Cholecystitis (http://emedicine.medscape.com/article/171886-overview)Cholecystitis is inflammation of the gallbladder that occurs most commonly because of an obstruction of the cystic duct from cholelithiasis. Uncomplicated cholecystitis has an excellent prognosis; the development of complications such as perforation or gangrene renders the prognosis less favorable.

Essential update: Early cholecystectomy superior to delayed cholecystectomy for acute cholecystitisIn a randomized, prospective, open-label, parallel group trial involving 304 patients with acute cholecystitis who underwent surgery within 24 hours of hospital admission and 314 patients who underwent surgery 7-45 days later, Gutt et al found that the early-surgery group had a significantly lower rate of complications (12% vs 34%; P < .001) and a significantly shorter mean length of hospital stay (5.4 days vs 10.0 days; P < .001).[1, 2] The 75-day morbidity was also significantly lower in the early-surgery group.

Signs and symptomsThe most common presenting symptom of acute cholecystitis is upper abdominal pain. The following characteristics may be reported:

• Signs of peritoneal irritation may be present, and the pain may radiate to the right shoulder or scapula

• Pain frequently begins in the epigastric region and then localizes to the right upper quadrant (RUQ)

• Pain may initially be colicky but almost always becomes constant• Nausea and vomiting are generally present, and fever may be notedPatients with acalculous cholecystitis may present with fever and sepsis alone, without history or physical examination findings consistent with acute cholecystitis.

Cholecystitis may present differently in special populations, as follows:

• Elderly (especially diabetics) – May present with vague symptoms and without many key historical and physical findings (eg, pain and fever), with localized tenderness the only presenting sign; may progress to complicated cholecystitis rapidly and without warning

• Children – May present without many of the classic findings; those at higher risk for cholecystitis include those who have sickle cell disease, serious illness, a requirement for prolonged total parenteral nutrition (TPN), hemolytic conditions, or congenital and biliary anomalies

The physical examination may reveal the following:

• Fever, tachycardia, and tenderness in the RUQ or epigastric region, often with guarding or rebound

• Palpable gallbladder or fullness of the RUQ (30-40% of patients)• Jaundice (~15% of patients)The absence of physical findings does not rule out the diagnosis of cholecystitis.

See Presentation for more detail.

DiagnosisLaboratory tests are not always reliable, but the following findings may be diagnostically useful:

• Leukocytosis with a left shift may be observed• Alanine aminotransferase (ALT) and aspartate aminotransferase

(AST) levels may be elevated in cholecystitis or with common bile duct (CBD) obstruction

• Bilirubin and alkaline phosphatase assays may reveal evidence of CBD obstruction

• Amylase/lipase assays are used to assess for pancreatitis; amylase may also be mildly elevated in cholecystitis

• Alkaline phosphatase level may be elevated (25% of patients with cholecystitis)

• Urinalysis is used to rule out pyelonephritis and renal calculi• All females of childbearing age should undergo pregnancy testingDiagnostic imaging modalities that may be considered include the following:

• Radiography• Ultrasonography• Computed tomography (CT)• Magnetic resonance imaging (MRI)• Hepatobiliary scintigraphy• Endoscopic retrograde cholangiopancreatography (ERCP)The American College of Radiology (ACR) makes the following imaging recommendations:

• Ultrasonography is the preferred initial imaging test for the diagnosis of acute cholecystitis; scintigraphy is the preferred alternative

• CT is a secondary imaging test that can identify extrabiliary disorders and complications of acute cholecystitis

• CT with intravenous (IV) contrast is useful in diagnosing acute cholecystitis in patients with nonspecific abdominal pain

• MRI, often with IV gadolinium-based contrast medium, is also a possible secondary choice for confirming a diagnosis of acute cholecystitis

• MRI without contrast is useful for eliminating radiation exposure in pregnant women when ultrasonography has not yielded a clear diagnosis

• Contrast agents should not be used in patients on dialysis unless absolutely necessary

See Workup for more detail.

