Return to Symposia Highlights for the Primary-Care Physician                                     Print This
A New Paradigm for the Treatment
of Constipation

The Pathophysiology of Constipation

When functioning normally, the colon reclaims fluid and some of the nutrients that have avoided absorption in the small bowel, thus contributing to fluid and electrolyte balance and allowing timely fecal emptying. Each day, the colon receives approximately one liter of fluid, salt, and fiber left over from the digestive process. Whereas it takes about 6 hours for material to progress from the mouth to the colon, it takes a full day to travel from the right side of the colon around to the rectum. During that passage, the normal bacterial flora in the right side of the colon break down fiber and nutrients by fermentation, primarily into short-chain fatty acids. Although these are absorbed to only a limited extent, they may provide as many as a few hundred calories of nutrition. As the material makes its way through the colon, approximately 90% of the fluid and almost all of the salt is absorbed, resulting in formed stools.

Lawrence R. Schiller, MD (Baylor University Medical Center, Dallas) explained that as these fermentation and absorption processes occur, the material in the colon gradually moves toward the rectum by a slow transit process that is not well understood. The viscous material arriving in the sigmoid colon remains there until the physiological stimulation induced by eating triggers the gastrocolonic reflex that empties the sigmoid content into the rectum. Were it not for the reservoir function of the rectum due to its unique anatomical structure, defecation would be immediate.

Unlike the rest of the colon, the rectum has both a complete circular muscle layer and a complete longitudinal muscle layer. At the end of the rectum, the circular layer thickens to form the internal anal sphincter. Together with the external anal sphincter, which consists of striated muscle, this provides some voluntary control of the defecation process. However, most of the control is provided by the pubo-rectalis muscle. The rectum, which lies in the hollow of the sacrum, is directed forward toward the symphysis pubis where it takes a 90º turn due to contraction of the puborectalis muscle. This contraction produces the rectoanal angle formed by the axis of the rectum and the axis of the anal canal. Defecation normally occurs only when the puborectalis muscle relaxes, resulting in the straightening of the rectoanal angle and allowing the passage of solid feces from the rectum into the anal canal. The internal and external anal sphincters are important for controlling the passage of liquid stool and gas that readily traverse the rectoanal angle when the puborectalis muscle is contracted.

There are several hypothetical mechanisms of constipation. It is commonly thought that excessive absorption results in abnormally dry stools that are difficult to pass, but this has never been demonstrated. Indeed, the absorption rate appears to be normal in patients with severe constipation. A more plausible explanation is colonic inertia, or abnormally slow colonic transit. This provides more time for absorption, potentially resulting in a reduction in the fluid volume proceeding distally. Slow transit also provides more time for fermentation, potentially resulting in the decomposition of stool solids and the formation of small, compacted stools. Another explanation of constipation is impaired evacuation caused by either megarectum (or capacious reservoir) or functional outlet obstruction such as failure of the puborectalis muscle to relax.

Because constipation is a symptom rather than a disease, it may be secondary to other conditions. Most prominent among these are endocrine and metabolic diseases (e.g., diabetes mellitus, hypothyroidism, hyperparathyroidism), collagen and vascular diseases, various neurological diseases, and pregnancy. Additionally, more than 30% of all agents listed in the Physicians’ Desk Reference have constipation as a side effect. In a recent study, 40% of screened subjects who met the Rome II criteria (see below) for constipation were taking constipating medications ( Adeniji OA, Di Palma JA. Am J Gastroenterol 2001;96:S140). Table 1 lists the medication classes most extensively used that are associated with constipation.

Patients who report abdominal pain as a major symptom in association with constipation may have constipation-predominant irritable bowel syndrome (IBS). This is a special situation because of the overlap of symptoms and psychological profiles of normal transit constipation patients with those with IBS. These similarities make both classification and treatment options less clear.

Despite the frequency of these underlying primary conditions, many individuals have idiopathic constipation, which is characterized pathophysiologically as either (i) slow transit constipation, the etiology of which is unknown, or (ii) functional outlet obstruction. Slow transit constipation, which accounts
for approximately 80% of idiopathic constipation, is thought to result from impaired colonic neuromuscular coordination that inhibits the distal passage of colonic content. In some cases it is secondary to functional outlet obstruction. It may also be part of a generalized motility disorder of the intestines. Diffuse gastrointestinal dysmotility consists of chronic intestinal pseudo-obstruction, hollow visceral myopathy, and various enteric nervous system disorders such as functional outlet obstruction.

Functional outlet obstruction has many etiologies ranging from chronic impairment of puborectalis muscle relaxation to forced defecation resulting in eversion of the rectal lining and plugging of the anal canal. Functional outlet obstruction is also associated with anterior rectal wall ulceration in which the rectoanal angle becomes more acute due to rectal prolapse, and with perineal descent, a neuropathic weakness common in mothers. Another cause of functional outlet obstruction is Hirschsprung’s disease, in which the development of the enteric nervous system is truncated at some point proximal to the internal anal sphincter. Paradoxical puborectalis and external anal sphincter contraction during defecation, also called spastic pelvic floor and anismus, consists of tightening while trying to relax the rectal reservoir musculature, and is probably the most common variant of functional outlet obstruction. Spastic pelvic floor syndromes are of interest because of apparent psychiatric involvement often including a history of physical or sexual abuse, somatization syndrome, malingering, obsessive-compulsive disorder, psychosis, or anxiety.

Table 1. Constipating Medications

•Analgesics
• Chemotherapeutic agents
• Anticholinergics
• Diuretics
• Anticonvulsants
• Metal ions
• Antihistamines
• Resins
• Antihypertensives

Approach to the Diagnosis and Management of Constipation

Jack A. Di Palma, MD from the University of South Alabama College of Medicine in Mobile, spoke on the diagnosis and management of adult constipation.
Although the Federal Register defines constipation as fewer than three bowel movements per week, a frequency-only definition overlooks most patients seeking care for constipation because of their typical complaints: difficulty passing stool, rectal discomfort, abnormal consistency of stool, distension, bloating, and a feeling of incomplete defecation. With this limitation in mind, the Second International Congress of Gastroenterology held in Rome promulgated revised diagnostic criteria (the Rome II Consensus) to combine frequency with the symptomatic profile. These criteria are a history of at least 12 weeks within a year, not necessarily consecutive, of abnormal discomfort or pain accompanied by at least two features from a cluster consisting of straining, lumpy or hard stools, a sensation of incomplete defecation or anorectal obstruction, the use of manual maneuvers (e.g., digital evacuation, support of the pelvic floor)—each in more than 25% of defecations—and/or fewer than three bowel movements per week. Loose stools must not be present and there must be insufficient criteria for IBS.

Evaluation of a patient presenting with constipation should include consideration of IBS, medication-related constipation, endocrinopathy, neuromuscular disorders, inertia or obstructed defecation, and colon cancer. The physical examination should include observation of the perineum and anus for masses, fissures, fistulas, or hemorrhoids. Cystocele, rectocele, intussusception, rectal prolapse, and pelvic floor dyssynergia may all contribute to outlet obstruction. Tenderness, the presence of a mass, and efficiency of puborectalis and anal sphincter contractions are determined by digital examination. Where appropriate, diagnostic testing includes a metabolic profile, thyroid-stimulating hormone (TSH, thyrotropin), radiologic structural evaluation, and radiopaque colon transit markers (Sitz markers) to detect colonic inertia. Barium X-ray defecography may be useful for defining the etiology of dyschezia of the anorectal angle and junction, and for evaluating the functional integrity of the puborectalis muscle. Anorectal manometry and electromyography (EMG) may also assist in evaluating outlet obstruction.

The patient’s complaint may include clues to the underlying cause of constipation. For example, prolonged and excessive straining, the need for vaginal or perineal pressure, and nonresponse to standard laxative therapy — even in association with soft stools — are all indicative of pelvic floor dysfunction. Patients with pelvic floor dysfunction have normal or slightly slowed colonic transit and prolonged rectal storage, and they typically report an inability to evacuate adequately.

The management of constipation begins with education including normal expectations, the importance of responding to the urge to defecate, and the value of light exercise. Patients should be aware that certain disruptions in routine, such as travel, may exacerbate their symptoms of constipation.

Standard laxative treatment consists of bulk laxatives (fiber, bran, psyllium, polycarbophil, methylcellulose), lubricating laxatives (mineral water), stimulating laxatives (surface-acting agents, diphenylmethane, ricenoleic acids, anthraquinones) , and osmotic agents (magnesium and phosphate salts, sorbitol, glycerin suppositories, lactulose, polyethylene glycol). For the treatment of chronic constipation, dietary and/or synthetic fiber promotes peristalsis and reduces transit time, though it is most effective in patients with normal colonic transit. In one trial population, 80% of patients with slow transit and 63% of patients with disorders of defecation did not respond to fiber, whereas 85% of patients without pathological findings on pretreatment testing improved or became symptom-free (Voderholzer WA et al. Am J Gastroenterol 1997;92:95). These data suggest that a dietary fiber trial should be conducted before technical investigations, which would be indicated only if fiber treatment fails. Bloating may be resolved by switching to a synthetic fiber. Fiber is the least expensive treatment option.

Magnesium salts are popular for treating both acute and chronic constipation, primarily because of their rapid onset of activity. Although the mechan-ism of action is not known, they appear to have a hyperosmotic property that induces water retention in the colon, leading to a cathartic effect. For several years, however, the mainstay of therapy for constipation has been lactulose, a galactose-fructose disaccharide. Because there is no human fructosidase, lactulose is poorly digested. Thus it is fermented by colonic bacteria into hydrogen, methane, water, and volatile fatty acids. This results in acidic feces of high water content, but also in discomfort, bloating, flatus, and diarrhea.

