Introduction
Background
Acute acalculous cholecystitis (AAC) represents inflammation of the gallbladder in the absence of demonstrated calculi. The disease process of AAC is distinct from that of the calculous variety, in which the primary initiating event is believed to be obstruction of the cystic duct. Acalculous cholecystitis typically occurs as a secondary event in patients who are hospitalized and are acutely ill with another disease.1,2
The diagnosis often is difficult and is often delayed because of comorbidities that decrease sensitivity and specificity of both clinical and imaging evaluation. A high degree of suspicion is required on the part of the physician. A much higher rate of complications is observed in patients with acalculous cholecystitis (eg, gangrene, perforation) because of the more fulminant course and coexistent disease. As a result, some authors propose the term necrotizing cholecystitis to reflect the fact that acalculous cholecystitis does not simply represent cholecystitis without stones.
Related eMedicine topics:
Acalculous Cholecystitis (from Gastroenterology)
Cholecystitis, Acute
Gallbladder Disease
Related Medscape topics:
Specialty Site Radiology
Specialty Site Gastroenterology
Resource Center Gallbladder and Biliary Disease
Resource Center Minimally Invasive Gastrointestinal Surgery
CME Transdermal Rather Than Oral Hormone Therapy May Help Avoid Cholecystectomy
CME New Guidelines Address Management of Common Bile Duct Stones
Pathophysiology
The pathophysiology of acalculous cholecystitis is multifactorial and is incompletely defined. At least 3 mechanisms appear to work in concert to produce the disease, including (1) systemic mediators of inflammation and trauma, (2) biliary stasis, and (3) generalized or localized ischemia. In turn, the mechanisms often result in functional or secondary mechanical obstruction of the cystic duct from inflammation and bile viscosity.
In some settings, extrinsic compression may contribute to the development of stasis. When it occurs, infection usually represents a secondary event and involves gram-negative enteric flora. In some patients, infection may be the primary event. Acute acalculous cholecystitis (AAC) has been described in association with infection by Salmonella (ie, typhoid fever), Staphylococcus, and Brucella species; in AIDS patients, cholecystitis has been described in association with infection by cytomegalovirus and Cryptosporidium organisms.3,4,5
In animal models, acalculous cholecystitis has been shown to develop after administration of systemic mediators of inflammation. Small-vessel necrosis in the gallbladder serosa and muscularis has been demonstrated after activation of factor XII–dependent pathways, platelet activating factor, endotoxin, or interleukin 2. This frequently is associated with gallbladder atony, which in turn predisposes patients to biliary stasis.
Biliary stasis results in more viscous bile, an increase in the concentration of the detergent bile salts, and sludge formation, which increases the bile histotoxicity to the gallbladder mucosa. Fasting, use of parenteral nutrition, use of narcotic analgesics, and the postoperative state all predispose patients to biliary stasis and are commonly seen in patients with ACC.
Generalized or localized ischemia further predisposes patients to biliary stasis; it may result in gallbladder wall necrosis and perforation. Hypovolemic shock, cardiogenic shock, and septic shock predispose patients to ischemia and are contributing factors. At times, ischemia is the primary cause; it may occur in the setting of small-vessel vasculitis or following therapeutic particulate embolization.
Individuals presenting with ACC in the outpatient setting typically are older patients with microvascular disease and other comorbidities.
Frequency
United States
In 7-22% of cases of cholecystitis, calculi are absent. The variability is mostly a result of differences in patient populations; a higher incidence is seen in burn and trauma centers and in pediatric populations. As many as 90% of cases of postoperative acute cholecystitis are acalculous in origin. Although in the critical care setting, cholecystitis frequently is acalculous, the overall incidence in this setting is estimated to be only 0.2%. In such cases, a high index of suspicion is required to make the diagnosis.
Mortality/Morbidity
Complications are much more common in the acalculous variety of cholecystitis than in the calculous variety because of the variable pathophysiology, comorbid conditions, and the frequent delay in diagnosis and treatment. Perforation or gangrene occurs in 40-60% of patients. Gangrene may be either diffuse or focal and is frequently associated with perforation. Approximately 40% of cases of cholecystitis that are complicated by perforation are of the acalculous variety. In more than one half of cases of emphysematous cholecystitis, the disease is of the acalculous type; often, these cases are associated with gangrene.
The mortality rate varies widely in the literature from 9-66%; mortality is attributed to delay in diagnosis, more frequent complications, and concurrent disease processes.
Race
No racial predilection has been identified for acalculous cholecystitis.
Sex
In most reported series regarding acalculous cholecystitis, the male-to-female ratio is 2-3:1.
