Overview
Acute Cholecystitis
1. Clinical Overview
Summary
Acute cholecystitis is gallbladder inflammation, 90-95% due to gallstone obstruction of cystic duct. Presents with RUQ pain >6 hours (vs biliary colic <6h), fever, Murphy's sign. Tokyo Guidelines grade severity. Early laparoscopic cholecystectomy (<72h) is preferred. Percutaneous drainage for critically ill.
Key Facts
- Definition: Gallbladder inflammation from cystic duct obstruction
- Cause: Gallstones (90-95%); acalculous (5-10%)
- Diagnostic test: RUQ ultrasound (95% sensitive)
- Treatment: Early laparoscopic cholecystectomy
2. Epidemiology
Overview
Acute cholecystitis is inflammation of the gallbladder, most commonly (90-95%) due to obstruction of the cystic duct by gallstones. It presents with persistent right upper quadrant pain, fever, and tenderness, distinguishing it from uncomplicated biliary colic which resolves spontaneously within 6 hours.
Classification
By Etiology:
- Calculous (90-95%): Gallstone impaction in cystic duct
- Acalculous (5-10%): Inflammation without stones; typically in critically ill patients
By Severity (Tokyo Guidelines 2018):
| Grade | Definition | Management |
|---|---|---|
| Grade I (Mild) | No organ dysfunction, limited inflammation | Early laparoscopic cholecystectomy |
| Grade II (Moderate) | WBC >18,000, mass, symptoms >2h, marked local inflammation | Early surgery if stable; delayed if high risk |
| Grade III (Severe) | Organ dysfunction (CV, neuro, respiratory, renal, hepatic, hematologic) | ICU care, urgent drainage, delayed surgery |
By Pathological Stage:
- Edematous cholecystitis (Day 1-4)
- Necrotizing/Gangrenous cholecystitis (Day 3-5)
- Suppurative cholecystitis (Day 7-10)
- Perforated cholecystitis (after Day 10)
Epidemiology
- Gallstone prevalence: 10-15% of adults in Western populations
- Annual incidence of cholecystitis in gallstone patients: 1-3%
- Gender: Females > Males (2:1) - "Fat, Female, Fertile, Forty"
- Peak age: 40-60 years
- Mortality: <1% uncomplicated; 10-50% acalculous/gangrenous
Etiology
Calculous Cholecystitis:
- Gallstone impaction in cystic duct (most common)
- Risk factors: Obesity, rapid weight loss, pregnancy, TPN, cirrhosis
Acalculous Cholecystitis Risk Factors:
- Critical illness (sepsis, trauma, burns, major surgery)
- TPN administration
- Prolonged fasting/NPO status
- Mechanical ventilation
- Diabetes mellitus
- Vasculitis, HIV/AIDS
3. Pathophysiology
Mechanism of Disease
Calculous Cholecystitis:
- Gallstone impaction: Stone obstructs cystic duct
- Bile stasis: Continued bile secretion with no outflow
- Distension: Gallbladder wall stretching → ischemia
- Chemical inflammation: Lysolecithin release from bile
- Secondary bacterial infection: Translocation through compromised wall
- Progression: Edema → Gangrene → Perforation
Acalculous Cholecystitis:
- Bile stasis: Fasting, TPN, opioids decrease gallbladder emptying
- Ischemia: Hypoperfusion in critical illness, vasculitis
- Mucosal injury: Concentrated bile, ischemia-reperfusion injury
- Rapid progression to gangrene: More fulminant course than calculous
Bacterial Pathogens
- Enteric gram-negatives: E. coli (most common), Klebsiella, Enterobacter
- Anaerobes: Bacteroides, Clostridium (especially in emphysematous)
- Gram-positives: Enterococcus, Streptococci
Complications
| Complication | Pathophysiology | Clinical Clue |
|---|---|---|
