A Clinical Approach to Constipation
`
`clinical CORNERSTONE • LOWER GI DISORDERS • Vol. 4 No. 4
`
`Douglas 0. Faigel, MD
`Associate Professor of Medicine
`Division of Gastroenterology
`Oregon Health & Science University
`Portland VA Medical Center
`Portland, Oregon
`
`The economic impact of constipation is large. 1 ne conamon prompts an estimaiea ~.:, mutwn physician
`visits per year, with 100,000 referrals to gastroenterologists. Almost all (85%) of these physician visits
`result in a prescription for a laxative. Each year, Americans spend ~$800 million on laxatives. For
`patients referred for diagnostic evaluation, the average cost is ~$3000, mostly due to the cost of
`colonoscopy. This article discusses the pathophysiology of constipation and presents a practical
`approach to evaluating and treating this disorder.
`
`DEFINITION
`Constipation is a common complaint heard in clini-
`cal practice. While prevalences as high as 20%
`have been quoted, the true prevalence is difficult to
`gauge precisely because of the difficulty in defining
`exactly what constipation is. The word "constipa(cid:173)
`tion" comes from the Latin "constipare," which
`means "to crowd together," a term the Romans
`used as meaning "to pack anything tightly." It was
`not until the 16th century that the word "constipa(cid:173)
`tion" came to mean "inspissated stool packed tight(cid:173)
`ly in a dilated colon."
`Physicians usually define constipation as
`"an inadequate stool frequency of less than 3 per
`week." This lower limit of normal was defined in
`population surveys of subjects eating a Western
`diet. It is clear this definition in and of itself is
`inadequate because patients often define consti(cid:173)
`pation as "difficulty in passing a stool, or a hard
`or lumpy stool consistency." A better definition
`can be found in "Rome II: A Multinational
`Consensus Document on Functional Gastro(cid:173)
`intestinal Disorders." The expert panel that wrote
`this document was originally convened in Rome
`to define functional disorders, such as irritable
`
`bowel syndrome, and this document was updated
`in 1999. Functional constipation is suspected in
`a patient with 12 weeks of symptoms that may
`include either a decreased stool frequency or dif(cid:173)
`ficulty in stool passage with a hard stool consis(cid:173)
`tency (Table I).
`Various risk factors for constipation have
`been identified. Women report constipation more
`often than men do, and older patients more often
`than younger patients. Constipation is associated
`with inactivity, low calorie intake, the number of
`medications being taken, low income, and low edu(cid:173)
`cation level. It is also associated with psychologic
`risk factors, such as clinical depression or a history
`of physical or sexual abuse. Interestingly, specific
`dietary factors, such as a low intake of fiber, have
`not been reported.
`
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`clinical CORNERSTONE
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`• LOWER GI DISORDERS • Vol. 4 No. 4
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`TABLE I.
`
`DIAGNOSTIC CRITERIA FOR FUNCTIONAL CONSTIPATION
`
`At least 12 weeks, which need not be consecutive, in the preceding 12 months of 2 or more of the following:
`
`• Straining in > 1 out of 4 defecations
`• Lumpy or hard stools in > 1 out of 4 defecations
`• Sensation of incomplete evacuation in > 1 out of 4 defecations
`• Sensation of anorectal obstruction/blockade in > 1 out of 4 defecations
`• Manual maneuvers to facilitate >1 out of 4 defecations (eg, digital evacuation, support of pelvic floor)
`
`• <3 defecations/week
`Loose stools are not present, and there is insufficient criteria for irritable bowel syndrome.
`
`Reprinted with permission from Thompson \"X/G, Longstreth GF, Drossman DA, et al. Functional bowel disorders and func(cid:173)
`tional abdominal pain. Gut. 1999;45(Suppl Il):Il43-II47.
`
`PATHOPHYSIOLOGY
`The pathophysiology of constipation can be classi(cid:173)
`fied as structural or functional abnormalities.
`Structural abnormalities cause constipation by
`obstructing the flow of feces. While the presence of
`a malignant neoplasm is the most serious concern,
`obstruction leading to symptoms of constipation
`may be caused by a benign neoplasm ( eg, lipoma or
`leiomyoma), an inflammatory stricture (eg, divertic(cid:173)
`ulitis, inflammatory bowel disease, postischemic
`injury), or adhesions. Patients often have other clini(cid:173)
`cal signs, such as distension, vomiting, weight loss,
`bleeding, or a narrowing of the stool caliber. In only
`a small minority of patients complaining of constipa(cid:173)
`tion is the cause obstruction.
