Irritable Bowel

Syndrome

Dr.Chakravarthy,P.S
PG in Gatroenterology
AMC/KGH
 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

Global Prevalence
 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

 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% )
 IBS demographics

• Clinical overlap between functional dyspepsia and

IBS- very common in China

• In Latin America- constipation predominance is

more frequent than diarrhea predominance
Pathophysiology
 Pathophysiology
ALTERED COLONIC AND SMALL BOWEL
MOTILITY :
• High-amplitude propagated
contractions (HAPCs)
• Enhanced gastrocolic response
• Rectal hypersensitivity

Diarrhoea
 Pathophysiology
• Increased segmental (nonpropulsive) contractions
• Decreased HAPCs
• Reduced rectal sensation

Constipation
? Precipitating factors of increased colonic
& small bowel motility

- distension, fatty meal, cholecystokinin,

- stress, anger, deoxycholic acid
- Autonomic dysfunction
-administration of corticotropin releasing
hormone (CRH)
• No consensus on the exact patterns of
motor derangement that induce
constipation or diarrhea.

• Motor abnormalities observed in IBS

??? Secondary than
primary
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.
• 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
• 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
 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

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

Mediators  5-hydroxytryptamine(5-HT)
(?? Central role in
inflammation) prostaglandins,
bradykinins, adenosine, nerve
growth factors
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)
• Fructose & sorbitol
malabsorption contributes
to IBS ??
( no difference from
controls on double blinded
trial)
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)
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)
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)
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
 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
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
Non-colonic symptoms

• Dyspepsia— in 42–87%
patients
• Nausea
• Heartburn
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
 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
 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
 Diagnosis

• Based on history & clinical examination

• Matching patient’s profile to clinical criteria
Diagnostic algorithm(WGO practice guidelines,2009)
 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
 IBS diagnostic cascade

Level 2
Level 1 with sigmoidoscopy

Level 3
Level 1 with stool studies

WGO practice guidelines

2009
 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
 Severity of disease
Rome foundation working team report,2011,Am J GE,July,2011
 Management

• EDUCATION AND SUPPORT

• DIET
• MEDICATION –laxatives,antispasmodics,antidiarrheals,
serotonin receptor drugs,antideprssants,
antibiotics,probiotics
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
Antispasmodics (Ali Phar Ther,Aug.2004,1253-1269)
Laxatives (Ali Phar Ther,Aug.2004,1253-1269)
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
Alosetron (Ali Phar Ther,Aug.2004,1253-1269)
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

Anti depressants (Ali Phar Ther,Aug.2004,1253-1269)
Antibiotics
• Nonabsorbable antibiotics – rifaximin(400mg TID for
10days)
• Treating a recurrence - not recommended

Probiotics

• Bifidobacterium lactis DN-173 010

• Bifidobacterium infantis 35624
Other Drugs
• Gabapentin,Pregabalin
• Leuprolide (GRH analogue)
• Colchicine ,Misoprostol - ?? Role in
refractory constipation
• Domperidone and erythromycin – prokinetic
role
• Octreotide
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
Lubiprostone (Aliment Pharmacol Ther
Nov.2008,vol.29, 329–341)
 Management
STEP SEVERITY LEVEL OF MANAGEMENT
CARE
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
 Choice of treatment
Predominant symptom First step Second step
Bloating Adjust, Treat constipation Probiotic,antibiotic,TCA,
SSRIs
Constipation Fibre supple./ Poly Lubiprostone
ethylene glycol
Diarrhea Loperamaide Alosetron
Abdominal pain Antispasmodic,peppermin TCAs,SSRIs,
t oil Psychotherapy
 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
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)
 Futuristic
therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
 Futuristic therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
 Futuristic
therapies
Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
 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
 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
THANK YOU
 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)