GIT MD Lectures_2024 Lectorials 1 and 2.pdf

The Gastrointestinal System Lectorial 1: Overview Dr Sherry Wu School of Biomedical Sciences University of Queensland Email: [email protected] http://apps.elearning.uq. edu.au/poll/69244  Objectives Basic understanding of the GI tract:...

The Gastrointestinal System Lectorial 1: Overview Dr Sherry Wu School of Biomedical Sciences University of Queensland Email: [email protected] http://apps.elearning.uq. edu.au/poll/69244  Objectives Basic understanding of the GI tract: Functions and processes Understand the digestion processes for carbohydrates, proteins, and fat Understand how GI tract is innervated & regulated – Autonomic nervous/smooth muscle system – Enteric nervous systems – Gut endocrine system – GIT receptors Basic understanding of common GI problems  Gastrointestinal Problems Varied Presentation Pain, abdominal or chest (e.g., Ulcer, diverticular disease – “out- pouching” in LI, gastric/duodenal ulcer/cancer, gallstones) Problem with food ingestion: nausea, vomiting, dysphagia, anorexia (Reflux, gastroparesis, obstruction) Diarrhoea, constipation, changing bowel movement (diverticular disease, gastroenteritis, IBS, IBD, diabetic neuropathy) GI bleeding (varices, ulcer, IBD, diverticular disease, colon cancer, gastroenteritis) Disease may be: Limited to GI tract (reflux, ulcer, diverticular disease, obstruction) Present as a systemic disorder with GI origin (vitamin malabsorption) The Digestive System gland Longitudinal organization Esophagus GI tract = 4.5 m long Stomach (in normal contractile state) GI tract = 9 m long (cadaver) Accessory digestive organs: Small Intestine Salivary glands, teeth, tongue Exocrine pancreas Biliary system – Liver + Large gallbladder Intestine Appendix Major Structures in GIT – Mouth – Pharynx – Oesophagus – Stomach – Small intestine Duodenum Jejunum Ileum – Large intestine Cecum Colon Rectum  Key Processes of GIT Motility: Movement of food throughout G.I.T. and maintenance of tone Secretion of digestive juices and digestion of food Absorption of digested products, water & electrolytes Circulation of blood throughout G.I.T. to carry away absorbed substances Control: Nervous and hormonal systems  Motility Muscular contractions that – Mix (mix with digestive juice; facilitate absorption by exposing digestive tract surfaces), and – Move forward the content within GIT (propulsive movements) Smooth muscle for most parts Skeletal muscle: – Mouth through early part of oesophagus – External anal sphincter  Motility: Peristalsis Movement along the tract Sequential contraction/relaxation of adjacent smooth muscle Usually- about 10cm bursts, but occasional entire length waves Motility and mechanical Digestion: Segmentation 1. Mix contents to promote digestion & absorption 2. Slow progression – contractions more frequent in proximal small intestine – Circular muscle – 12/min in duodenum, 8-9/min in jejunum/ileum – (Pacemaker cells in duodenum spontaneously depolarize faster) Intensity influenced by: Distension of the intestine (e.g., in duodenum) Gastrin (produced by G cells in pyloric gland area in stomach) – e.g., in ileum, gastroileal reflex Extrinsic nerve activity Parasympathetic stimulation enhances segmentation  Secretion Exocrine secretion – E.g., Exocrine pancreas Proteolytic enzyme – protein Pancreatic amylase – carbohydrate Pancreatic lipase – fat – E.g., Chief cells in oxyntic mucosa in stomach Pepsinogen – protein Endocrine secretion – E.g., G cells (produce gastrin) and D cells (produce somatostatin) in pyloric gland area (PGA) in stomach Digestive secretions are typically reabsorbed back into the blood after their participation in digestion Digestion of Carbohydrates Polysaccharides: – E.g., Starch from plants & Glycogen from meat & Cellulose from plant walls (indigestible fibre) Disaccharides (e.g., sucrose, lactose) Polysaccharides and disaccharides are digested into monosaccharides (absorbable units)  Carbohydrate Digestion Salivary Glands Enzyme Site of action Function Absorbable? Amylase Mouth and Hydrolyses Not yet (mostly) body polysaccharides to of stomach disaccharides and α- limit dextrins Exocrine Pancreas Enzyme Site of action Function Absorbable? Amylase Small Hydrolyses Not yet intestine polysaccharides to lumen disaccharides and α- limit dextrins Small Intestine Epithelial Cells Enzyme Site of action Function Absorbable? Disaccharidases Small intestine Hydrolyse disaccharides to Yes Maltase brush border monosaccharides Sucrase-isomaltase Lactase  Protein Digestion Proteins → Amino acids (AA) and small polypeptides Stomach Chief Cells Enzyme Site of action Function Absorbable? Pepsin Stomach Hydrolyses protein Not yet antrum to peptide fragments Exocrine Pancreas Enzymes Site of Function Absorbable action ? Trypsinogen Small Attack different Not yet Chymotrypsinogen Intestine peptide Procarboxypeptidase lumen fragments Activated by enteropeptidase in duodenum Small Intestine Epithelial Cells Enzyme Site of action Function Absorbable? Aminopeptidases Small intestine brush Hydrolyses peptide fragments Yes (AA and small border into AA peptides)  Fat Digestion Triglycerides (a glycerol + three fatty acid molecules) → monoglycerides and free fatty acids Exocrine Pancreas Enzymes Site of Function Absorbable? action Lipase Small Hydrolyses Yes intestine triglycerides to fatty lumen acids and monoglycerides Liver Substance Site of action Function Absorbable? Bile salts (NOT an Small intestine lumen Emulsify large fat globules for N/A enzyme) attack by pancreatic lipase  Absorption Small absorbable units + water, vitamins, and electrolytes Most of the ingested food → absorbed indiscriminately (more food consumed, more will be digested and absorbed) Typically, only the absorption of calcium and iron is adjusted to body’s needs Structure of GIT Wall Cross-section of GIT wall 4 Major layers 1 Mucosa 2 Muscularis 3 Externa Enteric Nervous 4 System  GIT: Mucosal Layer 1. Mucosa – Mucous membrane (inner epithelial layer; protective surface). Contains: Exocrine gland cells for secretion of digestive juices (e.g., chief and pariental cells) Endocrine gland cells for secretion of blood-borne GI hormones (e.g., G and D cells) Epithelial cells specialized for absorbing digestive nutrients – Lamina propria: Middle connective tissue layer; where the gut-associated lymphoid tissue (GALT) is located – Muscularis mucosa: Smooth muscle layer  GIT: Submucosa & Muscularis Externa 2. Submucosa – Thick connective tissue layer providing distensibility and elasticity – Contains larger blood and lymph vessels – Submucosal plexus nerve network 3. Muscularis Externa – Major smooth muscle coat of the GIT – Inner circular layer + Outer longitudinal layer – Contraction produces the propulsive and mixing movement – Myenteric plexus: lies between two muscle layers – Pacemaker cells known as the interstitial cells of Cajal locate here  GIT: Serosa 4. Serosa – Secretes watery, slippery fluid (serous fluid) to prevent friction between the digestive organs and surrounding viscera – Serosa is continuous with the mesentery, which suspends the digestive organs from inner wall of the abdominal cavity Regulation of Digestion  Regulation of Digestion Regulation of digestion requires the integrative control of GIT function. GIT = self-regulating system of organs Coordination of motor, 2 1 secretory, digestive & absorptive functions 3 1. Autonomic nervous/smooth muscle system 2. Enteric nervous systems 3. Gut endocrine system  1. Autonomic nervous/smooth muscle systems Autonomic smooth muscle function – Spontaneous, rhythmic cycles of depolarization and repolarization – Self induced electrical activity: Basic electrical rhythm (BER) – Interstitial cells of Cajal generate slow-wave potentials that propagate via gap junctions – Greater action potential → Higher cytosolic Ca2+ concentration → Greater cross-bridge activity → Stronger contraction Autonomic nervous system (extrinsic nerves) – Major purpose: Coordinate activity among different regions of the digestive system. – Influence motility and secretion by modifying activity of intrinsic plexuses, altering level of GI hormone secretion, or acting directly on smooth muscle and glands  Parasympathetic Innervation 1 Parasympathetic arises in 2 separate regions of the CNS 1) In the medulla: controls Damage oesophagus to ascending colon leads to via vagus nerves gastroparesis 2) In the sacral spinal cord: controls beyond ascending colon via pelvic nerves. Postsynaptic neurotransmitter: acetylcholine (+) 2 Parasympathetic system tends to increase smooth muscle motility and promotes secretion of digestive enzymes or hormones.  Sympathetic Innervation Sympathetic arise in the * spinal cord Forms synapses in superior cervical ganglion* and other T5-L2 ganglia with post-ganglionic cells projecting to the gut. Postsynaptic neurotransmitter: Noradrenaline (-) Sympathetic system inhibits digestive tract contraction and secretion.  