Monday, October 17, 2011

Functional Bowel Disorders

Functional Bowel Disorders
Michael Snyder, MD
Clinical Instructor
Colon and Rectal Surgery
University of Texas at Houston Health Center
Clinical Associate Professor
Baylor College of Medicine
Houston, Texas
http://www.fascrs.org/physicians/education/core_subjects/2005/functional_bowel_disorders/

Functional bowel disorders are syndromes characterized by chronic gastrointestinal tract symptoms in patients without significant infectious, metabolic or anatomical abnormalities. Functional gastrointestinal disorders can affect the entire digestive tract from the mouth to the anus. The two most common functional disorders seen by the colon and rectal surgeon are irritable bowel syndrome (IBS) and functional constipation which affect the mid to lower gastrointestinal tract.

Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS), the most frequent condition diagnosed in most gastroenterology practices, is responsible for over three million office visits annually. Depending on the diagnostic inclusion criteria, the prevalence of IBS in the United States is between six and twenty percent (1). Female predominance is as high as 2:1 in some studies. While it is primarily a disorder of younger people in the third or fourth decade of life, up to 23% of patients with IBS have symptoms that persist into old age. A new diagnosis of IBS should be made cautiously in patients older than 60, however, because this age group has an increased incidence of other colonic disorders with similar symptoms. Since there has never been a well-designed study on the natural history of IBS, the reasons for the female predominance are unclear. Whether this represents a true difference or is secondary to health care seeking behavior is uncertain. IBS is a chronic disorder with at least 75% of patients having persistent symptoms five years or more after the diagnosis is first considered (2).

The understanding of the pathophysiology of IBS has evolved significantly over the past half century. Originally IBS was thought to represent a nervous disorder with augmented gastrointestinal motility occurring in patients under stress. Recent research has shown that IBS is a complex multifaceted disorder. Abnormalities in intestinal motility in conjunction with heightened visceral sensory input and processing are important aspects of the disease. In many patients with IBS, abdominal pain in the immediate postprandial period is associated with either rhythmic contractions or high amplitude prolonged contractions. These alterations in the migratory motor complex can either delay or accelerate intestinal transit (3). In addition, increased sensitivity to pain in the gastrointestinal tract has been demonstrated in patients with IBS. Several studies have suggested that patients with IBS may process sensory input from the gastrointestinal tract differently and have an exaggerated response to intestinal distention (4). Finally, two studies have demonstrated that infectious gastroenteritis may increase the possibility of developing IBS later in life (5,6), presumably by damaging the enteric nerves responsible for peristalsis.

IBS is defined by abdominal discomfort associated with altered bowel habits. As there are no biochemical or structural markers, IBS is diagnosed by the absence of organic disease and the presence of a constellation of symptoms. The Rome II diagnostic criteria divide IBS into three relatively equal groups depending on the presence of diarrhea, constipation, or alternating diarrhea and constipation. These criteria for IBS require at least twelve weeks duration of symptoms in one year that need not be consecutive. Symptoms defining IBS are abdominal pain or discomfort relieved with defecation or associated with a change in the frequency or appearance of the stool. Nine symptoms supporting the diagnosis of IBS include (a greater than 25% occurrence of): 1) Fewer than three bowel movements per week, 2) More than three bowel movements per day, 3) Hard or lumpy stools, 4) Loose (mushy) or watery stools. 5) Straining during bowel movement, 6) Urgency, 7) Passing mucous during bowel movement, 9) Abdominal fullness, bloating or swelling. IBS with diarrhea is associated with one or more of the supportive symptoms numbered 2,4 or 6 and none of 1, 3 or 5. IBS with constipation is associated with one or more of the supportive symptoms numbered1,3 or 5 and none of 2, 4 or 6 (7). An individual patient may change from one diagnostic group to the other during the treatment of this, so symptom based management is currently recommended.

Patients prone to diarrhea find that the first stool in the morning is usually normal in consistency. Subsequent bowel movements, however, become more watery and mucoid, and are associated with intestinal cramps, rectal urgency and bloating. Symptoms are relieved with the passage of stool but often quickly return. Patients prone to constipation also note mucous either in the stool or separately. The stool consistency is often hard, and/or rocky. Many patients strain to complete defecation or experience incomplete evacuation. Fecal incontinence occurs in up to 20% of patients with IBS, primarily in those with concomitant diarrhea. This is possibly due to repetitive reflex relaxation of the sphincter mechanism associated with colonic spasms.

The evaluation of patients who fall into one of the Rome II criteria is limited as long as no "alarm" symptoms or signs are noted. These "alarm" symptoms or signs include hematochezia, weight loss greater than ten pounds, family history of colon cancer, recurring fever, anemia, and severe chronic diarrhea. Routine colonoscopy for colon cancer screening is no different than the general population. Based on the best current data, the probability of colorectal cancer, inflammatory bowel disease and infectious diarrhea is less than 1% among IBS patients without "alarm" symptoms or signs (8). As this is similar to that of healthy patients undergoing screening, the routine use of endoscopy, radiologic tests, or microbiological evaluation is unnecessary. The only exception occurs in those patients with IBS and diarrhea. The incidence of celiac sprue in these patients is 5% and routine testing of these patients should certainly be considered (9).

Because the precise etiology of IBS is unknown, and there is a lack of objective biochemical markers, treatment of IBS has focused upon the relief of symptoms. Treatment of IBS is indicated when the symptoms of IBS significantly decrease the quality of life. It should result in improvement of global IBS symptoms such as abdominal pain, bloating and altered bowel habits.

For patients with IBS and constipation initial treatment involves increasing both the amount of daily fiber to 25-30gms and water intake to 64oz a day. For many patients with mild symptoms this may be all that is required. If dietary changes are insufficient, fiber supplements such as methylcellulose or psyllium are added. While these products act as hydrophilic agents to bind water and prevent excessive dehydration, they do not relieve abdominal pain and may accentuate bloating. Other laxatives such as polyethylene glycol solutions have been used with some success, but also do not address the abdominal discomfort. Tegaserod, a selective serotonin type 4 receptor agonist, binds to the enteric receptors initiating the peristaltic reflex. Four randomized controlled trials have compared tegaserod 6mg b.i.d. to placebo and found significant global symptom relief in women with IBS and constipation. The use of tegaserod in men or in patients with alternating diarrhea and constipation is not established (10).

For patients with IBS and diarrhea, loperamide has been studied in randomized control trials and found to decrease stool frequency, improve stool consistency, but have no effect on abdominal pain or bloating. Low doses of tricyclic antidepressants may also decrease the frequency of diarrhea. In those women who fail to respond to this conservative therapy and who have severe diarrhea predominant IBS, the serotonin type 3-receptor antagonist alosetron may be used. Five randomized controlled studies have demonstrated efficacy. Side effects include constipation (25%) and ischemic colitis (84 cases in the literature)(10).

Therapy for the abdominal discomfort associated with IBS has been disappointing until recently. Traditionally, antispasmodic agents have been prescribed. Dicyclomine and hyoscyamine are the two agents available in the United States. The only trial to demonstrate efficacy of either medication was associated with a 70% rate of anticholinergic side effects (10). Since these side effects include constipation, the two antispasmodic medications should be used cautiously in IBS patients with constipation. Antispasmodic medications should be taken 30-60 minutes prior to a meal to prevent postprandial abdominal pain and bloating. Currently, however, the most effective and preferred medication for abdominal pain and bloating is the previously mentioned serotonin type 4 receptor agonist, tegaserod.

Other therapies for IBS include behavioral modification and investigational drugs. Anxiety and depression are noted in up to 20% of IBS patients. Behavioral therapy for IBS has been evaluated in sixteen randomized controlled studies. While none of these examined global IBS improvement, most studies demonstrated that attenuation of individual IBS symptoms correlated with a reduction in anxiety and depression. In patients with sleep disorders, the administration of melatonin significantly diminished abdominal pain and rectal urgency (11). Other medications with visceral analgesic properties are being investigated to include the kappa opioid agonist fedotozine and neurokinin receptor antagonists. Probiotics are also being evaluated because of promising results controlling flatulence in a controlled trial.

Constipation

Constipation, a common disorder seen by both primary care and specialty physicians, is responsible for more than 2.5 million annual office visits. Many people do not seek medical care and instead self medicate with a multitude of over the counter and alternative medications. Constipation is a symptom of many diseases and the medications used to treat them. It is interchangeably used to describe patients with stool that is difficult to pass, passes infrequently, or has a hard consistency. Because of a lack of consensus defining constipation in the literature, the International Congress of Gastroenterology formulated the Rome II criteria. They defined constipation as abdominal discomfort of at least twelve weeks duration in the previous twelve months (need not be consecutive) having two or more of the following symptoms; 1) Straining more than 25% of the time, 2) Lumpy or hard stools more than 25% of the time, 3) Anorectal blockage, 4) Incomplete evacuation, 5) Need for manual maneuvers, and 6) Less than three stools per week. In these patients loose stools may not be present and there should not be sufficient criteria for the diagnosis of irritable bowel syndrome (12).

The physiology of constipation primarily encompasses the transit of stool through the colon, rectum and anus. Stool enters the colon as a liquid and becomes solid during passage to the rectosigmoid. Segmental and high amplitude propagating contractions are the two major contractile activities in the colon. The propagating contractions are responsible for the movement of stool to the anal sphincter, which regulates eventual stool evacuation. These propagating contractions originate from pacemakers found in the muscle layer of the colon called the interstial cells of Cajal (13). The loss or inactivity of these cells may play a role in patients with slow transit constipation.

Defecation is the evacuation of stool from the rectum and is determined by the propulsive force of the stool and the resistance of the anus. It is triggered by distention of the rectum by stool. Propulsive force consists of voluntary increases in intra-abdominal pressure and involuntary high amplitude contractions of the rectum. Resistance to defecation decreases with voluntary straightening of the anorectal angle in conjunction with relaxation of the external sphincter and involuntary relaxation of the internal anal sphincter.

The etiology of constipation may be primary or secondary. The more common secondary causes of constipation are listed in Table 1. Many patients have multiple factors that may contribute to their constipation. Notably, medications, including over-the-counter and herbal preparations, are a factor in up to 40% of patients (14).

The evaluation of constipated patients begins with a thorough history and physical exam to identify one of the numerous secondary causes of constipation. A colonoscopy or combined sigmoidoscopy and barium enema should be considered to identify malignant or anatomical abnormalities in the colon and rectum. A careful examination of the perineum and anus will help exclude anatomical outlet obstruction, the presence of a rectocele and abnormal perineal descent. Laboratory testing includes thyroid functions and electrolytes to help diagnose metabolic and endocrine abnormalities contributing to the constipation.

If the initial evaluation does not reveal a secondary cause for the constipation, a transit study is recommended to objectively measure the severity, and helps establish the primary cause of the constipation. The initial study called a SitzMark test is performed with radio-opaque markers that are swallowed. Abdominal radiographs are obtained on days 3 and 5. The radiograph on day 3 confirms the patient ingesting the markers. The presence of more than 25% of the markers in the colon at day 5 is indicative of a positive test. Markers evenly spread throughout the colon are consistent with slow transit constipation, while those that congregate in the rectosigmoid are indicative of an outlet obstruction. A negative SitzMark test with fewer than 25% of the markers on day 5 is suggestive of normal transit constipation or a patient who is not compliant with the instructions regarding no laxative use during the testing.

Further evaluation of outlet obstruction consists of anal manometry and defecography. Anal manometry permits documentation of the anorectal inhibitory reflex to rule out a short segment Hirschrprung’s disease. In addition, normal manometric sphincter pressures during simulated defecation are useful in excluding outlet obstruction. Defecography is particularly useful in the diagnosis of intra-anal prolapse, rectoceles, and other pelvic floor abnormalities. Barium paste is placed into the rectum and the act of defecation is visualized. Anorectal angle visualization, perineal descent and the nonemptying of rectoceles can be objectively measured.

There are three types of primary constipation that are important to recognize. The first type, colonic inertia, is associated with a lack of urgency and intractability resulting in many patients having several days to weeks between bowel movements. Daily use of stimulant laxatives is typical and evacuation is uncommon without medication. While the etiology is idiopathic in nature, the patients are overwhelmingly young women. Increasing dietary fiber or fiber supplements may make symptoms of bloating and abdominal cramps worse. SitzMark studies are often markedly positive demonstrating a characteristic pattern of markers relatively evenly spaced throughout the colon. It is important to rule out coexisting outlet obstruction with defecography and/or anal manometry. The second type, normal transit constipation, is characterized by evacuation frequency and stool consistency that is within the normal range, but the patients feel constipated. Bowel management regimens and reassurance are often all that is necessary to treat these patients. The third type, anismus or obstructed defecation, is characterized by the sensation of incomplete evacuation and the need to strain to produce a stool. SitzMark studies may be positive with most markers present in the rectosigmoid. Physical examination along with defecography and/or anal manometry is critical in determining both the exact etiology and response to therapy.

