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Constipation: Prodding the Reluctant Gut

Charles A. Ternent, M.D.

Functional Bowel Disorders

Definition
A functional bowel disorder is a functional gastrointestinal disorder with symptoms attributable to the mid or lower gastrointestinal tract. The functional bowel disorders include irritable bowel syndrome (IBS), functional abdominal bloating, functional constipation, functional diarrhea and unspecified functional bowel disorders.(1)

Diagnosis
The Rome II diagnostic criteria for IBS include at least 12 weeks or more, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has two out of three features: (1) Relieved with defecation and /or (2) Onset associated with a change in frequency of stool; and/or (3) Onset associated with a change in form (appearance) of stool. Supportive symptoms of IBS include (a greater than 25% occurrence of) (I) Fewer than three bowel movements per week (II) More than three bowel movements per day (III) Hard or lumpy stools (IV) Loose (mushy) or watery stools (V) Straining during a bowel movement (VI) Urgency (VII) Feeling of incomplete bowel movement (VIII) Passing mucous during a bowel movement (IX) Abdominal fullness, bloating or swelling. (1)

Constipation-predominant IBS is associated with one or more of the supportive symptoms I, III or V and none of II, IV or VI.(1) If diarrhea or constipation are not dominant then the IBS is predominantly associated with abdominal discomfort or pain.(1)

Evaluation
A limited screen for organic disease is indicated to compliment a positive screen for IBS based on the Rome II criteria. Screening should include hematology, chemistry, erythrocyte sedimentation rate, stool examination for occult blood, stool for ova and parasites and gram stain, flexible sigmoidoscopy with biopsy in those with diarrhea, and a flexible sigmoidoscopy and air contrast barium enema or colonoscopy in those over 40 with a family history of colon polyps or cancer.(2) A high erythrocyte sedimentation rate, anemia and rectal bleeding are negative predictive factors for the functional bowel diseases and should alert the clinician to an alternate disease process that needs to be evaluated further.

Intractability in constipation predominant IBS can be further investigated with colon transit study, anorectal manometry, balloon expulsion test and dynamic proctography. Diarrhea-predominant IBS can be further evaluated with a lactulose H2 breath test, stool osmolarity and electrolytes, jejunal aspirate for ova and parasites and small bowel and colon transit. Pain-predominant IBS can be further evaluated with abdominal films and a small bowel series, lactulose H2 breath test and gastrointestinal manometry.(2)

Treatment
Diarrhea-predominant IBS can be treated with dietary restriction (lactulose, fructose, sorbitol), loperamide or diphenoxylate as well as cholestyramine. Tricyclic antidepressants significantly relieve diarrhea and associated pain at least due in part to the anticholinergic effect. Calcium channel blockers may be used as secondary treatment. 5HT3 (alosetron) and 5HT4 receptor antagonists may also be of benefit in controlling diarrhea-predominant IBS.(2)

Patients with pain-predominant IBS may benefit from treatment with antispasmodics with or without anxiolytics and avoidance of gas forming foods. Smooth muscle relaxants such as mebeverine, octylonium and cimetropium are worthy of further clinical trial in view of a mean response of pain in a meta-analysis of 68% compared to 31% for placebo.(2) New treatment modalities in clinical trial evaluation include the kappa opioid agonist fedotozine.(1,2)

Constipation-predominant IBS has been shown to improve significantly with bulking agents in clinical trials. Osmotic laxatives like milk of magnesia or lactulose or stool softeners may be added to the regimen if bulk agents alone are not sufficient. Tricyclic antidepressants may cause or aggravate constipation through the anticholinergic effect and should, therefore, be avoided in the subgroup with pain and constipation related IBS.(2)  The effectiveness of 5HT4 receptor agonists for treatment of chronic constipation, including constipation -predominant IBS has been shown in trials involving the use of tegaserod maleate (Zelnorm®) in females and patients under the age of 65.  Side effects including diarrhea and ischemic colitis have been reported and the agent has not been studied for chronic use over 12 weeks.

Other potential therapies for IBS include selective serotonin re-uptake inhibitors, anti-muscarinic agents, alpha-2 adrenergic agents, somatostatin analogs and Substance P antagonists.(2). The somatostatin analog Octreotide reduces orocecal transit time and increases colonic visceral sensory threshold in IBS, but has limited clinical applicability in view of its parenteral mode of administration.(1)

Constipation

Definition
Constipation is a symptom of many diseases and is a collective term used to imply that stools are either too hard, too infrequent or to difficult to pass. Constipation can be defined by the presence of two or more of the following symptoms over greater than three months when the patient is not taking laxatives: (a) straining at defecation >25% of the time, (b) lumpy and/or hard stools > 25% of the times, (c) sensation of incomplete evacuation >25% of the time and (d) less than three bowel movements per week.(3)

Historical Perspective
In the early part of the 20th century, Sir William Arbuthnot Lane advocated colectomy and ileorectal anastomosis for the treatment of a variety of disorders, including a condition referred then as chronic intestinal stasis or Arbuthnot Lanes' disease.(4) The majority of colectomies performed by Lane were for chronic constipation. Lane reported 93 patients treated for constipation by colectomy or bypass. Only eight of these patients were men and two-thirds of the women were aged 35 or under.(5)

Etiology
It is difficult to determine the underlying etiology of constipation in Lanes' patients. However, no evidence of megacolon was present in any of the 85 women with constipation. It is likely, therefore, that many of the women operated on by Lane had a normal sized colon and that they were suffering from idiopathic slow-transit constipation. Associations between constipation and disorders such as poor peripheral circulation, breast disease, infertility, estrogen deficiency and ovarian cysts have been described.(4,5) Other studies have associated chronic constipation with the toxic effects of laxatives. (5) Although slow-transit constipation without megarectum affects females almost exclusively, slow-transit constipation with megarectum affects males and females in equal proportion.(6-8) Table 1 summarizes the most common causes of constipation.

Table 1 Causes of Constipation


Endocrine

insulin-dependent diabetes mellitus, hypopituitarism, hypothyroidism, hypercalcemia, pseudo-hypoparathyroidism, pheochromocytoma, glucagonoma, pregnancy, reduction of steroid hormones in luteal and follicular phases of menstrual cycle

Metabolic disorders

porphyria, uremia, hypokalemia, amyloid neuropathy

Neurologic disorders

Parkinson's disease, cerebral tumors, cerebrovascular accidents, multiple sclerosis, scleroderma, meningocele, aganglionosis, Chagas disease, hyperganglionosis, autonomic neuropathy, spinal cord injury, major depression, anxiety, obsessional personality disorders

Surgery resulting in localized damage to autonomic nervous plexus

pelvic surgery (cystectomy, rectopexy, hysterectomy)

Pharmacologic agents

Opioids, anticholinergics, anticonvulsants, antacids (calcium and aluminum containing), anti-Parkinsonian agents, antihypertensive agents, chronic stimulant laxative abuse (senna, cascara, anthraquinones, bisacodyl), monoamine oxidase inhibitors, tricyclics, phenothiazines, alkaloids (vincristine), heavy metal poisoning (lead, mercury), arsenic, phosphorus, iron, oral contraceptives, muscle relaxants

Obstructive bowel diseases

Endometriosis, carcinoma, volvulus, hernia, benign strictures, pseudo-obstruction, polyps, adhesions

