33.3.1 Diet and Habits

Of outstanding importance are the epidemiologic studies of Burkitt, Painter, Walker, and others, ^{21 , 22 , 23} which have shown that the fiber content of our foodstuffs is the prime factor that determines the fecal weight or bulk and the rate of transit through the colon. Inadequate dietary fiber, common in the Western diet, produces sparse, inspissated stools, whereas populations with a high fiber diet may have a normal bowel habit of two or three large, soft motions per day. ²⁴ Because peristaltic movements are stimulated by distention of the intestine, they tend to be sluggish when the food bulk is insufficient to cause a normal amount of distention. Excessive ingestion of foods that harden stools, such as processed cheese, and inadequate fluid intake may be contributing factors. Lack of exercise also decreases colonic activity.

Repeatedly ignoring the call to stool results in insensitivity of the reflex initiated by a fecal mass in the rectum. This in turn results in adaptation of the sensory mechanism so that arrival of further propulsive waves fails to produce an adequate call to stool. Ultimately, all natural periodic urges disappear.

There is often a perception by patients that a daily bowel movement is necessary for good health. This belief may lead to the chronic abuse of harsh laxatives. After the bowel has been completely emptied by a purgative, it generally takes 2 days for fecal material to accumulate in sufficient quantity to stimulate the desire for a bowel action. Although this may seem self-evident, the absence of a bowel movement often increases the distress of a patient whose attention is focused on his or her bowel function. Further purgation (because of the failure to have a bowel movement the very next day) will unnecessarily abuse the intestine and ultimately lead to a complete loss of natural bowel habits (cathartic colon).

Environmental circumstances such as unfavorable working conditions, travel, and admission to hospital may cause the patient to ignore the call to stool. Some are obviously only temporary problems.

33.3.2 Structural or Functional Disorders

Constipation may be only one of several symptoms with which a patient with disorders of bowel structure will present. Constipation in association with other symptoms will lead the examining physician to the appropriate diagnosis, often with the aid of certain investigative modalities. Clearly, obstructive lesions explain constipation, but patients with these lesions may have alternating constipation and diarrhea. Similarly, individuals with painful anal lesions suppress the call to stool because of the fear of the pain of defecation. This suppression aggravates the problem because the stool becomes harder and more difficult to pass (a detailed discussion of each cause in this section is provided under the specific heading either later in this chapter or in relevant chapters).

Through the use of radiopaque markers, a slow transit rate—particularly along the transverse, descending, and sigmoid colon—can be demonstrated. Its exact cause is unclear. Patients with idiopathic megabowel have a dilated rectum or distal colon, but ganglion cells are present. Transit studies can also show abnormalities. Patients with irritable bowel syndrome have the dominant complaint of abdominal pain, with constipation only an associated finding in those with constipation-predominant disease. Constipation is not an uncommon symptom associated with diverticular disease and may result from the tendency of the colon to form closed high-pressure segments. Aganglionosis, whether it occurs congenitally in patients with Hirschsprung’s disease or is acquired because of the neurotoxin of Trypanosoma cruzi, will cause constipation.

33.3.3 Neurologic Abnormalities

Defects of innervation such as those that follow pelvic surgery and occur with diseases of the spinal cord and brain are factors contributing to constipation. Severe constipation occurs in all patients who sustain a spinal cord injury. Menardo et al ²⁵ and Levi et al ²⁶ demonstrated that patients with injuries between C4 and T12 have a marked prolongation of transit at the level of the left colon and rectum, with minor degrees of transit delay at the level of the right colon. Several surveys have revealed that constipation in patients with spinal cord injury has a significant impact on their quality of life. ^{27 , 28}

33.3.4 Psychiatric Disorders

Psychiatric disturbances are often associated with constipation. However, the medications used in the treatment of psychiatric illnesses very frequently contribute to or cause constipation in their own right. Some patients may become obsessed with their bowel function or lack thereof and resort to excessive laxative abuse. In addition, certain psychiatric patients will deny bowel actions while, in fact, their bowels are moving. Such patients can be detected with the use of radiopaque markers.

33.3.5 Iatrogenic Causes

A host of medications can contribute to constipation (frequent offenders are listed in Box 33.1). Bedpans are uncomfortable and should be replaced by bedside commodes whenever feasible.

33.3.6 Endocrine and Metabolic Causes

Patients with various endocrine abnormalities with their characteristic clinical patterns may experience constipation. Also included in this group are those patients who are pregnant.

33.4.1 Patient Evaluation

Clinical history and examination is the starting point of evaluation, and in many cases can differentiate slow transit constipation from obstructed defecation, although these subtypes coexist. Attention should be paid to any causative factors and “alarm” symptoms must be excluded.

33.4.2 History

Stool Consistency

This is an indicator of colonic transit and can be classified with the use of a reference chart, such as the Bristol Stool Chart that categorizes stool consistency into seven subtypes (▶ Fig. 33.1).

33.4.3 Physical Examination

In most patients with constipation, abdominal findings will be unremarkable. A stool-filled colon may be palpated. Rarely, a mass suggestive of a carcinoma or hepatomegaly suggestive of metastases may be found.

The anal region should be inspected carefully for findings such as fissures, hemorrhoids, fistulas, and abscesses. Digital examination might reveal a mass suggestive of a rectal neoplasm or a fecaloma. In female patients with a rectocele, the pocket-like defect of the anterior rectal wall can be demonstrated just above the anal sphincter. Almy ³⁰ pointed out that the absence of stool in the rectum suggests that the difficulty lies above the rectum and makes a disorder of defecation unlikely. This observation is not valid if the patient is using laxatives, enemas, or suppositories.

Anal sensitivity and reflexes should be checked. Deficient sensation may represent a neurogenic disorder and cutaneosphincteric reflexes may be absent. In patients with Hirschsprung’s disease, profuse fecal discharge occurs characteristically after rectal examination.

33.4.4 Stool Examination

Gross examination of the stool might reveal a large, hard mass or possibly the pellet-like stools characteristically seen in patients with diverticular disease or irritable bowel syndrome. Stool also should be examined for occult blood, and any positive findings should be investigated further. It has been suggested that determination of stool weight and examination of stool form are mandatory in the evaluation of constipation, because both aspects are closely correlated with colonic transit time, but this is rarely practical within the normal clinic setting. ^{28 , 31}

33.4.5 Biochemical Examination

Routine biochemical examination, including values for electrolytes, calcium, phosphate, urea, creatinine, thyroid stimulating hormone, and free thyroxine, is necessary to exclude those endocrine and metabolic disorders that can cause constipation.

Special biochemical investigations such as of gastrointestinal neuropeptides are of interest, but they are not readily available. Interest has grown in the effect of these neuropeptides on gastrointestinal motility. Using sensitive and specific radioimmunoassays, the concentration of gastrointestinal neuropeptides can be determined quantitatively. ³² The effect of these neuropeptides on the motor activity of the upper gastrointestinal tract (stomach, duodenum, and small intestine) has been established, ³² but the exact role of some of these peptides in the regulation of colonic motor activity has not been determined (▶ Table 33.2).

It has been suggested that gastrin and motilin have a stimulating effect on the peristaltic activity of the colon. ³² Patients with constipation have a smaller rise in circulating blood levels of gastrin and motilin after a meal, ³³ whereas reduced motilin levels have been reported in pregnancy, when there is a tendency toward constipation. ³⁴ However, it is still unknown whether or not these phenomena are primary or secondary. The pharmacokinetics, catabolism, and release of these hormones are very complex. For example, the release of vasoactive intestinal peptide (VIP) from intramural neurons, especially those neurons in the lamina propria and circular muscle of the gut, is induced by stimulation of preganglionic parasympathetic fibers. ³² This finding demonstrates the complex interaction between hormonal and neurogenic factors. Further investigation is necessary to determine the exact role of gastrointestinal hormones, especially in patients with slow-transit constipation.

33.4.6 Proctosigmoidoscopy

Endoscopic examination is mandatory to rule out the presence of a neoplasm. Nevertheless, in the vast majority of patients complaining of constipation, proctosigmoidoscopic examination will not reveal any abnormality. Frequently, patients with long-standing laxative abuse, mainly involving laxative ingredients of the anthracene family, will demonstrate melanosis coli—a discoloration of the mucosa that may range from light brown to black. In other patients, a solitary rectal ulcer, sometimes associated with anterior mucosal prolapse, will be found.

33.4.7 Luminal Imaging

Although plain films of the abdomen occasionally show the extent of fecal accumulation, the main diagnostic tool to demonstrate structural abnormalities in the colon is colonoscopy, which has the advantage over other modalities in obtaining mucosa imaging and biopsy for histological analysis. Contrast studies, such as barium enema, are largely obsolete and have been surpassed by CT colonography as the preferred radiological imaging technique, although it is generally reserved for patients who are unfit or unable to tolerate colonoscopic examination.

