trypsinogen and Cholelithiasis

The diagnosis of acute pancreatitis depends on a combination of clinical assessment and laboratory testing. Although the serum amylase is the cornerstone laboratory test used in establishing the diagnosis of acute pancreatitis, there are limitations in the sensitivity and specificity that may be important for the clinician to recognize. The serum lipase level may be especially useful in patients with alcohol-induced acute pancreatitis. A new urinary test strip that uses trypsinogen-2 may have a role in establishing the diagnosis of acute pancreatitis. In addition, several new laboratory tests and new interpretations of old laboratory tests may assist in establishing the etiology and severity of acute pancreatitis. This review summarizes important aspects of standard laboratory tests and novel laboratory approaches in establishing the diagnosis, etiology, and severity of acute pancreatitis.

Topics: Acute Disease; Alanine Transaminase; Amylases; Cholelithiasis; Humans; Lipase; Pancreatitis; Pancreatitis, Alcoholic; Sensitivity and Specificity; Severity of Illness Index; Trypsin; Trypsinogen

Topics: Acute Disease; Alcoholism; Apoptosis; Cathepsin B; Chemokines; Cholelithiasis; Cytokines; Humans; Necrosis; Oxidative Stress; Pancreatitis; Regeneration; Risk Factors; Trypsin; Trypsinogen

Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.

Topics: Acute Disease; Autoimmune Diseases; Child; Cholelithiasis; Female; Humans; Hypercalcemia; Male; Pancreas; Pancreatic Neoplasms; Pancreatitis; Pancreatitis, Alcoholic; Pregnancy; Reperfusion Injury; Trypsinogen

Topics: Acute Disease; Alcoholism; alpha 1-Antitrypsin; alpha-Macroglobulins; Cholelithiasis; Critical Care; Enzyme Activation; Humans; Metabolic Diseases; Pancreatitis; Parasympatholytics; Peritoneal Dialysis; Trypsinogen

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.

Topics: Acute Disease; Amylases; Animals; Body Water; Cathepsin B; Ceruletide; Cholecystitis; Cholelithiasis; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsin; Trypsinogen

Two major proteins have been identified in sodium citrate extracts of bovine pancreatic stones from 15 glands with lithiasis. They were found to have a molecular weight of about 24 000 and were further characterized by a variety of methods, including polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, isoelectric focusing, two-dimensional electrophoresis, immunodiffusion, immunoelectrophoresis and determination of N-terminal residues. These two immunologically and electrophoretically different proteins were definitely shown to be immunoreactive forms of anionic and cationic trypsinogens, which are normal components of pancreatic juice. However, in contrast with both secretory trypsinogens, the stone proteins displayed an important charge heterogeneity under isoelectric-focusing conditions. A possible role for both secretory trypsinogens in pancreatic lithogenesis is suggested by the reproducibility of the data. Finally, two minor proteins with a lower molecular weight (about 11 000--13 000) have also been found to be present in all extracts, but have not yet been identified.

Topics: Animals; Cattle; Cholelithiasis; Electrophoresis, Polyacrylamide Gel; Immunoelectrophoresis; Isoelectric Point; Molecular Weight; Pancreatic Juice; Trypsinogen

Topics: Amylases; Animals; Cholecystitis; Cholelithiasis; Dogs; Female; Lipase; Male; Phospholipases; Trypsin; Trypsinogen