Acute Cholecystitis

Etiology

Cystic duct obstruction represents the primary etiology of acute cholecystitis, often leading to bile stasis and subsequent inflammation. Under normal conditions, bile produced in the liver flows through the hepatic duct, entering the gallbladder via the cystic duct and continuing down the common bile duct into the gastrointestinal tract through the ampulla of Vater. After the ingestion of food—particularly meals high in fat—cholecystokinin (CCK) stimulates gallbladder contraction. In response, the gallbladder releases bile through the cystic duct and into the duodenum, where bile facilitates fat emulsification for efficient absorption.[5]

In addition to storing bile, the gallbladder also concentrates it. Disruption in bile homeostasis increases the risk of precipitation and stone formation. Factors contributing to this disruption include bile stasis, hepatic oversaturation of cholesterol and lipids, abnormal concentration processes, and cholesterol crystal nucleation.

When a gallstone obstructs the cystic duct, biliary colic may result, often presenting as pain or discomfort in the right upper quadrant or epigastrium. Acute calculous cholecystitis develops with persistent obstruction, leading to gallbladder distention and inflammation, typically confirmed when pain lasts longer than 6 hours. Acute acalculous cholecystitis, which occurs without gallstones, more commonly affects critically ill patients or those dependent on total parenteral nutrition (TPN) over extended periods.[6][7]

Regardless of the underlying cause, elevated intraluminal pressure within the gallbladder can increase transmural pressure, impair perfusion, and provoke inflammation. Without prompt relief, ischemia may progress to gangrene. A gangrenous gallbladder becomes vulnerable to infection by gas-forming organisms, potentially leading to emphysematous cholecystitis. These complications may culminate in gallbladder perforation, significantly raising morbidity and mortality.

Approximately 95% of individuals diagnosed with acute cholecystitis have gallstones.[8] However, incidental detection of gallstones in asymptomatic patients does not necessitate intervention. Estimates suggest that only 20% of such individuals will develop symptoms over a 20-year period, making routine prophylactic cholecystectomy unnecessary in the absence of symptoms.[9]

Epidemiology

Women, individuals with obesity, pregnant patients, and those in their 40s face a higher risk of developing gallbladder disease. Drastic weight loss or the presence of acute illnesses may further elevate this risk. A familial predisposition contributes to the formation of gallstones, indicating a genetic component in disease susceptibility.

Additionally, conditions that promote the breakdown of red blood cells, eg, sickle cell disease, contribute to an increased incidence of pigmented gallstones. These patients also show a higher likelihood of developing acute calculous cholecystitis due to the accumulation of pigment within the biliary system.

Pathophysiology

Acute cholecystitis may develop due to occlusion of the cystic duct or impaired gallbladder emptying. Inadequate bile drainage from the gallbladder leads to increased intraluminal pressure and distension, contributing to ischemia and inflammation of the gallbladder wall. Stagnant bile creates a favorable environment for bacterial colonization, further intensifying the inflammatory response.[10]

Without timely treatment, acute cholecystitis can progress to gallbladder perforation, sepsis, and potentially death. Gallstones—formed from substances such as bilirubinate or cholesterol—frequently contribute to the development of cholelithiasis and cholecystitis. In conditions, eg, sickle cell disease, the increased breakdown of red blood cells elevates serum bilirubin levels, promoting the formation of pigmented stones.[11] Patients with hyperparathyroidism and other conditions that cause elevated serum calcium levels may develop calcium-based gallstones.

Pregnant individuals face an elevated risk of gallstone formation due to delayed gallbladder emptying influenced by increased progesterone levels. Cholesterol stones represent the most commonly encountered type and tend to form in the presence of excessive cholesterol. Obstruction of the common bile duct caused by neoplasms or strictures may also disrupt bile flow and lead to stone formation due to persistent stasis.[12][13]

Histopathology

During the early phase, the gallbladder typically reveals extensive venous congestion and edema. With time, fibrosis and the presence of chronic inflammatory cells may appear. More advanced cases may present with gangrene or perforation.

History and Physical

Cholecystitis Clinical Features

Chronic cholecystitis often presents with gradually worsening right upper quadrant abdominal pain accompanied by bloating, nausea, vomiting, and intolerance to certain foods, particularly those that are greasy or spicy. Discomfort may radiate to the midback or right shoulder, and intermittent pain can persist for years before a definitive diagnosis is made.

Acute cholecystitis shares many of the same symptoms but with greater severity. The clinical presentation can resemble cardiac conditions, leading to potential diagnostic confusion. A hallmark finding of acute cholecystitis is inspiratory arrest during palpation of the right upper quadrant, commonly referred to as Murphy's sign. Episodes frequently follow a specific dietary trigger, most commonly the consumption of high-fat foods.

Evaluation

Accurate diagnosis of cholecystitis relies heavily on a thorough clinical assessment. However, laboratory studies, including a complete blood count (CBC) and a comprehensive metabolic panel (CMP), provide valuable diagnostic support. In chronic cholecystitis, these lab results may remain within normal limits. In contrast, acute or more severe cases often show elevated white blood cell counts (WBC) and increased liver enzymes. The presence of hyperbilirubinemia raises suspicion for a common bile duct obstruction. However, even in advanced gallbladder disease, laboratory values may occasionally remain normal.[14][15]

Evaluation should also include assessment of amylase and lipase levels to rule out pancreatitis. In the emergency department, a computed tomography (CT) scan frequently serves as the initial imaging study (see Images. Axial CT Abdomen Acute Cholecystitis and Abdomen CT, Acute Cholecystitis). This modality may reveal signs, including gallbladder distention, wall thickening, pericholecystic fluid, radio-opaque stones, and surrounding inflammation. When gallbladder pathology is suspected, abdominal ultrasound remains the preferred imaging method (see Images. Multiple Biliary Hamartoma and Ultrasound and Acalculous Cholecystitis). Findings suggestive of acute calculous cholecystitis include a thickened gallbladder wall >3 mm, edema, pericholecystic fluid, and the presence of gallstones (see Image. Cholecystitis).

In cases where ultrasound or CT findings do not clearly confirm acute cholecystitis, a hepatobiliary iminodiacetic acid (HIDA) scan may provide diagnostic clarity. Failure of the gallbladder to fill with radiotracer indicates cystic duct obstruction and supports a diagnosis of acute cholecystitis. When gallstones are absent, the use of cholecystokinin (CCK) during the HIDA scan may identify acalculous cholecystitis. An ejection fraction below 35% suggests a hypokinetic gallbladder, also referred to as biliary dyskinesia.[14][15]

Treatment / Management

Surgical Management Approaches

Initial management of acute cholecystitis typically involves intravenous fluid resuscitation and prompt initiation of broad-spectrum antibiotics effective against gram-negative rods and anaerobes. For patients deemed appropriate surgical candidates, early laparoscopic cholecystectomy during the initial hospitalization remains the preferred approach. Evidence consistently demonstrates that early surgical management reduces postoperative morbidity and mortality compared to delayed intervention in hospitalized patients.[16][17] In situations where laparoscopic cholecystectomy is not suitable, an open cholecystectomy provides an alternative surgical route.(B2)

Robotic-assisted cholecystectomy may be an option depending on the surgeon's expertise. While earlier robotic systems were associated with higher rates of bile duct injury, newer-generation platforms demonstrate improved safety profiles, with fewer serious complications and a lower likelihood of conversion to an open procedure compared to traditional laparoscopy.[18][19][20](B2)

Nonsurgical Management Approaches

Patients with milder chronic cholecystitis who are not candidates for surgery may benefit from dietary modifications, particularly a low-fat diet, although outcomes vary. Medical management with ursodiol has shown occasional success in dissolving gallstones, although its effectiveness remains limited.[21][22][4]

Severely ill or high-risk patients who cannot tolerate surgery may undergo percutaneous gallbladder drainage performed by interventional radiology. This intervention may serve as definitive therapy for elderly or comorbid patients or as a bridge to elective cholecystectomy within 4 to 8 weeks of drain placement.[23] In patients who decline surgery, interventional radiology can conduct outpatient tube studies to confirm cystic duct patency before drain removal. However, recurrence rates of acute cholecystitis after drain removal may reach up to 47%.[24]

Endoscopic alternatives, eg, cystic duct stent placement or transduodenal gallbladder drainage, offer additional options for patients unfit for surgery.[25][26] These procedures remain less widely available than percutaneous cholecystostomy, and long-term outcomes require further investigation.(B3)

Differential Diagnosis

Understanding the differential diagnosis of acute cholecystitis can prevent unwanted morbidity and mortality associated with this condition. A timely and accurate diagnosis of acute cholecystitis enables early treatment and reduces the risk of complications. The differential diagnoses of acute cholecystitis include: 

• Biliary colic
• Choledocholithiasis
• Cholangitis
• Pancreatitis
• Hepatitis
• Gastritis
• Hiatal hernia
• Peptic ulcer disease
• Appenditis 
• Mesenteric ischemia
• Small bowel obstruction

Prognosis

Untreated acute cholecystitis carries a significant risk of morbidity and mortality, especially among older adults. Free perforation of the gallbladder, a potential complication of unmanaged cholecystitis, corresponds with a mortality rate of 30%.[27]

Timely surgical intervention markedly improves outcomes. When managed with early cholecystectomy—performed within 72 hours of symptom onset—patients experience a 30-day morbidity rate of only 6.6% and a 30-day mortality rate of 1.1%. Early treatment plays a critical role in reducing complications and improving overall survival.[17] 

Complications

The complications of acute cholecystitis and associated treatments include:

• Intraabdominal abscess 
• Gallbladder perforation
• Cholecystoenteric fistulas
• Biloma
• Bile duct injury
• Hepatic injury
• Bowel injury
• Infection
• Retained stones in the bile duct
• Bleeding