Colon lengthening slows transit: is this the mechanism underlying redundant colon or slow transit constipation?

Abstract

The study by Heredia et al. (2010) in a recent issue of The Journal of Physiology shows that elongation of colon longitudinal muscle results in slow colonic transit. This study was performed in mice, but the results are probably applicable to humans. The study by Heredia et al. presents a new mechanism that may explain the association of elongated colon and poor motility and might be manipulated to overcome bowel lengthening and stasis. Their study shows that elongation of the longitudinal muscle triggers inhibition of the colonic migrating motor complex (CMMC), resulting in slow colonic transit. In humans, slow colonic transit occurs in patients with chronic constipation and is known as slow transit constipation (STC) (Hutson, 2009). Interestingly, we have observed that many patients with slow transit constipation have an elongated transverse colon (Fig. 1). The results from Heredia et al. suggest this elongation would inhibit colonic motility. Differences in colon length in children with constipation A, normal length colon; B, elongated transverse colon. Both images are from radioisotope transit studies with gamma camera images taken 24 h after ingesting a radioactive milk drink (Southwell et al. 2009). Note the large loop of transverse colon in B. The elongated colon is also narrower than the colon in A. Image provided by Dr Ian Yik (Surgical Research Group, Murdoch Childrens Research Institute, Royal Childrens Hospital, Melbourne, Australia). Elongated (called redundant) colon often occurs in patients with constipation. These patients are notable during colonic endoscopy because it is very hard to get along the length of the colon (Rex et al. 2007). Both colonic transit time and constipation symptoms increase with the number of redundancies and these are the patients that are least likely to respond to treatments (Raahave et al. 2009). Redundant bowel is often removed surgically. Propagating contractions in the proximal colon are highly propulsive and are a major determinant of proximal colonic flow in normal human colon (Dinning et al. 2008). High amplitude propagating contractions (HAPCs) underlie mass movements along the colon and may be similar to CMMC. Children with STC have reduced numbers of propagating contractions in the proximal colon (King, 2008) and lack of HAPC in constipated patients is associated with poor outcomes (van den Berg et al. 2006). Heredia et al. show that lengthening the colon inhibits CMMC in mice. Possibly the same is occurring in humans with colonic lengthening inhibiting HAPCs and so reducing colonic motility and slowing transit. STC can be associated with abnormal recto/sigmoid function (outlet obstruction, anorectal retention or functional fecal retention) or occur with normal recto/sigmoid function (Southwell et al. 2009). There is a lot of discussion about whether the defect is primarily at the outlet (ano-rectum) producing slowing of motility upstream as a secondary effect or if a defect can occur in the proximal colon without an outlet defect. Heredia et al.'s study shows the effects of elongation are different in the proximal and distal colon, and provides evidence that the proximal colon can inhibit motility in the distal colon. Thus it is possible that elongation can inhibit motility in the proximal colon primarily and this can then affect the distal colon. Heredia et al. also investigated the mechanism and showed that nitric oxide was released and activated inhibitory neurons reducing pellet propulsion and amplitude of colonic migrating motor complex (CMMC). Ileus (lack of movement of the bowel) develops after surgery and has been shown to be due to release of nitric oxide that then activates inhibitory neurons. Removal of the tonic nitrergic inhibition is a potent stimulus for human proximal colonic propagating sequences (Dinning et al. 2006). STC often develops after childbirth and there may be a connection between surgery (anaesthesia and caesarean) inducing nitric oxide release within the bowel and then leading to stasis in the ileum and in the colon. This study reveals a previously unrecognised mechanism for control of colonic motility: lengthening of the longitudinal muscle. If this mechanism can be manipulated in people, we may have a treatment for a currently poorly treated condition. Further detailed physiological studies of the effects of longitudinal muscle lengthening on migrating motor complexes in proximal and distal colon in other species should be helpful.