| Gangrenous cholecystitis | Gallbladder wall ischemia/necrosis | Out-of-proportion pain, sepsis |
| Emphysematous cholecystitis | Gas-forming organisms (Clostridium, E. coli) | Diabetic, crepitus, gas on imaging |
| Gallbladder perforation | Wall necrosis and rupture | Sudden pain relief then peritonitis |
| Cholecystoenteric fistula | Erosion into bowel | Gallstone ileus, pneumobilia |
| Mirizzi syndrome | Stone compressing common hepatic duct | Jaundice, dilated CBD |
4. Clinical Presentation
Symptoms
Atypical Presentations:
Physical Examination
Vital Signs:
Abdominal Examination:
| Sign | Description | Significance |
|---|---|---|
| Murphy's Sign | Inspiratory arrest during RUQ palpation | Most specific physical finding (65-95%) |
| RUQ tenderness | Localized to gallbladder fossa | Universal finding |
| Palpable gallbladder | May be appreciated in thin patients | Suggests hydrops |
| Peritoneal signs | Guarding, rebound, rigidity | Suggests perforation/peritonitis |
| Jaundice | Scleral icterus, skin yellowing | Consider choledocholithiasis |
Concerning Findings:
RUQ or epigastric pain
Constant (unlike colicky biliary colic), >6 hours duration
Radiation
To right shoulder/scapula (referred pain via phrenic nerve)
Nausea and vomiting
Present in 60-70% of patients
Anorexia
Common accompanying symptom
Fever/chills
Suggests secondary infection
History of prior episodes
75% have had previous biliary colic
Precipitant
Often follows fatty meal
5. Clinical Examination
(Integrated into Clinical Presentation above)
Red Flags
Life-Threatening Conditions
| Finding | Concern | Action |
|---|---|---|
| Charcot's triad (fever, jaundice, RUQ pain) | Ascending cholangitis | Emergent biliary decompression (ERCP) |
| Reynolds' pentad (+ hypotension, AMS) | Septic ascending cholangitis | ICU, emergent ERCP/drainage |
| Air in gallbladder wall (CT/X-ray) | Emphysematous cholecystitis | Emergent surgical consultation |
| Free peritoneal fluid | Gallbladder perforation | Emergent surgery |
| Severe sepsis/septic shock | Overwhelming infection | Aggressive resuscitation, urgent intervention |
| Acalculous cholecystitis in ICU patient | High mortality if delayed | Percutaneous cholecystostomy |
High-Risk Features
- Age >70 years
- Diabetes mellitus (gangrenous cholecystitis more common)
- Immunocompromised state
- Symptom duration >72 hours
- Total bilirubin >2 mg/dL
- WBC >18,000/μL
6. Investigations
Differential Diagnosis
| Diagnosis | Distinguishing Features | Key Investigations |
|---|---|---|
| Biliary colic | Pain <6 hours, resolves spontaneously, no fever | US normal wall thickness |
| Choledocholithiasis | Jaundice, elevated LFTs, dilated CBD | MRCP/ERCP for CBD stone |
| Cholangitis | Charcot's triad, toxic appearance | Blood cultures, urgent ERCP |
| Acute pancreatitis | Epigastric pain radiating to back, elevated lipase | Lipase >x ULN, CT findings |
| Peptic ulcer disease/perforation | Epigastric pain, peritonitis if perforated | Upright CXR, CT for free air |
| Acute hepatitis | Jaundice, elevated transaminases, risk factors | Hepatitis serologies, LFTs |
| Appendicitis (high cecum) | RLQ pain, migration, younger patients | CT findings |
| Right lower lobe pneumonia | Cough, dyspnea, referred abdominal pain | CXR infiltrate |
| Fitz-Hugh-Curtis syndrome | RUQ pain in young woman with PID | Pelvic exam, STI testing |
| Myocardial infarction (inferior) | ECG changes, troponin elevation | ECG, troponin |
Diagnostic Approach
