What are the causes of acalculous cholecystitis?

Causes of Acalculous Cholecystitis

Acalculous cholecystitis (ACC) is primarily caused by gallbladder ischemia and bile stasis in critically ill patients, with the majority of cases occurring after trauma or biliary surgery, though infectious agents (particularly Clostridium perfringens) and multiple concurrent pathogenic mechanisms also contribute to its development. 1

Primary Pathogenic Mechanisms

The pathogenesis of ACC involves multiple overlapping mechanisms that typically occur simultaneously:

Ischemia and Reperfusion Injury

• Gallbladder ischemia is the central mechanism, resulting from hypotension, shock, cardiac arrest, or severe visceral atherosclerosis 2, 3
• Patients with mesenteric vascular disease and visceral atherosclerosis are at particularly high risk when other factors like bile stasis are present 2
• Aortic dissection can directly cause gallbladder ischemia leading to ACC 4

Bile Stasis

• Bile stasis contributes significantly to ACC development, particularly in critically ill patients 1, 3
• Positive-pressure ventilation and total parenteral nutrition promote bile stasis 3

Infectious Causes

• Clostridium perfringens infection appears to be involved in the pathogenesis, causing spontaneous gangrene of the gallbladder 1
• Direct invasion of gallbladder epithelial cells by various pathogens can trigger ACC in previously healthy individuals 5

Vasculitis and Inflammatory Mechanisms

• Gallbladder vasculitis is an important pathogenic mechanism 5
• Abdominal vasculitis is associated with ACC development 3
• Eicosanoid proinflammatory mediators play a central role in the inflammatory cascade 3

High-Risk Clinical Conditions

Critical Illness and Trauma

• The majority of ACC cases follow trauma or biliary surgery 1
• ACC is an infrequent but underdiagnosed complication in critically ill patients 1

Cardiovascular Conditions

• Congestive heart failure 3
• Cholesterol embolization 3
• Shock or cardiac arrest 3

Metabolic and Systemic Diseases

• Diabetes mellitus 3
• Malignant disease 3

Medication-Related Causes

• High doses of narcotic agents may be a contributory factor 1
• Hypersensitivity reactions to antibiotics (particularly erythromycin) can precipitate acute acalculous cholecystitis with massive eosinophilic infiltrate 6
• Opioid therapy has been implicated in ACC pathogenesis 3

Special Populations

Pediatric Patients

• Children may develop ACC, especially after viral illnesses 3

Previously Healthy Individuals

• In patients without critical illness, infectious causes comprise the primary etiology 5
• Multiple pathogenic mechanisms may concurrently contribute in varying degrees 5

Important Clinical Caveat

ACC progresses rapidly to gallbladder perforation without prompt diagnosis and treatment, requiring a high index of suspicion in at-risk patients 1. The disease is likely underdiagnosed because localizing right upper quadrant pain and tenderness are often absent in sedated or ventilated patients 1.