UM 1010 GI Physiology powerpoint KT(3)(2).pptx

1 of 39 Physiology of the digestive system Control of the GI Tract Kathryn Taylor slides adapted from Darrell Brooks UM1010 ISCM 1 GI physiology  2 of 39 Lecture Outline The digestive tract Neu...

1 of 39 Physiology of the digestive system Control of the GI Tract Kathryn Taylor slides adapted from Darrell Brooks UM1010 ISCM 1 GI physiology  2 of 39 Lecture Outline The digestive tract Neural and Hormonal Control Mechanisms The role of the Enteric Nervous system Movement through the gut Parts of the GI tract and functions Mouth & oesophagus Stomach Small intestine Large intestine  3 of 39 Alimentary Tract General Principles of Gastrointestinal Function—Motility, Nervous Control, and Blood Circulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 63, 787-796 Alimentary tract. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  4 of 39 The gastrointestinal tract Continuous hollow tube - about 8 meters long Mechanically processes and moves food through the tract Chemically processes and digests food Absorbs nutrients and water The accessory organs - control secretions and breakdown food Teeth Tongue Salivary Glands Liver Gallbladder Pancreas  5 of 39 The digestive process  6 of 39 Neural and hormonal control mechanisms Autonomic nervous system Parasympathetic Sympathetic Peristalsis & motility Enteric nervous system Secretion & absorption Gut peptides Hormones Paracrines neurocrines  7 of 39 Autonomic nervous system (ANS)  Extrinsic nerves - long reflexes – external stimuli  Involves the CNS  Causes changes in motility and secretion Parasympathetic Vagus nerves Sympathetic Stimulate nerves digestion Inhibit digestion Pelvic  8 of 39 Enteric nervous system (ENS)  Contains all the elements of a nervous system  Intrinsic control – short reflexes - internal stimuli  Communicates with the parasympathetic and sympathetic but  Autonomous  Two well-organized neural plexuses:  myenteric plexus  submucosal plexus  9 of 39 Enteric nervous system (ENS) myenteric plexus : (Auerbachs plexus) between longitudinal and circular layers of muscle involved in control of digestive tract motility. submucosal plexus; (Meissners’s) between the circular muscle and the luminal mucosa senses the environment of the lumen and regulates gastrointestinal blood flow and epithelial cell function.  10 of 39 Typical cross section of the gut. General Principles of Gastrointestinal Function—Motility, Nervous Control, and Blood Circulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 63, 787- 796  11 of 39 Neural control of the gut wall General Principles of Gastrointestinal Function—Motility, Nervous Control, and Blood Circulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 63, 787-796 Neural control of the gut wall, showing the following: (1) the myenteric and submucosal plexuses (black fibers); (2) extrinsic control of these plexuses by the sympathetic and parasympathetic nervous systems ( red fibers); and (3) sensory fibers p... Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  12 of 39 GI Hormones Criteria must be met for a substance to be a true GI peptide 1.The substance must be secreted in response to a physiologic stimulus and be carried in the bloodstream to a distant site where it exerts its physiologic action 2. The function must be independent of any neural activity 3.It must have been isolated, purified, chemically identified and synthesized. There are other ‘candidate’ hormones Adhering to these criteria only 5 qualify as gastrointestinal hormones Gastrin Cholecytokinin- CCK Secretin Glucose dependent Insulinotrophic peptide GIP Motilin  13 of 39 Hormonal control - Enteroendocrine cells  In excess of 22 hormones and paracrines  Secreted by Enteroendocrine cells (EEC) in the mucosa  Single cells scattered through GI tract  Densely packed secretory vesicles  Sense luminal contents  chemical, osmotic and pH  release hormones and paracrines Sites of production of the five gastrointestinal hormones along the length of the gastrointestinal tract. The width of the bars reflects the relative abundance at each location.  