Acute Cholecystitis (Adult)

1. Clinical Overview

Summary

Acute cholecystitis is acute inflammation of the gallbladder, most commonly resulting from the sustained obstruction of the cystic duct by a gallstone (calculous cholecystitis, ~90% of cases). It is one of the most common surgical emergencies, accounting for a significant proportion of emergency hospital admissions. The condition ranges from mild, self-limiting inflammation to life-threatening gangrene, perforation, or sepsis. [1,2]

The modern management of acute cholecystitis is defined by the Tokyo Guidelines (TG18), which provide a standardized framework for diagnosis and severity grading. The historical "cool it off" approach with antibiotics and delayed interval surgery has been largely superseded by evidence supporting early laparoscopic cholecystectomy (within 72 hours to 7 days of symptom onset). This shift is supported by landmark trials showing that early surgery reduces total hospital stay and avoids the risk of recurrent biliary events while waiting for "interval" surgery. [3,4]

Key Facts

• Mechanism: Stone impaction in the cystic duct → increased intraluminal pressure → mucosal ischaemia → inflammatory mediator release (chemical) → secondary bacterial infection (50-85%).
• Murphy's Sign: The most pathognomonic sign (Sensitivity 97%). It is specifically defined as an inspiratory arrest during deep palpation of the Right Upper Quadrant (RUQ). [5]
• The "Seven Day" Rule: Cholecystectomy is ideally performed during the index admission. Beyond 7-10 days, local inflammation and fibrosis make laparoscopic dissection significantly more difficult.
• Acalculous Variant: Occurs in 10% of cases, typically in critically ill ICU patients. It carries a much higher mortality rate (up to 30%) and a higher risk of rapid gangrene. [6]
• Grade III (Severe): Defined by the presence of organ dysfunction. These patients often require percutaneous cholecystostomy as a bridge to stabilization rather than immediate surgery.

Clinical Pearls

The "Surgical Murphy" Pearl: Do not rely on "RUQ tenderness" alone. A true positive Murphy's sign requires the patient to stop their breath because the inflamed gallbladder hit your fingers. If they can keep breathing despite the pain, it's just tenderness.

The "Jaundice" Pearl: If a patient with suspected cholecystitis is jaundiced (Bilirubin > 34 μmol/L), you must rule out common bile duct stones (choledocholithiasis) or Mirizzi syndrome. Cholecystitis alone does not usually cause significant jaundice.

The "Biliary Colic vs. Cholecystitis" Pearl: Pain lasting > 6 hours, associated with fever and leukocytosis, is cholecystitis. Biliary colic is transient (less than 4-6 hours) and lacks systemic inflammatory markers.

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2. Epidemiology & Risk Factors

Incidence & Distribution

• Prevalence: 10–15% of the adult population in Western countries have gallstones; 1–3% of these will develop acute cholecystitis annually.
• Hospitalization: Cholecystectomy is the most common emergency surgical procedure performed by general surgeons.
• Gender: In younger adults, females are more affected (2:1 ratio), largely due to the effects of oestrogen on bile composition. This gap narrows with age. [7]

The "5 Fs" and Modern Risk Factors

The traditional mnemonic (Fair, Fat, Female, Forty, Fertile) remains a useful starting point, but clinical risk stratification is more nuanced: [8]

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3. Pathophysiology

1. Obstruction and Distension

The inciting event is almost always a stone impacting in the cystic duct or Hartmann's pouch. As the gallbladder continues to secrete mucus behind the obstruction, intraluminal pressure rises. This pressure compresses the intramural vessels, leading to venous and lymphatic congestion.