33.4.8 Defecating Proctogram

Defecography or evacuation proctography is an established radiologic technique to image the dynamic changes in rectal anatomy during expulsion of barium paste (▶ Fig. 33.2). This method offers the possibility of visualizing abnormalities such as anterior rectal wall prolapse, rectal intussusception, rectocele, and enterocele. ^{35 , 36} It also allows measurement of the anorectal angle, which is determined by the tone of the puborectalis and levator ani muscles. The angle becomes more obtuse during attempted evacuation due to relaxation of the pelvic floor. Failure to increase the anorectal angle on straining, sometimes associated with accentuation of the puborectalis impression, is considered a radiologic sign of anismus. In patients with fecal incontinence, the anorectal angle may be widened even at rest (▶ Fig. 33.3). It has been argued, however, that visual assessment of the anorectal angle is rather subjective and, therefore, unreliable. Several authors found wide interobserver and intraobserver variations in the measurement of this angle and concluded that its quantification has only limited clinical value. ^{37 , 38} Defecography also enables the determination of the position of the pelvic floor by calculating the distance between the anorectal junction and the pubococcygeal line. Demonstrating a drop in the anorectal junction of several centimeters or more below the pubococcygeal line signifies the pathologic descent of the pelvic floor. Evacuation proctography also provides a valid estimate of the rate and degree of rectal emptying. ³⁹ These parameters can also be assessed utilizing scintigraphic methods. ⁴⁰ The investigation of rectal emptying is considered a major step in the evaluation of constipation, because many patients with infrequent bowel movements also present varying degrees of defecatory impairment. It has been argued, however, that the estimation of time and degree of rectal emptying is rather inaccurate. ⁴¹ Furthermore, it is questionable whether a delayed and incomplete evacuation on proctography really represents impaired rectal emptying. Karlbom et al ⁴² analyzed the relations between proctography findings, rectal emptying, and colonic transit time in 80 constipated patients. The correlation between a sense of obstruction and rectal evacuation as evaluated by defecography was found to be very poor. Patients who claimed emptying difficulties actually had the most efficient evacuation. It has also been suggested that incomplete and prolonged evacuation on proctography may be caused by inability to raise intra-abdominal pressure, thereby simply reflecting inadequate straining. ⁴³ Despite these and other objections, evacuation proctography is still considered as one of the most useful tools in the investigation of patients with constipation and disturbed defecation.

33.4.9 Magnetic Resonance Proctography

More recently, MR proctography has gained popularity as an effective method for evaluating dynamic pelvic floor function (▶ Fig. 33.4). The main advantage over barium proctography is that it does not involve radiation exposure. It makes visualization of the bony landmarks easier and therefore the measurement of anorectal and pelvic floor movements during straining more accurate. Importantly, it allows visualization of the whole pelvis, including the bladder and uterus. It can provide useful information on extrarectal lesions that might cause constipation. It is becoming the investigation of choice in patients with multicompartmental pelvic floor dysfunction.

33.4.10 Colonic Transit Time

A major step in the evaluation of constipation is the measurement of colonic transit time. The technique can establish an abnormality but also can demonstrate a normal transit time in a patient with a bowel neurosis or in the occasional patient who denies having bowel actions. With the original method described by Hinton et al, ⁴⁴ 20 radiopaque markers of similar specific gravity to feces were ingested on one occasion on the first day before breakfast. Stools were collected and studied with radiography for 7 days or longer until all the pellets had been observed on a radiograph. A variation of this method has been described by Cummings and Wiggins. ⁴⁵ Markers of different shapes were ingested on three consecutive days. Subsequently, all markers present in a single stool collected on the fourth day were counted. This technique reduces the effect of day-to-day variation in transit time by providing 3-day transit studies from one radiograph. Although these marker-appearance methods do not provide accurate data on transit through the different colonic regions, they can be used as a simple test to assess whole-gut transit time. With the Hinton technique, Evans et al ⁴⁶ found that 95% of normal male and female individuals pass less than 20% of markers within 12 hours and more than 80% of markers within 120 hours. This finding was similar to the original observation of Hinton et al ⁴⁴ in male individuals. It has been argued that it is more convenient to measure the disappearance of a marker from the colon rather than its appearance in the stool. Therefore, Martelli et al ⁴⁷ described a technique whereby the patient ingests a single dose of 20 markers. The progression of the markers is followed by daily films of the abdomen until complete expulsion is noted or for a maximum of 7 days after ingestion of the markers. Normally all the markers have passed within 7 days. The arrival and disappearance of markers in three regions of the colon (right, left, and rectosigmoid) are assessed. For this purpose, the spinal processes and two lines from the fifth lumbar vertebra to the pelvic inlet serve as landmarks (▶ Fig. 33.5). Transit time is considered prolonged when more than 20% of the markers are still present within the colon, 5 days after ingestion. A drawback of interpretation of such studies is that evaluation of transit of contents in any segment is dependent on the amount of markers received from the proximal bowel. To reduce the radiation exposure, Metcalf et al ⁴⁸ developed a somewhat different technique by giving differently shaped markers on three successive days and taking an abdominal radiograph on the fourth day after ingestion and if necessary on days 7 and 10. Chaussade et al ⁴⁹ modified this technique by giving identical markers on three consecutive days. The quantification of regional colonic transit with these methods has been validated in healthy individuals. It is questionable, however, whether infrequent radiographs allow correct assessment of the site of delay in constipated patients with irregular mass movements, because the results will be very different if a radiograph is taken just before or just after such an event. It has been suggested that the use of radioisotopes provides more accurate information about regional colonic transit, because multiple images can be obtained with a low radiation dose. An additional advantage of scintigraphy is the clear delineation of the different colonic regions, even in patients with a significant overlap of bowel segments. The use of a radiolabeled meal also yields information about gastric emptying and small bowel transit. ⁵⁰ The radioisotope can also be administered in a coated capsule, which is designed to dissolve at the pH found in the distal part of the small bowel, ⁵¹ or as a liquid through a tube placed to instill it in the cecum or the ascending colon. ⁵²

Another technique to measure intestinal transit was developed by Ewe et al. ⁵³ They followed a metal particle on its way through the gastrointestinal tract by means of a portable detector. Basile et al ⁵⁴ used a magnetized steel sphere and localized this particle with biomagnetic instruments. With this technique they were able to demonstrate that the total colonic transit time in healthy volunteers was 44 ± 5 hours (mean ±SD). Similar figures have been reported by others. The normal values for whole-gut transit time, total colonic transit time, and segmental colonic transit time are listed in ▶ Table 33.3, ▶ Table 33.4, and ▶ Table 33.5.

