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Elizabeth Mentzer, PA-S Robert D. Hadley, Advisor

Elizabeth Mentzer, PA-S Robert D. Hadley, Advisor. IBS is a diagnosis of exclusion with a female predominance Affects at least 20% of the American population Classic Symptoms: Chronic abdominal pain or discomfort associated with chaotic bowel motility Heightened visceral sensitivity

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Elizabeth Mentzer, PA-S Robert D. Hadley, Advisor

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  1. Elizabeth Mentzer, PA-S Robert D. Hadley, Advisor

  2. IBS is a diagnosis of exclusion with a female predominance • Affects at least 20% of the American population • Classic Symptoms: • Chronic abdominal pain or discomfort associated with chaotic bowel motility • Heightened visceral sensitivity • Constipation dominant IBS, diarrhea dominant IBS or mixed

  3. At least 12 weeks or more, with onset of at least 6 months previously of recurrent abdominal pain or discomfort associated with two or more of the following: • Improvement with defecation; and/or • Onset associated with a change in frequency of stool; and/or • Onset associated with a change in form (appearance) of stool

  4. Common Treatments • Fiber Supplements • Antispasmodics • Ex. dicyclomine, hyoscyamine • Anti-diarrheals • Tricyclic Antidepressants • Amitryptaline for d-IBS • Probiotics • Lactobacillus plantarum or the combo. L. plantarum + L. acidophilus or Bifidobacterium • Antibiotics • New Possibilities • Mesalamine derivative (ATB-429) • Budesonide

  5. Post - Infectious IBS • Interstitial Cells of Cajal • Serotonin Pathway

  6. How do GI –Infections Lead to IBS? • Genetics • Polymorphisms of gene coding for cytokine production of Interleukin 10 (IL-10) • Increased Production of Tumor Necrosis Factor –α (TNF-α) • Mast Cell Activation • Mast cell release of inflammatory mediators could alter gastrointestinal motility • Relationship to IBS and Pain • Spacial relationships between mast cells and gastrointestinal nerves

  7. Pacemakers of the Gastrointestinal System • Play roles in intestinal motor activity, balanced control of gut motility and a functional role in neuronal motor activity • Located within close proximity to enteric nerve endings • Damaged ICCs (ex., immune reactions or endometriosis) could lead to disruption of musculature electrical activity leading to IBS symptoms

  8. Defects in 5-HT signaling could lead to colonic aberrations and sensations typical of IBS and Ulcerative Colitis (UC). • A 2004 study by Coates et al., found that: • IBS and UC patients all had significant reductions in expression of the SERT transcript when compared to control subjects as well as a reduction in the rate limiting enzyme TpH, which is essential for the biosynthesis of 5-HT • Is there a connection between IBS and UC?

  9. 5-HT and the relationship to ICCs • 5-HT may indirectly regulate proliferation of ICCs • Impaired and/or decreased numbers of ICCs have been associated with bowel dysfunction • A study by Gershon (2005), showed that decreased expression of SERT (required for the termination of 5-HT) could have negative downstream effects on 5-HT • As a result, constipation and diarrhea type symptoms were seen due to 5-HT desensitization or 5-HT amplification • Decreased SERT expression was also found in biopsies of UC patients -> Possible connection?

  10. So far there have been strong arguments for IBS being an inflammatory response • It may even be a mild form of UC • There is no single definitive answer for the pathogenesis of IBS yet.

  11. IBS is real • It is not a psychological problem • Stay up-to-date on drug therapies • Realize that patients with IBS need a tailored treatment plan. • Exclude other possibilities like celiac disease and endometriosis. • Treat based on a patient’s history • For example: presence or history of enteric infection, do other family members have it etc. • Be sympathetic and understanding as IBS can be life-altering

