Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes include a gallstone impacted in the common bile duct or the pancreatic duct, heavy alcohol use, systemic disease, trauma, elevated calcium levels, hypertriglyceridemia (with triglycerides usually being very elevated, over 1000 mg/dL), certain medications, hereditary causes and, in children, mumps. Acute pancreatitis may be a single event, it may be recurrent, or it may progress to chronic pancreatitis and/or pancreatic failure (the term pancreatic dysfunction includes cases of acute or chronic pancreatitis where the pancreas is measurably damaged, even if it has not failed).
In all cases of acute pancreatitis, early intravenous fluid hydration and early enteral (nutrition delivered to the gut, either by mouth or via a feeding tube) feeding are associated with lower mortality and complications. Mild cases are usually successfully treated with conservative measures such as hospitalization with intravenous fluid infusion, pain control, and early enteral feeding. If a person is not able to tolerate feeding by mouth, feeding via nasogastric or nasojejunal tubes are frequently used which provide nutrition directly to the stomach or intestines respectively.
Severe cases often require admission to an intensive care unit. Severe pancreatitis, which by definition includes organ damage other than the pancreas, has a mortality rate of 20%. The condition is characterized by the pancreas secreting active enzymes such as trypsin, chymotrypsin and carboxypeptidase, instead of their inactive forms, leading to auto-digestion of the pancreas. Calcium helps to convert trypsinogen to the active trypsin, thus elevated calcium (of any cause) is a potential cause of pancreatitis. Damage to the pancreatic ducts can occur as a result of this. Long term complications include type 3c diabetes (pancreatogenic diabetes), in which the pancreas is unable to secrete enough insulin due to structural damage. 35% develop exocrine pancreatic insufficiency in which the pancreas is unable to secrete digestive enzymes due to structural damage, leading to malabsorption.
Signs and symptoms
Common Common symptoms of acute pancreatitis include abdominal pain, nausea, vomiting, and low to moderate grade fever. The abdominal pain is the most common symptom and it is usually described as being in the left upper quadrant, epigastric area or around the umbilicus, with radiation throughout the abdomen, or to the chest or back. The abdominal pain initially may worsen with eating or drinking but may become constant as the disease progresses. Less common symptoms include hiccups, abdominal bloating and indigestion. Although these are common symptoms, frequently they are not all present; and epigastric pain may be the only symptom.
Grey-Turner's sign (hemorrhagic discoloration of the flanks) or Cullen's sign (hemorrhagic discoloration of the umbilicus) are associated with severe disease. However both signs are rare (occurring in less than 1% of cases of acute pancreatitis) and are not specific nor sensitive for diagnosis of acute pancreatitis. Pleural effusions (fluid in the lung cavity) may occur in up to 34% of people with acute pancreatitis and are associated with a poor prognosis. The 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)) is also associated with acute pancreatitis.
Complications Complications of acute pancreatitis may occur. Necrotic pancreatitis occurs when inflammation of the pancreas progresses to cell death. Acute fluid collections may form adjacent to the pancreas or necrotic collections (discrete areas of dead tissue) may also form adjacent to or within the pancreas. These may progress to pancreatic pseudocysts and walled off areas of dead tissue which may persist for longer than 4 weeks. Both can become secondarily infected. Other complications include gastric outlet obstruction, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, blood clot of the splenic vein, superior mesenteric vein and portal veins, duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, or pleural effusion.
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) , and malabsorption due to exocrine failure.
Tobacco use, recurrent episodes of acute pancreatitis, pancreatic tissue death, alcoholic pancreatitis are all risk factors for developing chronic pancreatitis.
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 May occur after instrumentation of the pancreatic duct or its opening to the duodenum (ampula of Vater) in procedures such as an endoscopic ultrasound or endoscopic retrograde cholangiopancreatography (ERCP). The risk after EUS is less than 1% and the risk after ERCP is 5-10%. Abdominal trauma Penetrating ulcers Carcinoma of the head of pancreas, and other cancer Drugs: acetaminophen with or without codeine, amiodarone, azathioprine, carbamazepine, cimetidine, cisplatin, clomiphene, enalapril, estrogen containing products or hormones, furosemide, isoniazid, metronidazole, methyldopa, pravastatin, valproic acid Infections: mumps, viral hepatitis, coxsackie B virus, cytomegalovirus, Mycoplasma pneumoniae, Ascaris Structural abnormalities: pancreas divisum, pancreatic masses or cysts that block the ducts. 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 Cystic fibrosis Anorexia or bulimia
Pathology
Pathogenesis Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. These enzymes are usually stored in an inactive (zymogen) form inside pancreatic acinar cells to prevent self-digestion. In acute pancreatitis, some of these inactive enzyme get activated prematurely, 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: apoptosis, which is physiologically controlled, and necrosis, which is less organized and more damaging. 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 (). 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 findings supporting the diagnosis with imaging and pancreatic enzymes (amylase and lipase). The Revised Atlanta Classification requires two out of three of the following findings for the diagnosis: abdominal pain consistent with pancreatitis, elevated amylase or lipase levels greater than 3 times the upper limit of normal, and imaging consistent with acute pancreatitis. Additional labs may be used to identify organ failure for prognostic purposes or to guide fluid resuscitation rate. If the lipase level is about 2.5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol. Serum lipase is more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis, and is the preferred test in the diagnosis.
Most, but not all individual studies support favor the diagnostic utility of lipase.In support of the superiority of the lipase:
Without support for 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.
Reduced lipase clearance due to kidney disease, gastrointestinal or hepatobiliary cancers, pancreatic enzyme hypersecretion, critical illness including due to neurosurgical causes have been shown to increase serum lipase and may complicate the diagnosis of acute pancreatitis.
Differential diagnosis The differential diagnosis includes:Bailey & Love's/24th/1123 Perforated peptic ulcer Biliary colic Acute cholecystitis Pneumonia Pleuritic pain Myocardial infarction
Computed tomography
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: