Traumatic pancreatitis

Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation.Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained.     

Acute pancreatitis

Pain, and nausea and vomiting are the two cardinal symptoms of acute pancreatitis. There are variations in the combinations of symptoms that appear in patients who have acute pancreatitis, but in most cases the combination fits one or another of five classifications. Blood amylase and urinary diastase determinations are valuable aids in the diagnosis of acute pancreatitis. These findings must be correlated with the stage of the disease. As the disease may be treated successfully (by means outlined) without surgical intervention, clinical diagnosis is important. Cholecystograms after an attack of acute pancreatitis, although advisable, should not be made too soon after subsidence, because of the danger of exacerbation.     

Cell death in pancreatitis: caspases protect from necrotizing pancreatitis

Mechanisms of cell death in pancreatitis remain unknown. Parenchymal necrosis is a major complication of pancreatitis; also, the severity of experimental pancreatitis correlates directly with necrosis and inversely with apoptosis. Thus, shifting death responses from necrosis to apoptosis may have a therapeutic value. To determine cell death pathways in pancreatitis and the possibility of necrosis/apoptosis switch, we utilized the differences between the rat model of cerulein pancreatitis, with relatively high apoptosis and low necrosis, and the mouse model, with little apoptosis and high necrosis. We found that caspases were greatly activated during cerulein pancreatitis in the rat but not mouse. Endogenous caspase inhibitor X-linked inhibitor of apoptosis protein (XIAP) underwent complete degradation in the rat but remained intact in the mouse model. Furthermore, XIAP inhibition with embelin triggered caspase activation in the mouse model, implicating XIAP in caspase blockade in pancreatitis. Caspase inhibitors decreased apoptosis and markedly stimulated necrosis in the rat model, worsening pancreatitis parameters. Conversely, caspase induction with embelin stimulated apoptosis and decreased necrosis in mouse model. Thus, caspases not only mediate apoptosis but also protect from necrosis in pancreatitis. One protective mechanism is through degradation of receptor-interacting protein (RIP), a key mediator of "programmed" necrosis. We found that RIP was cleaved (i.e. inactivated) in the rat but not the mouse model. Caspase inhibition restored RIP levels; conversely, caspase induction with embelin triggered RIP cleavage. Our results indicate key roles for caspases, XIAP, and RIP in the regulation of cell death in pancreatitis. Manipulating these signals to change the pattern of death responses presents a therapeutic strategy for treatment of pancreatitis.     

Mitochondrial injury in pancreatitis

Pancreatitis is an increasingly common disease that carries a significant mortality and which lacks specific therapy. Pathological calcium signalling is an important contributor to the initiating cell injury, caused by or acting through mitochondrial inhibition. A principal effect of disordered cell signalling and impaired mitochondrial function is cell death, either by apoptosis that is primarily protective, or by necrosis that is deleterious, both locally and systemically. Mitochondrial calcium overload is particularly important in necrotic injury, which may include damage mediated by the mitochondrial permeability transition pore. The role of reactive oxygen species remains controversial. Present understanding of the part played by disordered pancreatic acinar calcium signalling and mitochondrial inhibition offers several new potential therapeutic targets.     

Pancreatic polypeptide in pancreatitis

Pancreatitis is a disease with increasing incidence which can be divided into an acute and a chronic form. In both acute and chronic pancreatitis, changes in plasma concentration of pancreatic polypeptide (PP) and its regulation have been reported. In daily clinical work a serologic test for the precise diagnosis and staging of acute and chronic pancreatitis is still desirable. Therefore, many studies have investigated plasma concentrations of PP in acute and chronic pancreatitis as a diagnostic marker and as a therapeutic option to treat pancreatogenic diabetes mellitus. Although the study results are presently inconclusive and potentially contradictory, the findings are nevertheless encouraging, and indicate that PP might have a role in diagnosis, grading and estimation of the prognosis of pancreatitis. Further data and prospective controlled studies are needed to judge whether PP is of clinical value for diagnosing, staging and predicting long-term outcome in acute and chronic pancreatitis.     

Drinking and driving pancreatitis

Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol.