Irritable Bowel Syndrome Pathophysiology .pptx

IBS

1. IBS – PATHOPHYSIOLOGY & TREATMENT Dr.N.A.Rajesh Professor & Head Department Of Medical GE SRM Medical College Hospital & RC

2. OBJECTIVES WHAT IS IBS? UNDERSTANDING THE PATHOPHYSIOLOGY LIFESTYLE,HABITS & IBS PREVENTION & TREATMENT

3. IBS - Introduction Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease Abdominal pain & change in bowel function Significant impact on patient’s quality of life and a high socioeconomic burden. Prevalence varies greatly between countries because of differences in food, culture, and diagnosis Rome Foundation Global Study reported that the overall prevalence of IBS was 3.8% The highest prevalence observed in Women, Educated, Wealthy, Students and Younger individuals

4. IBS- Definition

5. OVERLAP OF IBS WITH OTHER FGIDs/DGBI It tends to overlap with other functional gastrointestinal diseases (FGIDs)/DGBIs 68% have overlap of 2 GI regions ( Esophageal , ,gastroduodenal, bowel & anorectal) 55% have IBS-FD overlap 2.3% have overlap of all 4 GI regions Anxiety & Depression were common characteristics in the mechanism of FGIDs 53% of IBS cases report pain in ≥ 3 non abdominal areas Headache, Fibromyalgia, LBA etc

6. PATHOPHYSIOLOGY In the past, IBS could not be explained by a clear etiology Traditionally been described as a disorder of visceral hypersensitivity and GI motor disturbances Etiopathogenesis is Multidimensional Peripheral factors Abnormal GI motility GI inflammation & altered gut permeability Luminal microenvironment alteration Microbiota dysbiosis SIBO Host-microbe interaction Bile acid malabsorption Pathogenic infection Dietary factors Neurohumoral dysregulation Altered serotonergic transmission Visceral hypersensitivity Central factors Psychological stress Cognitive dysfunction Abnormal emotional arousal system response Sleep dysfunction Genetic factors

7. PATHOPHYSIOLOGY Genetic Factors Complex polygenic, Atypical single gene aberrations (example - SCN5A) Genetic polymorphism of IBS pathogenesis –related genes related to Seratonin signalling Immune regulation Epithelial barrier function Bile acid synthesis DNA methylation changes Gut Microbiota Modulate gut brain axis & gut neuromuscular junction Alter immunity & integrity of the gut

8. PATHOPHYSIOLOGY With the increasing research ,the pathophysiological mechanisms of IBS has changed from functional to brain-gut interaction. Gut Brain Interactions GI tract sends signals that affect the brain, resulting in alterations in immune function, secretion, and motility Vagus nerve - main communication conduit between the brain and the microbiota Gut permeability and the brain function is significantly altered in patients with IBS Correcting the crosstalk between the ANS and CNS is an important in IBS prevention

9. PATHOPHYSIOLOGY Gut Brain Interactions CRF functions both centrally and peripherally & modulate body response to stress and stimulates IBS symptoms The binding of CRF to its receptors induces changes in smooth muscle contractility mucosal transport mucosal permeability visceral pain sensitivity

10. PATHOPHYSIOLOGY Gut Brain Interactions – Stress Psychological stress have a critical influence on the gut-brain axis Stress affect intestinal motility and permeability visceral sensitivity immune responses, gut microbiota composition Stress S ecretion of proinflammatory cytokines  A ctivates the HPA and hypothalamic-ANS axis  Induce release of CRF, adrenocorticotropic hormone, and cortisol  Affects gut homeostasis

11. PATHOPHYSIOLOGY Abdominal pain in IBS patients has been shown to be associated with structural changes of the brain. Rectal stimulation Activate the anterior cingulate cortex, prefrontal cortex, insula, thalamus, and cerebellum, and is higher in IBS Female IBS patients Increase in gray matter volume and cortical thickness in the primary and secondary somatosensory cortex and subcortical regions Decrease in the volume, surface, and cortical thickness of the gray matter in the posterior insula and superior frontal gyrus

12. PATHOPHYSIOLOGY Abnormal Oro anal transit time (OATT) is related to hydrogen and methane concentration in the gut More rapid OATT is associated with a higher severity of abdominal discomfort, rumbling, and nausea. Gut endocrine cells are scattered throughout the gastrointestinal tract and have sensory microvilli that sense gut pressure and gut contents microbial food metabolism in gut lumen stimulate the cells release hormones & neurotransmitters into the lamina propria Histamine, 5-HT, glutamate, and noradrenalin strengthen visceral pain γ-aminobutyric acid reduces gastrointestinal motility

13. PATHOPHYSIOLOGY Visceral hypersensitivity and gut barrier disruption Animal experiments have shown Apelin activates CRF and TLR4 , create a cycle of proinflammatory cytokine signaling - a key pathway for the pathological mechanism of IBS. The disruption of the gut barrier leads to an increase in lipopolysaccharides (LPS) and proinflammatory cytokines - a vital pathological mechanism that causes abdominal pain in patients with IBS.

