Shoba Krishnamurthy, M.D., Michael Shuffler, M.D., and Jan Hirschmann, M.D.

1.0 Introduction

1.1 Data sources

Original articles and reviews published in the English language literature between 1979 and 1998 were identified by MEDLINE search. Key words included constipation, colonic dysmotility, colonic inertia and pelvic floor dysfunction.

1.2 Definition

Although constipation is one of the most common chronic digestive complaints, there is no universally accepted or precise definition of this symptom. It has been variably defined as infrequent stools (less than 3/week), hard stools, difficult passage of stools or a feeling of incomplete evacuation. An international panel of experts have defined functional constipation as requiring 2 or more of the following criteria for a period of 3 months: 1) straining with defecation at least 25% of the time 2) lumpy or hard stool at least 25% of the time 3) sensation of incomplete evacuation at least 25% of the time or 4) two or fewer stools in a week [1]. The term functional implies that no organic cause could be identified.

2.0 Epidemiology

Various national surveys (National Health Interview Survey, National Hospital Discharge Survey, National Ambulatory Medical Care Survey and the Vital Statistics of the United States) report a prevalence of 2% with 2.5 million physician visits per year for constipation [2].These surveys also indicate that constipation is the most common digestive complaint, outnumbering all other chronic digestive conditions. Despite recognizing the frequent occurrence of constipation, its impact on national health is most likely underestimated because it seldom leads to hospitalization or death. The National Disease & Therapeutic Index statistics show that of physician visits for constipation, 31% were to general and family practitioners, 20% to internists, 15% to pediatricians and 4% to gastroenterologists [3]. The frequency of physician visits increases after age 65 to more than three times as often as younger individuals. In the US alone more than 3 million prescriptions are written yearly for laxatives and over $200 million are spent on over the counter laxatives [4]. Constipation is more common in women than men and affects non-whites more than whites. It has been more often associated with lower family income and education [5]. A recent survey suggests an increased prevalence of constipation associated with rural living, colder temperature and lower socioeconomic status [6].

3.0 Etiology

It is widely believed that inadequate intake of dietary fiber and fluids are a common cause of constipation, despite the lack of any medical evidence substantiating this impression. However, constipation and its consequences such as hemorrhoids are rarely described in third world countries and increased fiber intake has been shown to accelerate colonic transit and produce more frequent, bulky stools. Constipation can be caused by gastrointestinal disorders (colonic and anorectal disorders) (Table 1), drugs (Table 3), and metabolic (Table 4), endocrine (Table 5) and neurological disorders (Table 6) . Although inactivity and suppression of the urge to defecate are often considered causes of constipation, these factors have not been adequately studied.

3.1 Irritable bowel syndrome

Irritable bowel syndrome/functional constipation is the most common gastrointestinal disorder associated with constipation [7]. It is characterized by disordered intestinal motility and altered perception of sensations arising from the gastrointestinal tract. The onset is generally before age 35 and women outnumber men 2 to 1. The Manning criteria outlined below (Table 2) are useful in the diagnosis of irritable bowel syndrome [8].

The clinical features consist of abdominal pain, passage of small, hard stools, bloating and a sense of incomplete evacuation. Symptoms are induced or exacerabated by stress in 50% of cases and can be associated with psychologic disorders such as depression, anxiety and somatization. A history of being victims of physical or sexual abuse may be present in up to 50% of affected women [9]. The diagnosis depends on a long duration of symptoms beginning at a young age in the absence of nocturnal symptoms, weight loss, hematochezia and laboratory or radiographic abnormalities.

3.2 Diverticular disease

Diverticular disease is common in patients older than 60 years. Symptoms are similar to those of irritable bowel syndrome. Diverticular disease is thought to result from prolonged deficiency of dietary fiber which leads to hard stools. The increased intracolonic pressures resulting from the muscular effort necessary to propel hard stools leads to formation of diverticula. Diverticulitis and stricture formation can cause or worsen constipation.

3.3 Colon carcinoma

Colon carcinoma must be considered in any patient older than 50 with a recent history of constipation .A history of hematochezia, weight loss, personal history of colonic polyps or ulcerative colitis, and a family history of colon cancer, polyps and familial polyposis would support this diagnosis.

3.4 Congenital anomalies

Hirschsprung's disease is an uncommon disorder (1 in 5000 live births) caused by the absence of ganglion cells along a variable length of distal colon. The diagnosis should be considered when there is a history of constipation from birth or infancy. However, this disorder has also been diagnosed in much older age groups [10,11].

3.5 Motility Disorders

3.5.1 Colonic pseudo-obstruction

Colonic pseudo-obstruction caused by disorders of the smooth muscle or myenteric plexus can cause severe constipation and a prolonged colonic transit which responds poorly to laxatives [12]. A neuromuscular disorder is suspected in patients with severe constipation associated with colonic dilatation in the absence of mechanical obstruction.

3.5.2 Anorectal Disorders

Some of the anorectal disorders excluding the obvious structural abnormalities (anal stenosis, anal cancer, prolapse) can be included in the category of rectal outlet delay or pelvic outlet dysfunction.

3.5.3 Anismus

High resting anal pressure or failure of anal sphincter relaxation during defecation can impede evacuation of stool and has been called "anismus".

3.5.4 Puborectalis Syndrome

The puborectalis syndrome refers to the failure of the puborectalis to relax or a paradoxical increase in puborectalis contraction with attempting to defecate resulting in a functional obstruction to stool outflow.

3.5.5 Descending Perineum Syndrome

The descending perineum syndrome consists of excessive ballooning down of the perineum usually as a result of years of straining, vaginal deliveries, prior rectal or perineal surgical procedures. Rectoceles and enteroceles may also be present with the descending perneum and contribute to outlet obstruction.

3.6 Drugs

A large number of medications can cause constipation. Some of the more commonly used pharmacologic agents that may cause constipation are listed in (Table 3). Medications with anticholinergic properties (antidepressants, antiparkinson agents), opiate analgesics and calcium channel blockers delay colonic transit by their effects on intestinal smooth muscle and the autonomic nervous system. Diuretics have been thought to decrease stool water content and lead to harder stools, though this has not been studied [13].Calcium and aluminum containing antacids and nonsteroidal anti-inflammatory agents are commonly used medications which are available over the counter and can lead to constipation. Nonsteroidal anti-inflammatory agents may cause constipation by inhibiting prostaglandin synthesis [14,15].

3.7 Metabolic and Endocrine Disorders

(Table 4). Diabetes commonly causes constipation and can be present in 80-90% of patients with neuropathy (autonomic and peripheral) and 20% of patients without neuropathy [16].

(Table 5). Hypothyroidism commonly causes constipation and it may be the presenting or only symptom. It can sometimes be associated with a megacolon [17].

3.8 Neurological Disorders

(Table 6). Constipation is common in patients with Parkinson's disease and a megacolon is present in 10%. Antiparkinsonian medications can cause or worsen constipation. Impaired colonic transit as well pelvic floor dysfunction has been described in these patients. The pelvic floor and sphincteric muscles may be involved in the Parkinson's disease process [18]. Forty percent of patients with multiple sclerosis complain of constipation. Recent studies suggest that abnormalities of anorectal function which include increased threshold of the anorectal inhibitory reflex may contribute to constipation in these patients [19,20]. Paradoxical puborectalis contraction on attempted defecation has also been reported to be a cause of constipation in these patients [21].

4.0 Evaluation

4.1 History

The history should focus on defining the exact nature of the patient's complaint and include a detailed account of medication intake and symptoms of metabolic, endocrine and neurologic disease. A history of sexual and physical abuse should also be obtained in women.

4.2 Physical examination

A physical examination which includes a detailed evaluation of the gastrointestinal and neurologic systems is mandatory. Anorectal and perineal exam should include a search for perineal disease, rectal prolapse and anal fissures. A visual inspection during straining may reveal excessive descent (greater than 4 cms) and ballooning and indicate a possible descending perineum syndrome. A digital rectal exam may reveal a mass, stenosis or internal mucosal prolapse during straining.

4.3 Routine tests

Routine laboratory tests include a complete blood cell count, fecal occult blood tests, thyroid function tests, blood urea nitrogen, serum calcium, electrolytes and blood glucose determinations.

4.3.1 Imaging Studies

Patients with recent onset, persistent or severe symptoms should undergo further evaluation with a flexible sigmoidoscopy and a barium enema. In a patient with Hemoccult positive stool, iron deficiency anemia, family history of a first degree relative with colon cancer or familial polyposis, a colonoscopy is preferable. The evaluation of the colon may reveal a colorectal neoplasm, strictures, diverticula, mega colon or a narrowed distal segment with proximal colonic dilatation (Hirschsprung's disease).

