinal tract motility References Guyton & Hall Textbook of Medical Physiology. (2021) Hall, JE & Hall, ME. 14th Edition. – Chapter 63, General Principles of Gastrointestinal Function – Motility, Nervous Control & Blood Circulation pp787-796 Medical Sciences. (2019) Nash & Syndercombe Court. 3rd Edition. – Chapter 15, The Alimentary System, pp 687-735 Lippincott's Illustrated Reviews: Physiology. (2019) Preston & Wilson. 2nd Edition. – Chapter 29, Principles and Signaling – Chapter 30, Mouth, Oesophagus and Stomach – Chapter 31, Small and Large Intestine Medical Physiology. (2017) Boron, WF & Boulpaep, EL. 3rd Edition. – Chapter 41 Organisation of the Gastrointestinal System pp 852-862 Medical Physiology. (2013) Rhoades, RA & Bell, DR. 4th Edition. – Chapter 25 Neurogastroenterology and Motility pp 471-504 Kunze WA, Furness JB. The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol. 1999;61:117-42. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology. 1996;111(2):492-515. Sanders KM, Ward SM, Koh SD. Interstitial cells: regulators of smooth muscle function. Physiol Rev. 2014;94(3):859-907.