acute pancreatitis acute pancreatitis acute pancreatitis (ap) is a sudden inflammation of the pancreas. causes in order of frequency include: 1) a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; 2) heavy alcohol use; 3) systemic disease; 4) trauma; 5) and, in minors, mumps. acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis. acute pancreatitisother namesacute pancreatic necrosisstill from 3d medical animation of acute pancreatitisspecialtygastroenterology, general surgery mild cases are usually successfully treated with conservative measures: hospitalization, pain control, nothing by mouth, intravenous nutritional support, and intravenous fluid rehydration. severe cases often require admission to an intensive care unit to monitor and manage complications of the disease. complications are associated with a high mortality, even with optimal management. in this condition pancreas start secreting active enzymes like trypsin, chymotrypsin, carboxypeptidase instead of their inactive forms. since it cause several damages to ducts related to pancreas. signs and symptoms common severe epigastric pain (upper abdominal pain) radiating to the back in 50% of cases nausea vomiting loss of appetite fever chills (shivering) hemodynamic instability, including shock tachycardia (rapid heartbeat) respiratory distress peritonitis hiccup although these are common symptoms, frequently they are not all present; and epigastric pain may be the only symptom. uncommon the following are associated with severe disease: grey-turner's sign (hemorrhagic discoloration of the flanks) cullen's sign (hemorrhagic discoloration of the umbilicus) pleural effusions (fluid in the bases of the pleural cavity) grünwald sign (appearance of ecchymosis, large bruise, around the umbilicus due to local toxic lesion of the vessels) körte's sign (pain or resistance in the zone where the head of pancreas is located (in epigastrium, 6–7 cm above the umbilicus)) kamenchik's sign (pain with pressure under the xiphoid process) mayo-robson's sign (pain while pressing at the top of the angle lateral to the erector spinae muscles and below the left 12th rib (left costovertebral angle (cva)) mayo-robson's point – a point on border of inner 2/3 with the external 1/3 of the line that represents the bisection of the left upper abdominal quadrant, where tenderness on pressure exists in disease of the pancreas. at this point the tail of pancreas is projected on the abdominal wall. complications locoregional complications include pancreatic pseudocyst (most common, occurring in up to 25% of all cases, typically after 4–6 weeks) and phlegmon/abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis. systemic complications include acute respiratory distress syndrome (ards), multiple organ dysfunction syndrome, disseminated intravascular coagulation (dic), hypocalcemia (from fat saponification), hyperglycemia and insulin dependent diabetes mellitus (from pancreatic insulin-producing beta cell damage), malabsorption due to exocrine failure metabolic hypocalcemia, hyperglycemia, hypertriglyceridemia respiratory hypoxemia, atelectasis, effusion, pneumonitis, acute respiratory distress syndrome renal renal artery or vein thrombosis kidney failure circulatory arrhythmias hypovolemia and shock myocardial infarction pericardial effusion vascular thrombosis gastrointestinal gastrointestinal hemorrhage from stress ulceration gastric varices (secondary to splenic vein thrombosis) gastrointestinal obstruction hepatobiliary jaundice portal vein thrombosis neurologic psychosis or encephalopathy (confusion, delusion and coma) cerebral embolism blindness (angiopathic retinopathy with hemorrhage) hematologic anemia disseminated intravascular coagulation leucocytosis dermatologic painful subcutaneous fat necrosis miscellaneous subcutaneous fat necrosis arthalgia causes most common biliary pancreatitis due to gallstones or constriction of ampulla of vater in 40% of cases alcohol in 30% of cases idiopathic in 15-25% of cases metabolic disorders: hereditary pancreatitis, hypercalcemia, elevated triglycerides, malnutrition post-endoscopic retrograde cholangiopancreatography abdominal trauma penetrating ulcers carcinoma of the head of pancreas, and other cancer drugs: diuretics (e.g., thiazides, furosemide), gliptins (e.g., vildagliptin, sitagliptin, saxagliptin, linagliptin), tetracycline, sulfonamides, estrogens, azathioprine and mercaptopurine, pentamidine, salicylates, steroids, sodium valproate infections: mumps, viral hepatitis, coxsackie b virus, cytomegalovirus, mycoplasma pneumoniae, ascaris structural abnormalities: choledochocele, pancreas divisum radiotherapy autoimmune pancreatitis severe hypertriglyceridemia less common scorpion venom chinese liver fluke ischemia from bypass surgery heart valve surgery fat necrosis pregnancy infections other than mumps, including varicella zoster hyperparathyroidism valproic acid cystic fibrosis anorexia or bulimia codeine phosphate reaction pathology anatomy of the pancreas pathogenesis acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. this occurs through inappropriate activation of inactive enzyme precursors called zymogens (or proenzymes) inside the pancreas, most notably trypsinogen. normally, trypsinogen is converted to its active form (trypsin) in the first part of the small intestine (duodenum), where the enzyme assists in the digestion of proteins. during an episode of acute pancreatitis, trypsinogen comes into contact with lysosomal enzymes (specifically cathepsin), which activate trypsinogen to trypsin. the active form trypsin then leads to further activation of other molecules of trypsinogen. the activation of these digestive enzymes lead to inflammation, edema, vascular injury, and even cellular death. the death of pancreatic cells occurs via two main mechanisms: necrosis, which is less organized and more damaging, or apoptosis, which is more controlled. the balance between these two mechanisms of cellular death is mediated by caspases which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing atp depletion through inhibiting polyadp-ribose polymerase, and by inhibiting the inhibitors of apoptosis (iaps). if, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate. pathophysiology the two types of acute pancreatitis are mild and severe, which are defined based on whether the predominant response to cell injury is inflammation (mild) or necrosis (severe). in mild pancreatitis, there is inflammation and edema of the pancreas. in severe pancreatitis, there is necrosis of the pancreas, and nearby organs may become injured. as part of the initial injury there is an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily tnf-alpha and il-1. a hallmark of acute pancreatitis is a