Pathophysiology of functional constipation

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The pathophysiology underlying functional constipation might be multifactorial and is certainly not well understood. Functional constipation results from abnormal function of the colon, rectum and sphincter complex, and conscious and subconscious factors in the child. Two main subgroups are described: slow-transit constipation; and outlet obstruction, leading to retention of feces in the rectum and extending to the whole colon. It is unclear whether different pathophysiological mechanisms are involved in each of these forms of constipation.

Slow-transit constipation

This can be diagnosed by colonic transit time measurements, showing an overall delay in colonic transit time over the whole colon. Both

Pathophysiology of functional constipation 251

muscular (impaired contractility) and neural (uncoordinated activity) mechanisms may lead to impairment of propulsion of fecal contents leading to slow-transit constipation.12 Mechanisms underlying these entities might be an impairment of neural transmitter function, such as nitric oxide (NO) or substance P, or aberrations in the interstitial cells of Cajal. However, this entity remains extremely difficult to explain and might be secondary to the effect of stasis.

In addition to neuromuscular dysfunction, constipation can also result from massive fecal retention in the rectum. It has been shown that voluntary retention of feces can cause a delay in colonic transit in healthy volunteers. Similarly, massive fecal retention in children can also inhibit colonic transit and thus indirectly leads to prolonged transit time. In several children, slow-transit constipation after treatment changes to outlet obstruction with only a delay in the rectosigmoid region.

An alternative mechanism leading to constipation is the so-called outlet obstruction or abnormalities in the dynamics underlying defecation. In these children, the delay in colonic transit involves the rectum. This mechanism is found in approximately 40-60% of constipated children. It should be noted that 50% of constipated children, all presenting with the same symptomatology, have normal colonic transit time.13-15 This observation strongly suggests that abnormal transit times are secondary events in children with constipation. It is also supported by normalization of transit time in slow-transit constipation after successful treatment.

Another alternative mechanism might be abnormal sphincter function.16,17 Under normal circumstances, the pressure generated by the anal sphincter complex should drop during an attempt to defecate, allowing expulsion of fecal contents. As stated above, in 40% of children with constipation, colonic transit is delayed in the rectum, and it was suggested that this abnormal obstruction is the result of abnormal defecation dynamics. However, using anorectal manometry, a paradox for contraction in the anal sphincter complex is observed in more than 50% of constipated children. This contraction of the anal sphincter complex might lead to fecal accumulation and constipation. This abnormality might be the underlying pathophysio-

logical mechanism of childhood constipation, reflecting the observed stool withholding behavior/retentive posturing. Possible suggested causes leading to this behavior might be pain, resulting from the previous production of a large, hard stool; anal fissures; primary behavioral mechanisms; not taking time to visit the toilet; and avoiding other toilets, mainly at school. However, abnormal defecation dynamics have not only been observed in fecal retention and constipation, but similarly in children with functional non-retentive fecal soiling. In addition, a large study, comparing conventional treatment with additional biofeedback training in constipated children, showed that biofeedback training could normalize the aberrant sphincter contraction, but, it did not lead to a larger success rate in children receiving additional biofeedback training.1 These observations argue against a major contribution of abnormal defecation dynamics to the development of constipation in children.

As explained previously, different types of nerve endings, giving rise to sensations of flatus, urge to defecate and pain, sense the arrival of fecal material into the rectum. This sensory information is important for initiating the defecation process. Abnormalities in rectal sensation are believed to play an important role in the pathogenesis of constipation. Children usually report that they do not feel the sensation or urge to defecate. Several studies have investigated rectal sensitivity in children with constipation. In these studies, rectal sensation is determined by inflation of a rectal balloon, measuring the volume at which the sensation of urge is perceived. These studies showed impaired rectal sensation in a subgroup of patients with constipation. In the majority of children, however, rectal sensation was normal and present after insufflation of only 20 ml of air in the balloon. Rectal volumes are obviously age-dependent, with a barostat (an insufflatable rectal balloon that can keep the volume constant while varying the pressure, or vice versa) showing that one subgroup needs higher pressures with a normal volume to feel urge, but children in another subgroup need higher volumes with a normal pressure to feel urge.

