If a patient presents with nausea and epigastric pain, the cause may well be acute pancreatitis. Here is how the condition is diagnosed and treated.
Acute pancreatitis is generally managed in a hospital setting, but its symptoms can prompt a visit to the primary-care clinician for initial diagnosis. A pathologic inflammatory condition involving both the pancreas and surrounding tissues, acute pancreatitis results in more than 200,000 hospital admissions annually in the United States.1 For 75%-85% of patients, however, pancreatitis has a mild clinical course that usually resolves in five to seven days.2 Fewer than 1% of those with mild pancreatitis die as a result of the pathology, but the mortality for patients with severe disease approaches 30%.1 The annual cost of acute pancreatitis is estimated to be more than $3 billion.3
Pathophysiology and symptoms
Pancreatitis has a unique pathologic mechanism largely related to the fact that the pancreas serves a dual function as the body’s only combination endocrine/exocrine gland. In addition to the endocrine function involved in the release of insulin and glucagon for maintenance of serum glucose, the organ also manufactures, stores, and excretes enzymes that are ultimately released into the proximal small intestine to aid in the digestion of fats, carbohydrates, and proteins.4 These enzymes include amylase, lipase, and trypsin.
Amylase and lipase digest carbohydrates and fats, respectively, but the most abundant enzyme is trypsin, which is necessary for the digestion of proteins.3 Since the pancreas itself is composed largely of proteins and, to a lesser extent, fats, the enzymes are stored in an inactive form to prevent them from digesting the pancreatic and peripancreatic tissues. Pancreatitis occurs when the digestive enzymes, primarily trypsin, are activated within the pancreas.3 The end result is autodigestion of the pancreas and surrounding tissues.5 The exact mechanism by which this occurs has yet to be fully elucidated.6
Clinically, the patient with acute pancreatitis presents with abrupt onset of burning epigastric pain that often takes on a bandlike pattern across the upper abdomen and bores straight through to the back. Nausea and vomiting occur frequently, as do fever and diaphoresis. Dehydration occurs secondary to fluid losses from diaphoresis, fever, vomiting and lack of intake due to anorexia, as well as third spacing of fluid into peripancreatic tissues from the inflammatory reaction. (Third spacing refers to fluid migration from the first space [the bloodstream] and the second space [cells] into the third space [interstitial fluid between cells], usually as the result of vasodilating chemicals, such as histamine and prostaglandins. The chemicals are released during the inflammatory response.)
On physical exam, the patient with mild pancreatitis may appear only slightly uncomfortable with minimal epigastric discomfort, whereas those with severe disease often appear toxic and febrile and commonly exhibit decreased or absent bowel sounds and severe epigastric tenderness, distension, and guarding. Dehydration may be apparent with dry mucous membranes, tachycardia, hypotension, and orthostatic symptoms. Grey-Turner’s sign and Cullen’s sign—ecchymosis in the flank and periumbilical regions, respectively—result from pancreatic hemorrhage. While they occur in only 1% of pancreatitis cases, the two conditions are associated with a high mortality.6
Diagnosis and causes
To confirm the presence of pancreatitis, serum lipase and amylase determinations should be done. These enzymes will be elevated to a level paralleling the degree of pathology. Lipase is more specific to the pancreas than amylase and will remain elevated after amylase levels return to normal. However, if the pancreatitis is caused by hypertriglyceridemia or alcohol use, the amylase level may be normal.3,7
Elevation of amylase in the presence of normal lipase can indicate other causes of the symptoms, such as intestinal ischemia, ruptured ectopic pregnancy, intestinal perforation, and acute appendicitis. It is important to recall that amylase arises from both the pancreas and salivary glands in about equal proportions. Fractionation of the amylase will ascertain if the amylase is indeed from the pancreas.
A benign condition exists (macroamylasemia) in which the amylase is attached to an abnormal protein, rendering the complex too large to be filtered by the kidneys. In this case, a urine sample will fail to detect amylase. Renal failure will also result in a falsely elevated serum amylase level.
