Irritable Bowel Syndrome

Irritable Bowel Syndrome

• Functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of structural abnormalities

• Common cause of constipation with alternating bouts of diarrhea

• Affects all ages, females diagnosed two to three times more often than males

Diagnostic Criteria for IBSa

Recurrent abdominal pain or discomfort b at least 3 days per month in the last 3 months associated with two or more of the following:

1. Improvement with defacation2. Onset associated with a change in frequency of stool3. Onset associated with a change in form (appearance) of stool

a. Criteria fulfilled for the last 3 months w/ symptom onset at least 6 months prior to diagnosis.b. Discomfort means an uncomfortable sensation not described as pain. In pathophysiology research

and clinical trials, a pain/ discomfort frequency of at least 2 days a week during screening evaluation is required for subject eligibility

Fauci et.al. Harrison’s principles of Internal Medicine 2008 17th edition. McGraw-Hill USA

Rome II Criteria

• Used mainly in the context of research• Rome II criteria characterizes IBS as:

At least 12 weeks (which need not be consecutive), in the preceding 12 months, of abdominal discomfort or pain with two of the following three features:

(1) Relief by defacation (2) Onset associated with a change in frequency of stool (3) Onset associated with a change in stool

appearance.

National Institute for Health and Clinical Excellence, 2008

•(1) prandial urgency and abdominal pain/diarrhea and•(2) diarrhea with borborigmi and sense of incomplete rectal evacuation and thus limit its use.

However, this criteria exclude

some clinical features that

are recognized by clinicians as part of IBS such

as:

National Institute for Health and Clinical Excellence, 2008

Rome II Criteria

IBS: Signs and Symptoms

• All ages can be affected, but mostly, patients below 45 have their first symptoms

• Women are diagnosed with IBS two to three times as often as men and make up 80% of the population with severe IBS

• Pain or abdominal discomfort is a key symptom for the diagnosis of IBS

IBS: Signs and Symptoms

• Abdominal pain or discomfort is a prerequisite clinical feature of IBS

• Highly variable in intensity and location• In 25% of patients, pain is localized to the

hypogastrium, the right side in 20%, to the left side in 20%, and the epigastrium in 10%

• Frequently episodic and crampy, but it may be superimposed on a background of constant ache

IBS: Signs and Symptoms

• Eating or emotional stress exacerbates pain, but passage of flatus or stool relieves it

• Women commonly report worsening symptoms during the premenstrual and menstrual phases

• The most consistent clinical feature of IBS is alteration in bowel habits; and constipation alternating with diarrhea, usually with one of these symptoms predominating as the most common pattern

IBS: Signs and Symptoms

• Initially, constipation may be episodic, but eventually becomes continuous and increasingly intractable to treatment with laxatives

• Stool characteristics: • Usually hard with narrowed caliber, possibly reflecting

excessive dehydration caused by prolonged colonic retention and spasm

• repeated attempts at defecation in a short time span are common, because most patients also experience a sense of incomplete evacuation

It is not IBS when there is:

Painless diarrhea or constipation

Defecation straining, urgency or a feeling of incomplete bowel movement, passing mucus, and bloating are supportive symptoms not part of the diagnostic criteria

Sleep deprivation – unusual because abdominal pain is almost uniformly present only during waking hours

There is bleeding on bowel movement

IBS: Signs and Symptoms

If constipation is the predominant symptom, patients may have it weeks or months, interrupted with brief periods of diarrhea

If diarrhea is the predominating symptom, it usually consists of small volumes of loose stools

Most patients have stool volumes of < 200 mL

Nocturnal diarrhea does not occur in IBS

IBS: Signs and Symptoms

• Increased gas in IBS patients causes abdominal distention and increased belching or flatulence• Quantitative measurements reveal that most

patients who complain of increased gas generate no more than a normal amount of intestinal gas

• Most IBS patients have impaired transit and tolerance of intestinal gas loads; and tend to reflux gas from the distal to the more proximal intestine, which may explain the belching

IBS: Pathophysiology

• Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology.

• Unknown Cause• Intestinal contractions may be stronger and

last longer than normal– Food is forced through the intestines more quickly,

causing gas, bloating and diarrhea

IBS: Pathophysiology

Traditional theories: 3-part complex

• Altered GI motility • Visceral hyperalgesia• Psychopathology

A unifying mechanism is still unproven

IBS: Pathophysiology

Altered GI motility includes distinct aberrations in small and large bowel motility

• Colonic dysmotility demonstrates variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike potentials

• Clustered contractions in the duodenum and jejunum and prolonged propagated contractions in the ileum• Small bowel dysmotility manifests

• delayed meal transit in patients prone to constipation • accelerated meal transit in patients prone to diarrhea.• shorter intervals between migratory motor complexes (the predominant interdigestive small bowel motor

patterns).

IBS: Pathophysiology

Visceral hyperalgesia

• Enhanced perception of normal motility and visceral pain characterizes irritable bowel syndrome

• Patients who are affected describe widened dermatomal distributions of referred pain• Sensitization of the intestinal afferent nociceptive pathways that synapse in the dorsal

horn of the spinal cord provides a unifying mechanism

• Visceral afferent dysfunction manifests as exaggerated sensory responses to visceral stimulation which influences postprandial pain in 74% of IBS patients after the entry of food bolus to the cecum

• Lipids lower the threshold for the first sensation of gas, discomfort and pain in IBS

• Increased area of referred pain after lipid ingestion• Postprandial symptoms may be explained in part by nutrient-

dependent exaggerated sensory component of the gastrocolonic response

• Afferent pathway disturbances appear to be selective for visceral innervations with sparing of somatic pathways.