Functional

Irritable bowel syndrome, anismus, sedentary-bedridden patients

Dietary

Inadequate fiber or fluid intake

Primary or idiopathic

No specific underlying condition identified

Diagnostic Modalities
Preliminary evaluation of constipated patients starts with a thorough history and physical exam in order to identify changes in lifestyle, medication regimen or physical status. Patients undergoing workup of constipation should have a flexible sigmoidoscopy and barium enema for heme-negative stools or a colonoscopy for heme-positive stools. Such studies enable exclusion of malignancy and other anatomical abnormalities of the lower gastrointestinal tract. Laboratory bloodwork should include thyroid function tests, ionized calcium and glucose in order to evaluate for hypothyroidism, hypercalcemia and diabetes. Constipation refractory to dietary and lifestyle modifications benefits from manometric documentation of the anorectal inhibitory reflex (RAIR). RAIR allows differentiation between idiopathic constipation and aganglionosis in whom the reflex is absent. Anorectal manometry also allows documentation of anal sphincter pressures to rule out hypertonia and associated outlet obstruction. Dynamic proctography provides cineradiographic evidence of pelvic floor pathology, such as rectoceles, enteroceles and rectal prolapse, that may be responsible for outlet obstruction and difficulty with bowel movements. Intestinal transit studies allow objective measurement of constipation. Colon transit analysis enables determination of segmental and total colon transits and thereby identifies patients with normal and slow colonic transit.

Anatomy and Physiology
The cause of slow whole gut transit in patients with a normal-sized colon and intact rectoanal inhibitory reflex is not completely understood. Constipation symptoms can also be associated with a disorder of the striated muscle of the pelvic floor that contracts inappropriately with attempted defecation (anismus or paradoxical puborectalis) rather than relax as in normal individuals.(8) The epidemiology of constipation study in the United States noted an overall prevalence of constipation of 14.7%. Prevalence according to subtype was 4.6% for functional, 2.1% for IBS, 4.6% for outlet and 3.4% for IBS-outlet associated constipation.(9)

Studies of colonic motility have shown that patients with slow transit constipation do not have colonic hypersegmentation and that many have little spontaneous colonic activity or response to topical stimulation with bisacodyl.(10) This latter finding suggests a possible abnormality of the myenteric plexus. Peptide containing nerves of the colon appear to be normal, but there may be abnormalities in the morphology of the myenteric plexus.(11)

Failure of normal gastrin, motilin and pancreatic polypeptide release has been documented in patients with severe constipation, although this may represent a secondary phenomenon.(12,13) Measurement of sex hormones have shown abnormalities, such as hyperprolactinemia which may be related to amenorrhea and other reproductive symptoms common in these patients.(14) In addition, Kamm and coworkers in 1991 noted a constant reduction in estradiol, cortisol and testosterone in the luteal and follicular phases as well as reduced progesterone and , 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone in the follicular phase of women with severe chronic constipation.(15)

Treatment
In most cases, constipation can be treated with dietary manipulation, simple laxatives or enemas. However, there is a group of patients for whom medical management is unsatisfactory and in whom stimulant laxatives quickly loose their effect and may cause myenteric plexus damage.

One approach to the therapy of chronic constipation consists of stimulating, as physiological as possible, intestinal motility (Table 2). In the colon, high amplitude propagated contractions occur a few times a day, especially right after awakening and after meals. These so called mass movements or giant migrating contractions (GMC) provide the main propulsive force to fast colonic propulsion and often are followed by an urge to defecate. In idiopathic chronic constipation, the number and duration of these GMC's is smaller than in healthy subjects (16).

A new chemical class has been shown to specifically induce colonic motility in humans.  The effect is mediated by selective stimulation of serotonin 5HT4 receptors which facilitate cholinergic as well as non-cholinergic excitatory neurotransmission resulting in the enterokinetic effect.  Tegaserod maleate is one such agents currently available via prescription for short term treatment of constipation in patients under the age of 65.

Surgical treatment is undertaken in patients with chronic idiopathic constipation with great reluctance and only because patients are greatly disabled in view of inadequate medical management. The severity of constipation in these individuals that undergo colectomy is unusual. Local sphincter surgery or segmental colon resections do not benefit patients with slow transit constipation. Internal sphincterotomy may benefit a select group of individuals with hypertonic anal sphincter and impaired outlet, but will not alleviate symptoms from paradoxical puborectalis activity. Sigmoid colectomy can be performed for recurrent sigmoid volvulus. However, total abdominal colectomy with ileorectal anastomosis gives the best chance of a good functional result in patients with severe slow transit constipation refractory to medical management (Table 2). Following total abdominal colectomy with ileorectal anastomosis the life of patients can be transformed from an existence dominated by the absence of normal bowel function, abdominal discomfort and the use of laxatives, to normality in approximately 80-90%. Most patients report a return of the urge to defecate after colectomy.(3,18) Adequate selection of surgical intervention for constipation depends on careful identification and treatment of slow colonic transit and/or any associated pelvic floor pathology such as enteroceles, rectoceles and prolapse. Surgical management of carefully evaluated patients with slow transit constipation and concomitant pelvic floor hernias has been shown to yield satisfactory results in 89%.(19)
Although serious immediate postoperative complications are rare following total colectomy with ileorectal anastomosis, prolonged ileus tends to be a problem (38%). In addition, a high incidence of small bowel obstruction has been noted following colectomy for constipation. Diarrhea and fecal incontinence may also cause problems following total colectomy.(5)

