**2. Clinical features**

Patients withAP present to the emergency room with sudden and severe abdominal pain that usually starts in the epigastric region. In patients with gallstones, the pain spreads to the right upper quadrant and is more sharply limited. In 50% of patients, the pain spreads to the back, and is felt around the entire abdomen, like a belt. Nausea and vomiting may accompany,and in rare cases there may be pain on the left side of the abdomen [2, 46–49].

Physical examination findings can vary, depending on the severity of AP and any accompanying diseases. Initial findings typically include mild or generalized tenderness upon abdominal palpation, distension and diminished bowel sounds. In cases of obstruction due to gallstones, jaundice may be observed, while in severe AP, fever, hypotension, tachycardia, tachypnea and hypoxemia may be observed. In cases of pancreatic necrosis, ecchymotic lesions can be seen in the periumbilical region (Cullen's sign) or on the flanks (Gray Turner's sign) [2, 27, 50, 51].

## **3. Diagnosis**

Diagnosis is established based on the presence of two of three criteria: 1) Presence of clinical findings consistent with AP, 2) serum lipase or amylase levels three times greater than normal, and 3) characteristic findings of AP on imaging [2, 27, 47, 48, 52].

### **3.1 Laboratory**

In AP, enzymes pass from the basolateral membrane to the interstitial area, and then on to the systemic circulation due to the blockade of the secretion ofpancreatic enzymes, while the synthesis of enzymes continues, resulting in increased levels of pancreatic enzymes in the blood.

At the onset of AP, serum amylase starts to increase within 6–12 hours, peaks at 48 hours, and returns to normal within 3–5 days, although no increase in amylase levels will be observed in alcohol-induced pancreatitis and AP due to hypertriglyceridemia. Sensitivity and specificity in diagnosis are 67–83% and 85–98%,

respectively [2, 27, 48, 53, 54]. Elevated amylase levels may also be seen in nonpancreatic diseases, such as renal failure, salivary gland diseases, acute appendicitis, cholecystitis, perforations, intestinal obstructions or intestinal ischemia, and gynecological diseases. For these reasons, amylase alone is not sufficient for a diagnosis of AP [2, 48, 49]. The increase in serum lipase levels in AP is more specific. Following the onset of symptoms, the levels begin to increase within 8–10 hours, peak at 24 hours, return to normal within 8–14 days, with a sensitivity of 82–100% [2, 48, 53, 55], and may increase in alcohol-induced AP and AP due to hypertriglyceridemia. It is useful in delayed patients who present 24 hours after the onset of pain [48, 55, 56]. Aside from amylase-lipase, liver and kidney tests,a complete blood count should also be made in AP, as this will allow the assessment of the patient's clinical condition, the early identification of complications and the detection of organ failure, and will aid in a therapeutic evaluation. An alanine aminotransferase (ALT) liver function test value in excess of 150 U/L indicates gallstones [2, 47, 52]. There are also specific tests for AP that are not routinely used. Among the enzymes with early elevation are trypsinogen-activating peptide, urinary and serum trypsinogen and trypsin, phospholipase, carboxypeptidase, carboxyl ester lipase, colipase and pancreatic isoamylase [57–59], and an increase is also observed in inflammatory mediators such as C-reactive protein (CRP), interleukin IL-6, IL-8, IL-10, tumor necrosis factor (TNF) and PMN elastase. The elevation of inflammatory mediators is usually proportional to the severity of AP. A CRP level above 150 mg/dl within the first 48 hours has been associated with severe AP [60, 61].

### **3.2 Imaging**

Imaging can aid in determining the etiology of AP, or complications due to AP. Abdominal and chest radiographs may reveal appearances of pleural effusion, atelectasis and ileus accompanying AP. Radiographs should be evaluated to rule out other causes of abdominal pain. Abdominal ultrasound should be performed on every patient with suspected AP, and USG can detect findings that support AP, if present, such as gallstones, obstructions in the common bile duct, intraabdominal free fluid and diffuse enlarged and hypoechoic appearance in the pancreas, as well as peripancreatic fluid, necrosis and abscesses. A normal USG cannot exclude AP [2, 27, 47, 48, 52, 62], while Contrast-Enhanced Computed Tomography (CECT) has a sensitivity of 90% in the diagnosis of AP. However, AP is not routinely recommended for diagnosis, since it is mild and uncomplicated in most patients [2, 47, 48, 52], but may be recommended in cases where other causes of acute abdomen cannot be excluded, or for patients who show no improvement within 48–72 hours [48, 63, 64].

Among the patients considered for CECT, MRI is recommended rather that CECT for those with renal failure, pregnant patients and those with allergies to IV contrast agents [48, 63].

Serum triglyceride levels must be examined in patients with normal test results, but with a strong suspicion of AP, in those with pancreatic tumors aged over 40 years, in the presence of genetic factors in patients under the age of 30 and in recurrent AP cases [39, 48].

### **3.3 Differential diagnosis**

Other diseases that may cause abdominal pain should be excluded in a differential diagnosis.In particular, peptic ulcer disease, choledocholithiasis, cholangitis,

biliary obstruction, cholecystitis, perforated viscus, intestinal obstruction, mesenteric ischemia and hepatitis should be considered in differential diagnosis due to their clinical similarities to AP [2, 27].