`In the majority of patients, constipation is
`functional due to disordered motility of the colon or
`anorectum. Functional constipation can be subclas(cid:173)
`sified as primary or secondary, depending on
`whether an underlying cause is present, such as a
`systemic illness or the side effect of a medication.
`The most common medications that cause constipa(cid:173)
`tion are anticholinergics, analgesics, neurally acting
`agents such as opioids and antihypertensives, and
`cation-containing compounds such as iron supple(cid:173)
`ments and calcium preparations (Table II).
`Systemic illnesses (Table III) may cause constipa(cid:173)
`tion from metabolic derangements ( eg, thyroid dis(cid:173)
`ease or diabetes); destruction of gut muscle (ie, sys(cid:173)
`temic sclerosis); or neurologic disease, which may
`be either central ( eg, multiple sclerosis or spinal cord
`injury) or peripheral (eg, Hirschsprung's disease).
`
`In many if not most patients an underlying
`cause is usually not found. Primary functional con(cid:173)
`stipation is then diagnosed. These patients general(cid:173)
`ly have 1 of 2 disorders of colorectal motility:
`slow-transit constipation (colonic inertia) or pelvic
`floor dysfunction (outlet obstruction). In slow(cid:173)
`transit constipation, there is a prolonged time of
`passage of feces from cecum to rectum, which may
`be due to the absence or diminution of propagating
`peristaltic contractions or uncoordinated motor
`activity in the distal colon that may form a func(cid:173)
`tional barrier to the passage of feces. In pelvic
`
`floor dysfunction, there is an inability to pass feces
`that have collected in the rectum. The mechanisms
`involved in defecation are complex and the specific
`abnormalities poorly understood. It seems likely
`that in many of these patients there is a failure of
`the puborectalis or the external anal sphincter to
`adequately relax during defecation. In patients
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`TABLE 11.
`
`DRUGS ASSOCIATED WITH CONSTIPATION
`
`clinical CORNERSTONE
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`• LOWER GI DISORDERS • Vol. 4 No. 4
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`Class
`
`Anticholinergics
`• Antidepressants
`
`• Antiparkinson drugs
`
`• Antipsychotics
`• Antispasmodics
`
`Analgesics
`• Nonsteroidal anti-inflammatory drugs
`
`Neurally acting agents
`
`• Adrenergics
`
`• Anticonvulsants
`
`• Antihistamines
`• Antihypertensives
`
`• Calcium channel blockers
`
`• Opiates
`• Vinca alkaloids
`
`Cation-containing agents
`
`• Aluminum
`• Barium sulfate
`
`• Calcium
`• Iron supplements
`
`Example
`
`Amitriptyline
`
`Benztropine
`
`Haloperidol
`
`Dicyclomine
`
`Ibuprofen
`
`Clonidine, ephedrine, terbutaline
`
`Phenytoin
`
`Diphenhydramine
`
`~-blockers, diuretics
`Verapamil
`
`Morphine, codeine, loperarnide
`
`Vincristine
`
`Antacids
`
`Oral contrast agents
`
`Antacids, supplements
`Ferrous sulfate
`
`with pelvic floor dysfunction, a rectocele may be
`present.
`Marker studies (Sitzmarks®, Konsyl
`Pharmaceuticals, Inc., Fort Worth, Texas) are useful
`in discriminating between these 2 motility disor(cid:173)
`ders. Radiopaque markers are ingested and abdom(cid:173)
`inal radiographs are obtained 4 to 7 days later.
`Patients with normal motility pass the majority
`(>80%) of the markers within 5 days. Retention of
`markers distributed throughout the colon indicates
`colonic hypomotility, whereas collection within the
`rectum indicates a functional outlet obstruction
`(Figure 1).
`
`CLINICAL EVALUATION
`The initial evaluation should focus on elucidating
`whether there is an underlying cause for the consti(cid:173)
`pation (Figure 2). Removal of the cause, either by
`eliminating a causative medication or treating an
`
`underlying illness, may resolve the problem. The
`medical history and the physical examination
`should focus on the presence of underlying sys(cid:173)
`temic and neurologic illnesses (Table III).