14 of 39 Motility  Phasic contractions: short lasting contractions - movement of material in the small intestine  Peristalsis (waves of contractions-20cm)  Segmented contractions (10cm)  Tonic contractions: long lasting contractions - closing of a sphincter  Controlled movement of material though the tract  Maintains ordered sequence of events  Compartmentalisation ensures processes are complete before passing to next area  15 of 39 Peristalsis  Propulsion of material- peristalsis  Mediated by neurones in myenteric plexus -  Interstitial Cells of Cajal (ICC)  ICC are pacemakers of the gut (like in the heart) Santiago Ramón y Cajal  Found in myenteric plexus  Electrical activity spreads via gap junctions from ICCs to muscle  ICCs produce slow waves  differs in different regions of the GI tract  16 of 39 Slow waves  Slow waves- slow undulating changes in resting membrane potential- NOT action potentials (different from SA node in heart)  Don’t cause contraction until the threshold (- 40mV) is reached  Activated by  distention - bolus of food (chyme)- stimulates stretch receptors (local reflex) Oral contraction Aboral relaxation  Parasympathetic nerves (ACh)  17 of 39 Peristalsis General Principles of Gastrointestinal Function— Motility, Nervous Control, and Blood Circulation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 63, 787- 796 Peristalsis involves contraction and downstream relaxation in the esophagus, stomach and small intestine propel the contents toward the anus. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  18 of 39 Segmented contractions & Mass Mo t ilit y movements  Colon: 99% of the time Retain material (e.g. water reabsorption and fermentation) Mo t ilit y in t h e c o lo n Mixing contents Mo s t ly s e g m e nt a t i BER is f a s t e r d is t a k e e p s f a e c e s o ut o r e c t um  Mass movement of material into aboral end of colon Gastro-colic response Ma s s m o ve m e nt s 2-3 times per day pr o pe l t h e f ae c e s  19 of 39 Hirschprungs disease - TOXIC MEGA COLON Congenital disorder presents shortly after birth All or part of colon has no innervation aganglionic segment is strictured. Proximal to the strictured segment, the colon is dilated. 1:5000 children affected Surgical removal of the colon  20 of 39 Introduction:The Gastrointestinal System  21 of 39 The mouth - start of the journey  Mastication- breakdown food  Taste- inform brain about edibility/duration  Saliva production- lubrication, protection and digestion  Swallowing- movement of digested macromolecules to stomach  22 of 39 The mouth - Taste  Papillae: ‘taste organs’ Raised protrusions on the tongue Visible to the naked eye Located on the tongue, soft and hard pallet, pharynx, epiglottis and larynx. Contain the taste buds Each taste bud contains 3 kinds of cells: Epithelial cells, Support cells, Gustatory receptor cells (taste cells) Innervated by gustatory afferent nerves  23 of 39 The mouth - A taste bud  50-100 continuously maturing cells  Bud shields the cells from the oral cavity  Apical microvilli increase surface area  Receptor proteins exposed through the taste pore (3-5µM)  ION CHANNELS / RECEPTOR S located on villi All flavours are encoded by 5 taste modalities: Sweet, Salt, Sour, Bitter, Umami FUNCTIONS OF TASTE? One taste cell responds to one modality Ionotropic receptor Salt Na+, Sour H+ gated ion channels (K+/H+) Metabotropic receptors Sweet, Bitter, Umami  24 of 39 The mouth - Saliva production  Hypotonic solution containing more than 99% water and 1% dry matter such as proteins Water Bicarbonate ions- buffering capacity, protects from acid Mucous Enzymes α-amylase - released from the parotid gland which initiates carbohydrate digestion, lipase - secreted within glands of the mucosa of the tongue (linguinal) Proteins (100s) Multifunctional Anti- bacterial, Anti- viral, Anti- fungal, Tissue Coating, Lubrication & Viscoelasticity, Mineralization, Buffering, Digestion  25 of 39 The mouth & oesophagus- Swallowing Oral phase (voluntary) Preparatory phase- chewing and biting Transfer phase- Respiration inhibited and tongue forces bolus into pharynx Pharyngeal phase (involuntary) Movement of bolus from pharynx into oesophagus Oesophageal phase Delivers bolus to the stomach Esophageal manometry measures oesophageal motility & problems swallowing - dysphagia  26 of 39 Swallowing Mechanism Propulsion and Mixing of Food in the Alimentary Tract Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 64, 797-806 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  27 of 39 The stomach Gastric functions 1. Motility a. Gastric accommodation b. Trituration - gastric juices c. Gastric emptying 2. Digestion 3. Protection 4. Absorption Note. Anatomical and functional regions do not correspond  28 of 39 The stomach - gastric juice 1.Water and ions 2. HCl Provides low pH (as low as pH 1 or 2!) Prevents bacterial growth Catalyses cleavage of pepsinogens to pepsin 3. Pepsinogens Proenzyme of pepsin Pepsin breaks down proteins into peptides 4. Intrinsic factor Glycoprotein Binds to vitamin B12- allowing digestion in the ileum 5. Mucus Protects gastric mucosa 6. Gastrin From ‘G cells’ Regulates acid secretion  29 of 39 The stomach – gastric secretion A TEM of an active parietal cell Composite diagram of a parietal cell shows the ultrastructural differences between a resting cell (left) and an active cell (right). somatostatin  30 of 39 The stomach - HCl secretion (parietal cells) CO2 within the parietal cells reacts with H2O to form bicarbonate, and then H+ catalysed by the enzyme carbonic anhydrase H+ is actively transported by ‘proton pumps’ into the gastric lumen, in exchange for K+ ions Both K+ and Cl- diffuse passively down a concentration gradient out of the cell The bicarbonate produced is transported into the capillaries in exchange for Cl- ions by ‘antiporters’  31 of 39 The stomach – control of secretion & motility Acid secretion 1. Neuroendocrine (ACh) 2. Endocrine (gastrin) 3. Paracrine (histamine) 1. 3. 2.  32 of 39 The stomach – Gastric /Peptic Ulcers Mucus entraps alkali fluid-gastric mucosal barrier Break in mucosal barrier exposes underlying tissue to corrosive action (acid, proteases) by Alcohol, vinegar, bile, stress, NSAIDS & Bacterial infection - Helicobacter pylori Symptoms Abdominal pain Bloating Nausea/vomiting Bleeding- haemorrhage and anaemia  33 of 39 1.Excess secretion of acid and pepsin by the gastric mucosa Causes of 2. Diminished. ability of the Peptic gastroduodenal mucosal Ulcer barrier to protect against the digestive properties of the stomach acid–pepsin secretion  34 of 39 Urease can be H. Pylori infection easily detected using a breath test Bacteria produce urease, which Bacteri neutralises a gastric acid, burrow protecting the throug bacteria and producing h toxic mucus ammonia as a layer by-product Destruction of mucus layer exposes Bacteri epithelium to acid and a pepsin; multipl further y damage causes inflammation Source: Y_tambe, dual-license with GFDL and CC-by-SA, http://upload.wikimedia.org/wikipedia/commons/5/51/H_pylori_ulcer_diagra... and cell death  35 of 39 Lindsay, James, Kumar and Clark's Clinical Medicine, 13, 357-436 Helicobacter Helicobacter pylori. A. Organisms (arrowed) are shown on the gastric mucosa (cresyl fast violet (modified Giemsa) stain). B. Scanning electron microscopy, showing the spiral-shaped bacterium (arrowed). ( A, Courtesy of Dr Alan Phillips, Department... pylori Gastrointestinal disease Copyright © 2017 © 2017 Elsevier Ltd. All rights reserved.  36 of 39 The duodenum First loop of the small Intestines (25-40 cm long) Vital role in digestion of the bolus-often forgotten. Reflex inhibition of motility – enterogastric reflex ‘Brunner’s glands’ Secrete an alkaline fluid composed of mucin- anti-acid function by coating the duodenal epithelium Protecting it from the acidic chyme of the stomach Receives secretions from: Gall bladder (liver) Pancreas Site of metal ion absorption (Fe2+, Mn2+, Ni2+, Cu2+) What condition is iron deficiency a symptom? Iron overload occurs in hemochromatosis.  