Clinical Scoring
Tokyo Guidelines Diagnostic Criteria (TG18):
| Category | Criteria |
|---|---|
| A. Local signs | Murphy's sign, RUQ mass/pain/tenderness |
| B. Systemic signs | Fever >8°C, elevated CRP, elevated WBC |
| C. Imaging | Imaging findings consistent with acute cholecystitis |
Definite diagnosis: A + B + C or one item from each A and B + C Suspected diagnosis: A (local signs of inflammation)
Laboratory Studies
| Test | Expected Findings | Clinical Utility |
|---|---|---|
| CBC | Leukocytosis (>1,000), left shift | Supports diagnosis; WBC >8,000 suggests severe |
| CMP | May have mild transaminase elevation | Assess for choledocholithiasis |
| Total bilirubin | May be mildly elevated (<4 mg/dL) | Higher levels suggest CBD stone |
| Alkaline phosphatase | Often elevated | Biliary tract involvement |
| GGT | Elevated | Specific for biliary disease |
| Lipase | Normal or mildly elevated | Rule out pancreatitis; moderate elevation may occur |
| Lactate | Normal or elevated | Elevated suggests tissue ischemia/sepsis |
| Procalcitonin | May help distinguish | Elevated in bacterial infection |
Imaging Studies
Right Upper Quadrant Ultrasound (First-Line):
- Sensitivity: 88-95%
- Specificity: 80-90%
- Findings:
- Gallstones or sludge
- Wall thickening >3-4mm
- Pericholecystic fluid
- Sonographic Murphy sign (pain with probe pressure over gallbladder)
- Gallbladder distension (>4cm transverse, >10cm long)
- Advantages: Bedside, no radiation, excellent for stones
CT Abdomen/Pelvis:
- Role: When US inconclusive, assessing complications
- Findings: Wall thickening, stranding, stones (limited), gas (emphysematous), perforation
- Advantages: Better for complications, alternative diagnoses
- Disadvantages: Radiation, less sensitive for stones
HIDA Scan (Hepatobiliary Iminodiacetic Acid):
- Sensitivity: 90-95%
- Specificity: 85-95%
- Interpretation: Non-filling of gallbladder after 4 hours = cystic duct obstruction
- Use: When US inconclusive and high clinical suspicion
- Limitations: Time-consuming (1-4 hours), false positives in fasting/TPN patients
MRCP:
- Role: Suspected choledocholithiasis, planning for ERCP
- Advantage: Non-invasive CBD evaluation
Diagnostic Algorithm
- Clinical suspicion (RUQ pain + fever + tenderness)
- Labs: CBC, CMP, LFTs, lipase
- RUQ ultrasound (first-line)
- If US positive → Surgical consultation
- If US equivocal → Consider HIDA or CT
- If CBD dilation/elevated bilirubin → MRCP or ERCP
7. Management
Principles of Management
- NPO Status: Rest the biliary system
- IV Fluid Resuscitation: Correct dehydration
- Analgesia: Adequate pain control
- Antibiotics: Empiric coverage for biliary pathogens
- Surgical Consultation: Early involvement for cholecystectomy planning
- Source Control: Cholecystectomy or percutaneous drainage
Resuscitation
- IV Access: Large-bore IV access
- Fluids: Crystalloid bolus 20-30 mL/kg for dehydration/hypotension
- Electrolyte Correction: Monitor and replace K+, Mg2+
- Glucose Control: Tight glycemic management, especially in diabetics
Analgesia
| Medication | Dose | Notes |
|---|---|---|
| Morphine | 0.1 mg/kg IV | Titrate to effect |
| Hydromorphone | 0.5-1 mg IV | Alternative to morphine |
| Ketorolac | 15-30 mg IV | Adjunct; avoid if renal dysfunction |
| Acetaminophen | 1g IV | Antipyretic, adjunct analgesia |
Note: Historical concern about opioids causing sphincter of Oddi spasm is not clinically significant.
