Severe acute pancreatitis is related to increased early urinary levels of the activation Peptide of pancreatic phospholipase A(2).
OBJECTIVE
In acute pancreatitis, it is believed that generalized activation of pancreatic zymogens leads to autodigestion of the pancreas and if excessive to systemic organ injury. Under physiological circumstances, secretory phospholipase A(2) type I (sPLA(2)-I) is activated by trypsinogen, but the extent of this activation in acute pancreatitis is unclear. The aim of this study was to assess time course and level of activation of sPLA(2)-I and trypsinogen in acute pancreatitis, relative to severity.


METHODS
246 patients were enrolled into a prospective European multicenter study. 137 patients had mild and 35 had severe acute pancreatitis, and there were 74 control patients. Urinary samples were taken on admission and at 6-hour intervals for 48 h, then every 12 h up to 72 h, and finally daily for at least 5 days for measurement of the activation peptide of sPLA(2)-I (pro-phosphatase A(2); PROP) and trypsinogen activation peptide.


RESULTS
The median maximum PROP values were significantly elevated 48 h after symptom onset in patients with severe acute pancreatitis [1.52 (95% CI 0.8-2.9) nmol/l] as compared with patients with mild acute pancreatitis [0.72 (0.55-1) nmol/l, p = 0.002] and controls [0.49 (0.22-1.2) nmol/l, p = 0.001], but not before or after this time point. The best cutoff point for urinary PROP to predict overall severity was >1 nmol/l < or =48 h after symptom onset (negative predictive value = 88%), but the PROP levels failed to predict the development of multi-organ dysfunction.


CONCLUSIONS
Activation of sPLA(2)-I is associated with the early pathogenesis of acute pancreatitis, but not in the development of distant organ damage. This observation raises questions as to the theory of generalized zymogen activation being a principle mechanism involved in the pathogenesis of distant organ damage in acute pancreatitis.
Mayer
Jens M
JM
Department of General Surgery, University Hospital of Ulm, Germany.
Raraty
Michael
M
Slavin
John
J
Kemppainen
Esko
E
Fitzpatrick
John
J
Hietaranta
Antti
A
Puolakkainen
Pauli
P
Beger
Hans G
HG
Neoptolemos
John P
JP
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004792:Enzyme Precursors / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000150:complications; D009842:Oligopeptides / Q000652:urine; D010195:Pancreatitis / Q000150:complications / Q000503:physiopathology*; D010741:Phospholipases A / Q000652:urine*; D054467:Phospholipases A2; D011379:Prognosis; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000150:complications; D012720:Severity of Illness Index
D004792:Enzyme Precursors; D009842:Oligopeptides; C080396:trypsinogen activation peptide; D010741:Phospholipases A; D054467:Phospholipases A2; C085333:prophospholipase A2