Gastrointestinal · PANCE / PANRE

Acute Cholecystitis

Inflammation of the gallbladder, most often from a stone obstructing the cystic duct.

Also known as: acute cholecystitis, cholecystitis, calculous cholecystitis, acalculous cholecystitis

Overview

Acute inflammation of the gallbladder, most commonly caused by cystic duct obstruction by a gallstone (calculous cholecystitis, 90-95%) or, less commonly, in the absence of stones (acalculous cholecystitis, often in critically ill patients).

Epidemiology

Affects ~200,000 patients annually in the US. Female predominance (3:1). Increased risk with age and gallstone prevalence (~10-15% of US adults). Acalculous cholecystitis represents 5-10% of cases and carries higher mortality.

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Risk factors

Gallstones (4 F's: Female, Fat, Forty, Fertile/Fair)
Obesity, rapid weight loss, bariatric surgery
Pregnancy
Estrogen therapy
Diabetes (gallbladder hypomotility, emphysematous cholecystitis risk)
Sickle cell disease (pigment stones from hemolysis)
Cirrhosis
Critical illness, TPN, prolonged fasting, mechanical ventilation, burns, trauma — predispose to acalculous cholecystitis

Pathophysiology

Stone impaction in the cystic duct (Hartmann pouch) → gallbladder distension → mucosal injury → secondary bacterial infection (E. coli, Klebsiella, Enterococcus). Progressive ischemia leads to gangrene and perforation if untreated. Acalculous cholecystitis: stasis and ischemia in critical illness drive inflammation without obstruction.

Clinical presentation

Symptoms

Constant, severe RUQ or epigastric pain lasting >6 h (vs <6 h in biliary colic)
Radiation to right shoulder or interscapular area
Nausea and vomiting
Fever and chills
Anorexia

Signs / physical exam

RUQ tenderness with positive Murphy sign (inspiratory arrest on palpation of RUQ during deep inspiration)
Voluntary guarding
Tachycardia, low-grade fever
Palpable distended gallbladder in ~30%
Mild jaundice in ~10% (Mirizzi syndrome — extrinsic CBD compression by stone in cystic duct)

Classic findings

Postprandial RUQ pain lasting >6 h with fever, leukocytosis, and positive Murphy sign.

Differential diagnosis

Biliary colic — Episodic RUQ pain that resolves within hours, no fever, normal labs, no wall thickening on US — same pain mechanism without sustained obstruction
Choledocholithiasis / ascending cholangitis — Jaundice, elevated bilirubin, dilated CBD; Charcot triad if cholangitis
Acute pancreatitis (gallstone) — Epigastric pain radiating to back, lipase elevated >3× ULN
Hepatitis (viral, alcoholic) — Markedly elevated AST/ALT, jaundice, systemic symptoms
Peptic ulcer disease / perforation — Epigastric burning; free air on imaging if perforated
Right lower lobe pneumonia — Cough, dyspnea, hypoxia; CXR
Inferior MI — Atypical presentation, especially in diabetics; ECG and troponin
Fitz-Hugh-Curtis (perihepatitis) — Young woman with RUQ pain and PID; chlamydia/gonorrhea
Hepatic abscess — Fever, RUQ pain; CT shows fluid collection

Diagnostic workup

Diagnostic criteria

Tokyo Guidelines (TG18): (A) local signs — Murphy sign, RUQ mass/pain/tenderness; (B) systemic signs — fever, leukocytosis, elevated CRP; (C) imaging characteristic of cholecystitis. Definite diagnosis requires 1 from A + 1 from B + imaging.