Regulation of Digestion Regulation of digestion requires the integrative control of GIT function. GIT = self-regulating system of organs Coordination of motor, 2 1 secretory, digestive & absorptive functions 3 1. Autonomic nervous/smooth muscle system 2. Enteric nervous systems 3. Gut endocrine system  2. Enteric Nervous System Intrinsic (Enteric) nerves Located In the submucosa (submucosal plexus) and muscularis externa between circular & longitudinal muscle layers (myenteric plexus) Excitatory - Acetylcholine Control Inhibitory – Vasoactive intestinal Motility - Myenteric plexus peptide, nitric oxide Secretion/Absorption - Submucosal plexus Excitatory - Acetylcholine Intrinsic nerve activity can be influenced by endocrine, paracrine, and extrinsic nerve signals.  Overview of GI Neural Innervation Parasympathetic n.s Sympathetic n.s. Vagal nuclei CNS Preganglionic fibres Preganglionic fibres Sacral spinal Sympathetic cord ganglia Postganglionic fibres Enteric nervous system Myenteric Submucosal plexus plexus Smooth muscle Secretory Endocrine Blood (GI motility) cells cells vessels  Enteric Nervous System Myenteric Submucosal Plexus Plexus e.g., gastrin release interneurons interneurons Parasympathetic nerves Myenteric Submucosal Plexus Plexus Functions of the Myenteric Plexus (Muscularis Externa layer) Linear plexus; entire length of the GIT Control of the motor activity Stimulation leads to ↑ tone of gut wall ↑ increased intensity of contractions ↑ rate of contraction ↑ peristalsis Functions of the Submucosal Plexus (Submucosal layer) Local control within the inner walls of each gut segment Controls local absorption, secretion, contraction  Regulation of Digestion Regulation of digestion requires the integrative control of GIT function. GIT = self-regulating system of organs Coordination of motor, 2 1 secretory, digestive & absorptive functions 3 1. Autonomic nervous/smooth muscle system 2. Enteric nervous systems 3. Gut endocrine system  3. Gut Endocrine System Produced by specialized endocrine cells tucked within the mucosa of certain region of GIT – Can have excitatory or inhibitory influences on digestive smooth muscle and exocrine gland cells – E.g., Enterochromaffin-like (ECL), G and D cells in stomach ECL cells G cells D cells Stimulate Stimulate Inhibit parietal cells parietal, chief, parietal, G, and ECL cells and ECL cells Chief cells: Pepsinogen; Parietal cells: HCl + Intrinsic factors  GIT Receptors Receptor activation alters digestive activity through neural reflexes and hormonal pathways  GIT Receptors The digestive tract wall contains 3 types of sensory receptors: Chemoreceptors - chemical composition of luminal fluid Mechanoreceptors - stretch or tension in the gut wall Osmoreceptors - osmotic composition of the luminal fluid Smooth muscle cells – modify motility Exocrine gland cells (for Receptor Neural reflex controlling secretion of stimulation Secretion of hormones digestive juices), Endocrine gland cells (for varying secretion of GI hormones) The Gastrointestinal System Lectorial 2 Dr Sherry Wu School of Biomedical Sciences University of Queensland Email: [email protected]  Objectives Understand the four basic digestive processes of motility, secretion, digestion, and absorption for each digestive organ Understand the digestion processes for carbohydrates, proteins, and fat Basic understanding of common GI problems  Mouth – Digestion – Mechanical and chemical digestion occur in the mouth – Mechanical digestion results from chewing (mastication) – Chemical digestion begins Salivary amylase: – Initiates breakdown of starch (inactivated by acid but activity continues for significant time in stomach) – Starch → Maltose (a disaccharide) and α-limit dextrins Lingual lipase – Hydrolyses complex lipids (triglycerides) into fatty acids and glycerol – Remains activated in acid environment of stomach (less than 10% digestion of fat overall)  Saliva Extrinsic autonomic nerve Parasympathetic Sympathetic Dominant role in salivary Produces smaller volume of secretion thick saliva that is rich in Produces prompt and mucus abundant flow of watery Dry mouth – e.g., in saliva that is rich in stressful situations enzymes. Increase saliva production by salivary glands Salivary secretion is the only digestive secretion entirely under neural control. All other digestive secretions are regulated by both nervous system reflexes and hormones.  