The Physiology and Pathophysiology of Pancreatic Ductal Secretion

Abstract

The human exocrine pancreas consists of 2 main cell types: acinar and ductal cells. These exocrine cells interact closely to contribute to the secretion of pancreatic juice. The most important ion in terms of the pancreatic ductal secretion is HCO3. In fact, duct cells produce an alkaline fluid that may contain up to 140 mM NaHCO3, which is essential for normal digestion. This article provides an overview of the basics of pancreatic ductal physiology and pathophysiology. In the first part of the article, we discuss the ductal electrolyte and fluid transporters and their regulation. The central role of cystic fibrosis transmembrane conductance regulator (CFTR) is highlighted, which is much more than just a Cl channel. We also review the role of pancreatic ducts in severe debilitating diseases such as cystic fibrosis (caused by various genetic defects of cftr), pancreatitis, and diabetes mellitus. Stimulation of ductal secretion in cystic fibrosis and pancreatitis may have beneficial effects in their treatment.

Physiological and pathophysiological investigation of lacrimal and pancreatic ductal epithelial cells

“…Previous studies shown that bile acids such as CDCA strongly inhibits ion transporters through the destruction of mitochondrial function, resulting in impaired pancreatic ductal fluid and HCO 3 -secretion [68,74]. This effect of bile acids may have significance in the pathomechanism of AP.…”

“…One of the most accepted theories is that bile reflux into the pancreatic ductal system leads to AP. We know from animal studies, that retrograde infusion of bile acids into the pancreatic duct triggers pancreatitis [3,64,65]. Therefore the cytotoxic effects of bile acids have been widely investigated in the pancreas [66][67][68][69] [68,74].…”

“…In the absence of ATP i , the acid/base transporters fail to function properly, which finally causes decreased fluid and HCO 3 -secretion [74]. Impaired fluid secretion can lead to pancreatic injury and likely contributes to the development of pancreatitis [3,76].…”

“…Ursodeoxycholic acid (UDCA) is a secondary, hydrophilic bile acid, which is currently used for gallstone dissolution and considered as first-choice therapy in cholestatic diseases [77][78][79][80]. The mechanism by which UDCA increases liver function is not completely 3 -transport is inhibited under these conditions (A). In the LG basolateral Cl -uptake is mainly mediated by NKCC1 and AEs.…”

“…LGDEC lacrimal gland ductal epithelial cells [1][2][3]. Whereas, ductal fluid and electrolyte secretion are mainly mediated by the Na + /HCO 3 − cotransporter (NBC), the Cl − /HCO 3 − anion exchanger (AEs), the cystic fibrosis transmembrane conductance regulator Cl − channel (CFTR) and the CaCC [1,4].…”