Persistence of abdominal symptoms after successful surgery for idiopathic slow transit constipation. (Review Article).

ABSTRACT

To achieve predictable success in managing constipated patients, it is important that underlying pathophysiologic conditions be identified objectively, so that patients amenable to aggressive medical or surgical intervention can be identified. This review considers possible causes of persistence of abdominal symptoms after surgical relief of constipation.

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SEVERE CONSTIPATION in young adults is almost exclusively confined to young women. (1, 2) The severity of symptoms and the failure of medical therapy may ultimately lead to colectomy in these patients. (3) Many patients complain of symptoms other than constipation (such as bloating, abdominal discomfort, and occasionally vomiting after meals) that are not necessarily relieved by colectomy and achieving regular defecation, (4) suggesting that functionally abnormal gut may remain.

Kamm et al(3) and Yoshioka and Keighley(5) reported persistent abdominal pain and bloating in many patients after operation. In the first study,(3) 10 of the 44 patients required psychiatric treatment; likewise, 5 of the 40 patients in the second study needed similar therapy.(5) The reason(s) for persistent abdominal symptoms other than psychologic influences after surgical relieving of constipation remains unclear.

For the present study, a literature search using MEDLINE was done to identify all relevant published English-language articles (1966 to 2000). The keyword constipation was crossreferenced with the following terms: circulating gastrointestinal hormones, gastrin, cholycystokinin, secretin, motilin, neurotensin, vasoactive intestinal polypeptide, pancreatic polypeptides, glucagon, histamine, serotonin, norepinephrine, acetyicholine, gastric inhibitory peptide, prostaglandins, noncholinergic nonadrenergic peptides, endorphins, enkephalines, autonomic nervous system, sympathetic, and parasympathetic. The bibliographies of retrieved articles were searched manually.

NORMAL COLONIC MOTILITY 

Normal colonic motility depends on the interaction of neural and probably hormonal stimulation with the intrinsic properties of the colonic smooth muscle. Recent studies have attempted to analyze these factors under physiologic and pathophysiologic conditions.

Myoelectric and intraluminal pressure techniques are the two major methods that have been used to study colonic activity. (6) Investigation of the electrical activity of the smooth muscle (myoelectric activity) has provided new insight into the basic properties of the smooth muscle and its responsiveness to various excitatory and inhibitory stimuli.(3) Intraluminal pressure recordings have long been used to measure the contractile activity of colonic smooth muscle. Both of these techniques have been applied to patients with idiopathic severe constipation and have documented abnormal motility patterns in the basal state as well as after stimulation. (6)

Recordings of the electrical activity of intestinal smooth muscle have shown two waveforms: slow waves and spike potentials. The slow waves are phasic undulations in electrical potentials of the smooth muscle membrane. These changes in membrane activity appear to be determined by changes in sodium and potassium flux across the membrane. (7) This slow wave activity can be seen in the smooth muscle throughout the gastrointestinal tract.

The cyclic pattern occurs at regular intervals, with a reasonably constant time course and shape. The frequency varies for different areas of the gastrointestinal tract, with a frequency as high as 18 cycles per minute in the proximal small intestine and decreasing caudalward. In the distal colon, the predominant frequency is 6 cycles per minute. The slow wave electrical activity is constant, regardless of the contractile state of the muscle.

The spike potential waveform is characterized by a rapid deflection of the electrical recordings corresponding probably to transient changes in membrane potential due to calcium flux. (7) This spike potential activity is the electrical stimulus initiating muscular contraction. Spike potential occurs infrequently in the basal state, but its frequency is increased after meals and neural and hormonal stimulation.

In addition to these intermittent spike potentials, there are also intense and prolonged bursts of spike potentials that appear to move through regions of the small intestine and colon. This periodic intense activity is referred to as a "migrating spike burst" or "interdigestive migrating complex" and is associated with increased contractile activity. The function of this migrating spike burst is to propel distally the residual intraluminal contents. (8)

These two elements of the electromyogram of the gastrointestinal tract, the slow wave and the spike potentials, serve different functions and are subject to different influences. The slow wave activity is the electrical framework upon which other electrical and mechanical activity can be superimposed. The presence and frequency of this activity is uniform for a given area of the gut, and the frequency is not influenced by neural, hormonal, or pharmacologic stimulation; it appears to be an intrinsic property of the smooth muscle itself. The spike potentials occur in response to various modes of stimulation and have thus been referred to as the electrical response activity. This type of activity relates to the initiation of muscular contraction. While there is correlation between spike potentials and muscular contraction, the frequency of the mechanical contractile activity is determined actually by the frequency of the slow wave activity.

