Effects of bile salts on permeability and morphology of main pancreatic duct in cats

Abstract

We studied the changes in permeability and morphology in the main pancreatic duct of cats after exposure of the duct to specific bile salts. Cats were anesthetized and the main pancreatic duct was cannulated in the tail and head of the pancreas. The duct was perfused with sodium cholate (1, 1.5, 2, 15 mM) or sodium glycodeoxycholate (1, 2, 15 mM) for 60 min at pressures which never exceeded 20 cm water. Then the duct was perfused with fluorescein-tagged dextran molecules of specific size (3000, 20,000, or 40,000 daltons). Recovery of the dextran from portal venous blood indicated that the duct was permeable to that particular dextran. Normally the ducts were impermeable to even the 3000-dalton dextran, and perfusion with either 1 mM cholate or glycodeoxycholate did not change this. However, perfusion with either bile salt at concentrations above 1 mM progressively increased duct permeability. At this highest bile salt concentrations used, the ducts became permeable to molecules as large as 20,000 daltons. Morphologic changes paralleled the changes in permeability. Control animals had pancreatic ducts whose ultrastructure was indistinguishable from normal. Perfusion of the ducts with low concentrations of bile salt for up to 60 min resulted only in a loss of microvilli from the cell surface and an increase in cytoplasmic phagolysosomes. Perfusion with higher concentrations of bile salt for 5-60 min induced progressively severe alterations. These included disruption of the tight junctions and the swelling of intercellular spaces between the duct cells, flattening of the duct epithelium, and eventual cell loss which left a break in the epithelial lining of the duct. These studies indicate that the pancreatic duct in cats, exposed to specific bile salts at physiological concentrations and pressures, undergoes marked structural alterations. The duct becomes permeable to molecules at least as large as 20,000 daltons, whereas it is normally impermeable to molecules as small as 3000 daltons.

Bile Infection and Bile Acids Concentration in Bile in Acute Biliary Pancreatitis

“…In proper conditions these ducts do not transmit molecules smaller than 3000 Daltons (13). If the above is true, then the results of our own studies correspond, at least to some extent, with results of the experimental studies.…”

“…Permeability of pancreatic duct epithelium under the infl uence of bile acids has been proved, among others on animals (12,13). Studies during the recent years (Voronina, Fischer and Kim) concentrate on the attempt to explain molecular mechanisms concerning the damage of follicular cells by bile acids.…”

“…In case of coexisting cholelithiasis, bacteria colonizing gall-bladder and bile ducts are the fi rst element. Bile acids are the second potential factor, as their damaging infl uence on epithelium of bile ducts and pancreatic ducts, as well as pancreatic follicular cells was confi rmed by experimental works (11)(12)(13)(14)(15)(16).…”

Bile Acids Induce a Cationic Current, Depolarizing Pancreatic Acinar Cells and Increasing the Intracellular Na+ Concentration

“…Bile is considered a putative trigger of acute pancreatitis (1,2), although issue is still debated (3)(4)(5)(6). Bile acids have been shown to increase significantly the permeability of the ductal mucosal barrier in the pancreas (7)(8)(9), and recently two investigations demonstrated that bile acids are able to induce prolonged toxic cytosolic calcium signals in pancreatic acinar cells (1,10).…”

The effects of bile acids on pancreatic ductal cells

“…Therefore, researchers extensively investigated the effect of BAs on the morphology and permeability of the main pancreatic duct. In these in vivo studies various BAs were perfused through the cannulated main duct and the permeability of the pancreatic duct mucosal barrier was measured using different techniques (5,15,(37)(38)(39). It has been shown that BAs in high concentrations (2-15 mM), made the ducts permeable to molecules as large as 20,000-daltons, whereas they are normally impermeable to molecules over 3,000-daltons (5,15).…”