14. PATHOPHYSIOLOGY Microbiome The microbial diversity a decrease in Coli, Lactobacilli, Collinsella , and Bifidobacteria a increase in Enterobacteria, anaerobes, Escherichia coli, Ruminococcus gnavus , and Bacteroides in patients with IBS. Microbiota-gut-brain axis Dinan et al - Disturbances in the gut microbiota can affect brain function, behavior, and cognition Studies have shown that in 2/3 rd patients functional gastrointestinal symptoms preceded the mood disorder Koloski et al showed higher baseline levels of anxiety and depression - significant predictors of developing IBS

15. DIAGNOSIS No single or specific diagnostic tests for IBS Diagnosis is clinical & is based on Rome IV Criteria Exclude organic diseases Alarm symptoms Rectal bleeding, Weight loss, Nocturnal symptoms Recent change in bowel function Exclude somatoform/psychological disorders Screening tests Hemoglobin, CRP Fecal Calprotectin Colonoscopy Specialized tests if no response to primary treatment Anorectal manometry and balloon expulsion, colonic transit Tests for biochemical causes of diarrhea Sugar malabsorption – Abnormal D-Xylose test , Fat malabsorption – Fecal fat Bile acid diarrhea SIBO – Glucose Hydrogen Breath Test

16. MANAGEMENT The Asian experts called DGBI pathophysiological mechanisms as micro-organic factors Micro-organic factors Slow colon transit and Fecal evacuation disorder may be hidden behind the diagnosis of a patient with IBS-C. Dietary intolerance, including that of lactose and fructose, bile acid malabsorption, non-celiac wheat sensitivity, SIBO and GI infection may be the cause of symptoms in IBS-D. Therefore a multi-modality care targeting various pathophysiological mechanisms of IBS is superior to standard care. Personalized care - unrevealing these pathophysiological mechanisms in each patient through thorough History taking Physical examination and Investigation

17. MANAGEMENT IBS is a syndrome diagnosed by symptom -based criteria Goal of treatment is to relieve patient’s symptoms and improve the quality of life (QOL) All bothersome symptoms should be targeted while treating these patients rather than only the predominant symptoms Counseling, reassurance and lifestyle modification are important in the management of IBS Frequent counseling sessions and promoting physical activity (e.g. yoga, meditation ) Sleep disorders should be recognized & appropriately treated with pharmacotherapy Dietary intervention – Low FODMAP diet

18. Management Dietary FODMAP restriction is useful in a proportion of IBS patients A low-FODMAP ( fermentable oligosaccharides, disaccharides, monosaccharides, and polyols ) diet is particularly useful for Flatulence Bloating Abdominal pain Diarrhea

19. MANAGEMENT

20. MANAGEMENT The initial pharmacotherapy of IBS is primarily symptom based Antispasmodics are the first-line treatment of abdominal pain in patients with IBS and non-responsive patients may benefit from visceral neuromodulators Psychoactive pharmacotherapy ( visceral neuromodulators ) are useful to relieve abdominal pain in IBS patients Work both through central and peripheral mechanisms. These drugs work even in the absence of significant psychological comorbidity

21. MANAGEMENT The initial pharmacotherapy of IBS is primarily symptom based. Laxatives and Antidiarrheals are the first-line treatment for IBS-C and IBS-D , respectively Fiber supplements Water-soluble - psyllium, ispaghula, calcium polycarbophil, methylcellulose Insoluble - wheat bran Recommended dose - 20 g per day – improve constipation and abdominal pain Stimulant drugs such as senna and bisacodyl quite effective purgatives but may cause abdominal cramps Loperamide, Diphenoxylate, Ramosetron & Visceral NM with anticholinergic activity like Amytriptyline – useful in IBS -D

22. MANAGEMENT The initial pharmacotherapy of IBS is primarily symptom based Probiotics may be helpful Rifaximin Methane-producing IBS-C patients High breath methane on lactulose hydrogen breath test is seen in slow transit constipation Non constipated IBS also benefit from Rifaximin Psychological interventions are useful in those with psychiatric comorbidities or refractory IBS Patients with severe symptoms, non-responding patients and overlap disorders more often have psychological comorbidity Psychological interventions Pharmacotherapy Cognitive behavior therapy Gut-directed hypnotherapy Yoga and MBSRT

23. CONCLUSION IBS is a complex disease with multiple pathophysiological mechanisms A multidisciplinary approach that incorporates nonpharmacological and/or pharmacological treatments is emphasized. Individualized treatment plans are necessary for effectively managing IBS.

24. Thank You