Harrison’s Manual of Medicine
The differentiation between acute and chronic pancreatitis is based on clinical criteria. In acute pancreatitis, there is restoration of normal pancreatic function; in the chronic form, there is permanent loss of function and pain may predominate. There are two pathologic types of acute pancreatitis: edematous and necrotizing.
ETIOLOGY Most common causes in the U.S. are alcohol and cholelithiasis. Others include abdominal trauma; postoperative or postendoscopic retrograde cholangiopancreatography (ERCP); metabolic (e.g., hypertriglyceridemia, hypercalcemia, renal failure); hereditary pancreatitis; infection (e.g., mumps, viral hepatitis, coxsackievirus, ascariasis, Mycoplasma); opportunistic infections (CMV, Cryptococcus, Candida, TB); medications (e.g., azathioprine, sulfonamides, thiazides, furosemide, estrogens, tetracycline, valproic acid, pentamidine, dideoxyinosine); connective tissue diseases/vasculitis (e.g., lupus, necrotizing angiitis, thrombotic thrombocytopenic purpura); penetrating peptic ulcer; obstruction of the ampulla of Vater (e.g., regional enteritis); pancreas divisum.
CLINICAL FEATURES Can vary from mild abdominal pain to shock. Common symptoms: (1) steady, boring midepigastric pain radiating to the back that is frequently increased in the supine position; (2) nausea, vomiting.
Physical exam: (1) low-grade fever, tachycardia, hypotension; (2) erythematous skin nodules due to subcutaneous fat necrosis; (3) basilar rales, pleural effusion (often on the left); (4) abdominal tenderness and rigidity, diminished bowel sounds, palpable upper abdominal mass; (5) Cullen’s sign: blue discoloration in the periumbilical area due to hemoperitoneum; (6) Turner’s sign: blue-red-purple or green-brown discoloration of the flanks due to tissue catabolism of hemoglobin.
1. Serum amylase: Large elevations (>3 × normal) virtually assure the diagnosis if salivary gland disease and intestinal perforation/infarction are excluded. However, normal serum amylase does not exclude the diagnosis of acute pancreatitis, and the degree of elevation does not predict severity of pancreatitis. Amylase levels typically return to normal in 48–72 h.
2. Urinary amylase–creatinine clearance ratio may be helpful in distinguishing between pancreatitis and other causes of hyperamylasemia (e.g., macroamylasemia) but is invalid in the presence of renal failure. Simultaneous serum and urine amylase values are used. Cam/CCr = (amurine × Crserum) / (amserum × Crurine). Normal value is <4%.
3. Serum lipase level is more specific for pancreatic disease and remains elevated for 7–14 d.
4. Other tests: Hypocalcemia occurs in ~25% of pts. Leukocytosis (15,000–20,000/µL) occurs frequently. Hypertriglyceridemia occurs in 15% of cases and can cause a spuriously normal serum amylase level. Hyperglycemia is common. Serum bilirubin, alkaline phosphatase, and aspartame aminotransferase can be transiently elevated. Hypoalbuminemia and marked elevations of serum lactic dehydrogenase (LDH) are associated with an increased mortality rate. Hypoxemia is present in 25% of pts. Arterial pH < 7.32 may spuriously elevate serum amylase. The ECG may demonstrate ST-segment and T-wave abnormalities.
1. Abdominal radiographs are abnormal in 50% of pts but are not specific for pancreatitis. Common findings include total or partial ileus (“sentinel loop”) and spasm of transverse colon. Useful for excluding diagnoses such as intestinal perforation.
2. Ultrasound often fails to visualize the pancreas because of overlying intestinal gas but may detect gallstones or edema or enlargement of the pancreas.
3. CT can confirm diagnosis of pancreatitis (edematous pancreas) and is useful for predicting and identifying late complications. Contrast-enhanced dynamic CT is indicated for clinical deterioration, ³3 Ransom/Imrie signs (Table 152-1), other features of serious illness.
Table 152-1 Factors That Adversely Affect Survival in Acute Pancreatitis
DIFFERENTIAL DIAGNOSIS Intestinal perforation (especially peptic ulcer), cholecystitis, acute intestinal obstruction, mesenteric ischemia, renal colic, myocardial ischemia, aortic dissection, connective tissue disorders, pneumonia, and diabetic ketoacidosis.
Most (90%) cases subside over a period of 3–7 d. Conventional measures: (1) analgesics, such as meperidine; (2) IV fluids and colloids; (3) no oral alimentation; (4) treatment of hypocalcemia, if symptomatic; (5) antibiotics if there is established infection or prophylactically in severe acute pancreatitis—carbapenem agents cover a broad range of organisms and penetrate well into pancreatic tissue. Not effective: cimetidine (or related agents), nasogastric suction, glucagon, peritoneal lavage, and anticholinergic medications. Precipitating factors (alcohol, medications) must be eliminated. In mild or moderate pancreatitis, a clear liquid diet can usually be started after 3–6 d. Pts with severe gallstone-induced pancreatitis often benefit from early (<3 d) papillotomy.
