Diseases of the Gallbladder and Bile Ducts • 65
Therapy
Surgery provides definitive management for most patients with symptomatic gallbladder disease. In patients with cholecystitis, early cholecystectomy (within 24 to 48 hours) is associated with fewer complications and earlier hospital discharge. Compared with open cholecystectomy, laparoscopic cholecystectomy results in shorter hospital stays, less pain, and a more rapid recovery peri- od. When bile duct stones are suspected, intraoperative cholan- giography should be performed at the time of the cholecystec- tomy. If this procedure is not available, postoperative endoscopic retrograde cholangiopancreatography (ERCP) with sphinc- terotomy is an alternative. In patients with severe cholangitis or sepsis, urgent ERCP is essential to remove obstruction and allow biliary drainage.
In most patients with gallstone disease, drug therapy is sup- portive until definitive surgery can be performed. Diclofenac pro- vides pain relief in biliary colic and decreases the risk of develop- ing acute cholecystitis. Nonsteroidal inflammatory drugs are also
helpful in patients with acute cholecystitis with mild to moderate pain; patients with more severe pain may require narcotic analge- sia. Treat patients with acute cholecystitis, especially those with fever, leukocytosis, or complications, with broad-spectrum antibi- otics. Select antimicrobials to cover E. coli, Klebsiella sp., group D
Streptococcus sp., and Enterobacter sp. In critically ill patients,
including those with acute cholangitis, provide coverage for
Bacteroides and Pseudomonas as well. Appropriate antibiotic
regimens include ampicillin, gentamicin and metronidazole; cef- tazidime and metronidazole; or monotherapy with piperacillin/ tazobactam, ampicillin/sulbactam, or ticarcillin/clavulanic acid.
Ursodeoxycholic acid may be used in highly selected patients who are unable or unwilling to undergo surgery. Its use is limited to patients with cholesterol stones, patent biliary tracts, and func- tioning gallbladders.
Follow-Up
Most patients with asymptomatic gallstone disease should be fol- lowed for the development of symptoms. Patients who have had
Table 1. Differential Diagnosis of Acute Cholecystitis
Disease Notes
Acute cholecystitis Epigastric and RUQ pain with Murphy’s sign. Bilirubin <4 mg/dL (unless complicated by choledocholithiasis), AST, ALT may be minimally elevated.
Biliary crystals (microlithiasis, sludge) Typical biliary pain and no gallstones on imaging studies. Diagnosis made by aspiration of gallbladder bile from the duodenum or directly from the gallbladder at ERCP and microscopic examination. May cause pain, cholecystitis, or pancreatitis. Treated with cholecystectomy.
Biliary dyskinesia Typical biliary pain, no gallstones on imaging studies and a gallbladder ejection fraction less than 35%-40% at scintigraphy with cholecystokinin infusion. Symptoms usually relieved with cholecystectomy. This is a controversial diagnosis.
Acute cholangitis Charcot's triad (RUQ pain, fever, jaundice) or Reynold's pentad (Charcot's triad plus shock and mental status changes). Bilirubin >4 mg/dL. AST and ALT levels may exceed 1000 U/L.
Acute pancreatitis Mid-epigastric pain radiating to the back, nausea, vomiting, elevated amylase (>2 x normal) and lipase. Vomiting and hyperamylasemia are generally more pronounced than in acute cholecystitis.
Pyelonephritis (right) Costovertebral angle tenderness, evidence of urinary infection. Urinalysis helps to establish the diagnosis. Peptic ulcer disease RUQ or mid-epigastric pain. Perforated ulcer can mimic acute cholecystitis; free air on upright x-ray.
Acute viral hepatitis Prodromal syndrome, jaundice, AST and ALT levels generally >1000 U/L. Bilirubin level generally >4 mg/dL and usually much higher.
Acute alcoholic hepatitis Recent significant alcohol intake. RUQ pain, fever, jaundice, coagulopathy, leukocytosis, AST level usually two to three times greater than ALT level. Bilirubin level generally >4 mg/dL.
Fitz-Hugh-Curtis syndrome RUQ pain, pelvic adnexal tenderness, leukocytosis. Cervical smear shows gonococci. (gonococcal perihepatitis)
AST = aspartate aminotransferase; ALT = alanine aminotransferase; RUQ = right upper quadrant.
Table 2. Imaging Studies for Acute Cholecystitis
Test Notes
Right upper quadrant US scan 81%-98% sensitive, 70%-98% specific. Sonographic Murphy's sign (showing maximal tenderness directly over the visualized gallbladder) is >90% predictive of acute cholecystitis.
HIDA scan 85%-97% sensitive, 90% specific.