Summary: Mouth and Salivary Glands Motility Secretion Digestion Absorption Chewing Saliva Begin to digest No foodstuffs are Amylase carbohydrate absorbed here Mucus Absorb a few medications (e.g., Lysozyme nitroglycerin) Integration of GI Smooth Muscle Swallowing (deglutition) & Esophageal Reflex 2. Pharyngeal stage Bolus stimulates 1. Voluntary stage stretch receptors in 3. Oesophageal stage Bolus passed into oropharynx Involuntary oropharynx by Send impulses to passage of bolus tongue deglutition centre in through brain stem oesophagus into Involuntary passage of stomach bolus into oesophagus  Preventing Food from Entering Respiratory Airways During Swallowing Uvula elevated: prevent food from entering nasal passageways Tight closure of the vocal folds (glottis) Epiglottis folds backward to provide further Stroke: Loss of CNS control and upper protection from the food motor neurone function. Can entering the trachea significantly impair swallowing reflex and aspiration.  Peristaltic Waves Push Food Through the Oesophagus Pharyngeal pressure receptors stimulated → Afferent impulses to swallowing centre in medulla of brain stem → Activates muscles involved in swallowing Achalasia: lack of neuronal input into swallowing/peristalsis function & failure of lower oesophageal sphincter to relax. Symptom: Difficulty in swallowing (dysphagia)  Gastroesophageal Sphincter Prevents Reflux of Gastric Contents Contraction increases during inspiration – reduces chance of reflux If reflux occurs – acidity of gastric content irritate the oesophagus, resulting in heartburn Summary: Pharynx and Oesophagus Motility Secretion Digestion Absorption Swallowing Mucus None None 6-10 sec transit time only Provides lubrication Protects the oesophagus from damage by acid/enzymes in gastric juice in case if reflux occurs  Stomach 50 mL - 1L Acts as a mixing chamber & holding reservoir Bolus converted to creamy paste (chyme) Starch digestion continues Protein and Triglyceride digestion begins Thick muscle layer  Carbohydrate Digestion Salivary Glands Enzyme Site of action Function Absorbable? Amylase Mouth and Hydrolyses Not yet (mostly) body polysaccharides to of stomach disaccharides and α- limit dextrins Exocrine Pancreas Enzyme Site of action Function Absorbable? Amylase Small Hydrolyses Not yet intestine polysaccharides to lumen disaccharides and α- limit dextrins Small Intestine Epithelial Cells Enzyme Site of action Function Absorbable? Disaccharidases Small intestine Hydrolyse disaccharides to Yes Maltase brush border monosaccharides Sucrase-isomaltase Lactase  Protein Digestion Proteins → Amino acids (AA) and small polypeptides Stomach Chief Cells Enzyme Site of action Function Absorbable? Pepsin Stomach Hydrolyses protein Not yet antrum to peptide fragments Exocrine Pancreas Enzymes Site of Function Absorbable action ? Trypsinogen Small Attack different Not yet Chymotrypsinogen Intestine peptide Procarboxypeptidase lumen fragments Activated by enteropeptidase in duodenum Small Intestine Epithelial Cells Enzyme Site of action Function Absorbable? Aminopeptidases Small intestine brush Hydrolyses peptide fragments Yes (AA and small border into AA peptides)  Stomach Digestion Mechanical digestion – Food enters stomach, which gradually expands (receptive relaxation) and mixing waves occur every 15-25 sec Mechanical digestion to form chyme Forces chyme into duodenum (start of small intestine) Chemical digestion – HCL Denatures proteins – Pepsinogen converted to pepsin in presence of HCL and other pepsin molecules Hydrolyses peptide bonds (cleaves proteins) – Gastric lipase: hydrolyses triglycerides  Cells of the Gastric Glands Exocrine Destruction of parietal cells (e.g., autoimmune gastritis) resulting in significant loss of IF can lead to B12 deficiency → This can result in Pernicious anaemia Cells of the Gastric Glands Endocrine/paracrine  Exocrine product: Pepsinogen, HCL, and Intrinsic Factor Intrinsic factors Parietal cells (Binds to VitB12, triggers receptor mediated endocytosis in terminal ileum) HCl Chief cells Pepsinogen Pepsin (works best in Protein acidic environment) digestion pepsinogen Pepsin can also cleave pepsinogen to Zymogen granules generate more pepsin  Exocrine product: HCl Function: – Does not directly digest anything – Activates pepsinogen → pepsin, provides an acidic environment optimal for pepsin action – Facilitates