This document provides an overview of irritable bowel syndrome (IBS), including its definition, prevalence, demographics, pathophysiology, clinical features, diagnosis, differential diagnosis, severity assessment, management, and prognosis. Some key points are: - IBS is a functional bowel disorder characterized by abdominal pain associated with changes in bowel habits. It predominantly affects those aged 15-65 and is more common in women. - The pathophysiology involves altered gut motility, visceral hypersensitivity, abnormal gas handling, low-grade inflammation, food sensitivities, abnormal gut microbiota, and central nervous system dysregulation. - Diagnosis is based on symptoms meeting certain criteria and exclusion of organic diseases. Management focuses on

1. Irritable Bowel
Syndrome
Dr.Chakravarthy,P.S
PG in Gatroenterology
AMC/KGH

2. Definition
Irritable bowel syndrome (IBS) is a functional
bowel disorder in which abdominal pain or
discomfort is associated with defecation or a
change in bowel habit.
Bloating, distension, and disordered defecation are
commonly associated features.
WGO Practice Guidelines 2009

3. Global Prevalence

4. Epidemiology
• Mainly occurs between the ages of 15 and 65
• First presentation to physician - 30–50 yrs
• Prevalence is greater in women (except in India)
• Prevalence in children is similar to that in adults

5. IBS demographics
Studies in non-Western countries
• Lack of female predominance
• Greater frequency of upper abdominal pain
• Lower impact of defecatory symptoms on a
patient’s daily life
• Stool frequency - greater in the India as a
whole(99% )

6. IBS demographics
• Clinical overlap between functional dyspepsia and
IBS- very common in China
• In Latin America- constipation predominance is
more frequent than diarrhea predominance

7. Pathophysiology

8. Pathophysiology
ALTERED COLONIC AND SMALL BOWEL
MOTILITY :
• High-amplitude propagated contractions
(HAPCs)
• Enhanced gastrocolic response
• Rectal hypersensitivity
Diarrhoea

9. Pathophysiology
• Increased segmental (nonpropulsive) contractions
• Decreased HAPCs
• Reduced rectal sensation
Constipation

10. ? Precipitating factors of increased colonic &
small bowel motility
- distension, fatty meal, cholecystokinin,
- stress, anger, deoxycholic acid
- Autonomic dysfunction
- administration of corticotropin releasing
hormone (CRH)

11. • No consensus on the exact patterns of motor
derangement that induce constipation or
diarrhea.
• Motor abnormalities observed in IBS
??? Secondary than primary

12. VISCERAL HYPERSENSITIVITY :
• Balloon distension of rectum (1970)
• Found in 60% patients
• IBS pts more aware of intestinal gas/contractions
• Abnormal sensitization within the dorsal horn of
the spinal cord or higher up in the central nervous
system.

13. • Neurotransmitters - serotonin, neurokinins,
calcitonin gene-related peptide
• Capsaicin (redpepper) receptor on nerve fibers
increased in the rectosigmoid colon in IBS -
mediate visceral pain
• N-methyl-d-aspartate (NMDA) receptor
modulates central (spinal cord) neuronal
excitability

14. • Significant increase in serine proteases in
the stools of patients with IBS-D
• Serine proteases  ?? damage tight
junctions  increase intestinal permeability
• Inflammation is responsible for the
sensitization

15. ABNORMAL GAS PROPULSION AND
EXPULSION
• Retention of gas following gas infusion into the
small intestine is greater in patients with IBS
• Intestinal gas infusion - more discomfort than
controls
• ??? Involuntary suppression of abd.wall muscle
contraction during gas infusion  more distension
• ??? SIBO contribute to bloating…..uncertain

16. LOCAL INFLAMMATION
• Increased mast cells and activated T- lymphocytes above
normal in the mucosa in patients with IBS
• Lymphocytic infiltration of the myenteric plexus with
neuron degeneration - in severe IBS
• Recovery from a proved episode of bacterial enteritis in 7-
30% patients
( illness lasting > 3wks or caused by toxigenic
organisms)
• A central role of mast cells ???  abd.pain

17. Mediators  5-hydroxytryptamine(5-HT)
(?? Central role in inflammation)
prostaglandins, bradykinins,
adenosine, nerve growth factors

18. ROLE OF FOOD
• Wheat, dairy products, citrus fruits, potatoes, onions, and
chocolate
• 50% patients showed symptomatic improvement on
elimination of pptating diets – uncontrolled trial
• ?? Subtle forms of gluten intolerance in IBS-D patients
( symptomatic improvement in 70% IBS-D patients with
positive HLA-DQ2 status with gluten restricted diet)