Since spike potentials can occur only during a set period on the slow wave configuration, the frequency of the slow wave determines how often spike potentials can be generated, and thus the frequency of contraction. In disease states, either the slow wave activity or the spike potentials or both could be abnormal.

Intraluminal pressure studies have also provided insight into the contractile activity of colonic smooth muscle. A variety of techniques have been used, including pressure-sensitive balloons, water-filled catheters, and pressure sensing telemetry capsules.

The results of these various studies have shown three types of contractile patterns: (1) segmentation, (2) propulsion, and (3) mass movements. Segmental activity arises from contraction of isolated units of circular smooth muscle that constricts the bowel lumen. This type of activity is nonpropulsive and is believed to result in impedance to the distal flow of intraluminal contents. Increased segmentation may therefore result in constipation.

The presence and amplitude of the nonpropulsive segmental contractions are affected by many factors. Colonic segmentation increases in response to meals and diminishes during sleep. (9) Cholinergic drugs (eg, prostigmine) augment, whereas atropine-like or anticholinergic drugs inhibit segmental activity. It is also inhibited by 5-hydroxytryptamine. (10, 11) and by bradykinin. (12) Exogenous gastrin and pentagastrin do not appear to affect colonic segmentation, but the actions of the several molecular species of this hormone have not been investigated. (13-15) Injections of exogenous cholecystokinin (CCK) (16) or intraluminal administration of magnesium sulfate (which is said to increase release of CCK) are followed by augmented segmental activity. (17,18) The role of prostaglandins (PGs) is of great interest because they may be involved in the local control of intestinal tone. (19) In vivo, [PGF.sub.2[alpha]] infused intravenously is without effect, but [PGE.sub.2] inhibits segmental activity. (20)

Propulsive activity is less easily demonstrated in the colon than in the small intestine and esophagus. (6) This type of activity results from coordinated contractions of circular muscle, which are propagated over short distances in the colon. Such propagative waves may direct intraluminal contents distally.

Mass movements are infrequent high-amplitude contractions that propel material distally from the right colon to the left colon or from the descending colon to the rectosigmoid and rectum, usually in association with defecation. These waves of intense activity propel contents rapidly and may be stimulated by meals and by somatic activity; they are diminished by sleep. (21)

PATHOPHYSIOLOGY OF SLOW TRANSIT CONSTIPATION

Recent studies (22-24) have shown a reduction in the number, amplitude, and duration of propulsive high-amplitude waves in patients with slow transit constipation (STC), in patients with idiopathic constipation in which the transit was not specified, (25) and in constipated patients with normal transit. (24) An absent early postprandial motor response has been shown in patients with slow transit, differentiating these patients from those with unimpaired transit. (25) Some patients with intractable constipation had a minimal colonic motor response to intraluminal bisacodyl (25) or cholinergic stimulation with anticholinesterases, (22) compared with normal control subjects.

A significant proportion of studies have found degeneration of neurons in the myenteric plexus in severe idiopathic constipation (5,26) and in STC. (27-30) Krishmanurthy et al (26) suggested that this abnormality was definitive of a single disorder, probably congenital, and distinct from chronic idiopathic intestinal pseudoobstruction. (30) Several studies highlighting a variation in immunoreactivity or assay levels of a number of intrinsic neurotransmitters (31-33) have concluded that the results are representative of primary intrinsic neuronal disease. (34-39) This means that slow transit constipation may be a result of either generalized degeneration of intrinsic neurons or a disturbance in the balance of intrinsic neurons with different functional and neurochemical characteristics.