  12. Andresen V, Camilleri M. Irritable Bowel Syndrome: Recent and Novel Therapeutic Approaches. Drugs 2006; 66(8): 1073-1088. • Bercik P, Verdu EF, Collins SM. Is Irritable Bowel Syndrome a Low-Grade Inflammatory Bowel Disease? Gastroenterol Clin N Am 2005; 34: 235-245. • Bijkerk CJ, de Wit NJ, Stalman WA, Knottnerus JA, Hoes AW, Muris JW. Irritable Bowel Syndrome in Primary Care: The Patients’ and Doctors’ Views On Symptoms, Etiology and Management. Can J Gastroenterol 2003: 17(6): 363-368. • Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et.al. Molecular Defects in Mucosal Serotonin Content and Decreased Serotonin Reuptake Transporter in Ulcerative Colitis and Irritable Bowel Syndrome. Gastroenterol 2004; 126(7): 1657-1664. • Crentsil V. Will corticosteroids and Other Anti-inflammatory Agents Be Effective For Diarrhea Predominant Irritable Bowel Syndrome? Medical Hypotheses 2005; 65: 97-102. • Der T, Bercik P, Donnelly G, Jackson T, Berezin I, Collins SM, Huizinga JD. Interstitial Cells of Cajal and Inflammation-Induced Motor Dysfunction in the Mouse Small Intestine. Gastroenterol 2000; 119: 1590-1599. • Dhaliwal SK, Hunt RH. Doctor-Patient Interaction for Irritable Bwoel Syndrome in Primary Care: A Systematic Perspective. European Journal of Gastroenterol and Hepatology 2004; 16: 1161-1166. • Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, et.al. 5-Amino-2-hydroxybenzoic Acid 4-(5-Thioxo-5H-{1,2}dithiol-3yl)-phenyl Ester (ATB-429), a Hydrogen Sulfide-Releasing Derivative of Mesalamine, Exerts Antinociceptive Effects in a Model of Postinflammatory Hypersensitivity. JPET 2006; 319:447-458.

  13. Gershon, MD. Nerves, Reflexes, and the Enteric Nervous System; Pathogenesis of the Irritable Bowel Syndrome. J Clin Gastroenterol 2005; 39: S184-S193. • Giovania B, Vincenzo S, Roberto G, Cesare C, Graeme SC, Donatella S, et.al. Activated MastCells in Proximity to Colonic Nerves Correlate With Abdominal Pain in Irritable Bowel Syndrome. Gastroenterology 2004; 126: 693-702. • Gonsalkorale WM, Perrey C, Pravica V, Whorwell PJ, Hutchinson IV. Interleukin 10 Genotypes in Irritable Bowel Syndrome: Evidence for an inflammatorycomponent? Gut 2003; 52: 91-93. • Komuro T. Comparative Morphology of Interstitial Cells of Cajal: Ultrastructural Characterization. Microscopy Research and Technique 1999; 47: 267-285. • Longstreth GF. Definition and Classification of Irritable Bowel Syndrome: Current Consensus and Controversies. Gastroenterol Clin N Am 2005: 34: 173-187. • Marshall JK, Thabane M, Garg AX, Clark WF, Salvadori M, Collins SM. Incidence and Epidemiology of Irritable Bowel Syndrome After a Large Waterborne Outbreak of Bacterial Dysentery. Gastroenterology 2006; 131: 445-450. • McKay M, Bienenstock J. The Interaction Between Mast Cells and Nerves in the Gastrointestinal Tract. Immunology Today 1994; 15(11): 533-538. • O’Sullivan M. Inflammatory Mediators in Irritable Bowel Syndrome. Adelaide & Meath Hospital, Trinity College, Dublin Ireland. [cited 2007 Dec 10] Available From: www.med.unc.edu/ibs. • Remorgida V, Ragni N, Ferrero S, Anserini P, Torelli P, Fulcheri E. The Involvement of The Interstitial Cajal Cells and the Enteric Nervous system in Bowel Endometriosis. Hum Reprod 2005; 20(1): 264-271.

  14. Simonetta M, Pellegrini F. Relationships Between Neurokinin Receptor-Expressing Interstitial Cells of Cajal and Tachykininergic Nerves in the Gut. J Cell Mol Med 2006; 1: 20-32. • Spiller RC. Irritable Bowel Syndrome. British Medical Bulletin 2005; 72(1): 15-29. • Thaben M, Kottachchi DT, Marshall JK. Systematic Review and Meta-Analysis: The Incidence and Prognosis of Post-Infectious Irritable Bowel Syndrome. Aliment Pharmacol Ther 2007; 26: 535-544. • Tornblom H, Bethan L, Clover L, Knowles C, Vincent A, Lindberg G. Autoantibodies in Patients With Gut Motility Disorders and Enteric Neuropathy. Scand J Gastroenterol 2007; 42: 1289-1293. • Van der Veck Patrick PJ, Van den Berg M, de Kroon YE, Verspaget HW, Masclee AM. Role of Tumor Necrosis Factor-α and Interleukin-10 Gene Polymorphisms in Irritable Bowel Syndrome. Am J Gastroenterol 2005; 100: 2510-2516. • Wald A. Overview of Irritable Bowel Syndrome. Up To Date 2007. Gut 1999 [cited 2007 Nov 11] Available From: www.fda.gov/ohrms/dockets/ac/00/slides/3627s1_2_wald/tsl • Wouters MM, Gibbons SJ, Roeder JL, Distad M, Ou Y, Strege PR, et.al. Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors. Gastroenterology 2007; 133: 897-906.

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