The Role of Bile Acids in Gallstone-Induced Pancreatitis

Three different mechanisms through which gallstone migration could trigger pancreatitis. (A) The first Opie hypothesis predicts that obstruction of pancreatic outflow by an impacted gallstone represents the trigger for disease onset. It is immaterial whether or not bile flow is also impaired. (B) Opie's common channel hypothesis states that a gallstone impacted at the papilla creates a communication between the pancreatic and bile duct behind it, through which bile could enter the pancreatic duct and potentially reach the acinar cells. (C) In this scenario, the gallstone obstructs both ducts without the potential for bile reflux into the pancreas. Pancreatic outflow obstruction triggers the disease, but an additional bile duct obstruction would act as an aggravating factor by increasing circulating or interstitial bile acid concentrations.

Bile acid uptake and targets in pancreatic acinar cells. The scheme depicts the modes of bile acid entry via Na⁺-dependent co-transporters (NTCP) from the luminal surface or via HCO₃^–-dependent bile acid exchangers (OATP1) from the basolateral membrane. Perides et al²⁷ report bile acid (TLC-S) stimulation of a G-protein–coupled bile acid receptor 1 (Gpbar1) at the luminal surface. Previously reported inward-directed signals and targets of bile acid action in acinar cells involved: release of Ca⁺⁺ from intercellular stores (Ca⁺⁺), inhibition of SERCA-pumps, activation of PI3-kinase, Ryanodin receptors (RyRs) and IP3-receptors (IP3Rs), and Ca⁺⁺-independent mitochondrial depolarization.