Table 2 Treatment Options for Chronic Idiopathic Constipation


Underlying pathology

Correct causative underlying conditions and eliminate offensive medications if possible

Activity level

Increase mobility

Dietary manipulations

High fiber intake (20-30 g / day) Konsyl(r) / Metamucil(r) / Citrucel(r) 1 tbs.PO BID Increase non-caffeinated fluid intake (8-10 8 oz glasses / day)

Stool softeners

Sodium docusate 100 mg PO BID
Mineral oil 1 oz PO BID

Stimulant laxatives

Pericolace(r) 1 PO QD
Dulcolax(r) 5-15 mg PO if no BM for 3 or more consecutive days

Prokinetic agents

Tegaserod maleate (Zelnorm®) 6 mg PO BID for 4-6 weeks and repeat course once if effective

Enemas

Fleets(r) enema if no BM for 3 days

Osmotic agents

Milk of Magnesia 30-60 PO QD
Lactulose 30 ml PO QD-BID
Polyethyleneglycol (PEG) 10-20 oz PO QD
Miralax® 17 gm PO QD

Psychological support and evaluation as indicated

Counseling, MMPI

Surgical intervention

Subtotal colectomy with ileorectal anastomosis
Subtotal colectomy with ileostomy
Diverting ileostomy

Conclusion
Functional bowel diseases can be diagnosed based on the Rome II criteria which allow subgrouping of IBS into predominantly diarrhea, constipation or pain types. This stratification of IBS based on symptomatology also facilitates establishment of treatment modalities for specific IBS types. Idiopathic slow transit constipation represents another complex disorder. For the patients who develop severe and disabling idiopathic constipation, unresponsive to dietary modification or drugs, colectomy and ileorectal anastomosis can offer great benefit. Careful physiologic and anatomic evaluation of refractory idiopathic constipation and any associated pelvic outlet pathology should help to taper the surgical operation to meet the needs of the patient.

References

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  2. Camilleri M, Cho M-G. Review article: irritable bowel syndrome. Aliment Pharmacol Ther 1997;11:3-15.
  3. Velio P, Bassotti G. Chronic idiopathic constipation: pathophysiology and treatment. J Clin Gastroenterol 1996;22:190-196.
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  9. Stewart WF, Liberman JN, Sandler RF, et. al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999;94:3530-3540.
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  11. Wingate DL. Nervous control of the gut. Br J Surg 1985;suppl:S2-S6.
  12. Preston DM, Adrian TE, Christofides ND, et al. Pancreatic polypeptide and motilin response in functional bowel disorders. Scand J Gastroenterol 1983;18suppl.82:199-200.
  13. Preston DM, Adrian TE, Lennard-Jones JE, Bloom SR. Impaired gastrin release in chronic constipation. Gut 1983;24:A481.
  14. Preston DM, Rees LH, Lennard-Jones JE. Gynaecological disorders and hyperprolactenemia in chronic constipation. Gut 1983;24:A480.
  15. Kamm MA, Farthing MJ, Lennard-Jones JE, Perry LA, Chard T. Steroid hormone abnormalities in women with severe idiopathic constipation. Gut 1991;32:80-84.
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  17. Briejer MR. Assessment of the effects of R093877 after oral and intravenous administration on colonic motility patterns in fasted conscious dogs. Janssen Research Foundation, April 1997. Non-clinical Research Report R093877.
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