Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
See article on page 264
Penning et al’s paper is a brain-teaser (see page 264). It clearly shows is that, in the laboratory, the gall bladder behaves abnormally in patients with chronic constipation. What is much less clear, but very intriguing, is what the findings mean. Recently, the state of the gall bladder in patients with constipation has been attracting attention because of growing evidence that cholesterol gallstones can result from slow intestinal transit.1-3 Slow transit allows the colon to absorb excessive amounts of bacterially degraded substances, including the toxic bile acid, deoxycholic acid (DCA). When DCA reaches the liver, it makes it secrete more cholesterol into bile and when it reaches the gall bladder it hastens the crystallisation of cholesterol.2 ,4 So, patients with slow transit constipation should be at high risk of gallstones. Puzzle number one is that the patients in Penning et al’s study seem to have escaped gallstones (although this is not explicitly stated).
But was their gall bladder motility defect likely to lead to gallstones? Impaired gall bladder emptying is certainly a feature of patients with cholesterol gallstones.5 Indeed, it is believed to be a key factor in stone pathogenesis, if only because it favours the growth and retention of calculi within the gall bladder. Latest thinking is that the gall bladder of patients with gallstones may be a poor contractor because its wall is infiltrated with cholesterol, and perhaps inflamed by the high DCA concentrations in the bile inside it.4 ,6 It is tempting to welcome Penninget al’s findings as fitting in with this scheme, the slow transit of their patients having led to bile toxic to the gall bladder. However, there is a snag with this interpretation. In the characteristic motility defect of patients with gallstones the resting volume of the gall bladder is large,4 whereas in these constipated patients, the resting volume was smaller than normal—a finding which is unusual and curious.
Another difficulty in comparing these new data with published ones is the method used to demonstrate impaired gall bladder emptying, namely sham feeding. The results cannot be extrapolated to the natural stimulus of eating a meal. The response to cholecystokinin—the mediator of food induced contraction—was normal; indeed, in another study of constipated patients (who also had irritable bowel syndrome (IBS)), the response to a cholecystokinin analogue was actually greater than normal.7 So at least we can be sure of one thing—the gall bladder muscle is not to blame. Is it a problem of understimulation? Because the gall bladder’s response to sham feeding involves vagal cholinergic stimulation, Penning et al conclude that failure to respond is a sign of vagal neuropathy. This sounds logical but would be more convincing if tests of vagal function had been carried out and a relation shown between these and the gall bladder dysmotility.
Penning et al ignore the possibility of psychological factors. The response of the gastrointestinal tract to sham feeding is called the cephalic phase and it involves the higher centres of the brain. Having to chew and spit out a meal cannot be a pleasant experience. Suppose that some participants found it positively disgusting, would their gastrointestinal tracts, including their gall bladders, have reacted normally? The emotional reaction of the patients might have been stronger than that of the normal controls. Almost by definition, patients are anxious people (why else do they go to the doctor?) and so more liable to strong emotional reactions. Constipation can itself be a somatic expression of psychic distress8(though patients with functional gastrointestinal disorders who reach specialists are likely to deny their distress9).
In discussing their findings, Penning et al have avoided the biopsychosocial approach but, more conventionally perhaps, have suggested that constipated people have a widespread smooth muscle disorder encompassing the gall bladder as well as the intestine (not a new idea3). This is the language used in the past about IBS but the evidence that gall bladder function is abnormal in IBS, protean though that condition is, is inconsistent.10 Also, the trend in IBS is towards larger fasting volumes,11 not smaller as in Penninget al’s patients. A better analogy might be with functional dyspepsia, where impaired relaxation of the stomach seems to be a feature12 because impaired relaxation of the gall bladder could explain the small fasting volume in Penninget al’s patients.
This study, like many, raises more questions than it answers. It reminds us how little we understand the behaviour of our digestive systems. Functional disorders are difficult to study but study them we must because, more and more, these are the disorders which trouble the patients who face us in our clinics. And every study of a functional disorder should take account of psychosocial factors.