Gastrointestinal Physiology I PDF Past Paper - 2024

Student Feedback Exercise: Your Voice Matters! https://blue.nus.edu.sg/blue/ 1  Final Exam Information Final exam (50%): Date: 30th Nov 2024, Saturday Venue: MPSH2-A at 1pm. Format: Multiple-choice questions (MCQ) and open-ended questions Content: Week...

Student Feedback Exercise: Your Voice Matters! https://blue.nus.edu.sg/blue/ 1  Final Exam Information Final exam (50%): Date: 30th Nov 2024, Saturday Venue: MPSH2-A at 1pm. Format: Multiple-choice questions (MCQ) and open-ended questions Content: Week 8-13 Sections 1: Respiratory Physiology, 14 MCQs and 1 Open-ended question (20 points) Sections 2: Neural Physiology, 24 MCQs and 2 Open-ended question (44 points) Sections 3: Gastrointestinal Physiology, 22 MCQs and 2 Open-ended question (36 points) Overall: 60 MCQs and 5 Open-ended question (100 points) One A4 size sheet (double-sided) for notes is allowed. Electronic calculators are permitted. 2 Recap Neural stimulation threshold current 3 Recap 4 True A True Story: How competitive eating affects GI system From Youtube Chubbyemu 5  BN2201 Gastrointestinal Physiology I 6  Part I 1 General GI introduction 2 Motility: general concepts 3 Motility of the esophagus 4 Motility of the stomach 5 Motility of the small intestine 6 Motility of the large intestine 7 GI tract is a hollow tube Mouth Salivary glands Esophagus Stomach Pancreas Liver Gallbladder Small intestine Large intestine Image by BruceBlaus is licensed under CC BY 3.0 8 GI terminology Oral: referred to the mouth Gastric: referred to the stomach Gut: generic word for stomach and intestine Bowel or Enteric: referred to the intestine Hepatic: referred to the liver Visceral: Referred to the internal organs of the body Dictionary image by Stevebp is licensed under the Pixabay license, Diagram by McortNGHH (modified here) is licensed under CC BY-SA 4.0 9 The alimentary canal: anatomy Bottom left image by BruceBlaus is licensed under CC BY 3.0 10 GI compartmentalization: sphincters Muscular structures under nervous and hormonal control When constricted, movement of food is prevented Lower esophageal sphincters (LES) prevent acid reflux 11  Tissue organization in the GI wall Failure or Mucosa = Erosion (can self-heal) Failure or Muscularis = Ulcer (difficult to self-heal) 2 4 1 3 Diagram by OpenStax (modified here) is licensed under CC BY 3.0 12 Regulation mechanism in GI tract Endocrine Hormones released into the bloodstream Enteroendocrine cell (EEC), e.g., enterochromaffin-like cell (ECL) Neurocrine Extrinsic nervous system – Vagus nerve (Parasympathetic & Sympathetic ) Intrinsic nervous system (Enteric nervous system) – Myenteric plexus and submucosal plexus Paracrine Serotonin, released from enteric neurons, mucosal mast cells, and specialized EECs called enterochromaffin cells (EC), regulates smooth muscle function and water absorption 13 Integrated response to a meal GI activities Ingestion Motility- Propulsion and mechanical digestion Secretion - chemical digestion Absorption of nutrients Defecation Image by OpenStax CNX Project is licensed under CC BY 4.0 14 Involuntary muscle? 15 Types of muscles Image by www.scientificanimations.com is licensed under CC BY-SA 4.0 GI organs contain mostly smooth muscles Smooth muscle have slower and involuntary contractions Action potentials in GI smooth muscle are more prolonged (> 10 msec) than those in skeletal muscle and have little or no overshoot 16 Types of contractions Two key types provided by smooth muscles Phasic: fast and strong (seconds) Tonic: slow and sustained (minutes to hours) Main Pattern of mobility: Mixing (segmentation) , Propulsion (peristalsis) and pendular movement 17 Skeletal vs smooth Skeletal muscles: neural input leads to contraction Smooth muscles in the gut: spontaneous ”slow waves” have been observed almost everywhere in the gut (except the esophagus) Image above by OpenStax is licensed under CC BY 4.0, Image of slow waves from the paper: Ward et al J Phys (1994),480.1:91-97 18 Electrophysiology of the GI tract Interstitial Cells of Cajal (ICC): the pacemakers of the gut Initiate Slow wave, but NOT AP The frequency of ICC pacemaker activity differs in different regions of the GI tract: 3 per minute in the stomach 11-12 per minute in the duodenum 8-9 per minute in the ileum 3-4 per minute in the colon ICC diagram from the paper: Hirst GDS. J Phys (2001) 537.1, Image of Cajal by ZEISS Microscopy is licensed under CC BY-SA 2.0, Cajal’s drawing are in the public domain 19 ICC, ENS and smooth muscles ICC are electrically coupled to smooth muscle cells via gap junctions Image is taken from the paper: Radulovic M, et al J Neurogastroenterol Motil. 