Pathological trypsinogen activation has long been considered the hallmark of acute pancreatitis (AP) . Following an initial insult, such as ductal disruption or obstruction, cathepsin B activates trypsinogen to trypsin within the acinar cell. Trypsin then activates other pancreatic proenzymes, leading to autodigestion, further enzyme activation, and release of active proteases. Lysosomal hydrolases co-localize with pancreatic proenzymes within the acinar cell. Pancreastasis (similar in concept to cholestasis) with continued synthesis of enzymes occurs. Lecithin is activated by phospholipase A2 into the toxic lysolecithin. Prophospholipase is unstable and can be activated by minute quantities of trypsin [7, 8]. This leads to cell death and AP . After the insult, cytokines and other proinflammatory mediators are released. Most animal models support this mechanism.

The healthy pancreas is protected from autodigestion by pancreatic proteases that are synthesized as inactive proenzymes, which are then segregated into secretory zymogen granules at pH 6.2, by low calcium concentration, which minimizes trypsin activity. Protease inhibitors are present both in the cytoplasm and zymogen granules [5–8]. Enzymes are secreted directly into the ducts lessening exposure of the cytoplasmic contents.

Recently, animal models of AP without associated pathological intracellular trypsinogen activation, as required by the classic theory, have been developed. In these models, intracellular activation of trypsinogen to trypsin plays a role only in early acinar injury. For example, a knockout mouse model of pancreatitis in mice lacking the trypsinogen 7 gene has been developed [8, 9]. These mice develop pancreatitis even though they are unable to activate trypsinogen. In this model, nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) is activated early in the course of and appears to be the primary driver of the proinflammatory response. Even more recent studies have shown perturbation of mitochondrial permeability and function early in the evolution of experimental pancreatitis [10]. In this model, alcohol causes a collapse of the electrical gradient across the mitochondrial permeability transition pore leading to depletion of adenosine triphosphate (ATP) and acinar cell necrosis.

Whatever the true interpretation may be, time-course analysis shows that a burst of electron transfer reactions is associated with the disease initiation [11]. For example, in the experimental model of mild AP produced by excessive stimulation with caerulein, a cholecystokinin (CCK) analog, the spark from reactive oxygen species can be seen by chemiluminescence within 5 min. Simultaneously, there is a huge increase in stress-activated protein kinase. Within 10 min, there is an increase in amylase in the venous outflow of the pancreas. Similarly in endoscopic retrograde cholangiopancreatography (ERCP)-induced AP, analysis of peripheral blood by electron spin resonance spectroscopy identified the burst of reactive oxygen species by the end of the clinical procedure, followed by steep increases in serum levels of amylase, lipase, and trypsinogen.

Histopathologically, interstitial edema appears early. Later, as the episode of pancreatitis progresses, localized and confluent necrosis, blood vessel disruption leading to hemorrhage, and an inflammatory response in the peritoneum can develop. In mild pancreatitis, there is interstitial edema and an inflammatory infiltrate is found. There is no organ dysfunction. In severe pancreatitis, the inflammation is extensive and parenchymal necrosis is present. Multiorgan failure accompanies the inflammation. Following an episode of AP, all histological abnormalities resolve. The factor(s) that determine the severity of an episode of AP are unknown.

In adults, AP is one of the most common diseases of the gastrointestinal tract and remains a serious disease. In the USA, AP is the most common gastroenterology discharge diagnosis accounting for more than 553,000 hospital discharges, 881,000 ambulatory visits, and 3413 deaths a year [12, 13]. The incidence of AP varies between 4.9 and 73.4 cases per 100,000 worldwide.

In pediatrics, it is estimated that 2–13 new cases per 100,000 children occur annually. AP is ranked 14th among causes of death from gastrointestinal and liver diseases in adults [14]. In the last 15 years, studies have shown an increase in the annual incidence of AP . The case fatality rate for AP has decreased over time while the overall population mortality rate has remained unchanged. In adults, mortality from AP is approximately 3 % for interstitial pancreatitis and 15 % for necrotizing pancreatitis [13, 14]. Almost 20 % of children with AP develop a complication, and the mortality rate is approximately 4 % despite significant advances in the treatment of this disease [15, 16] .

In adults, 85 % of episodes of AP are due to alcohol and cholelithiasis. In contrast in children, the most common etiologies of AP are as follows: blunt abdominal injuries, biliary stones or microlithiasis (sludging), drug toxicity, and multisystem diseases such as the hemolytic uremic syndrome and inflammatory bowel disease [17–23]. Other cases follow solid organ and stem cell transplantation or are due to infections, anatomic anomalies, metabolic disorders, and mutations in susceptibility genes. Only 10–20 % of cases are now considered idiopathic. There is a widely used pneumonic, Tigar-O, which stands for toxic-metabolic, idiopathic, genetic, autoimmune, recurrent and severe AP and obstructive .

Criteria for the diagnosis of pancreatitis in children have recently been defined by an expert multinational committee as two of three of the following: abdominal pain, serum amylase, and/or lipase activity at least three times greater than the upper limit of normal and imaging findings characteristic of or compatible withAP [30]. These criteria are similar to those used in adults .

Serum lipase is now considered the test of choice for AP, as it is more specific than amylase for acute inflammatory pancreatic disease and should be determined when pancreatitis is suspected. Serum lipase remains elevated longer than amylase after disease presentation. The serum lipase rises by 4–8 h, peaks at 24–48 h, and remains elevated 8–14 days, longer than serum amylase. Serum lipase may also be elevated in non-pancreatic diseases (Table 33.7). Diabetic patients appear to have a higher median lipase compared with nondiabetic patients so an upper limit of normal greater than three to five times may be needed in diabetic patients [13, 31]. The clinical condition of the patient must be considered when evaluating amylase and lipase elevations. However, serum lipase ≥ 7 times the upper limit of normal within 24 h of presentation may be a simple clinical predictor of severe AP in children [15].