`Laboratory tests should include a complete blood
`cell count; electrolytes, including calcium, phos(cid:173)
`phorus, and magnesium; blood urea nitrogen; crea(cid:173)
`tinine; and glucose and thyroid function tests, with
`additional specialized blood tests as dictated by
`findings of the medical history and physical exami(cid:173)
`nation. A careful medication history should be
`taken that includes both prescription medications
`and any over-the-counter or herbal products the
`patient may be using. Polypharmacy can be a sig(cid:173)
`nificant problem, and often the best approach is to
`instruct patients to empty the contents of their med(cid:173)
`icine cabinets into a paper bag and bring them to
`their next appointment. This approach is especially
`useful for elderly patients or patients who may be
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`clinical CORNERSTONE
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`• LOWER GI DISORDERS • Vol. 4 No. 4
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`TABLE 111.
`
`SECONDARY CAUSES OF CONSTIPATION
`
`Neurogenic disorders
`
`Central
`
`• Cerebtovascular disease
`
`Metabolic disorders
`
`• Diabetes mellitus
`
`• Heavy metal poisoning
`
`• Hypercalcemia
`
`• Hypokalemia
`
`• Hypomagnesemia
`
`• Hypopituitarism
`
`• Hypothyroidism
`
`• Pheochromocytoma
`• Porphyria
`• Pregnancy
`
`• Uremia
`
`confused about exactly what medications they are
`taking. Psychologic factors should also be
`assessed.
`Of chief concern to patients. and physicians
`is a possible underlying malignancy or other ob(cid:173)
`structing process. Symptoms may include abdomi(cid:173)
`nal distension, weight loss, vomiting, change in
`stool caliber, bleeding, and anemia. Patients should
`be reassured that the symptoms of constipation are
`common and the likelihood of cancer as its cause is
`very low.
`The examiner should ask about specific fea(cid:173)
`tures of the constipation and determine the onset
`and duration of symptoms. Onset in childhood
`suggests the possibility of a congenital disorder,
`such as Hirschsprung's disease (a congenital
`absence of ganglionic cells in the rectum). A
`recent chfu1ge in bowel habit suggests an organic
`disorder, whereas that of several years' duration
`suggests a functional complaint. What feature does
`the patient find most distressing? Is it the infre(cid:173)
`quent passage of stool or straining or other maneu(cid:173)
`vers required for evacuation? Straining (the need
`for perinea! pressure) or digital extraction of stool
`suggests perinea! dysfunction. If the major com(cid:173)
`plaint is of symptoms between evacuations, such as
`
`cramps and bloating, then irritable bowel syndrome
`should be suspected and may be constipation pre-
`dominant. The use of laxatives, enemas, and sup-
`positories should be noted.
`In addition to looking for organic causes, a
`neurologic examination should be performed. The
`abdomen is examined for evidence of not only
`masses and organomegaly but also surgical scars.
`Anorectal and perinea! examinations are performed
`to search for perinea! disease or deformity. An anal
`fissure may be either a cause or a result of consti(cid:173)
`pation. The fissure may be seen by spreading the
`buttocks and using a bright examining light or may
`be found by pain elicited during digital examina(cid:173)
`tion. A careful digital examination assesses for a
`mass, anal canal stricture, or impacted stool.
`Instructing the patient to squeeze the examining
`finger assesses external anal sphincter and puborec(cid:173)
`talis function; a lack of voluntary squeeze suggests
`a neurologic problem. Perianal sensation to light
`touch should be assessed. Reflex contraction of the
`anal canal after pinprick of the perianal area (ie,
`anal wink) also can be used to test neurologic func(cid:173)
`tion. When the finger is removed, gaping of the
`anal canal further suggests a neurologic problem.
`Instructing the patient to strain may reveal rectal
`
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`clinical CORNERSTONE
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`• LOWER GI DISORDERS
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`• Vol. 4 No. 4
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`A. If 5 or less markers remain, patient
`has grossly normal colonic transit.
`
`B. Most rings are scattered about
`the colon. Patient most likely has
`hypomotility or colonic inertia.
`
`C. Most rings are gathered in the
`rectosigmoid. Patient has functional
`outlet obstruction.