Visceral hyperalgesia

IBS: Pathophysiology

Psychopathology

• Associations between psychiatric disturbances and irritable bowel syndrome pathogenesis are not clearly defined

• Patients show preferential activation of the prefrontal lobe, which contains a vigilance network within the brain that increases alertness• These may present as a form of cerebral dysfunction leading to the increased perception of

visceral pain.

IBS: Pathophysiology

Small bowel bacterial overgrowth

• Has been heralded as a unifying mechanism for the symptoms of bloating and distention common to patients with irritable bowel syndrome.

• Campylobacter, Salmonella and Shigella • Patients with Campylobacter infections who are toxin-positive are more likely to develop postinfective IBS. • Increased rectal mucosal enteroendocrine cells, T lymphocytes and increased gut permeability could

persist and may contribute to postinfective IBS.

IBS: Pathophysiology

Serotonin

• Imbalance in mucosal 5-HT availability caused by defects in 5-HT production, serotonin receptors, or SERT• May cause the increase in serotonin release contributing to the postprandial

symptoms of patients and provide a rationale for the use of serotonin antagonist as treatment for this disorder.

IBS: Diagnosis

The diagnosis of IBS relies on:

• Rome II diagnostic criteria• Other supportive symptoms such as defecation straining, urgency or a feeling of incomplete bowel movement, passing mucus,

bloating, lethargy, nausea, backache and bladder symptoms

Recognition of positive clinical features

Elimination of other organic diseases

IBS: Diagnosis

In people who meet the IBS diagnostic criteria, the following tests should be undertaken to exclude other diagnoses:

• CBC, ESR or plasma viscosity, C-reactive protein (CRP), antibody testing for coeliac disease (endomysial antibodies [EMA] or tissue transglutaminase [TTG]), sigmoidoscopic examination, stool examination for ova and parasites.

The laboratory features that argue against IBS include evidence of anemia, elevated ESR, presence of leukocytes or blood in stool, and stool volume > 200-30 mL/d

National Institute for Health and Clinical Excellence, 2008Fauci et.al. Harrison’s principles of Internal Medicine 2008 17th edition. McGraw-Hill USA

IBS: Management

Nonpharmacologic

Pharmacologic

Non-PharmacologicPatient Counseling and Dietary Alterations

• Reassurance and careful explanation of the functional nature of the disorder

Avoid food precipitants that aggravate symptoms

• such as coffee, disaccharides, legumes, and cabbage• excessive fructose and artificial sweeteners, such as sorbitol or mannitol, may cause diarrhea,

bloating, cramping or flatulence

dietary change (high fiber diet)

Pharmacologic

Stool-Bulking Agents

Antispasmodics

Antidiarrheal Agents

Antidepressant Drugs

Antiflatulence Therapy

Serotonin Receptor Agonist and Antagonists

Chloride Channel Activators

Stool-Bulking Agents

bran or hydrophilic colloid or psyllium

• The water-holding action of fibers may contribute to increased stool bulk because of the ability of fiber to increase fecal output of bacteria.

• Fiber also speeds up colonic transit in most persons. • In diarrhea-prone patients, whole-colonic transit is faster than average; however, dietary fiber can

delay transit. • stool-bulking agents bind water and thus prevent both excessive hydration or dehydration of stool.

• Inhibits the gastrocolic reflex• Provides temporary relief for symptoms such as painful cramps

related to intestinal spasm• Given 30 min before meals so that effective blood levels are

achieved shortly before the anticipated onset of pain

• Most anticholinergics contain natural belladonna alkaloids– may cause xerostomia, urinary hesitancy and retention, blurred vision,

and drowsiness– Use with caution in elderly

• dicyclomine (synthetic anticholinergics) – less effect on mucous membrane secretions and produce fewer undesirable side effects

Antispasmodics

Antidiarrheal Agents

Increases in segmenting colonic contractions, delays in fecal transit, increases in anal pressures, and reductions in rectal perception• 2–4 mg every 4–6 h up to a maximum of 12 g/d• Less addictive• most useful if taken before anticipated stressful events that are known to cause

diarrhea

Peripherally acting opiate-based agents

• the initial therapy of choice for IBS-D

loperamide

bile acid binder cholestyramine resin

Antidepressant drugs

TCA

• Imipramine- slows jejunal migrating motor complex transit propagation and delays orocecal and whole-gut transit.

• Desipramine- 86% improved abdominal pain

IBS - D

Antidepressant drugs

SSRI

• Paroxetine – accelerates orocecal transit• Citalopram – blunts perception of rectal distension and reduces gastrocolonic response• Mianserin with 5HT2 and 5HT3 receptor antagonist and α2-adrenoceptor antagonist effect – reduces pain, distress and functional disability • *efficacy needs further confirmation

IBS-C

Antiflatulence therapy

• Patients are advised to eat slowly or not chew gum or drink carbonated beverages

• Avoid flatogenic foods, exercise, lose weight, take activated charcoal

• May reduce rectal passage of gas without decreasing bloating and pain

Β-glycosidase

Serotonin receptor agonist and antagonist

•IBS-D•ALOSETRON•Reduces perception of painful visceral stimulation in IBS•Rectal relaxation, increases rectal compliance and colonic transit

Serotonin

receptor antagon

ist

Serotonin receptor agonist and antagonist

•Tegaserol•prokinetic activity stimulating peristalsis•Accelerate intestinal and ascending colon transit•* series of cardiovascular events

5HT-4 recept

or agonist

Chloride channel activators

bicylcic fatty acid

Stimulates chloride channels in apical membrane of intestinal epithelial cells.

* nausea and diarrhea

Lubiprostone

References:

• Fauci et.al. Harrison’s principles of Internal Medicine 2008 17th edition. McGraw-Hill USA

• National Institute for Health and Clinical Excellence, 2008