Gallbladder contractility : in vitro and in vivo studies

Pearce, Neil William (2004) Gallbladder contractility : in vitro and in vivo studies. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Cholecystectomy is a commonly performed operation, however the physiology of gallbladder motility and in particular the relationship between in vivo emptying and in vitro contraction are only partly understood. The large overlap between the symptoms of patients with gallstones and irritable bowel syndrome (IBS) has stimulated investigation of gallbladder emptying in these two groups.

Following a review of the current knowledge of gallbladder motility an in vitro model for studying gallbladder contractility is described. The in vitro response of gallbladder muscle strips to bradykinin is described and the receptor subgroups investigated. Contraction in response to bradykinin is dose dependent, in normal gallbladders this is mediated via the B1 receptor and via both B1 and B2 receptors in stone bearing gallbladders. This raises the possibility of a relationship to gallstones pathogenesis.

Sonographic estimation of in vivo gallbladder emptying is described and used to measure gallbladder emptying in normal individuals and gallstone and IBS patients in response to a standard fatty meal. Gallstone patients demonstrate low levels of emptying, suggesting that this may be a contributory factor in gallstone pathogenesis. A very high level of emptying is seen in patients with IBS.

Serum CCK-8 levels in response to a standard fatty meal are measured using a radio immuno assay in IBS patients and the normal group. IBS patients have higher fasting and peak levels of CCK-8. This suggests a possible role for cholecystokinin in the heightened visceral smooth muscle sensitivity seen in IBS.

In vivo gallbladder emptying and in vitro gallbladder strip contraction are compared in cholecystectomy patients. The results show weak correlation between gallbladder emptying and response to CCK in vitro and no correlation with in vitro response to bradykinin. This sheds doubt on the relevance of this in vitro model to the in vivo state. Further investigation of these findings is merited and future work is suggested.