break down of connective tissue and muscle fibres – Denature proteins – exposing more peptide bonds for enzymatic attack – Kills significant amount of microorganisms Exocrine product: HCl  Exocrine product: Pepsinogen, HCL, and Intrinsic Factor Stimulated by (through insertion of additional H+-K+ ATPase): ACh Intrinsic factors + Gastrin (G cells) Parietal cells (Binds to VitB12, triggers Histamine (ECL cells) receptor mediated Inhibited by: endocytosis in terminal Somatostatin (D cells) ileum) HCl Chief cells Pepsinogen Pepsin (works best in Protein acidic environment) digestion pepsinogen Pepsin can also cleave pepsinogen to Zymogen granules generate more pepsin Stimulated by: ACh Gastrin (G cells)  Parietal cell Resting state Activated state Increased surface area allowing more proton pumps to be inserted  Where are the gastrin receptors involved with acid secretion located? 3 (A) Position 1 (B) Position 2 (C) Position 3 (D) Position 4 2 1 4 http://apps.elearning.uq. edu.au/poll/69244  Sequence of events by which gastrin causes stimulation of acid secretion??  Will histamine released by gastrin cause responses in other organs such as skin and airways smooth muscle? (A) Yes (B) No http://apps.elearning.uq. edu.au/poll/69244  Would H2-blocker or Proton Pump Inhibitors (PPIs) be more efficient at blocking excessive gastric acid secretion? (A) H2-blocker (B) PPIs (C) They are equally effective (D) Neither of them work well for blocking acid secretion http://apps.elearning.uq. edu.au/poll/69244  What events occur in the cell during stimulation of the vagus nerve? How does caffeine affect gastric acid secretion? (A) Increases gastric secretion (B) Decreases gastric secretion (C) No effect on gastric secretion http://apps.elearning.uq. edu.au/poll/69244 How does caffeine affect gastric acid secretion?  Gastrin ECL cell Histamine  Gastrin ECL cell Histamine  Major Gastric Hormones Gastrin – Main factor that increases HCl secretion during meal digestion – Stimulates parietal and chief cells – Stimulates ECL cells to produce histamine, which in turn stimulate parietal cells Histamine – Released from ECL cells in response to Ach and gastrin – Acts locally on parietal cells to increase HCl secretion Somatostatin – Released from D cells in response to acid – Inhibits secretion by parietal cells, G cells, and ECL cells (turning off acid producing pathway)  Regulation of Gastric Secretion Cephalic phase and Motility – Sight/smell/taste/thought of food recognised by cerebral cortex – Nerve impulses sent to medulla oblongata – vagal output – Sends impulses to submucosal plexus (in submucosa) » Increases secretion from gastric glands and stomach motility (via gastrin secretion) Gastric phase – When food reaches stomach, stimulates Stretch receptors Chemoreceptors (monitor pH) – Stimulate secretion of Gastrin (by G cells) Intestinal phase – Stimulation of intestinal receptors, as food enters small intestine, stimulates secretion of duodenal hormones: Secretin – reduces gastric secretion (acid in duodenum induces secretin secretion) Cholecystokinin (CCK) - inhibits gastric emptying (fat in duodenum induces CCK secretion) – Slows exit of chyme from stomach into duodenum.  Prof Barry J. Marshall AC Peptic Ulcer (Dr Robin Warren) Nobel prize in Medicine, 2005 Helicobacter pylori: Cause of more than 80% of all peptic ulcers Motile, have 4-6 flagella, which enable them to tunnel through and reside under the stomach’s thick layer of alkaline mucus Secretes toxins that cause persistent inflammation Weakens the gastric mucosal barrier by 3D H.pylori Images © ConcreteBob Software disrupting the tight junction between the gastric epithelial cells Produce urease, which breaks down urea (end product of protein metabolism) into ammonia (NH3) and CO2.  Peptic Ulcer Other factors: – Alcohol and NSAIDs: chemicals that can break the gastric mucosal barrier Pepsin and HCl act on the stomach wall as well as on food Treatments – Antibiotics – H-2 Histamine receptor blocker Histamine potentiates the acid-promoting actions of Ach and gastrin – Proton pump inhibitors Blocks the pump that transports H+ into the stomach lumen  Summary: Stomach Motility Secretion Digestion Absorption Receptive Gastric juice Carbohydrate No absorption relaxation; HCL digestion of foodstuffs peristalsis Pepsin continues Can absorb Mucus Protein digestion lipid-soluble Intrinsic factor begins substances (e.g., alcohol, aspirin)