Hypercalcemia causes acute pancreatitis by pancreatic secretory block, intracellular zymogen accumulation, and acinar cell injury.
BACKGROUND
Because hypercalcemia is a known etiologic factor for human acute pancreatitis, studies of the pancreatic pathophysiology and pathomorphology of experimental hypercalcemia have potential clinical significance.


METHODS
Rats received central venous infusion of either 0.6 mmol/kg per hour CaCl2 or 0.9% NaCl infusion for 12 hours. Pancreatic tissue samples were obtained and prepared for electron microscopy. Tissue homogenates were examined for DNA, lactate dehydrogenase (LDH), protein, amylase, and calcium contents. Basal or stimulated (cerulein 0.25 microL/kg per hour) pancreatic secretions were analyzed for volume, protein, and amylase output, as well as protein composition on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).


RESULTS
The tissue calcium content and the ratio of LDH to DNA was unchanged after calcium infusion, but the ratios of total protein to DNA and of amylase to DNA were significantly larger. Basal output of pancreatic juice volume, protein, and amylase were significantly lower. SDS-PAGE of pancreatic juice revealed weakening of a 70,000-d band and appearance of lower molecular weight bands in two samples. Ultrastructural examination demonstrated accumulation of zymogen granules in the acinar cell, large autophagic vacuoles containing remnants of condensing vacuoles.


CONCLUSIONS
These findings suggest that hypercalcemia induces pancreatic injury via a secretory block, accumulation of secretory proteins, and possibly activation of proteases.
Frick
T W
TW
Department of Surgery, University of Zurich Hospital, Switzerland.
Mithöfer
K
K
Fernández-del Castillo
C
C
Rattner
D W
DW
Warshaw
A L
AL
D000208:Acute Disease; D000818:Animals; D003594:Cytoplasmic Granules; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors; D006934:Hypercalcemia / Q000150:complications*; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D010189:Pancreatic Juice / Q000737:chemistry; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D004792:Enzyme Precursors