Labs

CBC — leukocytosis with left shift
BMP
LFTs — mildly elevated AST/ALT and alk phos (~30%); marked elevation suggests choledocholithiasis or cholangitis
Lipase — exclude pancreatitis
CRP
Blood cultures if septic

Imaging

RUQ ultrasound — first-line; findings: gallstones, gallbladder wall thickening >3 mm, pericholecystic fluid, sonographic Murphy sign, distended gallbladder
Hepatobiliary iminodiacetic acid (HIDA) scan — most sensitive/specific; non-visualization of gallbladder after 1-4 h confirms cystic duct obstruction; used when ultrasound equivocal
CT abdomen — when alternative diagnoses considered, complications suspected (perforation, emphysematous cholecystitis), or HIDA unavailable
MRCP — when choledocholithiasis suspected
EUS — high-resolution evaluation for CBD stones

Diagnostic algorithm

TG18 Severity Grade	Criteria	Management
Grade I (Mild)	No organ dysfunction, mild local inflammation	Early laparoscopic cholecystectomy
Grade II (Moderate)	WBC >18,000, palpable mass, duration >72 h, marked local inflammation	Early laparoscopic cholecystectomy at center with expertise
Grade III (Severe)	Organ dysfunction (CV, neuro, respiratory, renal, hepatic, hematologic)	Stabilize → percutaneous cholecystostomy or delayed surgery

Tokyo Guidelines (TG18) acute cholecystitis severity grading and management.

Treatment

First-line

NPO, IV fluids, analgesia (NSAIDs and opioids; morphine traditionally avoided over sphincter of Oddi concerns but clinically used)
IV antibiotics — piperacillin-tazobactam, ceftriaxone + metronidazole, or ertapenem (broaden for severity)
Early laparoscopic cholecystectomy — within 72 h preferred; equivalent outcomes to delayed cholecystectomy with shorter total hospitalization (ACDC trial)
Convert to open if anatomy unclear, severe inflammation, or aberrant biliary anatomy suspected

Second-line / adjunct

Percutaneous cholecystostomy tube — for poor surgical candidates (severe sepsis, ICU patients, high comorbidity) with planned interval cholecystectomy or definitive drainage
Endoscopic gallbladder drainage (EUS-guided) — emerging alternative for non-operative candidates
Delayed cholecystectomy 6-8 weeks if patient unable to undergo early surgery and inflammation has cooled
Treat acalculous cholecystitis with percutaneous cholecystostomy in critically ill patients

Complications

Gangrenous cholecystitis
Gallbladder perforation — localized abscess or biliary peritonitis
Empyema of the gallbladder
Emphysematous cholecystitis — gas in gallbladder wall; diabetics; Clostridium perfringens, E. coli; HIGH mortality, requires emergent cholecystectomy or open drainage
Mirizzi syndrome — cystic duct stone compresses CBD causing obstructive jaundice
Cholecystoenteric fistula — gallstone ileus (stone erodes into duodenum, lodges at ileocecal valve — Rigler triad: pneumobilia, SBO, ectopic stone)
Sepsis, multiorgan failure
Postcholecystectomy syndrome (persistent symptoms post-surgery — sphincter of Oddi dysfunction, retained stones)

PANCE pearls

Early laparoscopic cholecystectomy (<72 h) is preferred over delayed surgery (CHOCOLATE, ACDC trials).
Murphy sign: inspiratory arrest during RUQ palpation. Sonographic Murphy sign is more specific than clinical exam.
HIDA scan is the most accurate test for acute cholecystitis when ultrasound is equivocal — non-filling of the gallbladder at 1-4 h confirms cystic duct obstruction.
Acalculous cholecystitis: think in critically ill, TPN, mechanically ventilated, post-trauma, burn patients — high mortality; cholecystostomy often first-line.
Emphysematous cholecystitis: diabetic patients, gas in gallbladder wall on imaging, polymicrobial including Clostridium; surgical emergency.
Gallstone ileus (Rigler triad): pneumobilia + small bowel obstruction + ectopic gallstone; treat with enterolithotomy ± delayed cholecystectomy.
Mirizzi syndrome: cystic duct stone compressing CBD; preoperative MRCP critical to avoid bile duct injury.
Sickle cell patients with pigment stones — perioperative care includes transfusion to Hgb ~10 to reduce sickling.
Pregnancy: laparoscopic cholecystectomy is safe in 2nd trimester; avoid 1st (teratogenicity) and 3rd (technical difficulty).

References

Tokyo Guidelines TG18 — Yokoe M et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci 2018;25:41-54
CHOCOLATE Trial — Loozen CS et al. Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high-risk patients (CHOCOLATE). BMJ 2018;363:k3965
WSES 2020 — Pisano M et al. 2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy. World J Emerg Surg 2020;15:61

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