2015;21(4):494-502. It is licensed under CC BY-NC 4.0 20 Contraction in the gut Top two panels of the image is taken from the paper: Radulovic M, et al J Neurogastroenterol Motil. 2015;21(4):494- 502. It is licensed under CC BY-NC 4.0 Slow waves alone will not cause significant contraction. Slow waves (from ICC) + appropriate ENS input cause contraction. When slow wave reaches a threshold amplitude -> contraction Amplitude of the slow wave is altered by release of neurotransmitters from enteric neurons. This nonzero resting tension of smooth muscle is called tone 21 Motility: the esophagus Upper Esophageal Sphincter Lower Esophageal Sphincter 18 - 25 cm long in adult humans Musculature type: some skeletal (striated) voluntary muscles, but majority of smooth muscles Controlled by somatic and autonomic nerves from the swallowing centre in the brain Image by OpenStax CNX Project is licensed under CC BY 4.0 22 14 / 23 Motility of the esophagus: peristalsis Image by OpenStax C N X Project is licensed under CC B Y 3.0 Stimulation of the pharynx by the presence of a bolus initiates a decrease in pressure (= opening) of the UES and a peristaltic wave of contraction along the esophagus. Stimulation of the pharynx also relaxes the smooth muscle of the LES to prepare for entry of food. 23 Relaxation of LES – receptive relaxation Swallowing in the form of pharyngeal stimulation induces neural reflex relaxation of the LES and the proximal part of the stomach to allow entry of food. 24 Motility of the stomach 15-25 cm long in adult humans Empty stomach ∼50 ml Fully distended stomach ∼ 4 litres Image by OpenStax CNX Project is licensed under CC BY 4.0 25 Motility of the stomach: fed state Immediately after eating (”fed state”): mixing, grinding and emptying 26 Motility of the stomach: fed state Immediately after eating (”fed state”): mixing, grinding and emptying 27 Motility of the stomach: fasting state In between meals (”fasting state”): the Migrating Motor Complex (MMC) clears up the stomach Every ∼100 minutes (unless new food comes in) 5-10 minutes of luminally occlusive contractions 28 Motility of the small intestine 2.5-4 cm diameter (half of the large intestine) Duodenum: ∼25 cm, Jejunum: ∼2.5 meters, Ileum: ∼3.6 meters Length in cadavers is almost double (muscle tone) About two hours for food to clear the whole small intestine. Musculature type: smooth muscles only Image by OpenStax CNX Project is licensed under CC BY 4.0 29 Motility of the small intestine: migrating motor complex ~ 90min interval Pattern of electrical activity observed in the gastrointestinal tract in a regular cycle during fasting 30 Motility of the small intestine: Patterns Stretch & contract Pendular movement Image on the left by OpenStax College is licensed under CC BY 3.0, Image on the right by Boumphreyfr is licensed under CC BY-SA 3.0 31 Motility of the small intestine: patterns 32 Motility of the large intestine 6 cm diameter (roughly double the small intestine) 1.5 meters long in living humans The appendix is often not considered part of the large intestine, but clinically very relevant because of infections Musculature type: smooth muscle cells (some striated voluntary muscle cells in the outer anal sphincter) 33 Image by OpenStax CNX Project is licensed under CC BY 4.0 Motility of the large intestine: patterns 1 segmental propulsion: content shuttled back and forth between one haustra and the next but eventually aborally. Useful for storage of food and re-absorption of fluids. 