A relatively simple method for assessing colonic transit is using the Sitzmarks (Konsyl Pharmaceuticals, Texas) method. A single Sitzmarks capsule containing 24 radiopaque markers is taken on day 0 by mouth with water and a plain abdominal X-ray is taken on day 5 (▶ Fig. 33.6). The patient is instructed to refrain from laxatives, enemas, or suppositories for 5 days. Patients who expel at least 80% of the markers have grossly normal transit. For patients who have more than 20% of markers remaining a further capsule is given along with a bulking agent and a further X-ray is performed at day 10 to determine the location and extent of the markers. If the markers are scattered throughout the colon, slow transit is suggested. If most of the markers are gathered in the rectosigmoid, a functional outlet obstruction may be present.

33.4.11 Anorectal Manometry

A number of authors advocate the use of anorectal manometry during the initial evaluation of constipation and disturbed defecation to develop individualized and more effective modes of treatment. ^{61 , 62}

In patients with Hirschsprung’s disease, rectal distention does not induce internal sphincter relaxation. This is referred to as the rectoanal inhibitory reflex (RAIR). Absence of RAIR response to rectal distension is a reliable test in the diagnosis of Hirschsprung’s disease. ^{63 , 64} Although manometry is clearly useful in discriminating Hirschsprung’s disease from other forms of constipation, its role in the evaluation and management of non-Hirschsprung’s constipation remains unclear. There are few data correlating manometric findings with clinical symptoms and outcome of treatment. Studying encopretic children, Loening-Baucke et al ⁶³ demonstrated that the response to different treatment modalities could be predicted by manometric findings. Borowitz et al ⁶⁵ studied 44 children with chronic constipation and encopresis. Spasm of the external anal sphincter during attempted defecation was correlated with the patient’s age at onset and duration of symptoms, but manometric findings were not predictive of the ability to defecate. They also questioned the conceptual understanding of childhood constipation, based on the assumption that a diminished sense of rectal distention and paradoxical contraction of the external anal sphincter are the principal causes of constipation and obstructed defecation. In adults, similar conflicting findings have been observed. Pluta et al ⁶⁶ studied 24 female patients with severe and disabling slow-transit constipation who underwent a subtotal colectomy followed by ileorectal anastomosis. No correlation was noted between the results of the operation and the manometric parameters, except in one case. Patients requiring abnormally high pressures inside a distending rectal balloon for sensory perception and internal anal sphincter relaxation did worse than the others. Another striking predictive factor, noted by these authors, was a history of psychiatric illness.

Many demonstrable pressure abnormalities can be detected by anorectal manometry in patients with idiopathic constipation. The reflex may be normal, the amplitude of relaxation may be less than that in normal controls, or the reflex may be totally absent. The resting pressure of the anal canal may be greater than expected and occasionally is accompanied by a rectoanal inhibitory reflex with an amplitude greater than normal. ⁶⁷

In several studies, elevated anal resting pressures have been found in patients with idiopathic constipation, but in other studies no pressure abnormalities could be detected. Although some authors suggested a normal amplitude of the internal sphincter reflex, these findings are not supported by the results of two other studies that showed the amplitude of relaxation is less in patients with idiopathic constipation than in normal controls. In patients with severe chronic constipation without megarectum, the threshold for the internal sphincter reflex apparently was normal, whereas in patients with a megarectum the threshold was elevated.

Despite the conflicting published data, manometry should continue as part of the evaluation of the severely constipated patient. Only by the continued study of these patients will there be a resolution of the discrepancies that have been reported to date.

