Reticuloendothelial System Blockade Promotes Progression from Mild to Severe Acute Pancreatitis in the Opossum

Abstract

ObjectiveTo examine the relation between hepatic reticuloendothelial system (RES) dysfunction and the development of acute biliary pancreatitis. In an opossum model, the authors tested the hypothesis that RES blockade can turn the mild pancreatitis seen after pancreatic duct obstruction (PDO) into the severe form. Summary Background DataBiliary obstruction is considered the decisive event in gallstone pancreatitis. Suppression of the RES occurs during biliary obstruction. MethodsEighteen opossums were placed into three groups of six animals each: group A, RES blockade with -carrageenan; group B, PDO; and group C, PDO and RES blockade with carrageenan. The severity of pancreatitis was evaluated by enzyme serum levels and percentage of pancreatic tissue necrosis. RES capacity was measured by dynamic liver scintigraphy, and hepatic blood flow was documented using the hydrogen clearance technique. ResultsNo changes in hepatic blood flow occurred in groups A to C. RES capacity was suppressed in groups A and C; in group B, RES function remained unchanged. In group A, amylase and lipase levels remained normal, 3 Ϯ 1.9% of pancreatic tissue were necrotic. The animals in group B developed mild edematous pancreatitis with an increase in amylase and lipase levels and 15 Ϯ 10% of pancreatic necrosis. In group C, amylase and lipase increased significantly and histology revealed severe necrotizing pancreatitis, with 72 Ϯ 11% of necrotic areas. ConclusionsArtificial RES blockade can promote the progression from mild pancreatitis as observed after PDO to the severe necrotizing form of the disease. Thus, RES dysfunction resulting from biliary obstruction might be an important cofactor in the pathogenesis of bile-induced pancreatitis.Acute biliary pancreatitis is an inflammatory disease that varies in severity and outcome. Mild edematous pancreatitis usually results in morphologic and functional recovery, whereas severe necrotizing pancreatitis is often associated with multisystemic complications and a death rate of 10% to 50%. 1 The reason for this variety in manifestation is not known. The identification of factors determining the severity of acute pancreatitis is essential to improve the understanding of the pathophysiology of bile-induced pancreatitis and its complications.Obstruction of the terminal biliopancreatic ductal system is considered to be the triggering event in human gallstone pancreatitis. Opie, 2 in 1901, postulated that reflux of bile, caused by a gallstone impacted in a common terminal biliopancreatic duct, initiates the process of pancreatic inflammation. Today, most authors disagree with this socalled common channel theory, and not reflux of bile but simultaneous obstruction of the biliary and the pancreatic ducts and their pathophysiologic consequences are considered to be the determining factors in the development of severe pancreatitis.

Early Changes in Pancreatic Acinar Cell Calcium Signaling after Pancreatic Duct Obstruction

“…(a) Bile duct ligation alone is known to raise circulating cholecystokinin levels in the blood and could, by itself, exert a stimulatory effect on the pancreas (14). (b) It has been suggested that bile duct obstruction could be a confounding or aggravating factor for the events involved pancreatic duct obstruction-induced pancreatitis (15,16). (c) Ligation of the pancreatic duct system in mice without compromising the unimpaired flow of bile is technically more prone to surgical complications than ligation of both ducts and the latter is a more likely to reflect the situation that arises when a gallstone is impacted at the papilla.…”

Gallstone pancreatitis: positive correlation between severe pancreatitis and passed stone

“…In gallstone pancreatitis, stone impaction may occur either at the choledochoduodenal junction below the confluence of the biliary and pancreatic ducts, which produces a common channel, or at the confluence of the biliary and pancreatic ducts, which produces obstruction of both ducts. The common channel theory proposed by Opie24 has been challenged by the observation that pancreatic duct pressure exceeds biliary duct pressure, suggesting that, even if a common channel existed, reflux of pancreatic juice into the biliary duct, rather than flow of bile into the pancreas would be expected 29. Fumino et al30 showed clinical evidence of two‐way regurgitation: pancreaticobiliary reflux (PBR) and biliopancreatic reflux (BPR), in patients with anomalous arrangements of the pancreaticobiliary ducts (AAPBD).…”

“…They also noted that abdominal pain with hyperamylasemia was significantly more frequent in patients with PBR than in patients with BPR, and hypothesized that hyperamylasemia in patients with AAPBD is caused by cholangiovenous reflux. Today, most authors disagree with the common channel theory proposed by Opie 29…”

Comparative Analysis of Hepatic CD14 Expression between Two Different Endotoxin Shock Model Mice: Relation between Hepatic Injury and CD14 Expression

“…CAR is preferentially incorporated by the Kupffer cells in the liver [36]. Administration of CAR to animals also creates an experimental model of jaundice [37].…”