In the normal physiologic situation, noncolonic hormones may affect colonic motility by their role in gut reflexes. (40,41) In constipated patients, Preston et al (42) showed impaired release of circulating motilin, pancreatic polypeptide, and gastrin in response to ingestion of water; Sjolund et al (43) showed reduced basal and postprandial levels of motilin. However, more recently, van der Sjip et al (44) found no difference in circulating levels of a panel of upper gastrointestinal hormones, including neurotensin, motilin, gastrin, and pancreatic polypeptides, though they did show alterations in somatostatin. Basal levels increased, but stimulated incremental levels decreased and glucagon decreased. These discrepancies may result from using different test meals, small number of patients studied, and/or specimens from various parts of the colon.

EXTRACOLONIC MOTILITY ABNORMALITIES

A few studies have shown a range of functional gastrointestinal abnormalities in patients with slow transit constipation. Esophageal abnormalities in such patients include disturbed upper and lower sphincter, (45) as well as abnormal coordination in the body of the esophagus. (45,46)

Reynolds et al (46) examined gastric emptying in 4 severely constipated patients and found it to be abnormal for solid emptying in 3 and for liquids in 1. Bannister et al (47) found that the time to empty 50% of a radiolabeled solid meal was normal in a group of constipated patients. Stivland et al (48) found significant delays in the postlag phase of gastric emptying in 2 of 8 severely constipated patients. van der Sijp et al (49) found no statistical difference between constipated and normal subjects in the lag phase of solid emptying. The proportion of liquid and solid remaining in the stomach at 360 minutes was markedly different in patients with STC and normal controls. Seven of 11 patients had excess gastric retention of liquid, and 6 of 10 had excess gastric retention of solid at 360 minutes. In 1 patient, this was marked, with up to 40% of liquid and 48% of solid retained.

In agreement with earlier reports, MacDonald et al (50) found that solid, phase gastric emptying was profoundly delayed in patients with STC, though it was normal in constipated patients after childbirth. The delayed gastric emptying identified in patients with STC may be a component of pangastrointestinal tract abnormality in these patients or due to colonic inertia, as it has been shown in animals and humans. (51,52)

Small bowel motility may also be abnormal in these patients. (47,49,53) Bannister et al (47) showed a significantly slower small bowel transit time of the front of a radioisotope column in constipated women. Kumar et al (51) found an increased motility index during phase II activity in the small bowel of such patients, together with an increase in the frequency of the migrating motor complex.

van der Sijp (49) found that when the stomach had emptied 50% of the solid meal, the small bowel in the normal controls had transported significantly more solids to the cecum than in constipated patients; the median proportion of solid-phase radioisotope present in the small bowel at the time of 50% gastric emptying was 45% in the constipated patients and 33% in the healthy controls. All patients with normal gastric emptying had normal small bowel transit time, while all those with delayed gastric emptying also had slow small bowel transit. (49)

A recent study, (54) investigated gastric emptying in 12 severely constipated patients before and after subtotal colectomy and ileorectal anastomosis. The majority of patients showed improvement in gastric emptying, 1 month after surgery, though it remained abnormal. One year after operation, gastric emptying was normal in 4 patients but remained abnormal in 2.

SUMMARY

The persistence of abdominal symptoms after successful surgery for management of idiopathic chronic constipation may be related to proximal gastrointestinal dysmotility. This upper gastrointestinal dysmotility may be part of a pangastrointestinal abnormality, or it may result from abnormal circulating levels of neuropeptides and/or noncolonic gastrointestinal hormones. More patients need to be studied to confirm this initial impression.

References

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RELATED ARTICLE: KEY POINTS

* Persistence of abdominal symptoms in constipated patients after surgical relief of constipation suggests that functionally abnormal gut may remain.

* Slow transit constipation may be a result of either generalized degeneration of intrinsic neurons or a disturbance in the balance of intrinsic neurons with different functional and neurochemical characteristics.

* Impaired release of circulating gut hormones might also be a cause.

From the Department of General Surgery, Birmingham Heartlands Hospital, Birmingham, England.

Reprint requests to Ahmed M. El-Tawil, MD, Birmingham Heartlands Hospital, Department of General Surgery, Birmingham B9 5SS UK.