Treatment of functional constipation begins with dietary manipulation consisting of a high fiber diet (25-30gm/day) and augmented water intake (64oz/day). Most patients can be effectively managed with dietary measures alone or in conjunction with occasional laxative or enema use. For those patients who fail dietary measures, treatment with mild stimulating or osmotic laxatives can be safely done. Polyethylene glycol (PEG) is a poorly absorbed large polymer with substantial osmotic activity. When used in a solution that does not contain any salt, PEG can be ingested in large amounts without any harmful effect. PEG also binds water to the stool improving the consistency in many constipated patients. Other osmotic agents include non-absorbed carbohydrates such as lactulose. These agents also bind water and soften the stool. Complications include fermentation with consequent bloating, flatus and abdominal cramping.

Additional therapies for refractory constipation have attempted to address the lack of normal high amplitude contractions in the colon found in patients with slow transit constipation. The selective serotonin type 4 receptor agonist, tegaserod, is currently recommended for women with IBS and constipation. It acts by stimulating the serotonin type 4 receptors with a pronounced enterokinetic effect. Constipation was improved in 5-19% of women compared to placebo (15). Previous serotonin type 4 agonists such as cisipride and prucalopride also induced strong contractions of the proximal colon, but because of cardiac arrhythmias and carcinogenesis respectively, they have been withdrawn from the market. Another way to recreate the high amplitude contractions appears to be colonic pacing. In a small study pacing induced rectal evacuation in two-thirds of patients with total colonic inertia (16). Further studies will determine if it will become a replacement for extirpative surgical intervention.

Other medical approaches to stimulating the enteric neural plexuses include serotonin reuptake inhibitors, cholecystokinnin antagonists, antimuscarinic agents and serotonin type 1-receptor agonists. All these agents are currently being investigated and are not yet commercially available.

The surgical approach to constipation is one of last resort. Obstructive defecation is initially treated with biofeedback that improves symptoms in up to 70% of patients, although a rare patient may benefit from internal sphincterotomy. In patients with slow transit constipation refractory to medical therapy, attempt at segmental resection of the colon is unsuccessful. Total abdominal colectomy with ileorectal anastomosis is the preferred operation. Relief of abdominal pain and return to normal bowel function occur in up to 90% of patients with total abdominal colectomy. Risks of the surgery include ileus in approximately one-third of patients, small bowel obstruction, diarrhea, and possible incontinence (17).

Conclusion

Functional bowel diseases such as IBS and constipation are common disorders. The Rome II criteria permit more objective diagnosis and patient stratification. Therapy is determined by the major symptom or symptom complex. Therapy is often simply dietary modification, but may require medications, biofeedback and rarely surgery. As more knowledge about the enteric neural pathways and the influence of various neurotransmitters on bowel motility is discovered, focused treatment regimens with fewer side effects should be possible.

Table 1. Common Causes of Constipation

Dietary
Low fiber diet, inadequate fluid intake, ingestion of stool hardening foods.

Functional
Inadequate toilet facilities, depression, psychosis, ignoring need for bowel movement, immobility.

Endocrine, Metabolic
Diabetes mellitus, hypothyroidism, hypoparathyroidism, pregnancy, hypopituitarism, hypokalemia, hypercalcemia.

Neuropathy
Cerebrovascular accident, Parkinson’s disease, multiple sclerosis, trauma, cerebral or spinal tumors, colonic inertia, Ogilvie’s syndrome, Hirschprung’s disease, Chagas’ disease.

Medication
Analgesics, anticonvulsants, antihistamines, antihypertensives, diuretics, chemotherapeutics, anticholinergics, metal ions and minerals.

Structural
Neoplasm, diverticular disease, inflammatory bowel disease, volvulus, ischemic colitis, endometriosis, anastomotic stricture.

Anal Outlet
Thrombosed hemorrhoids, anal fissure, rectal prolapse, proctitis, rectocele, nonrelaxing puborectalis, hypertrophic internal anal sphincter.

Bibliography

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3.Kellow JE, Phillips SF, Miller IJ, et al. Dysmotility of the small intestine in irritable bowel syndrome. Gut. 1988;29:1236-43.
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13.Ward SM. Interstial cells of Cajal in enteric neurotransmission. Gut. 2000;47(suppl 4):iv40-3.
14.Adeniji OA, DiPalma JA. Prevalence of medication-associated constipation. Am J Gastroenterol. 2001;96:SI40.
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16.Shafik A, Shafik AA, El-Sibai O, Ahmed I. Colonic pacing; a therapeutic option for the treatment of constipation due to total colonic inertia.
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