CT scan Expensive; most useful to diagnose complications such as perforation, cholangitis, and gangrenous cholecystitis. MRI scan or MRCP scan 100% for cystic duct obstruction; 69% for gallbladder wall thickening; 93% for cystic duct obstruction; 83% for
gallbladder wall thickening. Extremely expensive; not universally available.
a cholecystectomy should follow up with their surgeons for eval- uation of post-operative complications such as biliary tract injury or infection. This is particularly important for patients who under- go surgery for cholecystitis because they have a higher rate of post- operative complications.
Book Enhancement
Go to www.acponline.org/essentials/gastroenterology-section .html to view an x-ray showing pneumobilia. In MKSAP for
Students 4, assess yourself with items 21-24 in the Gastro-
enterology and Hepatologysection.
Bibliography
Cohen SM, Kim AI, Faust TW.Acute Cholecystitis. http://pier.acponline .org/physicians/diseases/d642. [Date accessed: 2008 Jan 11] In: PIER [online database]. Philadelphia: American College of Physicians; 2008.
DiSario JA.Gallstones. http://pier.acponline.org/physicians/diseases/ d183. [Date accessed: 2008 Jan 11] In: PIER [online database]. Philadelphia: American College of Physicians; 2008.
Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient have acute cholecystitis? JAMA. 2003;289:80-6. [PMID: 12503981] 66 • Gastroenterology and Hepatology
A
cute pancreatitis occurs when the pancreatic enzyme trypsinogen is prematurely activated to trypsin, which in turn activates pancreatic zymogens. The resulting pan- creatic autodigestion leads to an inflammatory response which causes further pancreatic damage. In severe cases, the inflamma- tion may progress to a systemic inflammatory response, resulting in multiorgan system failure and death. The most common eti- ologies of acute pancreatitis in the United States are biliary obstruction and alcohol. Pancreatitis may be caused by medica- tions such as sulfonamides, estrogens, valproic acid, thiazide diuretics, and furosemide. Other etiologies include familial pan- creatitis, hypertriglyceridemia, hypercalcemia, sphincter of Oddi dysfunction, biliary ductal obstruction, vasculitis, trauma, surgery, endoscopic retrograde cholangiopancreatography (ERCP), cystic fibrosis, and penetrating peptic ulcer. As much as 20% of acute pancreatitis is idiopathic. Mild pancreatitis is usually self-limited, but more severe disease causes significant morbidity and mortali- ty. Repeated episodes of acute pancreatitis may result in chronic pancreatitis and pancreatic endocrine and exocrine insufficiency.Prevention
The best preventive measures for pancreatitis involve avoiding known etiologic agents and medical or surgical management of other precipitating factors. Endoscopic retrograde cholan- giopancreatography is a well-established cause of acute pancre- atitis. Use of safer, non-invasive imaging such as magnetic reso- nance cholangiopancreatography (MRCP) decreases the risk of
procedure-related pancreatitis. However, MRCP cannot replace ERCP for therapeutic drainage of the biliary system.
Diagnosis
The most common symptom of acute pancreatitis is abdominal pain (Table 1). The pain may be epigastric or diffuse. It typically peaks in 30 minutes to a few hours, is moderate to severe, constant, and radiates to the back. The pain usually is not positional, although it may improve when sitting up or leaning forward. Nausea and vomiting are common; the pain of acute pancreatitis is usually not alleviated with vomiting.
Abdominal tenderness is common in pancreatitis, but peri- toneal signs should prompt a search for a perforated viscus. Diminished bowel sounds may point to an associated ileus. Some physical findings may suggest a specific etiology; jaundice suggests biliary obstruction, and eruptive xanthomas suggest hypertriglyc- eridemia. History and physical exam should also evaluate the pos- sibility of complications of acute pancreatitis. Nausea, vomiting, and anorexia frequently result in dehydration, hypotension, and tachycardia. High fever suggests infection. Large pseudocysts may be palpable and painful. Grey-Turner or Cullen’s signs (painless ecchymosis of the flanks and periumbilicus, respectively) suggest retroperitoneal bleeding.
The diagnosis of pancreatitis relies heavily on the serum amy- lase and lipase, which are elevated in 75%-90% of patients. Serum lipase is more specific and stays elevated longer than amy- lase. Leukocytosis and electrolyte abnormalities are common.
Chapter 16
Acute Pancreatitis
Nora L. Porter, MD
67
Table 1. Differential Diagnosis of Acute Pancreatitis (AP)
Disease Notes
Perforated viscus (see Chapter 13) Very sudden onset; intraperitoneal air present on x-ray. In AP, the pain gradually increases over 30 minutes to 1 hour. Acute cholecystitis and biliary colic Pain tends to be located in the epigastrium and right upper quadrant and radiates to the right shoulder or shoulder (see Chapter 15) blade. In AP, the pain tends to radiate to the back. Ultrasound shows thickened gallbladder, pericholecystic fluid. Intestinal obstruction (see Chapter 13) Pain is colicky. In AP, the pain is constant. Obstructive pattern is seen on CT or abdominal series.