4.3.2 Trial of Fiber

If the above evaluation is entirely normal the patient should be started on a high fiber diet (25-30 gms/day) which can include high fiber cereals or grains (Table 8) or supplemental fiber (Table 7). Gradually increasing doses of fiber should be suggested since a sudden increase can cause abdominal bloating and discomfort. Most patients will respond to these simple measures and if constipation resolves no further work up is required.

4.4 Motility Studies

In patients with persistent or intractable symptoms who complain primarily of infrequent defecation, a colonic transit study using radio-opaque markers is indicated [22,23]. This is a simple, well validated test of overall colonic transit. It is performed by having the patient ingest a commercially available capsule containing twenty four radio-opaque rings on day zero, the day after the patient has had a bowel movement. Abdominal radiographs are obtained on days five and seven. Normal subjects pass 80% of the markers by day five and 100% by day seven. The patient should avoid laxatives or enemas during the test. Since patient reported stool frequency can often be unreliable, this test is an excellent way of objectively confirming infrequent defecation and prolonged colonic transit time [24].

4.4.1 Abnormal test

An abnormal test with markers scattered throughout the colon suggests slow transit constipation or "colonic inertia". These are uncommon causes of constipation and suggest a neuromuscular disorder of the colon [25,26,27]. These patients are best referred to a gastroenterologist for further evaluation and management.

4.4.2 Normal colonic transit

A normal colonic transit study in a patient who complains of severe constipation may suggest a psychiatric disorder and further evaluation and referral should be considered [28].

4.4.3 Retained Markers in Distal Colon

If the colonic transit study demonstrates the radio-opaque markers being primarily retained in the rectum or distal sigmoid area; or if a patient complains mainly of difficulty evacuating stool, further tests of anorectal function would be warranted. Difficulty evacuating stool may also be described as a feeling of anal blockage, needing to press or splint the perineal area, digital disimpaction, prolonged defecation (greater than 10 minutes to complete a bowel movement) or assuming an unusual position during defecation. These patients are best referred to a gastroenterologist for further evaluation.

4.4.4 Anorectal Function tests [29,30,31] Defecography

Defecography is a dynamic study performed after instilling a thick barium paste into the rectosigmoid and obtaining video fluoroscopic images while the patient defecates sitting on a radiolucent commode. This study is most useful in demonstrating anatomical abnormalities such as intussusception, rectocele and enterocele. However, there is not always a good correlation between the presence of anatomic abnormalities, symptoms and improvement with surgical treatment. It is felt to be of potential value in corroborating the results of other tests such as anorectal manometry in patients with inappropriate puborectalis contraction and in documenting anatomic abnormalities, but there is not enough data to support its routine use. Anorectal manometry

Anorectal manometry provides information about resting anal sphinter tone, squeeze pressure and the presence or absence of internal anal sphincter relaxation in response to rectal distension and external anal sphincter pressure changes during efforts to expel the manometer or rectal balloon. The presence of high resting anal pressure and inappropriate contraction of the external anal sphincter during attempted defecation suggests anismus or pelvic floor dyssynergia.. The absence of the rectoanal inhibitor reflex suggests a diagnosis of Hirschsprung's disease (see Figures 5 and 6) and the presence of internal anal sphincter relaxation in response to rectal distension excludes Hirschsprung's disease. Therefore, manometry is a simple screening test for this uncommon disorder in children and adults with lifelong constipation. There are no controlled clinical trials validating the usefuleness of anorectal manometry in the diagnosis and treatment of constipation. The Balloon Expulsion Test

A balloon expulsion test can be used as a screening test of support symptoms of inability to defecate. A 50-60 ml balloon is placed in the rectum and inflated with the patient in the left lateral decubitus position. A string from the balloon attaches to a container to which weights can be added. If the patient is unable to expel the balloon spontaneously, sequential weights are added to facilitate expulsion. The normal range of weights is 0-200 gms. Inability to expel the balloon suggests anismus or pelvic floor dysfunction. Electromyography

Electromyography provides information regarding the innervation and function of the pelvic floor muscles. The primary utility of EMG is in making the diagnosis of paradoxical puborectalis contraction and for performing biofeedback training. Rectal biopsy

Rectal biopsy is useful in the diagnosis of Hirschsprung's disease and occassionally in the diagnosis of neuropathies (neuronal intranuclear inclusion disease and neuronal intestinal dysplasia).