Age
The average age of patients with acalculous cholecystitis is greater than 50 years.
Presentation
Acute acalculous cholecystitis most commonly occurs in hospitalized patients who did not have gallbladder disease previously but who have severe concomitant medical and surgical conditions. Known populations at risk include postoperative patients (especially patients who have undergone abdominal surgery), patients with extensive burns, patients with trauma, and patients receiving prolonged parenteral nutrition. Other reported associations include prolonged fasting, use of high-dose opioid analgesics, and mechanical ventilation.
A small subset of patients present in the outpatient setting with symptoms that are easier to localize. Clinical and imaging evaluation are much more accurate in this setting. These patients are diagnosed earlier in the disease course and have a better prognosis.
In the pediatric population, acute cholecystitis is rare; approximately one half of cases occur in the absence of demonstrated calculi. These patients are more likely to present in the outpatient setting and most often are treated with cholecystectomy.
The most frequent physical and laboratory findings include fever, right upper quadrant (RUQ) pain, nausea, leukocytosis, and elevation of liver-associated enzymes and bilirubin. All of these clinical parameters are nonspecific. In almost all instances in which it can be evaluated, abdominal pain is present; however, it is often not localized to the RUQ. Fever is present in two thirds of patients, and leukocytosis and liver function abnormalities are present in approximately 80%.
Preferred Examination
Early imaging evaluation is required for patients with acalculous cholecystitis, and frequently, multiple diagnostic tests are performed. No single imaging study is ideal. The 3 primary imaging modalities often are complementary, with ultrasound (US) or CT providing anatomic information and evaluation of adjacent structures and cholescintigraphy providing functional information.6,7
US and cholescintigraphy should be the initial imaging tests performed to evaluate possible acute acalculous cholecystitis (AAC).
CT is preferred if other diseases in the differential diagnosis are more likely or if CT needs to be performed for another indication.
Limitations of Techniques
All available modalities have a significant false-positive and false-negative rate and generally are better at excluding, rather than confirming, the presence of acalculous cholecystitis.
Although it is unusual for acalculous cholecystitis to occur in patients with a normal gallbladder, on both US and cholescintigraphy examinations, the gallbladder may be found to be normal early in the course of the disease. For patients who continue to experience clinical deterioration and for whom clinical evaluation is not possible or fails to demonstrate an alternative source, many authors recommend maintaining a low threshold for instituting empiric, minimally invasive therapy in the form of percutaneous cholecystostomy.
Differential Diagnoses
Cholangitis, Recurrent Pyogenic
Cholecystitis, Acute
Cholelithiasis
Pancreatitis, Acute
Other Problems to Be Considered
The differential diagnosis for patients suspected of having acalculous cholecystitis is broad because comorbid conditions typically are present, the ability to evaluate the patient's symptoms is reduced, and the most common clinical and laboratory manifestations of acalculous cholecystitis are nonspecific. Almost any infectious or inflammatory process may result in nonspecific findings. In patients with more localized symptoms, the primary diseases in the differential diagnosis are calculous cholecystitis, ascending cholangitis, acute hepatitis, and pancreatitis.
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References
Kalliafas S, Ziegler DW, Flancbaum L, Choban PS. Acute acalculous cholecystitis: incidence, risk factors, diagnosis, and outcome. Am Surg. May 1998;64(5):471-5. [Medline].
Shridhar Ganpathi I, Diddapur RK, Eugene H, Karim M. Acute acalculous cholecystitis: challenging the myths. HPB (Oxford). 2007;9(2):131-4. [Medline].
Katsinelos P, Pilpilidis I, Papaziogas B, Chatzimavroudis G, Paroutoglou G, Mimidis K, et al. Fatal acute acalculous cholecystitis as an early complication after radiation therapy.. Chirurgia (Bucur). Mar-Apr 2008;103(2):223-6. [Medline].
Iaria C, Arena L, Di Maio G, Fracassi MG, Leonardi MS, Famulari C, et al. Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature. Int J Infect Dis. Jul 2008;12(4):391-5. [Medline].
Yombi JC, Meuris CM, Van Gompel AM, Ben Younes M, Vandercam BC. Acalculous cholecystitis in a patient with Plasmodium falciparum infection: a case report and literature review. J Travel Med. May-Jun 2006;13(3):178-80. [Medline].
D''Agostino HB, vanSonnenberg E, Sanchez RB, et al. Imaging of the percutaneous cholecystostomy tract: observations and utility. Radiology. Dec 1991;181(3):675-8. [Medline].