Abnormal rectal sensation does not seem to be an important pathophysiological entity. In fact, a number of studies in children with constipation have documented a normal anal resting pressure, as well as a normal maximal rectal squeeze pressure.

To date, no consistent abnormalities in motility testing have been recorded in children with constipation. There were no differences in motility parameters between children with long-standing constipation and those who have had constipation for only a short period. Furthermore, there were no indications of neuromuscular damage due to abnormalities caused by constipation or its therapy.

Therefore, it is fair to conclude that, there is no current explanation of the cause(s) of constipation or suggested pathophysiological mechanisms. All assumed mechanisms have been found to be normal in the majority of children with constipation with a mainly uniform clinical presentation.

Children with functional non-retentive fecal soiling, in studies on its pathophysiology, show normal anal sphincter resting pressure, normal maximal squeeze pressure and normal rectal sensation. Also, colonic transit time measurements were normal in all children with this entity.18-20

Medical history

Symptoms of constipation in most children start in more than 38-65% before the age of 6 months, and some have even described bowel problems in 40% of children in the first months of life. Stool habits might change, owing to stress factors and change in nutrition, for instance change from breast feeding to formula feeding. Specific questions regarding the presence of soiling and encopresis should be asked, and also regarding the frequency and whether it is present at night-time. These children produce an enormous amount of stool once every 7-30 days, which is almost never spontaneously presented as a symptom during a first doctor's visit. It must also be asked whether this enormous amount of stool has been produced just before the visit to the doctor (the rectum might then be empty for rectal examination). Questions about retentive posturing should be asked, but might be difficult to answer; nevertheless, the parents might notice whether stools are produced with pain and also if any of these symptoms started after a period in which defecation and stools were completely normal. When the frequency is less than three times a week, soiling and encopresis are present, and large amounts of stool are occasionally produced, the diagnosis of functional constipation is likely. When a child has a painful stressful production of hard stools without soiling and encopresis and retentive posturing, even at an almost normal frequency, constipation will still be considered probable by the physician, and a therapeutic attempt should be initiated.21-23

In developed societies most children are toilet trained by the age of 2-3 years. There is no relation between failed toilet training and the development of constipation or functional non-retentive fecal soiling. Before the age of 4 years, the diagnosis of constipation can be made only on low or decreased frequency of defecation, production of occasional voluminous stools, production of hard stools with discomfort, pain and/or retentive posturing. In infants, the diagnosis of constipation can be inferred when they cry before, during and after defecation, and this consists of firm, hard stools. Behavioral problems occur often, but they are almost invariably secondary to the social consequences and depend on individual styles of coping. Such problems typically improve considerably once the defecation difficulties are successfully treated. However, poor social behavior, or an inadequate parent-child relationship may be associated with the continuation of defecation problems. Urinary problems, diurnal and also nocturnal enuresis, are secondary to the defecation problems and usually improve after successful treatment.

Physical examination

Abdominal masses should be gently looked for by palpation in the lower abdominal quadrants and suprapubic area. The stool mass might be palpable extending from the pelvis, but smaller scybala might also be detected. Usually, a bimanual palpation through a rectal examination with one hand combined with abdominal palpation with the other hand, clearly defines the rectal mass of stool the best. At the first visit a rectal examination should be attempted in all children who present with constipation or non-functional fecal retention. Only in 10-15% of children is the fear of examination too high, when this procedure has to be omitted. Otherwise, it is well perceived and gives the essential information about the rectal fecal mass. Anal fissures can be clearly visualized by spreading the anus, and during the examination anatomical abnormalities should be inspected, checking the anal position in the perineum and its asymmetry: an ectopic anus can in fact be the cause of constipation. The inspection of the lower lumbar and sacral spine areas should be focused on dimpling, surgical scars and hair tufting. Also, tendon reflexes should be evoked. Usually, the school-aged child has stools or soiling in his underpants and one should be aware of the production of a large amount of stool just prior to the visit to the physician. That might interfere with the examination results. Fissures are considered to be related to the initiation of constipation only in very young infants; an abdominal and/or rectal mass is found in 30-100%, depending on the investigator.24

Differential diagnosis

Over 90% of pediatric patients with constipation have functional constipation or non-retentive functional fecal soiling. Only in a very small number of children is a distinct etiology established, and these cases are not easily overlooked.