2 mass movement: a ”clearing” mechanism similar to MMC. Details of the haustra (modified here) by OpenStax College is licensed under CC BY 3.0 34 Part I summary 1 General GI introduction 2 Motility: general concepts 3 Motility of the esophagus 4 Motility of the stomach 5 Motility of the small intestine 6 Motility of the large intestine 35 10 min Break 36  P Part II 1 Stats on GI disorders 2 Esophagus and Dr Clouse 3 Assessing and treating the stomach 4 Various ways of looking from inside 37 GI disorders FGID (Functional gastrointestinal disorders) defined as ”any combination of motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing”. Estimated 40% worldwide prevalence in 2020. An older estimate (2000) of associated costs is 85bn$/year in the US alone. Image from Sperber et al, Gastroenterology. In press. Available online 12 April 2020 is licensed under CC BY-NC-ND 4.0. The 2000 cost estimate is from Sandler RS et al Gastroenterology. 2002 May;122(5):1500-11. 38 3 / 23 GI disorders: why is BME needed? MANY underlying diseases Diabetic gastroparesis Idiopathic gastroparesis Cyclic vomiting syndrome Intestinal pseudo-obstruction FEW common symptoms Functional dyspepsia Pain Acahalasia Feeling of bloating GERD Abdominal discomfort Small bowel bacterial overgrowth Nausea/vomiting Hirschsprung’s disease Diarrhea Barrett’s esophagus... FEW others Chronic constipation Irritable Bowel Syndrome Inflammatory Bowel disease... MANY others 39 Esophageal manometry Video of esophageal manometry - assessing the function and motility of the esophagus 40 Clouse plots Named after Dr Ray E. Clouse (1951-2007) Image from an article by Jeffrey L Conklin (J Neurogastroenterol Motil. 2013 Jul; 19(3): 281–294) is licensed under CC BY-NC 3.0 (adapted here by adding the axis) 41 What is going on where the arrow is pointing in the Clouse Plot? The lower esophageal sphincter is relaxing in response to swallowing 42 GERD: an extremely prevalent disease Gastro-esophageal reflux disease (GERD) occurs when LES becomes leaky and the acid content of the stomach gets into the esophagus. Affecting an estimated 18-27% of general population.† Video from Mayo clinic on GERD. † Antunes C, Aleem A, Curtis SA. Gastroesophageal Reflux Disease. [Updated 2020 Jul 8]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441938/ 43 8 / 23 GERD: treatment options In order of normal temporal sequence for patients 1 Lifestyle modifications 2 Drugs. Two types: limit acidic secretions in the stomach or increase contractility (prokinetic agents) 3 Surgical options. One interesting one is the Linx device approved in 2012 for patients ”..who continue to have chronic GERD symptoms despite medical therapy for the treatment of reflux”. Roughly 80% efficacy with some patients reporting difficulty swallowing.† Video on Linx from UC Irvine † See Zadeh et al Med Devices (Auckl). 2018; 11: 291–300. 44 Assessing gastric motility: x-ray fluoroscopy Key features: INPUT: Barium sulfate solution (contrast agent) PROCEDURE: taking X-ray images over time OUTPUT: Proportion of meal in the stomach vs time + walls of the GI organs. 45 Assessing gastric motility: γ-scintigraphy Principles of γ-scintigraphy Input: Radiolabeled meal (can be solid, liquid or in a capsule) Output: Proportion of meal in the stomach vs time (gastric emptying) Image is from the article: Parker HL et al Neurogastroenterology and Motility. 2017;29:e13122. It is licensed under CC BY 4.0 46 Assessing gastric motility: γ-scintigraphy Video of liquid γ-scintigraphy Video of capsule γ-scintigraphy Scintigraphy (from Latin scintilla, "spark"), also known as a gamma scan, where radioisotopes attached to drugs/substances are taken internally and the emitted gamma radiation is captured by external detectors (gamma cameras) to form two-dimensional images in a similar process to the capture of x-ray images. 47 Quantifying gastric emptying: the Siegel model The ”Siegel model” is one of the proposed equations to describe the fraction of a meal in the stomach (y ) over time (t) y = 1 − (1 − e−kt ) β where β and k are parameters that depend on the type of food as well as the patient’s gastric motility. y Small opening in pylorus 1 solids (β > 1) liquids (β < 1) 0.5 time(min) tlag For solids, tlag is defined as the time taken to reach maximum emptying rate (this 2 is where the concavity of the red curve changes). To calculate t lag , ddty2 = 0 leads to† tlag = ln(β) k where ln is the natural logarithm † Optional proof - Link to the Siegel paper (optional). 