manifestation of the inflammatory response, namely the recruitment of neutrophils to the pancreas. the inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage. histopathology the acute pancreatitis (acute hemorrhagic pancreatic necrosis) is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessel necrosis (hemorrhage). these are produced by intrapancreatic activation of pancreatic enzymes. lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces as well as vessel damage. necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. it is possible to find calcium precipitates (hematoxylinophilic). digestion of vascular walls results in thrombosis and hemorrhage. inflammatory infiltrate is rich in neutrophils. due to the pancreas lacking a capsule, the inflammation and necrosis can extend to include fascial layers in the immediate vicinity of the pancreas. diagnosis acute pancreatitis is diagnosed using clinical history and physical examination, based on the presence of at least 2 of 3 criteria: abdominal pain, elevated serum lipase or amylase, and abdominal imaging findings consistent with acute pancreatitis. additional blood studies are used to identify organ failure, offer prognostic information, and determine if fluid resuscitation is adequate and whether endoscopic retrograde cholangiopancreatography is necessary. blood investigations – complete blood count, kidney function tests, liver function, serum calcium, serum amylase and lipase imaging – a triple phase abdominal ct and abdominal ultrasound are together considered the gold standard for the evaluation of acute pancreatitis. other modalities including the abdominal x-ray lack sensitivity and are not recommended. an important caveat is that imaging during the first 12 hours may be falsely reassuring as the inflammatory and necrotic process usually requires 48 hours to fully manifest. differential diagnosis the differential diagnosis includes: perforated peptic ulcer biliary colic acute cholecystitis pneumonia pleuritic pain myocardial infarction biochemical elevated serum amylase and lipase levels, in combination with severe abdominal pain, often trigger the initial diagnosis of acute pancreatitis. however, they have no role in assessing disease severity. serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14 days after treatment. serum amylase may be normal (in 10% of cases) for cases of acute or chronic pancreatitis (depleted acinar cell mass) and hypertriglyceridemia. reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase), bowel obstruction, infarction, cholecystitis, and a perforated ulcer. if the lipase level is about 2.5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol. decreased serum calcium glycosuria regarding selection on these tests, two practice guidelines state: "it is usually not necessary to measure both serum amylase and lipase. serum lipase may be preferable because it remains normal in some nonpancreatic conditions that increase serum amylase including macroamylasemia, parotitis, and some carcinomas. in general, serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis" "although amylase is widely available and provides acceptable accuracy of diagnosis, where lipase is available it is preferred for the diagnosis of acute pancreatitis (recommendation grade a)" most, but not all individual studies support the superiority of the lipase. in one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase. another study found that the amylase could add diagnostic value to the lipase, but only if the results of the two tests were combined with a discriminant function equation. while often quoted lipase levels of 3 or more times the upper-limit of normal is diagnostic of pancreatitis, there are also other differential diagnosis to be considered relating to this rise. computed tomography axial ct in a patient with acute exudative pancreatitis showing extensive fluid collections surrounding the pancreas. regarding the need for computed tomography, practice guidelines state: ct is an important common initial assessment tool for acute pancreatitis. imaging is indicated during the initial presentation if: the diagnosis of acute pancreatitis is uncertain there is abdominal distension and tenderness, fever >102 f (38,9 c), or leukocytosis there is a ranson score > 3 or apache score > 8 there is no improvement after 72 hours of conservative medical therapy there has been an acute change in status: fever, pain, or shock ct is recommended as a delayed assessment tool in the following situations: acute change in status to determine therapeutic response after surgery or interventional radiologic procedure before discharge in patients with severe acute pancreatitis abdominal ct should not be performed before the first 12 hours of onset of symptoms as early ct (<12 hours) may result in equivocal or normal findings. ct findings can be classified into the following categories for easy recall: intrapancreatic – diffuse or segmental enlargement, edema, gas bubbles, pancreatic pseudocysts and phlegmons/abscesses (which present 4 to 6 wks after initial onset) peripancreatic / extrapancreatic – irregular pancreatic outline, obliterated peripancreatic fat, retroperitoneal edema, fluid in the lessar sac, fluid in the left anterior pararenal space locoregional – gerota's fascia sign (thickening of inflamed gerota's fascia, which becomes visible), pancreatic ascites, pleural effusion (seen on basal cuts of the pleural cavity), adynamic ileus, etc. the principal value of ct imaging to the treating clinician is the capacity to identify devitalised areas of the pancreas which have become necrotic due to ischaemia. pancreatic necrosis can be reliably identified by intravenous contrast-enhanced ct imaging, and is of value if infection occurs and surgical or percutaneous debridement is indicated. magnetic resonance imaging while computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis, magnetic resonance imaging (mri) has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris. additional utility of mri includes its indication for imaging of patients with an allergy to ct's contrast material, and an overall greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis. another advantage of mri is its utilization of magnetic resonance cholangiopancreatography (mrcp) sequences. mrcp provides useful information regarding the etiology of acute pancreatitis, i.e., the presence of tiny biliary stones (choledocholithiasis or cholelithiasis) and duct anomalies. clinical trials indicate that mrcp can be as effective a diagnostic tool for acute pancreatitis with biliary etiology as endoscopic retrograde cholangiopancreatography, but with the benefits of being less invasive and 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