During the last decade, attention has been focused on rectal wall properties. Grotz et al investigated rectal wall contractility in controls and in patients with chronic severe constipation. They found that in patients with constipation, the increase in rectal tone following a meal and after the administration of a cholinergic agonist was significantly blunted. According to these authors, the reduced rectal tone contributes to the inability of these patients to expel stool. ⁶⁸ Other workers from the Netherlands used an electronic barostat assembly to examine rectal tone in response to an evoked urge to defecate. Under radiological control, an infinitely compliant polyethylene bag was inserted over a guide wire into the proximal part of the rectum. Additionally, a latex balloon was introduced into the distal part of the rectum. This latex balloon was inflated until an urge to defecate was experienced. Simultaneously, rectal wall tone was assessed by measuring the variations in bag volume. These variations were expressed as percentage changes from the baseline volume. Comparing female controls and women with obstructed defecation, a significant difference was found regarding mean distending volume required to elicit an urge to defecate (median values: 125 vs. 320 mL of air). Twenty-four patients (24%) did not feel an urge to defecate at all. In all controls, the evocation of an urge to defecate induced a pronounced increase in rectal tone, proximal to the distending balloon. In symptomatic patients, this increase in rectal tone was significantly lower. Thirty-one patients (31%) showed no increase in rectal tone at all. ⁶⁹ It has been shown that rectal tone increases after a meal. This phenomenon is absent or blunted in women with obstructed defecation. ⁷⁰ These data indicate that the sensorimotor function of the rectum is impaired in patients with obstructed defecation. Afferent parasympathetic nerves are thought to mediate rectal filling sensations. These nerves run from the rectum through branches, which are situated on each side of the rectum around the cervix uteri and both lateral vaginal surfaces. This extensive network of nerve fibers can be damaged during hysterectomy and also during rectopexy with division of the lateral ligaments. It is well known that in some women, obstructed defecation starts following pelvic surgery. Varma and Smith studied rectal function in 14 women with intractable constipation following hysterectomy. These patients had significantly decreased rectal sensory perception. ⁷¹ It has been shown that constipation occurs more frequently the more radical a hysterectomy is performed. ⁷² Based on an experimental study in dogs, Shafik et al addressed the important role of the parasympathetic nervous system in the defecation mechanism. ⁷³ These and other data do suggest that a deficit of the afferent parasympathetic nerves contributes to the impaired sensorimotor function of the rectum in women with obstructed defecation.

33.4.12 Electromyography

Electromyography (EMG) can be used as a functional test for the investigation of muscle activity and is a reliable method for the evaluation of electrical activity in the external anal sphincter and puborectalis muscles (Chapter 2). ⁷⁴

Through electrophysiologic techniques it has been shown that damage can occur to the nerve supply of the external sphincter and the puborectalis muscle in patients with chronic constipation; this damage is probably due to perineal descent during defecation straining. ⁷⁵ Paradoxical contraction of the pelvic floor during attempted evacuation is considered as the principal cause of functional obstructed defecation, that is, obstructed defecation not associated with a structural abnormality. The terms most frequently used to describe this condition are anismus, spastic pelvic floor syndrome, and nonrelaxing puborectalis syndrome. Despite many limitations, EMG is probably the most specific test providing the best assessment of pelvic floor activity during straining (▶ Fig. 2.29).

33.4.13 Balloon Expulsion Test

The balloon expulsion test is another method commonly used to reach the diagnosis of anismus. This simple test was introduced by Preston and Lennard-Jones in 1985. ⁷⁶ It has been reported that almost all controls are able to expel a water-filled rectal balloon, whereas many constipated patients fail to do so. Although this observation underscores the difference between controls and patients, it does not signify that the inability to expel a balloon represents anismus. Normal rectal evacuation requires adequate intrarectal pressure, which can be raised by increasing intrapelvic pressure, achieved by voluntary contraction of the diaphragm and abdominal wall muscles. Propulsive contractile activity of the rectal wall is another contributing factor. It has been reported that constipated patients with both prolonged evacuation and pelvic floor descent on proctography are not able to void a small nondeformable rectal balloon because they fail to raise intrarectal pressure. ⁷⁷ This finding suggests that failure to raise intrapelvic pressure is a major cause of inadequate evacuation.

The aforementioned diagnostic tests are generally recommended, because it is difficult to differentiate subgroups of constipation based on symptoms alone. Despite this recommendation, the clinical utility of these tests is still not known. Recently, Rao et al conducted a systematic review of studies assessing the clinical value of these tests in patients with constipation. Their search revealed no methodologically sound studies, and identified several pitfalls. First, no single test appears to provide a pathophysiological basis for constipation. Often, several tests are required to identify the underlying mechanism. Second, the inclusion criteria for patients with constipation were either not defined or when available there were significant interstudy differences. Third, a reference or gold standard test is still missing. Despite these pitfalls, the authors concluded that, “there is good evidence to support the use of these tests in order to define subtypes of constipation and aid treatment.” ⁷⁷

33.4.14 Special Examinations

Routine Histologic Examination

In patients with solitary rectal ulcer syndrome, performing a biopsy is mandatory to confirm the diagnosis and exclude an underlying carcinoma. Histologic examination will reveal fibromuscular obliteration of the lamina propria, hypertrophy of the muscularis mucosa, and displacement of glands into the submucosa (▶ Fig. 33.7). ^{78 , 79}

When Hirschsprung’s disease is suspected, a biopsy is indicated because, classically, aganglionosis is diagnostic of Hirschsprung’s disease (▶ Fig. 33.8). There is no consensus as to whether the best biopsy technique is the superficial punch biopsy, deep full-thickness biopsy, or mucosal suction biopsy. Usually biopsy specimens are taken 2 to 3 cm above the dentate line, as recommended by Aldridge and Campbell, ^{80 , 81} who demonstrated a normal hypoganglionic zone in the region of the internal sphincter. This hypoganglionic zone extends proximally from the dentate line an average of 4 mm in the myenteric plexus, 7 mm in the deep submucous plexus, and 10 mm in the superficial submucous plexus. In two studies, it was suggested that the optimal level at which the biopsy should be taken is 1.0 to 1.5 cm above the dentate line. ^{81 , 82} The authors chose this lower range because taking rectal biopsy specimens at a higher level may result in a missed diagnosis of ultrashort-segment aganglionosis. ⁸³ It is not certain how the measurements in these reports from pediatric patients might apply to the adult.

Several difficulties arise in the histopathologic interpretation of biopsy specimens. First, the distal segment of bowel does not contain neurons for up to 25 mm from the distal edge of the internal sphincter, and the normal value for adults is unknown. Second, the severity of the clinical course correlates poorly with the length of the aganglionic segment. A third problem with the histopathologic interpretation lies in the potential existence of “skip” lesions. A fourth problem concerns the qualitative appearance of the nervous plexus. Fifth, although hypoganglionosis causes constipation, the range in the normal number of ganglion cells is not known. ⁸⁴ Finally, the diagnostic accuracy with routine hematoxylin and eosin staining on superficial biopsies is low, as was demonstrated in a study showing an accuracy of only 61%. ⁸²

Ultrastructural studies of colonic biopsies from patients with a history of long-term laxative abuse, primarily involving anthraquinone derivatives or bisacodyl, indicated that submucosal nerve fibers might be severely damaged. These alterations may correlate morphologically to the clinically evident disturbance of gut motility. ⁸⁵

Acetylcholinesterase Staining

Increased acetylcholinesterase activity has been demonstrated in patients with Hirschsprung’s disease. ^{86 , 87 , 88 , 89} With acetylcholinesterase staining, an increased number of enlarged, brown-stained nerve fibers can be found in either the submucosa or the lamina propria (▶ Fig. 33.9). According to Ikawa et al, ⁸² this technique has many advantages over routine hematoxylin and eosin staining. The authors demonstrated 99% accuracy in the differentiation of patients with Hirschsprung’s disease from patients with idiopathic constipation. Park et al ⁹⁰ demonstrated a 97% diagnostic accuracy compared with a 74% accuracy of hematoxylin and eosin staining. Routine hematoxylin and eosin staining of superficial biopsy specimens failed to reveal ganglion cells in 39% of their patients without Hirschsprung’s disease, all of whom required repeat superficial biopsy studies or even deep full-thickness biopsies while under general anesthesia. Using acetylcholinesterase staining, this problem can be eliminated. Even if the submucosa is not included in the superficial biopsy, the diagnosis still can be made by studying the lamina propria. The histochemical demonstration of acetylcholinesterase activity in suction rectal biopsy specimens is considered an accurate technique and has been recommended in screening for Hirschsprung’s disease. ⁹¹

Monoclonal Antineurofilament Antibodies

It has been proposed that a distinct visceral neuropathy may be present in patients with idiopathic slow-transit constipation and in patients with idiopathic megacolon. However, with the use of conventional light microscopy (hematoxylin and eosin staining), no abnormalities have been found. Examining resected colon specimens with silver staining (Smith’s method), Preston et al ⁹² demonstrated complete loss of the argyrophil plexus with a marked increase in Schwann cells, indicating that extrinsic damage to the plexus had occurred. Based on these findings, the authors theorized that the myenteric plexus abnormality is not the primary cause but may be the result of long-standing laxative use. Using conventional light microscopy, Krishnamurthy et al ⁹³ found no apparent abnormalities of the myenteric plexus in 12 patients who underwent subtotal colectomy for constipation. In contrast, silver stains of the myenteric plexus showed quantitatively reduced numbers of argyrophilic neurons in 10 patients, morphologically abnormal argyrophilic neurons in 11, decreased numbers of axons in 11, and increased numbers of variable-size nuclei within ganglia in all 12. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. ⁹³

Koch et al ⁸⁰ found decreased colonic VIP in patients with idiopathic chronic constipation. This finding could not be confirmed by Tzavella et al, ⁹⁴ who found normal levels of VIP and decreased levels of the excitatory neurotransmitter substance P in rectal biopsies from patients with slow-transit constipation.

An immunostaining technique using monoclonal antibodies raised against neurofilament (NF2F11; Sanbio) has been described for the investigation of bowel innervation anomalies. ⁹⁵ In the normally functioning bowel, some axons of the submucous plexus and the myenteric plexus do stain with these monoclonal antibodies (▶ Fig. 33.10a). In contrast to this subtotal (partial) staining in normal bowel, heavy total axon-bundle staining has been found in the aganglionic segment of patients with Hirschsprung’s disease (▶ Fig. 33.10b).

Schouten et al ⁹⁶ were able to demonstrate that in 29 out of 39 patients with slow-transit constipation, the apparently normal axon bundles in the myenteric plexus stained markedly less than normal or failed to stain at all with the monoclonal antibody. In 17 patients, this reduced or absent neurofilament expression was found along the entire length of the colon, whereas in 12 patients only a portion of the colon was affected. The same picture was found in the proximal ganglionic segment in 18 of 22 patients with persistent constipation after colectomy for aganglionosis (▶ Fig. 33.10c). ⁹⁷

Because intrinsic innervation is lacking in patients with Hirschsprung’s disease, the stained axon bundles in the aganglionic segment can only be of extrinsic origin. Therefore, the lack of axonal staining in patients with constipation indicates a disturbed extrinsic innervation. It is unlikely that this is a secondary phenomenon caused by laxatives because the same condition was found in neonates with severe constipation who were never treated with laxatives. Two studies have revealed increased serotonin levels in the colonic mucosa and normal serotonin levels in the colonic muscularis propria of patients with slow-transit constipation. ^{98 , 99} The question is why colonic motility is reduced and transit is prolonged despite local high and normal serotonin levels. It has been suggested that abnormal expression of the serotonin receptors in the colonic wall contributes to colonic inertia. Recently, Zhao et al were able to demonstrate a reduced expression of serotonin receptors in the left colon of patients with this type of constipation. ¹⁰⁰ Wedel et al compared the colonic enteric nervous system of patients with slow-transit constipation with the enteric nervous system of controls. They performed a morphometric analysis of the submucous plexus and the myenteric plexus. This analysis was based on Protein Gene Product 9.5 immunohistochemistry. In patients with slow-transit constipation, the total ganglionic area and neuronal number per intestinal length as well as the mean neuron count per ganglion were significantly decreased within the myenteric plexus and the external part of the submucous plexus. The ratio of glia cells to neurons was increased in myenteric ganglia but not in submucous ganglia. The observed quantitative alterations of the colonic enteric nervous system resemble the histologic features by oligoneuronal hypoganglionosis. ¹⁰¹ Two recent studies provide further evidence for these findings. Bassotti et al examined the surgical specimens from 26 patients with slow-transit constipation. They used conventional and immunohistochemical methods. Comparing patients and controls they found a significant decrease in enteric neurons, glial cells, and interstitial cells of Cajal in the constipated patients. ¹⁰² Similar findings have been reported by Lee et al. ¹⁰³ Although all these data provide evidence for the neuropathologic deficit in patients with slow-transit constipation, it is still not known whether these alterations of the colonic enteric nervous system are secondary to long-standing constipation or represent a primary defect.

33.4.15 Psychological Evaluation

The exact role of psychological factors as related to bowel function has not been defined clearly, but suggestions of such influence have been made. Tucker et al ¹⁰⁴ suggested that stool weight and bowel frequency correlated with personality as much as with variations in fiber intake. Heavier stools tended to be produced by individuals who were more socially outgoing, more energetic and optimistic, and less anxious and who described themselves in more favorable terms than others. A common cause of withholding stool during childhood has been attributed to conflict between parent and child over bowel function.

It is well known that constipation and disturbed defecation occur primarily in women. It is still not clear why these conditions are characterized with such preponderance. One explanation might be the relationship between hysterectomy and changes in bowel habits. Another explanation for the female preponderance might be the fact that women are prone to develop a symptomatic rectocele. It is unlikely, however, that the adverse side effects of hysterectomy and the defecation difficulties due to rectoceles account for all the cases of constipation and disturbed defecation. It is well known that many patients use somatization as a defensive strategy for dealing with psychological distress. This unconscious defense mechanism can be uncovered by several psychological tests such as the Minnesota Multiphasic Personality Inventory (MMPI). In 1989, Devroede et al ¹⁰⁵ used the MMPI to compare women with idiopathic (functional) constipation and women with arthritis. The authors reported that many constipated women demonstrated a “conversion V” profile pattern, which indicates the presence of a somatization defense structure. This finding has been confirmed by others. ¹⁰⁶ In 1990, Drossman et al ¹⁰⁷ demonstrated that a history of sexual and physical abuse is a frequent experience in women seen in a referral-based gastrointestinal practice and is particularly common in those with functional gastrointestinal disorders. Of 209 consecutive female patients, 89 (44%) reported a history of abuse, but only 17% had informed their physicians. This extremely high prevalence of a past history of sexual abuse is similar to that found by Leroi et al, ¹⁰⁸ who reported that 40% of patients suffering from functional disorders of the lower gastrointestinal tract gave a history of having been victims of sexual abuse in contrast to only 10% of patients with organic disease. The prevalence was similar in private practice and university hospital settings. The most frequent symptom of abused patients was constipation. The prevalence of abuse was four times greater in patients with lower rather than upper functional motor disorders. The risk of having a history of sexual abuse was nine times greater among patients with manometric evidence of anismus. The clinical implications of these findings are noteworthy. Because the vast majority of abused patients do not report their hidden history, this type of information must be actively sought.

