Porth's Essentials of Pathophysiology, 4e

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Disorders of Hepatobiliary and Exocrine Pancreas Function

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that cause pancreatic injury, resulting in an intense inflammatory response. The acute inflammatory response itself causes substantial tissue damage and may progress beyond the pancreas to produce a systemic inflammatory response syndrome and multiorgan failure (see Chapter 20). Although a number of factors are associated with the development of acute pancreatitis, in the United States alcohol abuse and gallstones account for 70% to 80% of all cases. 47–51 The precise mechanisms whereby alcohol exerts its action are largely unknown; however, alcohol is known to be a potent stimulator of pancreatic secretions, and it also is known to cause partial obstruc- tion of the sphincter of the pancreatic duct. In the case of biliary tract obstruction due to gallstones, pancreatic duct obstruction or biliary reflux is believed to activate the enzymes in the pancreatic duct system. Acute pan- creatitis also is associated with hyperlipidemia, hyper- calcemia, infections (particularly viral), abdominal and surgical trauma, and drugs such as thiazide diuretics. Clinical Manifestations. The manifestations of acute pancreatitis can range from mild with minimal organ dysfunction to severe and life-threatening. Overall, about 20% of persons with acute pancreatitis have a severe course, and 10% to 30% of those with severe pancreatitis die. 49,50 The diagnosis of acute pancreatits is made by the presence of 2 of the 3 following symptoms: (1) abdominal pain;which is usually severe, located in the epigastric or left upper quadarant and may radiate to the back, chest, or flank areas; (2) serum amylase or lipase greater than 3 times the upper limit of nor- mal; and (3) classic signs on abdominal imaging. Serum lipase may remain elevated slightly longer than amylase. However, the level of elevation of the serum amylase or lipase does not correlate with the severity of the disor- der. The white blood cell count may also be increased, and hyperglycemia and an elevated serum bilirubin level may be present. Abdominal ultrasonography is usually performed to assess for gallstones. Both CT scans and dynamic contrast-enhanced CT of the pancreas are used to detect necrosis and fluid accumulation. Physical examination findings are variable and include fever, tachycardia, hypotension, severe abdominal ten- derness, respiratory distress, and abdominal distention. Recognized markers of severe disease include laboratory values that measure the inflammatory response (e.g., C-reactive protein), scoring systems that assess inflam- mation or organ failure, and findings on imaging studies. Clinical findings such as thirst, poor urine output, pro- gressive tachycardia, tachypnea, hypoxemia, agitation, confusion, a rising hematocrit level, and lack of improve- ment in symptoms within the first 48 hours are warn- ing signs of impending severe disease. Complications include the systemic inflammatory response, acute respi- ratory distress syndrome, acute tubular necrosis, and organ failure. An important disturbance related to acute pancreatitis is the loss of a large volume of fluid into the retroperitoneal and peripancreatic spaces and the abdominal cavity. Signs of hypocalcemia may develop, probably as a result of the precipitation of serum calcium in the areas of fat necrosis.

Treatment. Determination of the cause is important in guiding the immediate management and preventing recurrence. Treatment measures depend on the severity of the disease. Persons who present with persistent or severe pain, vomiting, dehydration, or signs of impend- ing severe acute pancreatitis require hospitalization. Treatment measures are directed at pain relief, “putting the pancreas to rest” by withholding oral foods and flu- ids, and restoration of lost plasma volume. Meperidine rather than morphine usually is given for pain relief because it causes fewer spasms of the sphincter of the pancreatic duct. Gastric suction is instituted to treat dis- tention of the bowel and prevent further stimulation of the secretion of pancreatic enzymes. Intravenous fluids and electrolytes are administered to replace those lost from the circulation and to combat hypotension and shock. Intravenous colloid solutions are given to replace the fluid that has become sequestered in the abdomen and retroperitoneal space. Complications. Sequelae in persons surviving an episode of severe acute pancreatitis include fluid collections and infection. 49 In 40% to 60% of persons with acute necro- tizing pancreatitis, the necrotic debris becomes infected, usually by gram-negative organisms from the alimentary canal, further complicating the condition. 47 Fluid collec- tions with a high level of pancreatic enzymes are usually associated with pancreatic duct disruptions and may even- tually form pseudocysts (a collection of pancreatic fluid enclosed in a layer of inflammatory tissue). A pseudocyst most often is connected to a pancreatic duct, so that it continues to increase in mass. The symptoms depend on its location; for example, jaundice may occur when a cyst develops near the head of the pancreas, close to the com- mon duct. Pseudocysts may resolve or, if they persist, may require surgical intervention. Chronic Pancreatitis Chronic pancreatitis is characterized by progressive and permanent destruction of the exocrine pancreas, fibro- sis, and, in the later stages, destruction of the endocrine pancreas. 3,4,52,53 Most factors that cause acute pancre- atitis can also cause chronic pancreatitis. However, the chief distinction between the two conditions is the irre- versibility of pancreatic function that is characteristic of chronic pancreatitis. By far the most common cause of chronic pancreatitis is long-term alcohol abuse. Less common causes are long-standing obstruction of the pancreatic duct by pseudocysts, calculi, or neoplasms, autoimmune disorders, primary sclerosing cholangitis, inflammatory bowel disease, cystic fibrosis (discussed in Chapter 23), and hereditary pancreatitis, a rare autoso- mal dominant disorder. Chronic pancreatitis is manifested by episodes that are similar, albeit of lesser severity, to those of acute pancreatitis. Patients have persistent, recurring episodes of epigastric and upper left quadrant pain; the attacks often are precipitated by alcohol abuse or overeating. Anorexia, nausea, vomiting, constipation, and flatulence are common. Eventually the disease progresses to the