Irritable Bowel Syndrome 

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. Osler coined the term mucous colitis in 1892 when he wrote of a disorder of mucorrhea and abdominal colic with a high incidence in patients with coincident psychopathology. Since that time, the syndrome has been referred to by sundry terms, including spastic colon, irritable colon, and nervous colon.

In the past, irritable bowel syndrome has been considered a diagnosis of exclusion; however, it is no longer considered a diagnosis of exclusion, but it does have a broad differential diagnosis.^[1] No specific motility or structural correlates have been consistently demonstrated; however, experts suggest the use of available guidelines can minimize testing and aid in diagnosis.

Traditional theories regarding pathophysiology may be visualized as a 3-part complex of altered GI motility, visceral hyperalgesia, and psychopathology. A unifying mechanism is still unproven.

Altered GI motility

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

The myoelectric activity of the colon is composed of background slow waves with superimposed spike potentials. Colonic dysmotility in irritable bowel syndrome manifests as variations in slow-wave frequency and a blunted, late-peaking, postprandial response of spike potentials. Patients who are prone to diarrhea demonstrate this disparity to a greater degree than patients who are prone to constipation.

Small bowel dysmotility manifests in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhea. In addition, patients exhibit shorter intervals between migratory motor complexes (the predominant interdigestive small bowel motor patterns).

Current theories integrate these widespread motility aberrations and hypothesize a generalized smooth muscle hyperresponsiveness. They describe increased urinary symptoms, including frequency, urgency, nocturia, and hyperresponsiveness to methacholine challenge.

Visceral hyperalgesia

Visceral hyperalgesia is the second part of the traditional 3-part complex that characterizes irritable bowel syndrome.

Enhanced perception of normal motility and visceral pain characterizes irritable bowel syndrome. Rectosigmoid and small bowel balloon inflation produces pain at lower volumes in patients than in controls. Notably, hypersensitivity appears with rapid but not with gradual distention.

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.

Psychopathology

Psychopathology is the third aspect. Associations between psychiatric disturbances and irritable bowel syndrome pathogenesis are not clearly defined.

Patients with psychological disturbances relate more frequent and debilitating illness than control populations. Patients who seek medical care have a higher incidence of panic disorder, major depression, anxiety disorder, and hypochondriasis than control populations. A study has suggested that patients with irritable bowel syndrome may have suicidal ideation and/or suicide attempts strictly as a result of their bowel symptoms.^[2] Clinical alertness to depression and hopelessness is mandatory. This is underscored by another study that revealed that patient complaints that relate to functional bowel disorders may be trivialized.

An Axis I disorder coincides with the onset of GI symptoms in as many as 77% of patients. A higher prevalence of physical and sexual abuse has been demonstrated in patients with irritable bowel syndrome. Whether psychopathology incites development of irritable bowel syndrome or vice versa remains unclear.

Microscopic inflammation

Microscopic inflammation has been documented in some patients.^[3] This concept is groundbreaking in that irritable bowel syndrome had previously been considered to have no demonstrable pathologic alterations.

Both colonic inflammation and small bowel inflammation have been discovered in a subset of patients with irritable bowel syndrome, as well as in patients with inception of irritable bowel syndrome after infectious enteritis (postinfectious irritable bowel syndrome). Risk factors for developing postinfectious irritable bowel syndrome include longer duration of illness, the type of pathogen involved, smoking, female gender, an absence of vomiting during the infectious illness, and young age.^[4]

Laparoscopic full-thickness jejunal biopsy samples revealed infiltration of lymphocytes into the myenteric plexus and intraepithelial lymphocytes in a subset of patients in one study.^[5] Neuronal degeneration of the myenteric plexus was also present in some patients.

Patients with postinfectious irritable bowel syndrome may have increased numbers of colonic mucosal lymphocytes and enteroendocrine cells. Enteroendocrine cells in postinfectious irritable bowel syndrome appear to secrete high levels of serotonin, increasing colonic secretion and possibly leading to diarrhea.

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. This has led to proposed treatments with probiotics and antibiotics.

The fecal microflora also differs among patients with irritable bowel syndrome versus controls. A sophisticated molecular analysis suggested an alteration in the patterns and the contents of gut bacteria.^[6]

The causes of irritable bowel syndrome remain poorly defined, but they are being avidly researched.

Postulated etiologies of irritable bowel syndrome

Abnormal transit profiles and an enhanced perception of normal motility may exist. Up to one third of patients with irritable bowel syndrome may have altered colonic transit. Delayed colonic motility may be more common in patients with constipation-predominant irritable bowel syndrome than in healthy controls. Similarly, accelerated colonic transit may be more common in patients with diarrhea-predominant disease than in healthy controls.^[7] Local histamine sensitization of the afferent neuron causing earlier depolarization may occur.

