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

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?

11. 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.

12. 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

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