COMPLICATIONS It is important to identify pts who are at risk of poor outcome. Increased mortality has been observed with the presence of ³3 Ransom/Imrie prognostic criteria at admission or within 48 h (Table 152-1). Fulminant pancreatitis requires aggressive fluid support and meticulous management. Mortality is largely due to infection.
Systemic Shock, GI bleeding, common duct obstruction, ileus, splenic infarction or rupture, DIC, subcutaneous fat necrosis, ARDS, pleural effusion, acute renal failure, sudden blindness.
1. Sterile or infected pancreatic necrosis—necrosis may become secondarily infected in 40–60% of pts; typically within 1–2 weeks after the onset of pancreatitis. Most frequent organisms: gram-negative bacteria of alimentary origin, but intraabdominal Candida infection increasing in frequency. Necrosis can be visualized by contrast-enhanced dynamic CT with infection diagnosed by CT-guided needle aspiration. Laparotomy with removal of necrotic material and adequate drainage should be considered for pts with sterile acute necrotic pancreatitis if pt continues to deteriorate despite conventional therapy. Infected pancreatic necrosis requires aggressive surgical debridement and antibiotics.
2. Pancreatic pseudocysts develop over 1–4 weeks in 15% of pts. Abdominal pain is the usual complaint, and a tender upper abdominal mass may be present. Can be detected by abdominal ultrasound or CT. In pts who are stable and uncomplicated, treatment is supportive; if there is no resolution within 6 weeks, consider CT-guided needle aspiration/drainage, surgical drainage, or resection. In pts with an expanding pseudocyst or complicated by hemorrhage, rupture, or abscess, surgery should be performed.
3. Pancreatic abscess—ill defined liquid collection of pus that evolves over 4–6 weeks. Can be treated surgically or in selected cases by percutaneous drainage.
4. Pancreatic ascites and pleural effusions are usually due to disruption of the main pancreatic duct. Treatment involves nasogastric suction and parenteral alimentation for 2–3 weeks. If medical management fails, pancreatography followed by surgery should be performed.
CHRONIC PANCREATITIS Chronic pancreatitis may occur as recurrent episodes of acute inflammation superimposed upon a previously injured pancreas or as chronic damage with pain and malabsorption.
ETIOLOGY Chronic alcoholism most frequent cause of pancreatic exocrine insufficiency in U.S. adults; also hypertriglyceridemia, hypercalcemia, hereditary pancreatitis, hemochromatosis. Cystic fibrosis most frequent cause in children. In 25% of adults, etiology is unknown.
SYMPTOMS AND SIGNS Pain is cardinal symptom. Weight loss, steatorrhea, and other signs and symptoms of malabsorption common. Physical exam often unremarkable.
LABORATORY No specific laboratory test for chronic pancreatitis. Serum amylase and lipase levels are often normal. Serum bilirubin and alkaline phosphatase may be elevated. Steatorrhea (fecal fat concentration ³9.5%) late in the course. The bentiromide test, a simple, effective test of pancreatic exocrine function, may be helpful. D-Xylose urinary excretion test is usually normal. Impaired glucose tolerance is present in >50% of pts. Secretin stimulation test is a relatively sensitive test for pancreatic exocrine deficiency.
IMAGING Plain films of the abdomen reveal pancreatic calcifications in 30–60%. Ultrasound and CT scans may show dilation of the pancreatic duct. ERCP often reveals irregular dilation of the main pancreatic duct and pruning of the branches.
DIFFERENTIAL DIAGNOSIS Important to distinguish from pancreatic carcinoma; may require radiographically guided biopsy.
Aimed at controlling pain and malabsorption. Intermittent attacks treated like acute pancreatitis. Alcohol and large, fatty meals must be avoided. Narcotics for severe pain, but subsequent addiction is common. Pts unable to maintain adequate hydration should be hospitalized, while those with milder symptoms can be managed on an ambulatory basis. Surgery may control pain if there is a ductal stricture. Subtotal pancreatectomy may also control pain but at the cost of exocrine insufficiency and diabetes. Malabsorption is managed with a low-fat diet and pancreatic enzyme replacement (8 conventional tablets or 3 enteric-coated tablets with meals). Because pancreatic enzymes are inactivated by acid, agents that reduce acid production (e.g., omeprazole or sodium bicarbonate) may improve their efficacy (but should not be given with enteric- coated preparations). Insulin may be necessary to control serum glucose.
COMPLICATIONS Vitamin B12 malabsorption in 40% of alcohol-induced and all cystic fibrosis cases. Impaired glucose tolerance. Nondiabetic retinopathy due to vitamin A and/or zinc deficiency. GI bleeding, icterus, effusions, subcutaneous fat necrosis, and bone pain occasionally occur. Increased risk for pancreatic carcinoma. Narcotic addiction common.
For a more detailed discussion, see Greenberger NJ, Toskes PP: Acute and Chronic Pancreatitis, Chap. 304, p. 1792;, Toskes PP, Greenberger NJ: Approach to the Patient with Pancreatic Disease, Chap. 303, p. 1788, in HPIM-15.