`
`Figure 1. Markers are ingested on Day 0. The patient is instructed to use no laxatives, enemas, or suppositories
`for 5 days. Abdominal radiographs are obtained on Day 5. The pattern of marker retention helps differentiate
`between normal (A), colonic hypomotility (B), or a functional outlet obstruction (C). Reprinted with permission
`from Sitzmarks [brochure]. Fort Worth, Tex: Konsyl Pharmaceuticals, Inc.; /999.
`
`prolapse, perinea! descent, or bulging of a rectocele
`into the vagina. A stool specimen may be tested for
`occult blood.
`
`DIAGNOSTIC TESTS
`The primary goals of diagnostic testing are to rule out
`a secondary cause of constipation, such as obstruc(cid:173)
`tion, and to aid in therapy. Visualization of the
`colonic lumen should be done in patients where
`colonic obstruction is suspected and in patients >50
`years of age who have not previously undergone
`colon cancer screening. Visualization may be done
`with either flexible sigmoidoscopy, colonoscopy, or
`barium enema. Colonoscopy has been shown to be
`
`15
`
`superior to barium enema for the detection of cancer,
`but whether it is superior in the evaluation of consti(cid:173)
`pation has not been demonstrated. Barium enema
`may also occasionally miss a distal rectal mass; for
`this reason, flexible sigmoidoscopy is often performed
`in addition to the barium enema. The presence of a
`solitary rectal ulcer indicates rectal prolapse.
`Studies of colorectal motility may be useful
`in patients with severe refractory symptoms. Marker
`studies may help to distinguish normal from slow(cid:173)
`transit and outlet-obstructive constipation (Figure 1).
`Anorectal manometry measures sphincter
`pressures, autonomic reflex pathways, and sensation.
`In the resting state, a basal sphincter pressure is
`maintained by the smooth muscle of the internal anal
`sphincter. In response to rectal distension (by a bal(cid:173)
`loon), this muscle should reflexively relax. If it does
`not, this may indicate Hirschsprung's disease in
`which a congenital absence of intramural ganglion
`cells leads to the loss of internal anal sphincter relax(cid:173)
`ation, resulting in outlet obstruction of feces. Con(cid:173)
`firmation of Hirschsprung's disease requires deep
`biopsies of the rectal wall to demonstrate the absence
`of neurons. The external anal sphincter, which is
`composed of voluntary striated muscle, is assessed
`by anorectal manometry and is done by asking the
`patient to squeeze the anal probe. A high resting
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`clinical CORNERSTONE
`
`• LOWER GI DISORDERS • Vol. 4 No. 4
`
`History and physical examination
`Medication review
`
`Metabolic profile
`• Electrolytes
`• Glucose
`• Thyroid
`Rule out structural disease
`• Colonoscopy
`• Barium enema
`• Sigmoidoscopy
`
`Therapeutic trial
`• Fiber
`• Stool softeners
`• Osmotic laxatives
`
`Figure 2. Initial evaluation and treatment of idiopathic constipation.
`
`pressure with little augmentation by voluntary
`squeeze suggests spasm of the muscles of the
`pelvic floor (ie, anismus). Sensation is assessed
`by inflating the rectal balloon to various volumes.
`Impaired sensation may indicate a central nervous
`system disorder or a peripheral neuropathy. Testing
`the patient's ability to expel a 50-mL balloon is
`often done at the same time and is somewhat useful
`in assessing for major dysfunctions of evacuation.
`Defecography is seldom performed. It can
`be done either radiographically with a barium
`
`enema or scintigraphically. Defecography may
`reveal a failure of the anorectal angle to open (ie,
`become more obtuse) or may document the degree
`of pelvic floor descent. Failure of the anorectal
`angle to open and decreased descent are features
`of impaired pelvic floor relaxation (ie, anismus).
`Excessive descent also can be a pathophysiologic
`mechanism of constipation and responds to surgical
`pelvic floor resuspension procedures.
`
`TREATMENT
`Table IV lists the commonly used medications for
`constipation. Dietaty and lifestyle modifications
`may be helpful in improving a patient's symptoms.