Antibiotic Therapy
Mild-Moderate (Grade I-II):
| Regimen | Dose | Duration |
|---|---|---|
| Ceftriaxone + Metronidazole | 2g + 500mg IV q24/12h | Until cholecystectomy |
| Cefazolin + Metronidazole | 2g + 500mg IV q8/12h | If low-risk for resistance |
Severe (Grade III) or Healthcare-Associated:
| Regimen | Dose | Duration |
|---|---|---|
| Piperacillin-Tazobactam | 4.5g IV q8h | Until source control + 4-7 days |
| Meropenem | 1g IV q8h | If ESBL risk or severe allergy |
| + Vancomycin | 15-20mg/kg IV q8-12h | If MRSA risk |
Duration: Continue for 4-7 days after source control achieved
Surgical Management
Laparoscopic Cholecystectomy (Definitive Treatment):
- Timing options:
- Early (within 72 hours): Preferred; lower morbidity, shorter hospital stay
- Delayed (6-12 weeks): Reserved for high-risk patients after cooling down
- Conversion to open: 5-15% of cases
- Intraoperative cholangiogram: If CBD stone suspected
Open Cholecystectomy:
- Indicated for: Unclear anatomy, dense adhesions, bleeding, injury
Subtotal Cholecystectomy:
- When complete removal unsafe due to inflammation/scarring
- Leave posterior wall attached to liver
Non-Surgical Management
Percutaneous Cholecystostomy:
- Indications:
- Critically ill patients (Grade III)
- Poor surgical candidates
- Failed conservative management
- Acalculous cholecystitis in ICU patients
- Technique: US or CT-guided transhepatic or transperitoneal drainage
- Success rate: 90% for symptom relief
- Follow-up: Interval cholecystectomy when stable (6-12 weeks)
Endoscopic Gallbladder Drainage:
- Emerging alternative to percutaneous drainage
- EUS-guided transmural drainage
8. Complications
Disposition
Admission Criteria
- All patients with acute cholecystitis require admission
- Surgical floor: Uncomplicated, stable patients
- ICU: Grade III severity, septic shock, multi-organ dysfunction
ICU Criteria
- Hemodynamic instability requiring vasopressors
- Respiratory failure
- Altered mental status
- Multi-organ dysfunction
- Gangrenous/emphysematous cholecystitis
Discharge Criteria (Post-Cholecystectomy)
- Tolerating oral intake
- Adequate pain control on oral medications
- Afebrile for ≥24 hours
- Stable vital signs
- No signs of bile leak or bleeding
- Understanding of discharge instructions
Follow-Up Recommendations
| Situation | Follow-Up |
|---|---|
| Post-laparoscopic cholecystectomy | Surgeon in 1-2 weeks |
| Percutaneous cholecystostomy | Surgeon in 1-2 weeks; plan for interval surgery |
| Incidental choledocholithiasis | Gastroenterology for ERCP |
| Pathology concerning for malignancy | Oncology referral urgently |
11. Patient/Layperson Explanation
Condition Explanation
- "Your gallbladder has become infected and inflamed, likely due to a gallstone blocking the drainage tube."
- "The gallbladder stores bile, which helps digest fatty foods. When it becomes blocked, it can get infected."
- "The standard treatment is surgical removal of the gallbladder, which you can live normally without."