Dykes et al ¹⁰⁹ performed a psychological enquiry among patients with chronic constipation. These patients were assessed for evidence of previous and current affective disorders. A previous episode of psychiatric illness was noted in 64% of the patients, whereas a current affective disorder was observed in 61% of the subjects. Based on these findings, the authors suggest that patients who present to surgical departments with chronic intractable constipation should routinely have a psychological assessment. It is well known that the vast majority of patients with constipation, especially those with a slow colonic transit, are women. ¹¹⁰ It has been suggested that aspects of female identity provide clues to the underlying nature of this condition. Mason et al conducted a study to examine possible emotional difficulties related to female identity in women with idiopathic constipation and compared the findings with an age-matched group of healthy women and with an age-matched group of women with Crohn’s disease. Women with idiopathic constipation were found to have increased psychological and social morbidity, characterized by anxiety, depression, and social dysfunction. They also had increased somatization, less satisfaction in their sexual life, and an altered perception about female self. ¹¹¹ It has been shown that this type of morbidity is associated with altered rectal mucosa blood flow, indicating autonomic dysfunction. ¹¹² Chan et al observed defective use of coping strategies in patients with functional constipation. These differing coping mechanisms were reflected in an absent or blunted rectal sensory perception. ¹¹³ It has been shown that biofeedback alone is not successful in the treatment of abused patients with anismus. ¹¹⁴ The clinical outcome could be improved by adding psychotherapy to biofeedback conditioning.

Patients with mental illness are liable to the development of megacolon, and constipation may be a presenting symptom of a depressive illness. Patients with anorexia often develop intractable constipation, presumably caused in part by inadequate food intake. A patient may deny the passage of stool, although a transit study may demonstrate clearly that defecation actually has occurred. The denial of passage of stool emphasizes the need to obtain objective evidence of a prolonged transit time before any operative treatment is contemplated.

33.5.1 Dispelling Myths

Patients must be reassured first that there is a wide variation of normality with regard to the frequency of bowel movements. The folklore and mythology associated with the need for daily evacuation must be dispelled. Advertising encourages self-purgation by making people feel guilty about constipation and by portraying daily bowel movements as the secret to a healthy and happy life. Erroneous concepts such as the belief that toxic substances may be absorbed into the body without a daily bowel movement must be cast aside.

33.5.2 Associated Symptoms and Daily Activity

Martelli et al ⁴⁷ noted that constipation is not without associated symptoms and complications. The authors noted the disappearance of a multitude of symptoms after successful surgical treatment of constipation. Symptoms described included hard stools, stools difficult to evacuate, abdominal distention and bloating, and anorexia. Signs included fecalomas, abdominal masses, and abdominal tenderness. To this list, Thompson ¹¹⁵ added foul breath, furred tongue, flatulence, headache, and irritability. Regardless of the cause of constipation, absence of the numerous associated symptoms should allow the patient to function better in his usual daily activity.

33.5.3 Potential Disease

Although the immediate adverse effect of low-fiber diets may be constipation, the long-term adverse effects may include diverticular disease and malignancy, as noted in studies that link the low-fiber content of the usual Western diet with an increased risk of colon carcinoma and diverticulosis. ²² Three studies suggest the link between carcinoma and constipation. ^{116 , 117 , 118} More women with carcinoma of the colon had antecedent constipation than a comparable group of controls without constipation. More men with carcinoma of the rectum had a history of constipation. In a study by Wynder and Shigematsu, ¹¹⁸ having three stools per week for a long period of time was considered a risk factor. However, in a penetrating review, Cranston et al ¹¹⁹ examined the evidence linking dietary fiber to gastrointestinal disease. They noted that fiber increases stool weight, decreases whole-gut transit time, and lowers colonic intraluminal pressure. Although fiber may be of benefit in the treatment of constipation, irritable bowel syndrome, and diverticular disease, its role in the prevention or treatment of other gastrointestinal disease has not been established.

The most recent effort to evaluate the association between dietary fiber intake and risk of colorectal carcinoma was reported by Park et al. ¹²⁰ From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Carcinoma, 725,628 men and women were followed up for up to 6 to 20 years across studies. In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal carcinoma in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with reduced risk of colorectal carcinoma.

No available data substantiate the claim that volvulus of the large bowel is frequently preceded by long-standing constipation. In many cases, hard stools with straining are the initiating factors in the development of fissures and hemorrhoids.

33.5.4 Economic Considerations

Constipation creates an economic problem of staggering proportions. In 2005, purchases of laxatives in ethical and proprietary markets (drugstores and hospitals), excluding other points of sale, totaled an astounding sum of $79,504,000 in Canada and $650,624,300 in the United States (D. Rhodes, personal communication, 2006; IMS Canada Drug Store and Hospital purchases, 2005; IMS America, Drug Store audit and provider perspective). Because these values do not include the consumption of all laxatives, the true figures are undoubtedly much higher. A common misconception is that nonprescription medication is totally safe and without adverse effects. However, if a bowel movement is induced by a laxative, it may be several days before enough stool is present for another bowel movement. Therefore, when an individual attempts to maintain a daily bowel movement with the prolonged use of laxatives, a vicious cycle may develop in which either more of the same laxative or a more potent one must be used. A “cathartic colon” then may develop. Such long-standing use of laxatives creates a varying degree of financial burden on a given patient.

33.6.1 Medical Treatment

Related posts:

18 Rectal Prolapse 19 Benign Neoplasms of the Colon and Rectum 27 Diverticular Disease of the Colon 21 Colon Carcinoma: Epidemiology, Etiology, Pathology, and Diagnosis 30 Mesenteric Vascular Diseases 32 Intestinal Stomas

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