Changed dietary habits might decrease the intake of fluids and food. The change from breast milk to formula feeding as an initiating point is highly suggestive of constipation.

A careful perianal examination will disclose an imperforate anus, or an abnormal anteriorly displaced anus, as well as other congenital anatomic and structural defects.

Spinal abnormalities are indicated by abnormalities of the skin, and also growth impairment and a combination of fecal and urinary incontinence or constipation.

Metabolic disturbances are related to severe dehydration, as is seen in diabetes insipidus, hypocal-cemia and renal tubular acidosis, and are not easily overlooked.

Hypothyroidism is screened for in the neonatal period and might still occur later, but is not easily overlooked as a symptom complex in a child.

Hirschsprung's disease is suspected after a delayed production of meconium beyond 48 h after birth, and continuing defecation problems usually with distended abdomen and poor appetite, failure to gain weight and vomiting. Also, the history would often document episodes of acute, severe enterocolitis with explosive diarrhea. Clinically, the diagnosis is made by insertion of a catheter through the anus in the distended part, after which decompression follows (see Chapter 17).

Also, Hirschsprung's disease might involve a very small segment of the anorectum and present as constipation. In practice, this is seen only on extremely rare occasions. We have not made this diagnosis in our practice for decades.

Recently, magnetic resonance imaging (MRI) of the pelvis and distal colon has been proposed in order to detect small abnormalities, cysts, tumors or tethered cord which may be the basis of constipation without any other neurological symptom. This approach, however, has not been performed in a large population, and is currently awaiting some protocol definitions.25

Examinations Plain abdominal X-ray

On a plain abdominal radiograph some amount of stool is always visible. The simple report of 'stools in the colon' should therefore not be regarded as indicative of constipation. Barr et al tried to develop a scoring system to define constipation. Although this scoring system is used to diagnose constipation in children with chronic abdominal pain as the only symptom, the method is subject to large intra- and interobserver variability.26,27

Colonic transit times are measured by the Metcalf method. Swallowed radio-opaque tiny rings allow the intestinal transit to be measured. This test shows normal transit times in half of the constipated children and is therefore only useful to diagnose slow-transit constipation, a clinical entity usually apparent with night-time soiling and resis tance to treatment. The upper limit of colonic transit is 63 h. A colonic transit time delayed to more than 100h is defined as slow-transit constipation. A palpable rectal mass is always found. The method can also be used to support the diagnosis of functional non-retentive fecal soiling, but it has no place in the general management of children with constipation.

Barium enema

A barium enema performed in the unprepared colon might delineate the transition zone in Hirschsprung's disease in young infants, but is of limited value, as the transition zone is often difficult to see and might only be of value to the operating surgeon preoperatively after the diagnosis has been made.


Defecography uses a relatively high radiation exposure and is difficult and unreliable in children.

Anorectal manometry

Anorectal manometry is a relatively safe, minor invasive technique. With an open perfusion system, pressures may be assessed in anal sphincter muscles at rest, at squeezing and during straining. During defecation, the pelvic pressure or rectal pressure increases, owing to abdominal muscle contraction, and the anal canal pressure decreases, creating a difference to allow defecation. A rectal balloon might be inflated to assess the rectal anal inhibitory reflex against relaxation of the internal anal sphincter. In the clinical setting, except for Hirschsprung's disease, the majority of children have normal anorectal pressures.

Rectal sensitivity after inflation of a balloon is normal. Children who have abnormal defecation dynamics, in an attempt to defecate the balloon, will contract the anal sphincters at the same time that they contract the abdominal musculature. This can be shown on a screen and children can learn to relax instead of having this paradoxical contraction during defecation of the anal muscula ture. The training by reinforcement is called biofeedback training.

Anorectal manometry is normal in children with functional constipation or functional non-fecal retention, and therefore this should not be used.1

Colonic manometry

Colonic manometry28 requires colonoscopic placement of the catheter with motility recordings, which are measured the day after placement. Colonic motility can be tested over hours, possibly with bisacodyl administration to enable propagated contractions to be endured. This test is reserved for children with intractable constipation. Some investigators can differentiate children with functional fecal retention from those with no neuropathy or myopathy of the colon with this technique. The technique is still used in a few centers; however, its value in the diagnostic process of constipation has to be assessed.

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