48 Visualizing gastric emptying and sieving 49 Regulation of gastric emptying Differentiating different type of liquids y solid 1 glucose solution protein solution 0.5 time(min) Downstream receptors sense chemical composition and send signals back to the stomach regulating opening and closure of pylorus depending on the chemical nature of the solution Diagram of the stomach is licensed under the Pixabay license 50 Gastroparesis Screenshot from the website of the International Foundation for Gastrointestinal Disorders 51 Therapeutic options (1): drugs Prokinetic drugs are the main option: 1 Directly stimulate enteric neurons to release more neurotransmitters (e.g., Acetylcholine) 2 Stimulate receptors in the chemoreceptor trigger zone in the CNS (including vomiting center) Pill Image is licensed under the Pixabay license 52 16 / 23 Therapeutic options (2): Enterra device Enterra video (patient) Enterra video (doctor) 53 Images from the FDA website Therapeutic options (2): Enterra device Mechanisms of action ”The mechanism(s) by which Enterra works is not well understood but may involve indirect neuromodulation of parasympathetic nerves and/or ganglia which regulate gastric function.” (FDA, 2019) Current most credible hypothesis: Gastric Electrical Stimulation (GES) stimulates the ENS and the vagus nerve (afferent pathway) which leads to stimulation of the vomiting center in the brain and, in turn vagal efferent pathway 54 Other stomach diagnostics: electrogastrography (EGG) Key features: INPUT: recording from skin electrodes OUTPUT: Dominant frequency of slow waves It is also possible to record the magnetic field for the stomach (magnetogastrography), but not yet in clinical use. 55 Looking from inside: colonoscopy Colonoscopy animation Colonoscopy video Output: Observe the GI walls (same as upper GI endoscopy) and possibly taking biopsies. Used for cancer screening (colorectal cancer is the most common cancer in Singapore †) For average-risk individuals, screening to start at age 50: Colonoscopy every 10 years † Chan PWW et al Singapore Med J 2017; 58(1): 24-28 56 Looking from inside: upper GI endoscopy Endoscopy video Output: Observe the GI walls. Also taking tissue for biopsy, if necessary (a biopsy is a laboratory examination performed on a tissue removed from a patient). Endoscopy image by Cancer Research UK is licensed under CC BY-SA 4.0 57 Looking from inside: small intestine endoscopy The small intestine is the hardest to reach anatomically. Double balloon technique Capsule endoscopy Double balloon video Pillcam video Image of the PillCams is from the paper:Ciuti et al, IEEE Reviews in Biomedical Engineering, vol. 4, pp. 59-72, 2011. 58 video capsule endoscopy verus traditional endoscopy 1. Access to the small intestine: Traditional endoscopy cannot fully visualize the mid and distal parts of the small intestine (jejunum, ileum). video capsule endoscopy (VCE) is the most effective non-invasive tool for this purpose. 2. Less invasive: VCE avoids sedation, making it suitable for patients who cannot tolerate anesthesia or invasive procedures. 3. Intermittent bleeding detection: In cases of intermittent GI bleeding, the capsule can capture images continuously as it passes through the bowel, increasing the likelihood of detecting elusive sources of blood loss. 59 Beyond Camera - ingestible bacterial-electronic system Gastrointestinal bleeding detection Genetically encoded bacteria to Mimee et al. Science 2018 respond to inflammation-associated molecules Inda-Webb et al. Nature 2023 60  nd 2Your gut - the second brain? Contracting Ex vivo in Krebs/PBS buffer from 10s min to hours Nature 606, 94–101 (2022) Not just in controlling things like our appetite, but may contribute to our mental well- being — and potentially event to disorders ranging from anxiety to Parkinson's disease. 61 Part II summary 1 Stats on GI disorders 2 Esophagus and Dr Clouse 3 Accessing and treating the stomach 4 Ways of looking from inside 62