`Increasing dietary fiber over 1 to 2 weeks is often
`helpful, but results are gradual. Foods with a high
`fiber content include bran; fruits (apricots, apples,
`pears, melons); vegetables (asparagus, beans, broc(cid:173)
`coli, carrots, beets, cauliflower, other greens); and
`whole wheat cereals, breads, and pastas. Patients
`who find that increasing the amount of dietary
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`cli11ical CORNERSTONE
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`• LOWER GI DISORDERS • Vol. 4 No. 4
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`TABLE IV.
`
`COMMONLY USED MEDICATIONS FOR CONSTIPATION
`
`Laxative Type
`
`Fiber
`Psyllium
`Methy lcellulose
`
`Emollient laxatives
`Docusate
`Mineral oil
`
`Saline laxatives
`M,agnesinm snlfatP
`Magnesium phosphate
`Magnesium citrate
`
`Hyperosmolar laxatives
`Polyethylene glycol
`Sorbitol
`Lactulose
`
`Stimulant laxatives
`Bisacodyl
`
`Senna
`
`Castor oil
`
`Dosage
`
`Onset of Action (h)
`
`Side Effects
`
`1-2 tsp qd-tid
`1 tsp up to tid
`
`100-500 mg PO
`14-45 n1L
`
`15 g PO
`lOgPO
`200mLPO
`
`0.5--4L
`15-30 mL
`15-30 mL
`
`30 mg PO
`10 mg PR
`2-4 tabs qd-bid
`
`15-60 mL PO
`
`Bloating, flatulence
`Less bloating
`
`Skin rashes
`Decreased absorption
`vitamins, lipoid
`pneumonia
`
`Magnesium toxicity
`(with renal insufficien(cid:173)
`cy), cramps
`
`Abdominal bloating
`
`Abdominal cramps
`Rectal irritation
`Degeneration of
`colonic neurons (?)
`Nutrient malabsorption
`
`fiber is impractical may benefit from a fiber supple(cid:173)
`ment. A number of fiber supplements are available
`but there is little information to recommend one
`over another, and a patient may have to try several
`before finding one that is acceptable. Fiber supple(cid:173)
`ments are given twice daily with water; however,
`fiber therapy may increase gaseousness. Increasing
`a patient's physical activity may also be beneficial.
`If a patient does not respond to fiber therapy
`then additional therapy is indicated. Patients who
`complain of hard, lumpy, difficult-to-pass stools
`may benefit from an oral stool softener such as
`docusate, a mineral oil lubricant, or a glycerine sup(cid:173)
`pository. There are many laxatives on the market,
`but available data do not document that laxatives are
`superior to fiber or that one laxative class is superior
`to another. Gastroenterologists have been concerned
`that stimulant laxatives, such as senna or bisacodyl,
`may result in damage to the enteric nervous system.
`Chronic damage could result in a dilated floppy
`colon (so-called "cathartic colon") and worsen the
`
`patient's symptoms; however, it is also likely that
`nerve damage and colonic atony precede, rather than
`being caused by, laxative use. While there is less
`reticence to recommend stimulant laxatives, it still
`may be prudent to rely on osmotic laxatives as first(cid:173)
`line therapy.
`Osmotic laxatives work via osmotic retention
`of fluid in the gut. Saline and hyperosmolar laxa(cid:173)
`tives work via an osmotic mechanism. The com(cid:173)
`monly used saline laxatives are magnesium salts,
`such as magnesium hydroxide, magnesium sulfate,
`and magnesium citrate. Because an appreciable
`amount of the magnesium is absorbed, these should
`be used with caution in patients with renal impair(cid:173)
`ment due to the risk of magnesium toxicity. Saline
`laxatives are inexpensive and for most patients effec(cid:173)
`tive. Of the hyperosmolar laxatives, the nonab(cid:173)
`sorbable sugars lactulose and sorbitol are digested by
`gut bacteria and may produce gas and bloating. In
`general, they are more expensive than the saline lax(cid:173)
`atives, and lactulose is more expensive than sorbitol.
`
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`clinical CORNERSTONE
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`• LOWER GI DISORDERS • Vol.4 No.4
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`Polyethylene glycol solutions, traditionally used as
`purgatives prior to colonoscopy, can be effective in
`the treatment of refractory constipation but are
`given in larger volumes than are other laxatives.
