Pancreatitis-induced ascitic fluid and hepatocellular dysfunction in severe acute pancreatitis.
BACKGROUND
Multiple organ failure (MOF) is the most serious complication in severe acute pancreatitis, contributing to its high mortality. It has been suggested that changes of high-energy phosphates, intracellular pH, and intracellular cation homeostasis are closely related to hepatocellular injury associated with MOF.


METHODS
Phosphorus metabolites, intracellular pH (pHi), and intracellular Na+ concentration ([Na+]i) were measured in rat livers in vivo using 31P and 23Na NMR spectroscopy after deoxycholic acid (DCA)-induced pancreatitis or intraperitoneal injection (ip) of pancreatitis-induced ascitic fluid (PAF).


RESULTS
Two hours after induction of DCA-pancreatitis, the liver experienced significant intracellular acidosis (pHi = 6.99 +/- 0.16) and sodium loading (75 +/- 9 mM) and a reduction in its energy state (beta-ATP/Pi = 0.2 +/- 0.03 and Pi = 164 +/- 12). Although ip injection of PAF into healthy rats did not induce systemic hypotension, the livers under these conditions also developed severe disturbances in hepatocellular ion homeostasis and depletion of its bioenergetics. The longer the abdomen was exposed to the PAF, the worse the changes were. At 3 h after ip injection of PAF, hepatic [Na+]i significantly increased (42 +/- 3 mM) along with a significant decrease in pHi (7.30 +/- 0. 03). At 6 h after ip injection of PAF, the hepatic beta-ATP/Pi ratio decreased to 0.34 +/- 0.05 and Pi increased to 97 +/- 27.


CONCLUSIONS
PAF induced severe hepatocellular acidosis, rapid accumulation of hepatic intracellular sodium, impaired hepatic cytosolic phosphorylation potential, and increased hepatic utilization of ATP. These effects may account for the eventual development of liver dysfunction associated with necrotizing pancreatitis.
Ueda
T
T
Department of Surgery, University of California Davis School of Medicine, Davis, California, 95616, USA.
Ho
H S
HS
Anderson
S E
SE
Takeyama
Y
Y
D000208:Acute Disease; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism* / Q000503:physiopathology; D003840:Deoxycholic Acid; D004734:Energy Metabolism / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D003840:Deoxycholic Acid; D010758:Phosphorus; D012964:Sodium