Flancbaum L, Choban PS. Use of morphine cholescintigraphy in the diagnosis of acute cholecystitis in critically ill patients. Intensive Care Med. Feb 1995;21(2):120-4. [Medline].
Boland GW, Slater G, Lu DS, et al. Prevalence and significance of gallbladder abnormalities seen on sonography in intensive care unit patients. AJR Am J Roentgenol. Apr 2000;174(4):973-7. [Medline].
Helbich TH, Mallek R, Madl C, et al. Sonomorphology of the gallbladder in critically ill patients. Value of a scoring system and follow-up examinations. Acta Radiol. Jan 1997;38(1):129-34. [Medline].
Molenat F, Boussuges A, Valantin V, Sainty JM. Gallbladder abnormalities in medical ICU patients: an ultrasonographic study. Intensive Care Med. Apr 1996;22(4):356-8. [Medline].
Boland GW, Lee MJ, Leung J, Mueller PR. Percutaneous cholecystostomy in critically ill patients: early response and final outcome in 82 patients. AJR Am J Roentgenol. Aug 1994;163(2):339-42. [Medline].
Byrne MF, Suhocki P, Mitchell RM, et al. Percutaneous cholecystostomy in patients with acute cholecystitis: experience of 45 patients at a US referral center. J Am Coll Surg. Aug 2003;197(2):206-11. [Medline].
Conway JD, Russo MW, Shrestha R. Endoscopic stent insertion into the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease. Gastrointest Endosc. Jan 2005;61(1):32-6. [Medline].
England RE, McDermott VG, Smith TP, et al. Percutaneous cholecystostomy: who responds?. AJR Am J Roentgenol. May 1997;168(5):1247-51. [Medline].
Johlin FC, Neil GA. Drainage of the gallbladder in patients with acute acalculous cholecystitis by transpapillary endoscopic cholecystotomy. Gastrointest Endosc. Sep-Oct 1993;39(5):645-51. [Medline].
Nemcek AA Jr, Bernstein JE, Vogelzang RL. Percutaneous cholecystostomy: does transhepatic puncture preclude a transperitoneal catheter route?. J Vasc Interv Radiol. Nov 1991;2(4):543-7. [Medline].
Patel M, Miedema BW, James MA, Marshall JB. Percutaneous cholecystostomy is an effective treatment for high-risk patients with acute cholecystitis. Am Surg. Jan 2000;66(1):33-7. [Medline].
Tazawa J, Sanada K, Maekawa S, et al. Gallbladder aspiration for acute cholecystitis in high-surgical-risk patients. J Gastroenterol Hepatol. Apr 2003;18(4):463-5. [Medline].
vanSonnenberg E, D''Agostino HB, Goodacre BW, et al. Percutaneous gallbladder puncture and cholecystostomy: results, complications, and caveats for safety. Radiology. Apr 1992;183(1):167-70. [Medline].
Ginat D, Saad WE. Cholecystostomy and transcholecystic biliary access. Tech Vasc Interv Radiol. Mar 2008;11(1):2-13. [Medline].
Griniatsos J, Petrou A, Pappas P, Revenas K, Karavokyros I, Michail OP, et al. Percutaneous cholecystostomy without interval cholecystectomy as definitive treatment of acute cholecystitis in elderly and critically ill patients. South Med J. Jun 2008;101(6):586-90. [Medline].
Chopra S, Dodd GD 3rd, Mumbower AL, et al. Treatment of acute cholecystitis in non-critically ill patients at high surgical risk: comparison of clinical outcomes after gallbladder aspiration and after percutaneous cholecystostomy. AJR Am J Roentgenol. Apr 2001;176(4):1025-31. [Medline].
Cullen JJ, Maes EB, Aggrawal S, et al. Effect of endotoxin on opossum gallbladder motility: a model of acalculous cholecystitis. Ann Surg. Aug 2000;232(2):202-7. [Medline].
Prevot N, Mariat G, Mahul P, et al. Contribution of cholescintigraphy to the early diagnosis of acute acalculous cholecystitis in intensive-care-unit patients. Eur J Nucl Med. Oct 1999;26(10):1317-25. [Medline].
Tsakayannis DE, Kozakewich HP, Lillehei CW. Acalculous cholecystitis in children. J Pediatr Surg. Jan 1996;31(1):127-30; discussion 130-1. [Medline].
Further Reading
Keywords
acalculous cholecystitis, gallbladder inflammation, acalculous gallbladder inflammation, cholecystitis, gallbladder disease, biliary tract disease, digestive system disease, necrotizing cholecystitis, acute acalculous cholecystitis