`Stimulant laxatives increase intestinal water
`secretion and motility. Castor oil is hydrolyzed by
`intestinal lipases to ricinoleic acid, which stimulates
`secretion and motility. The anthraquinones ( cascara
`sagrada, senna) increase fluid a11d electrolyte secre-
`tion in the distal ileum and colon and require
`intestinal microorganisms for conversion to the
`pharmacologically active state. The anthraquinones
`are associated with melanosis coli (a benign accu(cid:173)
`mulation of pigment in the colonic mucosa) and
`atrophy of the smooth muscle and myenteric plexus.
`The diphenylmethanes (phenolphthalein, bisacodyl)
`inhibit intestinal sodium and glucose absorption to
`increase intestinal fluid and directly stimulate
`colonic motility. Phenolphthalein* undergoes
`enterohepatic circulation and may have a long dura(cid:173)
`tion of action (phenolphthalein is no longer avail(cid:173)
`able in the United States). Bisacodyl is also a gas(cid:173)
`tric irritant, and the oral formulation is enteric coat(cid:173)
`ed and should not be broken or chewed.
`Promotility agents have been disappointing
`as treatment for constipation. Metoclopramide,
`which is often used to enhance gastric motility, has
`little effect on the colon. Cisapride has modest
`efficacy but has been withdrawn from the US mar(cid:173)
`ket. Serotonin via the 5-HT4 receptor may enhance
`intestinal smooth muscle activity. Specific 5-HT4
`agonists are now being evaluated. Tegaserod,* a
`partial 5-HT 4 agonist that increases canine colonic
`motility, has modest effect in increasing stool fre(cid:173)
`quency and improving stool consistency in patients
`with irritable bowel syndrome; however, it remains
`under evaluation by the FDA.
`Patients with disordered defecation, such as
`pelvic floor spasm (ie, anismus), may respond
`poorly to both fiber and laxatives. For these
`patients, biofeedback therapy may be beneficial,
`although there are few formal evaluations for con(cid:173)
`stipation. The success of biofeedback therapy
`varies with the motivation of the patient and the
`intensity of the program.
`
`*Use not FDA approved.
`
`Surgery is rarely needed for constipation.
`Hirschsprung's disease is treated with surgical
`resection of the aganglionic section and coloanal
`anastomosis. Patients with colonic inertia unre(cid:173)
`sponsive to medical therapy are treated with subto(cid:173)
`tal colectomy and ileorectal anastomosis. These
`patients should be evaluated for diffuse motility
`disorders of the stomach and small intestine
`because the outcome of patients \Vith these disor-
`ders is poor. Pelvic resuspension may be beneficial
`in patients with rectocele and prolapse.
`
`SUMMARY
`The evaluation and management of the patient with
`constipation begins with a clinical assessment of the
`patient for comorbidities or medications that could be
`causing the symptoms. Visualization of the colon with
`flexible sigmoidoscopy, colonoscopy or barium enema
`should be done if there is a clinical suspicion of cancer
`or obstruction, or in patients aged >50 years who have
`not undergone colon cancer screening. Treatment
`should begin with fiber therapy, stool softeners, and
`osmotic laxatives (eg, milk of magnesia) as needed.
`
`SUGGESTED READING
`Camilleri M. Review article: tegaserod. Aliment
`Pharmacol Ther. 2000;15:277-289.
`Diamant NE, Kamm MA, Wald A, Whitehead WE.
`AGA technical review on anorectal testing tech(cid:173)
`niques. Gastroenterol. 1999;116:735-760.
`Knowles CH, Scott M, Lunniss PJ. Outcome of
`colectomy for slow transit constipation. Ann Surg.
`1999;230:627- 638.
`Locke GR III, Pemberton JH, Phillips SF. AGA
`technical review on constipation. Gastroenterol.
`2000;119:1766-1778.
`Prather CM, Ortiz-Camacho CP. Evaluation and
`treatment of constipation and fecal impaction in
`adults. Mayo Clin Proc. 1998;73:881-886.
`Thompson WG, Longstreth GF, Drossman DA, et
`al. Functional bowel disorders and functional
`abdominal pain. Gut. 1999;45(Suppl II):II43-II47.
`Whitehead WE. Patient subgroups in irritable
`bowel syndrome that can be defined by symptom
`evaluation and physical examination. Am J Med.
`1999;107:33S-40S.
`
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