If serum liver enzymes are elevated, a gallstone impacted in the distal end of the common bile duct should be considered as the causative factor.
Leukocytosis is often seen in cases of acute pancreatitis. Additionally, third spacing of fluids in the peripancreatic region can lead to dehydration with elevated blood urea nitrogen and creatinine and hemoconcentration.
Imaging is useful in diagnosing acute pancreatitis, with CT scanning being the most beneficial.6,7 Ultrasound can help identify a gallstone as the cause of pancreatitis, and MRI is useful for exploring the bile and pancreatic ducts for the presence of stones or neoplasm. MRI is a viable alternative for those unable to receive CT contrast because of renal failure or allergies.6,7
The role of alcohol and gallstones
More than 80% of acute pancreatitis cases are caused by alcohol ingestion or gallstones.3 About 10% of chronic alcohol users will develop acute pancreatitis. Chronic alcohol intake is thought to result in increased manufacture of lipase and destructive lysosomes by the pancreas, as well as sensitization of the pancreatic cells to naturally occurring chemicals, such as cholecystokinin, which may activate pancreatic enzymes.8.9
The pathologic mechanism of gallstones is more fully understood. Small stones travel down the bile duct and get lodged at the end, distal to the area where the pancreatic duct attaches—a condition known as choledocholithiasis. The result is obstruction of the flow of pancreatic enzymes, allowing them to accumulate in the organ. Elevated liver enzymes in the setting of acute pancreatitis point toward choledocholithiasis as the cause, with an alanine aminotransferase greater than three times the upper limit of normal having a positive predictive value of 95% for gallstone pancreatitis in the nonalcoholic patient.3,5 Recent studies show that microlithiasis or bile sludge can be identified in up to 75% of patients,7 suggesting that gallstone pancreatitis is even more common than previously thought.
Endoscopic retrograde cholangiopancreatography, a sedating procedure in which a scope is passed through the esophagus into the duodenum and ultimately into the common bile duct, can be performed to extract the stones.
On rare occasions, a medication may be at fault—more than 100 drugs are suspected as possible causes of pancreatitis (Table 1).10 Drug-induced pancreatitis generally develops within a few weeks of starting the medication, but in the case of two agents—didanosine and valproic acid—it may take several months.6 Hypertriglyceridemia is also known to cause acute pancreatitis; triglyceride levels ≥500 mg/dL bring the highest risk, with an average level of 450 at the time of presentation. Other causes are presented in Table 2.6
Management and potential complications
Studies have shown that medications are ineffective in altering the clinical course of acute pancreatitis.5 Management, therefore, is aimed at pain control, hydration, maintaining adequate nutrition, and prevention or control of complications (Table 3).
Acute pancreatitis is associated with a number of complications, some of which may be life-threatening. The more common ones are addressed below.
Hypovolemia: Hypovolemia results from a combination of fever, poor oral intake, vomiting, and third spacing of fluids into the peripancreatic region. The patient may require up to 10 L of fluid daily for the first several days.6 Nausea and vomiting can be controlled with antiemetics and oral feeding status. If an ileus is present, nasogastric-tube placement and suction will help relieve the nausea, vomiting, and distension but will not shorten the duration of the episode.7
Acute respiratory distress syndrome (ARDS): Typically occurring between the second and seventh day of an episode of acute pancreatitis, ARDS is associated with increased mortality.6 Shortness of breath or dyspnea indicates the need for a chest radiograph and an arterial blood gas determination. Treatment involves intubation and ventilation with positive end-expiratory pressure.
Disseminated intravascular coagulation (DIC): Systemic clots within the microcirculation, followed by hemorrhage, signals DIC. It is thought to occur as a result of elevated serum levels of trypsin, which activates prothrombin, resulting in coagulation. Initially, the blood is hypercoagulable, but as the clotting factors are depleted, the patient is at risk for hemorrhage. Clotting factors should be monitored, and the patient should be watched closely for signs of hemorrhage.
Infection/pancreatic necrosis: Localized infection, pancreatic abscess, and sepsis can occur as a result of acute pancreatitis, particularly in the setting of pancreatic necrosis. The risk of mortality increases if the necrotic tissue becomes infected, which generally occurs after one week.
The patient should be monitored for fever, leukocytosis, and failure to improve clinically. Diagnosis is suggested by the presence of retroperitoneal gas bubbles on a CT scan and confirmed by percutaneous CT-guided aspiration of the pancreas with immediate Gram’s stain and culture and sensitivity. Antibiotic therapy is guided by lab analysis. In addition, surgical debridement of necrotic areas and drainage of infected areas is carried out.
Anyone who has spent time at the bedside of someone with acute pancreatitis can attest to the severity of pain that often accompanies the disease. The pain has been described as a chemical burn within the abdomen. Meperidine has long been the therapeutic agent of choice because it is thought to increase the pressure within the sphincter of Oddi less than other narcotics. But some experts recommend alternative narcotics because normeperidine, the main metabolite of meperidine, has been shown to cause seizures.3,11
The physiologic stress of acute pancreatitis results in hypermetabolism, thus creating increased nutritional needs.4 Since the patient generally has no appetite and is dealing with intense pain, nausea, and vomiting, oral feedings are not practical. Options include enteral feedings via gastric or jejunal tubes and hyperalimentation. Current data show that enteral feedings are associated with decreased rates of infection, reduced length of hospital stay, decreased need for surgery, and decreased costs.5 There is evidence that early enteral feeding (within 48 hours of admission) also decreases the severity of acute pancreatitis, as well as the rate of complications.3,7 A dietitian is helpful in calculating caloric and nutritional requirements. Oral feedings can generally be resumed when the patient is pain-free and no longer nauseous, no complications are present, and serum amylase and lipase levels have returned to normal.7
Acute pancreatitis is a unique pathology that is potentially life-threatening. Early diagnosis and recognition of complications is the key to successful management.
Mr. Askey is a certified registered nurse practitioner in the Department of Hepatology/Gastroenterology at the Guthrie Clinic in Sayre, Pa., and a contributing editor to The Clinical Advisor.
1. Carroll JK, Herrick B, Gipson T, Lee SP. Acute pancreatitis: diagnosis, prognosis and treatment. Am Fam Physician. 2007;75:1513-1520.
2. Lugli AK, Carli F, Wykes L. The importance of nutrition status assessment: the case of severe acute pancreatitis. Nutr Rev. 2007;65:329-334.
3. Amerine E. Get optimum outcomes for acute pancreatitis patients. Nurse Pract. 2007;32:44-48.
4. Sargent S. Pathophysiology, diagnosis, and management of acute pancreatitis. Br J Nurs. 2006;15:999-1005.
5. Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med. 2006;354:2142-2150.
6. DiMagno EP, Chari S. Acute pancreatitis. In: Feldman M, Friedman LS, Sleisenger MH, eds. Sleisinger & Fordtran’s Gastrointestinal and Liver Disease. 7th ed. Philadelphia, Pa.: WB Saunders; 2002:913-937.
7. Grendell JH. Acute pancreatitis. In: Friedman SL, McQuaid KR, Grendell JH, eds. Current Diagnosis and Treatment in Gastroenterology. 2nd ed. Norwalk, Conn.: Appleton & Lange; 2003:489-495.
8. Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago, Illinois, USA, November 2002. Pancreas. 2003;27:281-355.
9. Apte MV, Wilson JS, McCaughan GW, et al. Ethanol-induced alterations in messenger RNA levels correlate with the glandular content of pancreatic enzymes. J Lab Clin Med. 1995;125:634-640.
10. Badalov N, Baradarian R, Iswara K, et al. Drug-induced pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol. 2007;5:648-661.
11. Holcomb SS. Stopping the destruction of acute pancreatitis. Nursing. 2007;37:42-47.