5.0 Management

The initial management of constipation includes simple measures to which most patients respond well. If an underlying cause is identified this should be appropriately treated.

5.1 Therapeutic trial of fiber

The general principles of treatment include the following: an increase in fiber intake to 25 gms of dietary fiber or supplemental fiber. Patients should also be advised to increase their fluid intake to 6-8 glasses per day. The laxative effect of fiber may take 3-5 days to become evident. Dietary fiber is defined as edible plant polysaccharides which are resistant to digestion by intestinal enzymes and therefore not absorbed in the small intestine. Fiber is composed of soluble and insoluble substances which include cellulose, hemicellulose, pectins, gums and lignin. Cellulose is the only component of fiber that is truly fibrous. Bran cereals and whole grain products are the most concentrated sources of insoluble fiber and are the most effective for increasing stool weight and size. Water soluble fibers found in fruits, vegetables, oat products and legumes are less effective in increasing stool size. The physical form of fiber also influences its effect on stool weight. The larger the particle size the more effective the fiber. For example finely ground wheat bran has less effect on stool weight than coarse bran. The mechanisms by which different fibers help in constipation include (1) increasing stool volume due to unabsorbed mass, (2) providing substrate for growth of colonic bacteria which in turn increase stool weight, (3) increased water holding capacity, (4) stimulation of colonic contractility by microbial breakdown products (gases and short chain fatty acids) and (5) shortened colonic transit time [32,33,34,35]. The fiber content of some commercial fiber supplements and foods are listed in (Table 7) and (Table 8).

5.2 Chronic and routine use of laxatives

Chronic and routine use of laxatives should be discouraged. The potential side effects of laxatives include abdominal cramping, flatulence, dehydration, malabsorption, electrolyte imbalance and fecal incontinence. However, some individuals may require a regular regimen of laxatives. There are a large number of laxatives available and the choice of a laxative may depend on patient tolerance and preference. It would reasonable to start with a mild laxative such as milk of magnesia (magnesium hydroxide) or mineral oil. The other saline laxatives such as magnesium sulphate or citrate are more potent. Non absorbable disaccharides (lactulose, sorbitol) have the disadvantage of causing excessive bloating and flatulence. Stool softeners (docusate salts) are widely used but have not been clearly shown to be effective. If the milder laxatives are ineffective, the next choice of agents would be stimulant laxatives such as anthroquinones (senna, cascara), castor oil, phenolphthalein and bisacodyl [36,37,38]. Polyethelene glycol solutions (Colyte, Golytely) can be used but are generally more expensive [39]. Different laxatives are listed with doses and side effects in (Table 9).

5.3 Suppositories and enemas

Suppositories and enemas can be used for treatment when prompt or immediate relief is desired. Habit training (i.e. attempting a bowel movement at a scheduled time each day usually after a meal) or contingency training (i.e. using an enema if bowel movement does not occur after two days) have been used in the management of constipation of children but have not been adequately studied in adults [40]. Tap water enemas or sodium biphosphate kits can be used. Hot water, soap suds, peroxide and strong hypertonic solutions are irritating to the colonic mucosa and should not be used.

5.4 Surgery

The above laxatives may not be very effective in more severe constipation as seen in patients with "colonic inertia". Surgical treatment may have to be considered when even aggressive medical management fails. The procedure of choice is subtotal colectomy with ileorectal anastomosis. The surgery can be very successful in carefully selected patients. These patients should be selected on the basis of the following criteria: (a) severe chronic constipation with disabling symptoms which are interfering significantly with quality of life and unresponsive medical therapy; (b) slow transit constipation of the colonic inertia pattern; (c) normal gastric emptying and normal small bowel motility; (d) normal anorectal function [41,42,43,44]. Surgical failure usually indicates a more generalised gastrointestinal neuromuscular disorder or pelvic floor dysfunction. A newer surgical procedure known as MACE (Malone antegrade continent enema) has been described to treat constipation in some patients. In this procedure a continent fistula between the cecum/appendix is constructed. This fistula permits controlled purging of the colon. The initial results are encouraging, however, this procedure needs to be evaluated further [45].

5.5 Biofeedback

In disorders of the pelvic floor, biofeedback is the mainstay of treatment. This treatment is aimed at retraining the muscles of the pelvic floor to relax appropriately during defecation. In addition to biofeedback, increased dietary fiber, psychologic counselling and physical therapy may also be necessary [46,47,48].