Mesenteric vascular occlusion The classic triad for mesenteric ischemia is postprandial abdominal pain, weight loss, and abdominal bruit. (see Chapter 13)
Dissecting aortic aneurysm Sudden onset. Pain may radiate to the lower extremity. In AP, the pain gradually increases over 30 minutes to 1 hour (see Chapter 1) and does not radiate to the lower extremity.
Myocardial infarction (see Chapter 3) Myocardial infarction should be in the differential diagnosis in all patients with upper abdominal pain.
Appendicitis (see Chapter 13) The pain may start in the epigastrium but eventually migrates to the right lower quadrant. Ultrasound and CT are very helpful in the diagnosis of appendicitis.
Diabetic ketoacidosis (see Chapter 8) Blood glucose is always elevated, anion gap always present. Blood glucose may be elevated in severe AP but usually develops later in the clinical course. Acidosis may be present in severe AP.
Calcium and triglycerides should be measured to evaluate possi- ble etiologies.
Chest and flat and upright abdominal radiographs are obtained to exclude bowel perforation or obstruction. Abdominal ultra- sonography is performed to exclude gall stones. In patients with moderate or severe pancreatitis, or those who do not improve clin- ically within 48 to 72 hours, use contrast-enhanced, thin-section CT scan of the abdomen to confirm the diagnosis, to exclude other intra-abdominal processes, to grade the severity of pancre- atitis, and to diagnose local complications such as pancreatic necrosis, pseudocyst, or abscess. MRI is used if there is a con- traindication to intravenous radiocontrast.
In addition to local complications, pancreatitis may cause sig- nificant systemic complications including hypocalcemia, hyper- glycemia, renal insufficiency, disseminated intravascular coagula- tion, and acute respiratory distress syndrome. Therefore, obtain in all patients with pancreatitis a complete blood count, electrolytes, calcium, blood glucose, BUN, creatinine, prothrombin time, and partial thromboplastin time. Pulse oximetry or, in more critically ill patients, arterial blood gases should also be obtained (Table 2). Scoring systems such as the Ranson, Glasgow, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores are used to determine prognosis. However, these scoring systems lack sensitivity and specificity and should not supplant clin- ical findings such as third-space fluid loss or remote organ failure in determining risk. Organ failure, the most important indicator of severity, is defined by the presence of shock (systolic blood pres- sure <90 mm Hg), pulmonary insufficiency (PaO2<55 mm Hg),
renal failure (serum creatinine >2 mg/dL), or gastrointestinal bleeding (>500 mL/24h).
Therapy
Keep patients without oral intake until there is clear clinical improvement, and treat aggressively with intravenous fluids. In more severe cases, where patients are not able to receive oral
nourishment for a few weeks, nutritional support with enteral jeju- nal feeding, or with total parenteral nutrition if enteral feeding is contraindicated, may be required. Use of nasogastric suction is limited to patients with refractory vomiting due to ileus.
Obtain early ERCP in patients with bile duct stones, cholan- gitis, or biliary pancreatitis. Patients with persisting pancreatitis, persistent elevation of transaminase levels, or dilated bile ducts may have retained bile duct stones and may also benefit from ERCP. Stone extraction with biliary sphincterotomy improves the outcome, prevents further attacks of acute biliary pancre- atitis, and reduces pancreatitis-related complications. Surgery is indicated for pancreatic necrosis and pancreatic abscess because the mortality rate with medical management is >50%. Pancreatic pseudocysts that fail to resolve may need surgical drainage. Cholecystectomy is indicated in patients with biliary pancreatitis to prevent recurrence.
There is no specific drug therapy for acute pancreatitis. Provide symptomatic treatment of pain, nausea, and vomiting. Treat doc- umented infections (cholangitis, abscess, infected pseudocyst) with antibiotics. Choice of antibiotics should be based on bacter- ial identification and susceptibility when available. Empiric antibi- otic therapy for non-infected pancreatic necrosis is controversial. If antibiotics are used, evidence-based regimens include ceftazidime, amikacin, and metronidazole; ofloxacin and metronidazole; or monotherapy with imipenem, meropenem, or cefuroxime. Patients with interstitial (non-necrotizing) pancreatitis without evidence of infection do not receive antibiotics.