Polyethylene glycol (PEG) laxative is a high molecular weight PEG that is metabolically inert and not susceptible to fermentation. It obligates intraluminal water retention. It is odorless, colorless, and flavorless and requires only once-a-day dosing. In a 14-day randomized, placebo-controlled trial involving 151 subjects with constipation defined as having fewer than three bowel movements per week, patients treated with 17 g of oral PEG had significantly more bowel movements per week than controls (2.7 vs. 1.5; p<0.001). Importantly, however, during the second week, placebo subjects had a mean of 2.7 bowel movements compared with 4.5 for PEG subjects (p<0.01). Investigators and study subjects rated treatment effectiveness, stool consistency, and ease of passage significantly improved in the active treatment group (p<0.001) with no treatment-related adverse events or clinically significant laboratory findings (Di Palma JA et al. Am J Gastroenterol 2000;95:446).

Additional options for the treatment of constipation include colchicine and misoprostil, both of which have diarrhea as a predominant side effect. The 5HT4 agonists cisapride, prucalopride, and tagaserod are also effective in this setting, but they face regulatory obstacles. Recombinant brain-derived neurotropic factor (r-metHuBDNF) and neurotropoin-3 (NT-3) are investigational agents with promise in treating chronic constipation in the future.

Childhood Defecation Disorders

Samuel S. Nurko, MD, MPH (Harvard Medical School) observed that between 5% and 10% of school-age children suffer from defecation disorders, and that constipation accounts for approximately 3% of pediatric outpatient visits and 25% of visits to pediatric gastroenterologists. For most children with constipation, there is no underlying organic cause. The Pediatric Working Group on Childhood Functional Gastrointestinal Disorders (Rome II) has differentiated four defecation disorders (Rasquin-Weber A et al. Gut 1999;45 (Suppl II):1160). They are (i) infant dyschezia, (ii) functional constipation in infants and preschool children, (iii) functional fecal retention from infancy to 16 years of age, and (iv) functional non-retentive fecal soiling in children older than 4 years.

Of these four disorders, the most common is functional fecal retention. This consists of a history of 12 weeks of passage of large-diameter stools at intervals of less than two per week together with retentive posturing and avoidance of defecation by intentionally contracting the pelvic floor. As the pelvic muscles fatigue, the patient uses gluteal muscles to avoid defecation. Over time this condition, which typically begins with painful defecation or fear of painful defecation, may result in rectal dilation and decreased sensation which, in turn, may result in overflow incontinence. Thus soiling is common in this disorder. Moreover, this condition is difficult to treat and may relapse frequently.

Although functional fecal retention is the most common variant of chronic constipation in children, the differential diagnosis must rule out many of the underlying factors discussed by Dr. Schiller and Dr. Di Palma. Hirschsprung’s disease, metabolic or neuropathic abnormalities, lead intoxication, and bovine milk allergy are additional potential causes of constipation in children. Among the common indicators of potential organic involvement in childhood constipation are failure to thrive, severe abdominal distention, structural lumbosacral abnormalities, abnormalities of the anal canal such as an anteriorly displaced anus, neurological abnormalities, and the presence of occult blood in the stool. Any of these warrants a thorough work-up potentially including abdominal X-rays, colonic transit studies, barium enema, anorectal manometry, rectal biopsy, colonic manometry, spinal MRI, and/or specific blood testing.

The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) has adopted treatment guidelines for childhood constipation (Baker S et al. J Ped Gastroenterol Nutr 1999;29:612; Nurko SS et al. Contemp Pediatr 2001;18:56). The mainstay of therapy consists of child and family education on the nature and frequency of the problem as well as behavioral interventions, with positive reinforcement and cessation of punitive parental reaction to soiling. The emphasis is on minimizing the emotional and physical distress associated with defecation. Medication, the subject of the next treatment phase, is less controversial than it once was, partly because it has been shown that the addition of laxative therapy to behavioral modification results in a cure rate of approximately 51% compared with 36% with education and behavioral modification alone. Following demonstration of this margin of benefit from multimodal therapy in 1991, laxative therapy became standard care.

Pharmacologic intervention consists of initial disimpaction by either oral or rectal means followed by maintenance therapy. Oral disimpaction is advocated by most groups because of the invasiveness, potential trauma, and difficulty of administering rectal means. Traditionally the principal agents used in oral disimpaction have been mineral oil, osmotic laxatives such as milk of magnesia, and stimulant laxatives. Re-cently, lavage solutions such as PEG have been shown to be effective, although they gen- erally involve hospitalization because of nasogastric administration. Preliminary trial data suggest that disimpaction by oral PEG solutions may replace this procedure, but confirmation via large randomized trials is needed. For maintenance therapy, osmotic laxatives plus intermittent stimulant laxatives to prevent recurrences of rectal accumulation have been standard. Data indicate that oral PEG solutions may be of value in this setting as well, but because they have not been approved for long-term use in children, their use is limited at present pending additional efficacy and safety trials.

Despite multimodal therapy, a significant proportion of children fail to respond adequately. Nonresponse appears to occur in approximately 30% of children treated for constipation regardless of treatment used. Long-term studies indicate that up to 30% of children may still need laxatives after 5 to 10 years
following diagnosis. This is generally attributed to the fact that many of the mysteries of impaired colonic transit and anorectal function remain to be unlocked.

 

Return to Symposia Highlights for the Primary-Care Physician                                     Print This

All contents Copyright © 1999 - 2002 Medical Association Communications