5.6 Prokinetic agents

Prokinetic agents are currently under investigation, the preliminary results are encouraging. The traditional p. agents (metoclopramide and cisapride) have been tried and are occassionally helpful. Newer selective colonic prokinetic agents are currently under investigation and preliminary results are encouraging.

6.0 Fecal Impaction

6.1 Epidemiology and etiology

Fecal impaction is the inability to pass hard stools. It is a common complication of constipation in frail elderly people, though it can occur in any age group. Mentally and physically impaired individuals are at higher risk for developing a fecal impaction. Decreased rectal sensation and colonic motility, painful rectal lesions and ignoring the urge to defecate because of dementia, physical weakness and disabilities may predispose to fecal impaction. As stool remains longer in the colon continued water absorption by the mucosa results in a hard bolus of stool which can become large and impossible to pass through the anus [49,50].

6.2 Diagnosis

In patients with chronic constipation, additional symptoms of abdominal distension, paradoxical diarrhea with fecal incontinence, rectal discomfort, nausea and vomiting should raise the suspicion of fecal impaction. Urinary frequency, urinary incontinence and respiratory compromise with decreased oxygenation can also be present. Fever, abdominal tenderness, palpable masses in the left lower quadrant may be present. Rectal exam may reveal hard stool. However, absence of stool in the rectum may indicate a more proximal impaction.

Laboratory evaluation may show leukocytosis and electrolyte abnormalities. A plain abdominal radiograph may show large amount of stool in the colon. In severe cases a dilated colon and air fluid levels in the colon may be seen. A water soluble contrast solution (gastrograffin/meglumine diatrizoate) should be used if colonic obstruction or perforation is suspected.

6.3 Management

(1) The first step in the treatment should include manual removal of hard stool from the rectum. A local anesthetic lubricant should be used to help gradually dilate the anus by inserting two fingers and then trying to fragment the stool mass by a scissor like or criss cross motion of the two fingers. In female patients transvaginal pressure can also be used to fragment the stool.

(2) After disimpaction, enemas (oil retention or tap water)or suppositories can be used to remove the stool. Gastrograffin enemas can also be used to soften the stool and remove it.

(3) If the impaction is higher, polyethylene glycol solutions (Colyte/Golytely) up to 4L can be very effective. Other laxatives can also be used once a colonic obstuction or perforation has been excluded.

(4) Once the impaction has been cleared,a regular bowel regimen should be instituted which should include increased fiber (dietary and supplemental), exercise, regularly scheduled attempts at defecation, increased fluid intake and laxatives, enemas or suppositories as needed. These measures are important to prevent further episodes of impaction. The doses of fiber and laxatives will have to be titrated to result in a soft bowel movement every 1-2 days [51].

Laxative Abuse: Because stimulant laxatives are easily available they can be abused. This can lead to diarrhea ,electrolyte and acid-base imbalance, melanosis coli in severe cases renal failure, protein losing enteropathy and steatorrhea can occur. Abnormalities of the submucosal and myenteric plexus have been described in animal models and humans. A term called "cathartic colon" has been used to describe radiologic abnormalities in patients on long term laxatives. These abnormalities consist of loss of haustral markings, strictures, colonic dilatation and a gaping ileocecal valve [52]. It is unclear if these abnormalities are truly a result of laxative abuse. The risks of long term have not been adequately studied and appear to be exaggerated. There is currently insufficient evidence to support the notion that laxatives lead to colonic damage [53].

7.0 Summary

Constipation is a common problem, though estimates of prevalence vary widely because there is no generally accepted definition of constipation. Constipation can be a symptom of many underlying disorders, but in approximately half the patients no cause can be found even after systematic objective testing .These patients may have misperceptions about the normal range of bowel movements or psychological causes for their bowel dysfunction and may require psychotherapy.

Most patients with chronic constipation can be managed with conservative measures such as education, fiber supplements and adequate fluid intake. For those who do not respond to these measures diagnostic tests of colonic and anorectal function help in selection of appropriate treatments.

Chronic use of laxatives should generally be avoided, though it may be appropriate for some patients to use stimulant laxatives on a long-term basis under the supervision of a physician. Pelvic floor dyssynergia can be treated by biofeedback training. Surgery (colectomy with ileorectal anastomosis) should be used as a last resort in carefully selected patients. Guidelines for referral to a gastroenterologist are outlined in (Table 10).