19. • Fructose & sorbitol
malabsorption contributes
to IBS ??
( no difference from
controls on double blinded
trial)

20. ABNORMAL COLONIC FLORA AND SMALL
INTESTINAL BACTERIAL OVERGROWTH
• Increased colonic fermentation, production of excess gas
symptoms  ?? Role of probiotics
• High prevalance of SIBO in IBS
(based on H2 breath tests & clinical response to non-
absorbable antobiotics)

21. CENTRAL DYSREGULATION
• Alterations in the brain response to visceral stimuli in IBS
( functional MRI & PET)
• Greater activation of the mid-cingular cortex following
delivered or anticipated rectal distention
(explains why anxiety or stress can enhance perception of
visceral pain, whereas relaxation or distraction decreases
pain in IBS)

22. PSYCHOLOGICAL FACTORS
• Depression, anxiety, and somatization are the most
common coexistants in IBS (40% to 94% of patients)
• H/O sexual, physical, or emotional abuse - more often
( abuse  ?? Alters brain response to visceral pain)
• Childhood stress – gastric suction– 3times more risk
• Anxiety secondary to intestinal inflammation (?TNF-alfa)

23. GENETIC FACTORS
• Familial clustering
• Greater concordance in monozygotic twins
• Potential genes :
a) lower expression of IL-10 gene
b) sodium channel mutation (SCN5)
c) serotonin type III receptor gene – functional varient

24. Clinical features
Symptoms
• Bloating
• Abnormal stool form (hard
and/or loose)
• Abnormal stool frequency (less
than three times per week or
over three times per day)
• Straining at defecation
• Urgency
• Feeling of incomplete
evacuation
• The passage of mucus per
rectum

25. Behavioral features
• Symptoms present for > 6 months
• Stress aggravates symptoms
• Frequent consultations for nongastrointestinal symptoms
• History of previous medically unexplained symptoms
• Aggravation after meals
• Associated anxiety and/or depression

26. Non-colonic symptoms
• Dyspepsia— in 42–87% patients
• Nausea
• Heartburn

27. Non-GI symptoms
• Lethargy
• Backache and other muscle and joint pains
• Headache
• Urinary symptoms: — Nocturia — Frequency and
urgency of micturition — Incomplete bladder emptying
• Dyspareunia, in women
• Insomnia
• Low tolerance to medication

28. Alarming features
History
• Blood in the stool
• Family H/O colon
cancer, IBD, celiac disease
• Fever
• Onset after age 50 years
• Nocturnal symptoms (awakening
the patient from sleep)
• Chronic diarrhea
• Progressive dysphagia
• Recurrent vomiting
• Severe chronic constipation
• Short history of symptoms
• Travel history to locations endemic
for parasitic diseases
• Weight loss

29. Alarming features
Physical Examination
• Abdominal mass
• Arthritis (active)
• Dermatitis herpetiformis or
pyoderma gangrenosum
• Occult or overt blood on rectal
examination
• Signs of anemia
• Signs of intestinal obstruction
• Signs of intestinal
malabsorption
• Signs of thyroid dysfunction

30. Diagnosis
• Based on history & clinical examination
• Matching patient’s profile to clinical criteria

34. Diagnostic algorithm(WGO practice guidelines,2009)

35. IBS diagnostic cascade
Level 1
• History, physical examination, exclusion of alarm
symptoms, consideration of psychological factors
• Blood counts, ESR or C-reactive protein, stool studies
(white blood cells, ova, parasites, occult blood)
• Thyroid function, tissue transglutaminase (TTG) antibody
• Colonoscopy and biopsy
• Fecal inflammation marker (e.g., calprotectin)
WGO practice guidelines 2009

36. IBS diagnostic cascade
Level 2
Level 1 with sigmoidoscopy
Level 3
Level 1 with stool studies
WGO practice guidelines 2009

37. Differential Diagnosis
• Celiac sprue/ gluten enteropathy
• Lactose intolerance
• Inflammatory bowel disease
• Colorectal carcinoma
• Acute diarrhea ( protozoal / bacterial)
• Small-intestinal bacterial overgrowth (SIBO)
• Diverticulitis
• Pelvic inflammatory disease /Endometriosis

38. Severity of disease
Rome foundation working team report,2011,Am J GE,July,2011

39. Management
• EDUCATION AND SUPPORT
• DIET
• MEDICATION –laxatives,antispasmodics,antidiarrheals,
serotonin receptor drugs,antideprssants,
antibiotics,probiotics