Causes related to enteric infection

Colonic muscle hyperreactivity and neural and immunologic alterations of the colon and small bowel may persist after gastroenteritis. Psychological comorbidity independently predisposes the patient to the development of postinfectious irritable bowel syndrome. Psychological illness may create a proinflammatory cytokine milieu, leading to irritable bowel syndrome through an undefined mechanism after acute infection.

Infection with Giardia lamblia has been shown to lead to an increased prevalence of irritable bowel syndrome, as well as chronic fatigue syndrome. In a historic cohort study of patients with G lamblia infection as detected by stool cysts, the prevalence of irritable bowel syndrome was 46.1% as long as 3 years after exposure, compared with 14% in controls.^[8]

Central neurohormonal mechanisms

Abnormal glutamate activation of N- methyl-D- aspartate (NMDA) receptors, activation of nitric oxide synthetase, activation of neurokinin receptors, and induction of calcitonin gene–related peptide have been observed.

The limbic system mediation of emotion and autonomic response enhances bowel motility and reduces gastric motility to a greater degree in patients who are affected than in controls. Limbic system abnormalities, as demonstrated by positron emission tomography, have been described in patients with irritable bowel syndrome and in those with major depression.

The hypothalamic-pituitary axis may be intimately involved in the origin. Motility disturbances correspond to an increase in hypothalamic corticotropin-releasing factor (CRF) production in response to stress. CRF antagonists eliminate these changes.

Additional etiologic factors

As discussed in Pathophysiology, Pimentel and colleagues have proposed that small bowel bacterial overgrowth provides a unifying mechanism for the common symptoms of bloating and gaseous distention in patients with irritable bowel syndrome.^[9]

Bloating and distention may also occur from intolerance to dietary fats. Reflex-mediated small bowel gas clearance is more impaired by ingestion of lipids in patients with irritable bowel syndrome than in patients without the disorder.

Studies of elimination and challenge diets have suggested that poorly absorbed short-chain carbohydrates, in the form of fructose and fructans, may create symptoms among patients with irritable bowel syndrome, as measured by a visual analogue scale.^[10]

Research suggests that neuronal degeneration and myenteric plexus lymphocytosis may exist in the proximal jejunum. Additionally, colonic lymphocytosis and enteroendocrine cell hyperplasia have been demonstrated in some patients.

Population-based studies estimate the prevalence of irritable bowel syndrome at 10-20% and the incidence of irritable bowel syndrome at 1-2% per year. Of people with irritable bowel syndrome, approximately 10-20% seek medical care. An estimated 20-50% of gastroenterology referrals relate to this symptom complex. The incidence is markedly different among countries.

American and European cultures demonstrate similar frequencies of irritable bowel syndrome across racial and ethnic lines. However, within the United States, survey questionnaires indicate a lower prevalence of irritable bowel syndrome in Hispanics in Texas and Asians in California. Populations of Asia and Africa may have a lower prevalence of irritable bowel syndrome. The role of different cultural influences and varying health care–seeking behaviors is unclear.

In Western countries, women are 2-3 times more likely to develop irritable bowel syndrome than men, although males represent 70-80% of patients with irritable bowel syndrome in the Indian subcontinent. Women seek health care more often, but the irritable bowel syndrome–specific influence of this occurrence remains unknown. Other factors, such as a probably greater incidence of abuse in women, may confound interpretation of this statistic.

Patients often retrospectively note the onset of abdominal pain and altered bowel habits in childhood. Approximately 50% of people with irritable bowel syndrome report symptoms beginning before they were aged 35 years. The development of symptoms in people older than 40 years does not exclude irritable bowel syndrome but should prompt a closer search for an underlying organic etiology.

Irritable bowel syndrome is a chronic relapsing disorder characterized by recurrent symptoms of variable severity; however, life expectancy remains similar to that of the general population. Clinicians must be forthcoming with patients because knowledge may help allay undue fears as their disease waxes and wanes. Irritable bowel syndrome does not increase the mortality or the risk of inflammatory bowel disease or cancer.

The principal associated physical morbidities of irritable bowel syndrome include abdominal pain and lifestyle modifications secondary to altered bowel habits. Work absenteeism resulting in lost wages is more frequent in patients with irritable bowel syndrome.

Patient education remains the cornerstone of successful treatment of irritable bowel syndrome. Teach the patient to acknowledge stressors and to develop avoidance techniques.

For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Chronic Pain.