Follow-Up
In general, acute pancreatitis is a self-limited condition that does not recur if the precipitating factor is removed. In patients with alcohol abuse, advise abstinence from alcohol or refer for coun- seling and appropriate treatment. In patients with high triglyc- eride levels, control with a combination of a dietary regimen and, if indicated, triglyceride-lowering medications. In patients with
68 • Gastroenterology and Hepatology
Table 2. Laboratory and Other Studies for Acute Pancreatitis (AP)
Test Notes
Serum amylase levels Cutoff values just above normal: 90% sensitive; 70% specific. Cutoff values three times the upper limit of normal: 60% sensitive; 99% specific.
Serum lipase levels Cutoff values three times the upper limit of normal: 90%-100% sensitive; 99% specific. Aminotransferase levels Elevated levels raise the suspicion for biliary pancreatitis.
Triglyceride level Hypertriglyceridemia can be the underlying etiology of AP.
Calcium level Hypercalcemia is a cause of AP and hypocalcemia can be a complication of AP.
BUN and creatinine levels The incidence of renal insufficiency is 4%, 22%, and 45% in patients with interstitial, noninfected necrotic and infected necrotic AP, respectively.
Glucose level Glucose levels can increase and are negative prognostic factor. PT/PTT May be elevated in AP complicated by DIC.
Abdominal and chest radiographs Can exclude perforated viscus or obstructed bowel. Abdominal ultrasound Evaluate for presence of gallstones.
CT The test of choice to determine the presence of local complications. Test for arterial hypoxemia Pulse oximetry in mild cases of AP and arterial blood gas in severe cases of AP.
elevated calcium levels, begin appropriate medical or surgical man- agement to prevent recurrence of hypercalcemia. If a specific drug precipitated the pancreatitis, discontinue its use and substitute another as needed.
Book Enhancement
Go to www.acponline.org/essentials/gastroenterology-section .html to view CT scans showing pancreatic calcifications and inter- stitial and necrotizing pancreatitis. In MKSAP for Student 4, assess
yourself with items 25-29 in the Gastroenterology and
Hepatologysection.
Bibliography
Draganov P, Toskes P.Acute Pancreatitis. http://pier.acponline.org/ physicians/diseases/d268. [Date accessed: 2008 Jan 13] In: PIER [online database]. Philadelphia: American College of Physicians; 2006.
Whitcomb DC.Clinical practice. Acute pancreatitis. N Engl J Med. 2006; 354:2142-50. [PMID: 16707751]
70
G
astrointestinal reflux disease (GERD) is an extremely common disorder characterized by symptoms of heart- burn and regurgitation. GERD is a multifactorial disor- der that is associated with impaired esophageal motility and defects in the lower esophageal sphincter (LES) and the antireflux barri- er located at the gastroesophageal junction. These findings result in the prolonged exposure of the esophagus to gastric contents. The most common cause of GERD is transient LES relaxations. Although the presence of acid is central to the pathogenesis of GERD, increased gastric acid secretion is not a risk factor for GERD, and few patients with this disorder actually secrete excess acid. The major complication of GERD is Barrett’s esophagus, which can progress to esophageal adenocarcinoma.Diagnosis
The diagnosis of GERD is suggested by symptoms of heartburn and regurgitation occurring after meals, aggravated by recum- bency, bending, or physical exertion, and relieved by antacids. Patients with classic symptoms rarely require confirmatory testing (including testing for H. pylori). Atypical, extra-esophageal man- ifestations may occur and can include wheezing, shortness of breath, chronic cough and hoarseness, chest pain, choking, hali- tosis, and sore throat. Physical exam findings are less prominent, but may include wheezing, pharyngitis, and dental erosions.
Response to empiric therapy confirms the diagnosis; patients not responding may require further investigation with 24-hour ambulatory pH testing. GERD associated with dysphagia may represent a complication of long-term acid reflux, including stric- ture, ulceration, or adenocarcinoma, and requires evaluation with upper endoscopy. GERD presenting atypically or unresponsive to empiric therapy also warrants the consideration of an alternative diagnosis such as infectious esophagitis, pill esophagitis (alen- dronate and doxycycline are common causes), esophageal motil- ity disorders, esophageal cancer, nonulcer dyspepsia, peptic ulcer disease, cardiac disease, and biliary disease (Table 1).
Therapy
Smoking cessation, elevation of the head of the bed, avoiding recumbency after eating, and sleeping in the left lateral decubitus position can be helpful. Alcohol, fatty foods, chocolate, pepper- mint, tomato juice, citrus juices, onions and garlic are avoided. Theophylline, nitrates, anticholinergic agents, calcium-channel blockers, alpha-adrenergic antagonists, and diazepam may all induce GERD, and their elimination (if possible) may improve symptoms. Surgical intervention is an option for patients who wish to avoid life-long medication, but it is not likely to improve symp- toms that were unresponsive to proton pump inhibitors.
Treatment aims to eliminate symptoms, heal esophagitis, prevent complications, and maintain remission. Antacids are