40. Antispasmodics
• Anticholinergics –
dicyclomine,propanthelene,hyoscyamine
• Non-anticholinergics- imetropium,pinaverium
• Peppermint oil- 0.2ml TID 30 min before food
Laxatives
• Osmotic laxatives may aggravate bloating & pain
• Stimulant laxatives – safer
• Lubiprostone – 24 micgm BID
WGO practice guidelines 2009

41. Antispasmodics (Ali Phar Ther,Aug.2004,1253-1269)

42. Laxatives (Ali Phar Ther,Aug.2004,1253-1269)

43. Antidiarrheals
• Loperamide – effective when used prophylactically
2-16mg/d
• Cholestyramine
• Bismuth subsalicylate
Serotonin-Receptor Drugs
• Alosetron ( 5-HT3 antagonist) efficacious in severe IBS-D
• Starting dose – 0.5 to 1 mg/d
• Can be escalated upto 1mg BID in absence of side effects
• Adverse effects – ischemic colitis (0.1% pts), constipation
(33%)
WGO practice guidelines 2009

44. Alosetron (Ali Phar Ther,Aug.2004,1253-1269)

45. Antidepressants and Anxiolytics
Tricyclic antidepressants(TCAs) - might improve global
well-being more than symptoms
• Start at a low dose (e.g., 10 to 25 mg of desipramine or
nortriptyline) and increase the dose by 10 to 25 mg
weekly, aiming for a dose of 75 mg initially
• Most beneficial in IBS-D
Selective serotonin reuptake inhibitors (SSRIs)
• Fewer side effects
• More beneficial in IBS-C
WGO practice guidelines 2009

46. Anti depressants (Ali Phar Ther,Aug.2004,1253-1269)

47. Antibiotics
• Nonabsorbable antibiotics – rifaximin(400mg TID for
10days)
• Treating a recurrence - not recommended
Probiotics
• Bifidobacterium lactis DN-173 010
• Bifidobacterium infantis 35624

48. Other Drugs
• Gabapentin,Pregabalin
• Leuprolide (GRH analogue)
• Colchicine ,Misoprostol - ?? Role in refractory
constipation
• Domperidone and erythromycin – prokinetic role
• Octreotide

49. Nonpharmacological methods
• Aim to reduce avoidance behavior
• Regular mealtimes, the intake of sufficient fluids, and
sufficient physical activity
• Cognitive/behavioral therapy
• Behavioral techniques
- Relaxation techniques/ Contingency management
• Hypnosis

50. Lubiprostone (Aliment Pharmacol Ther
Nov.2008,vol.29, 329–341)

51. Management
STEP SEVERITY LEVEL OF
CARE
MANAGEMENT
1 Mild Primary Diagnosis,explanat
ion,reassurance,
follow-up
2 Moderate Secondary Reinforce step 1
3 Severe Tertiary Avoid over-
testing,add
TCA/SSRI,
alosetron for
severe
diarrhea;treat
anxiety/depression
;refer to pain clinic

52. Choice of treatment
Predominant symptom First step Second step
Bloating Adjust, Treat constipation Probiotic,antibiotic,TCA,
SSRIs
Constipation Fibre supple./ Poly
ethylene glycol
Lubiprostone
Diarrhea Loperamaide Alosetron
Abdominal pain Antispasmodic,peppermin
t oil
TCAs,SSRIs,
Psychotherapy

53. What’s new ???
IBS-C
• 5-HT4 receptor agonists-
Tegaserod (withdrawn d/t cardiac events)
Prucalopride,Naronapride,Velusetrag
(no cardiac risk & more efficacy in early studies)
• Guanylate cyclase C agonists
Linaclotide -Chey et al(2012)- 46% pts improved
approved for use in the USA by the FDA in August
2012 for adults

54. Adsorbents
• AST 120, a carbon-based adsorbent
(absorption of histamine, serotonin, bacterial products and
bile acids )
32% pts improved in priliminary studies
5-HT3 receptor antagonist – Ramosetron
( RC trial – 343 patients, no significant benefit)

55. Futuristic therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)

56. Futuristic therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)

57. Futuristic therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)

58. Prognosis
• Relapses are common
• 9-10% develop organic disease a median of 15
years after diagnosis
• Poor prognosis
excessive psychological distress
anxiety, long duration of complaints

59. Take Home Message
• No more a vague symptom complex
• Pathophysiology ???
• History & examination is of prime importance
• Always R/O organic disease before diagnosis
• Treatment – predominantly symptomatic
• Behavioral therapy is important
• Newer drugs in pipeline

60. THANK YOU

61. References
• Sleisenger’s text book of GI diseases,9th edition
• WGO practice guidelines,2009
• Cochrane database
• Alimentary phar & therapeutics,reviews 2004-06
• Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)