ManagementTreatment of cholecystitis depends on the severity of the condition and the presence or absence of complications.

For acute cholecystitis, initial treatment includes bowel rest, IV hydration, correction of electrolyte abnormalities, analgesia, and IV antibiotics. Options include the following:

• Sanford guide – Piperacillin-tazobactam, ampicillin-sulbactam, or meropenem; in severe life-threatening cases, imipenem-cilastatin

• Alternative regimens – Third-generation cephalosporin plus metronidazole

• Emesis can be treated with antiemetics and nasogastric suction• Because of the rapid progression of acute acalculous cholecystitis to

gangrene and perforation, early recognition and intervention are required.

• Supportive medical care should include restoration of hemodynamic stability and antibiotic coverage for gram-negative enteric flora and anaerobes if biliary tract infection is suspected.

• Daily stimulation of gallbladder contraction with IV cholecystokinin (CCK) may help prevent formation of gallbladder sludge in patients receiving TPN

For cases of uncomplicated cholecystitis, outpatient treatment may be appropriate. The following medications may be useful in this setting:

• Levofloxacin and metronidazole for prophylactic antibiotic coverage against the most common organisms

• Antiemetics (eg, promethazine or prochlorperazine) to control nausea and prevent fluid and electrolyte disorders

• Analgesics (eg, oxycodone/acetaminophen)Surgical and interventional procedures used to treat cholecystitis include the following:

• Laparoscopic cholecystectomy (standard of care for surgical treatment of cholecystitis)

• Percutaneous drainage• ERCP• Endoscopic ultrasound-guided transmural cholecystostomyEndoscopic gallbladder drainage

PathophysiologyNinety percent of cases of cholecystitis involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing

acalculous cholecystitis.[3]

Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis.

Although the exact mechanism of acalculous cholecystitis is unclear, several theories exist. Injury may be the result of retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder never receives a cholecystokinin (CCK) stimulus to empty; thus, the concentrated bile remains stagnant in the lumen.[4, 5]

A study by Cullen et al demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult.[6] Endotoxin also abolished the contractile response to CCK, leading to gallbladder stasis.

PrognosisUncomplicated cholecystitis has an excellent prognosis, with very low mortality. Most patients with acute cholecystitis have a complete remission within 1-4 days. However, 25-30% of patients either require surgery or develop some complication.

Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Perforation occurs in 10-15% of cases. Patients with acalculous cholecystitis have a mortality ranging from 10-50%, which far exceeds the expected 4% mortality observed in patients with calculous cholecystitis. In patients who are critically ill with acalculous cholecystitis and perforation or gangrene, mortality can be as high as 50-60%.

EtiologyAn estimated 10-20% of Americans have gallstones, and as many as one third of these people develop acute cholecystitis. Cholecystectomy for either recurrent biliary colic or acute cholecystitis is the most common major surgical procedure performed by general surgeons, resulting in approximately 500,000 operations annually.

Age distribution for cholecystitisThe incidence of cholecystitis increases with age. The physiologic explanation for the increasing incidence of gallstone disease in the elderly population is unclear. The increased incidence in elderly men has been linked to changing androgen-to-estrogen ratios.

Go to Pediatric Cholecystitis for more complete information on this

topic.

Sex distribution for cholecystitisGallstones are 2-3 times more frequent in females than in males, resulting in a higher incidence of calculous cholecystitis in females. Elevated progesterone levels during pregnancy may cause biliary stasis, resulting in higher rates of gallbladder disease in pregnant females. Acalculous cholecystitis is observed more often in elderly men.

Prevalence of cholecystitis by race and ethnicityCholelithiasis, the major risk factor for cholecystitis, has an increased prevalence among people of Scandinavian descent, Pima Indians, and Hispanic populations, whereas cholelithiasis is less common among individuals from sub-Saharan Africa and Asia.[8, 9] In the United States, white people have a higher prevalence than black people.