Pathogenesis of IBS -- Update

Summarized by Robert W. Griffith, MD
November 28, 2002 (Reviewed: November 13, 2004)

Introduction

Irritable bowel syndrome (IBS) affects about 10% of all adults, and is almost twice as common in women than in men. It's associated with considerable morbidity and expense, due to time off work, and increased health costs. In the past it's often been classified as a psychosomatic disorder, but research is now beginning to establish the underlying mechanisms causing the syndrome. And with that understanding, effective treatments may not be far behind. A review in Lancet has reported on progress in understanding this disorder.

Consensus on diagnosis?

A shift has taken place in diagnosing IBS. At one time, it was a diagnosis of exclusion; now most physicians ascribe to the Rome II Criteria, which were issued in 1999. The Rome II Criteria are:

• Pain or discomfort for 12 weeks of the previous 12 months, associated with two of the following three:
  - Relief with defecation,
  - Looser or more frequent stools,
  - Harder or less frequent stools.
• Symptoms cumulatively lending support to the diagnosis:
  - Abnormal stool frequency (>3/day, or <3/week)
  - Abnormal stool form
  - Abnormal stool passage (straining, urgency, incomplete emptying)
  - Passage of mucus
  - Bloating or feeling of abnormal distension

There should also be an absence of so-called 'alarm indicators' - signs suggesting that organic disease is a more likely diagnosis. These include: age at onset > 50, progressive severe symptoms, nocturnal symptoms waking the patient, persistent diarrhea, bleeding or evidence of anemia, weight loss, vomiting, fever, and a family history of colon cancer.

Controversy still exists as to whether IBS, functional dyspepsia, chronic fatigue syndrome, and fibromyalgia represent different manifestations of a single somatic syndrome, similar to somatisation disorder. It seems likely that IBS is a distinct entity, based on population-based studies examined by factor analysis and cluster analysis. However, the female preponderance, psychological associations, and response to antidepressants and psychotherapy remain to be explained if IBS is to be etiologically differentiated.

Although patients with IBS seem to have a high degree of psychopathology (generalized anxiety, depression, hypochondriasis), this may be an effect of selection, as distressed persons are more likely to be referred to specialist centers.

Pathogenesis of the condition

The symptoms of IBS may be related to visceral hypersensitivity, altered intestinal motility and transit activity, and stress. And genetic factors may be responsible for disturbed pain signaling, the central processing of afferent signals, and defective descending anti-nociceptive impulses.

Visceral hypersensitivity, as shown by disproportionate pain in response to rectal balloon distension, is only found in 60% of patients with IBS. However, it can be readily induced by creating anticipation into the test protocol; if distension is steadily increased, IBS patients have a lower pain threshold than controls, whereas random 'dosing' produces similar results in patients and controls. During anticipation of, and actual, rectal distension in IBS patients, imaging studies show increased regional blood flow in the anterior cingulated cortex.

Patients with IBS may complain of diarrhea, constipation, or neither of these symptoms. Clearly altered colonic motility is an important feature of the condition. Exacerbation of symptoms after eating point in this direction - possibly related to increased sensitivity to cholecystokinin-1. Bloating may be due to a greater retention of gas in IBS patients, compared with normal subjects.

Intolerance to specific foods may lead to poor digestion, excessive gas, and abnormal transit times. Many IBS patients complain of such intolerance; wheat and milk are the chief subjects of such complaints.

Inflammatory conditions of the intestines produce mediators, such as bradykinins and 5-hydroxytryptamine (5HT), which induce visceral hypersensitivity and increased motor responses. The enterocromaffin cells, which produce 5HT, increase in number with infections; this may explain the success of a 5HT3 antagonist (alosetron) in diarrhea-predominant IBS. The role of 5HT in both afferent and efferent signaling between the gut and brain is further emphasized by the effectiveness of a partial 5HT4 agonist (tegaserod) in constipation-predominant IBS.

Psychological factors have been frequently reported to play a causal role in IBS, and psychiatric diagnoses are increased in IBS patients referred for specialist help, but there is no such association in patients managed outside specialist clinics.

Patients report that situations involving acute stress aggravate IBS, but it's more likely that chronic stress is of greater relevance. Examples include separation or bereavement.

Finally, genetic factors can play a role. IBS is twice as common in monozygotic as in dizygotic twins. However, twin studies suggest that environmental factors probably have a stronger influence than genetic factors do. Some congenital motility disorders are recognized, and these may account for a subset of IBS cases.

In a separate article we summarize recent views on the differential diagnosis and management of IBS (see link below).

Source

• Irritable bowel syndrome: a little understood organic bowel disease? N. Talley, R. Spiller, Lancet, 2002, vol. 360, pp. 555--564

Related Links
Differential Diagnosis and Management of IBS -- Update
Diverticular Disease
Cyberounds: Irritable Bowel Syndrome (IBS)

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