Post-Cholecystectomy Instructions
Diet:
- Start with clear liquids, advance as tolerated
- Low-fat diet for first 2-4 weeks to minimize diarrhea
- Some patients experience temporary diarrhea after fatty meals
- Most patients can resume normal diet within 1 month
Activity:
- Light activity immediately; avoid heavy lifting >10 lbs for 2 weeks
- May shower after 24-48 hours
- Return to desk work: 1 week
- Return to physical labor: 2-4 weeks
Wound Care:
- Keep incisions clean and dry
- Steri-strips fall off naturally in 7-10 days
- Watch for signs of infection
Warning Signs Requiring Return
- Fever >38.5°C (101.3°F)
- Increasing abdominal pain or distension
- Persistent nausea/vomiting
- Jaundice (yellowing of eyes or skin)
- Dark urine or pale stools
- Redness, swelling, or discharge from incisions
- Difficulty breathing
9. Prognosis & Outcomes
Special Populations
Elderly (>65 years)
- Higher rate of gangrenous (15-20%) and perforated cholecystitis
- Often present with vague symptoms
- Higher surgical mortality: 5-10% vs <1% in younger patients
- Consider percutaneous drainage if poor surgical candidate
- Frailty assessment guides intervention choice
Pregnant Patients
- Cholecystitis is second most common non-obstetric surgical emergency
- Safest timing: Second trimester for surgery
- Ultrasound is diagnostic modality of choice
- Laparoscopic cholecystectomy safe in all trimesters if indicated
- Conservative management higher failure rate than non-pregnant
- Untreated: 25% fetal mortality, 6% maternal mortality in complicated cases
Diabetic Patients
- Higher rate of acalculous and emphysematous cholecystitis
- May have blunted pain response
- Higher perforation rates (20-30%)
- More likely to have gangrenous cholecystitis
- Strict glucose control important perioperatively
- Lower threshold for imaging and intervention
Critically Ill/ICU Patients
- Acalculous cholecystitis in 1-3% of ICU patients
- Often presents as unexplained sepsis
- Higher mortality (30-50%) if missed
- Bedside ultrasound crucial for diagnosis
- Percutaneous cholecystostomy preferred over surgery
- Maintain high index of suspicion
Immunocompromised Patients
- Higher complication rates
- May lack typical inflammatory response
- Consider opportunistic infections (CMV, Cryptosporidium)
- Broader antibiotic coverage
- Lower threshold for intervention
Quality Metrics
Performance Indicators
| Metric | Target | Rationale |
|---|---|---|
| Time to antibiotics | <3 hours | Reduces progression |
| Time to surgery (uncomplicated) | <72 hours | Improved outcomes |
| Laparoscopic approach | >0% | Standard of care |
| 30-day mortality | <1% uncomplicated | Quality benchmark |
| Readmission rate | <5% | Marker of complications |
| Bile duct injury rate | <0.5% | Surgical quality indicator |
Documentation Requirements
- Time of symptom onset
- Vital signs including temperature trends
- Physical examination findings including Murphy sign
- Laboratory results (CBC, LFTs, lipase)
- Imaging findings and interpretation
- Tokyo severity grade
- Antibiotic timing, choice, and rationale
- Surgical consultation time and plan
- Pain management approach
- Disposition and follow-up plan
10. Evidence & Guidelines
Key Clinical Pearls
Diagnostic Pearls
- Murphy's sign is key: Deep inspiration arrest with RUQ palpation
- Pain >6 hours distinguishes from biliary colic: Colic resolves on its own
- Sonographic Murphy is more sensitive: Pain with probe over gallbladder
- Wall thickening + stones + fluid is classic triad: On ultrasound
- Normal LFTs don't exclude CBD stones: 30-40% of CBD stones have normal LFTs
- High bilirubin with normal ALP suggests hemolysis, not obstruction
Treatment Pearls
- Early surgery is preferred: Within 72 hours has best outcomes
- Don't wait for surgery to start antibiotics: Begin empirically
- Grade III needs ICU and drainage first: Surgery can wait
- Percutaneous cholecystostomy saves lives in critically ill patients
- Antibiotics alone fail in 40%: Definitive treatment is cholecystectomy
Disposition Pearls
- All acute cholecystitis needs admission: No outpatient management
- Plan for definitive treatment before discharge: Schedule cholecystectomy
- Delayed surgery has higher complication rates: Adhesions, inflammation persist
- Follow pathology: Incidental gallbladder cancer requires additional surgery
12. References
- Yokoe M, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):41-54.
- Okamoto K, et al. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):55-72.
- Gallaher JR, Charles A. Acute Cholecystitis: A Review. JAMA. 2022;327(10):965-975.
- Ansaloni L, et al. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg. 2016;11:25.
- Gurusamy KS, et al. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Cochrane Database Syst Rev. 2013;(6):CD005440.
- AAST Practice Guidelines Committee. American Association for the Surgery of Trauma emergency general surgery guidelines. J Trauma Acute Care Surg. 2019.
- Regimbeau JM, et al. Antibiotics vs Cholecystectomy for Acute Cholecystitis. N Engl J Med. 2014;371(9):866-867.
- UpToDate. Acute cholecystitis: Clinical features, diagnosis, and management. 2024.