37 of 39 The duodenum - Pancreas Exocrine gland (85%) – Acinus (similar to salivary gland but no myoepithelial cells) 1. Water and ions Neutralize duodenal contents to prevent damage and 2. Bicarbonate pH for enzymes 3. Enzymes –essential for normal digestion Endocrine gland (2%) – Islets of Langerhans α cells – glucagon ß cells – insulin Cystic fibrosis transmembrane conductance  38 of 39 The duodenum – Pancreas – water and bicarbonate  Secretion of pancreatic juice is primarily under hormonal control.  CCK acts on acinar cells causes the production of pancreatic juice rich in enzymes but low in volume.  Secretin acts on the pancreatic ducts to cause copious secretion of a very alkaline pancreatic juice that is rich in HCO3− and poor in enzymes.  Together, CCK and secretin add enzymes to the pancreatic juice and ensure that they are washed into the intestine Acinar cells Duct cells  39 of 39 The duodenum - Pancreatic Enzymes Trypsinogen - trypsin Chymotrypsinogen - chymotrypsin Proteins Proelastase - elastase Procarboxypeptidase - carboxypeptidase Lipase and phospholipase- Fats Nucleases- Nucleic acids α-amylase- Carbohydrates Acinar cells CCk: cholecystokinin  40 of 39 The Liver - structure  Hepatic artery - oxygenated blood  Portal vein - nutrient rich blood from gut  Hepatic vein - deoxygenated blood from the liver  Bile - produced by the liver and concentrated in gall bladder (x15) - biliary system  Divided into lobules  Portal triad- bile duct, portal vein and hepatic artery  Central canal- hepatic  41 of 39 The Liver - bile Bile is alkaline (pH7.8 - 8.6) contains: Water bile pigments (bilirubin) salts, cholesterol and lecithin (micelles) Bile salts emulsify fats (micelles) - large surface area (facilitates action of lipase enzymes) 95% bile salts reabsorbed in terminal ileum by active transport and returned via hepatic portal vein to liver to be recycled Secretion controlled by: Secretin stimulates bile secretion CCK stimulates release of bile by Relaxing Sphincter of Oddi Contracting gall bladder  42 of 39 Key points so far…. Stomach ↑ gastrin release ↑ Acid production and motility Duodenum ↑ Secretin and CCK release ↑ GIP release Inhibits gastric activity Stimulate pancreas and gall bladder Pancreas Release of enzymes for digestion Gall bladder Contraction and release of bile for emulsification of fats  43 of 39 The jejunum & ileum Latter portion of the small Intestines (about 2.5 m) Large surface area - facilitates absorption Achieved by 3 orders (strata) of folding Absorption – pancreatic enzymes water Digestion - Carbohydrate – monosaccharides protein – peptides & amino acids lipid - free fatty acids Secretion of Fluid – Crypt cells- NaCl Goblet cells- mucus EECs-hormones Panneth cells- defensins  44 of 39 The jejunum & ileum - absorption vs. secretion Malabsorption – Food and drink Absent or defective digestive enzymes Defects in transporter proteins Diseases or infections of small intestine Examples Lactase deficiency - lactose intolerance Coeliac disease – abnormal immune response to gluten – loss of mucosal epithelium  45 of 39 The large intestine - anatomy 1.5m length and thicker than SI From Ilocecal valve → rectum Regions: Caecum – a pouch that compress material into faecal matter Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Anus Tenia coli – 3 bands longitudinal muscle shorter than colon forms haustra by Saculations No villi High concentration of goblet cells- mucus secretion  46 of 39 The large intestine - motility Slow movement of contents Segmented contractions Retain material in the proximal colon (water Mo t ilit reabsorption and fermentation) Mixing contents Mass movements – 2-3 times a day movement of material into aboral end of colon- ready for defecation Pacemakers of the gut produce slow waves Couples to motility Different subtypes  47 of 39 MBBS learning outcomes Describe the normal physiology of the parts of the GI system Outline the process of digestion, its neural and hormonal control for the digestion of carbohydrates, fat and proteins. Identify the role of ion channel signalling in the GI