2. Chemical Inflammation

Initial injury is not bacterial. The retained bile is concentrated, and the enzyme phospholipase A converts biliary lecithin into lysolecithin, which is directly toxic to the gallbladder mucosa. This triggers the release of prostaglandins (I2 and E2), which further stimulate secretion and inflammation. [9]

3. Bacterial Colonization

While the initial phase is chemical, secondary bacterial infection occurs in 50-85% of cases within 24-48 hours. The most common isolates are:

• Escherichia coli (Commonest)
• Klebsiella species
• Enterococcus faecalis
• Bacteroides fragilis (Usually in perforated or gangrenous cases)

4. Progression to Necrosis

If the pressure is not relieved, arterial supply is compromised, leading to gangrenous cholecystitis (the most common complication). This may progress to perforation, which can be localized (abscess), free (biliary peritonitis), or chronic (cholecystoenteric fistula). [10]

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4. Clinical Presentation

Symptom Evolution

1. Prodrome: History of intermittent "biliary colic" (episodic RUQ pain after fatty meals).
2. Acute Phase: Constant, severe RUQ or epigastric pain lasting > 6 hours. Often radiates to the right scapula or shoulder (Boas' sign).
3. Systemic: Nausea, vomiting, and low-grade fever are common.

Physical Signs

• Murphy's Sign: Deep palpation under the right costal margin while the patient inhales; positive if inspiration is halted by pain.
• RUQ Guarding: Localized peritoneal irritation.
• Palpable Mass: In 20% of cases, an inflamed, distended gallbladder wrapped in omentum may be felt.
• Jaundice: Suggests a "Mirizzi effect" or secondary stones in the common bile duct.

Severity Grading (TG18)

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5. Investigations

1. Laboratory Assessment

• FBC: Leukocytosis with a left shift is common.
• CRP: Highly sensitive; a CRP > 100 mg/L is a strong predictor of gangrenous change.
• LFTs: Usually normal in pure cholecystitis. A raised ALP/GGT or Bilirubin warrants an MRCP to check for CBD stones.
• Amylase/Lipase: To exclude gallstone pancreatitis.

2. Imaging: The Diagnostic Hierarchy

• Ultrasound (First-line): Sensitivity 88%, Specificity 80%. Look for:
  • Gallstones and/or sludge.
  • Gallbladder wall thickening (> 4 mm).
  • Pericholecystic fluid.
  • Sonographic Murphy's Sign (maximal tenderness directly over the gallbladder). [11]
• HIDA Scan (Gold Standard for Diagnosis): Used if US is inconclusive. Non-visualization of the gallbladder confirms cystic duct obstruction.
• CT Abdomen: Excellent for identifying complications (gas in the wall, perforation, or abscess) but less sensitive than US for small stones.
• MRCP: Mandatory if CBD stones are suspected (e.g., dilated CBD on US or abnormal LFTs).

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6. Management: The Acute Algorithm

Management Flowchart (ASCII)

                  [ACUTE CHOLECYSTITIS (TG18)]
                               |
                  +------------v------------+
                  |  INITIAL RESUSCITATION  | (NBM, IV Fluids, Analgesia)
                  |  ANTIBIOTICS (IF SEPTIC)|
                  +------------+------------+
                               |
                  +------------v------------+
                  |    ASSESS TG18 GRADE   |
                  +------------+------------+
                   /           |           \
           [GRADE I]       [GRADE II]      [GRADE III]
               |               |                |
        +------v------+ +------v------+  +------v------+
        | EARLY LAP   | | EARLY LAP   |  | RESUSCITATE |
        | CHOLE       | | CHOLE       |  | & STABILIZE |
        | (less than 72h-7d)   | | (Expert)    |  +------+------+
        +-------------+ +------+------+         |
                               |         +------v------+
                        [IF HIGH RISK]   | PERCUTANEOUS|
                               |         | DRAINAGE    |
                        +------v------+  +------+------+
                        | DRAINAGE    |         |
                        +-------------+  [INTERVAL SURGERY]

1. Medical Management

• Fluids: Correct electrolyte imbalances and dehydration.
• Analgesia: NSAIDs (e.g., Diclofenac) are highly effective for biliary pain; Opioids (Morphine) for severe pain.
• Antibiotics: Indicated for Grade II/III or sepsis. Standard regimen: Piperacillin-Tazobactam or Ceftriaxone + Metronidazole. [12]

2. Surgical Management

• Laparoscopic Cholecystectomy: The gold standard.
• Timing: Landmark studies (ACERTA, Cochrane) prove that surgery within 7 days is superior to "interval" surgery (6 weeks later). It reduces total hospital stay and complications.
• The Critical View of Safety (CVS): A mandatory intra-operative requirement before clipping. The surgeon must see:
  1. Calot's triangle cleared of fat/fibers.
  2. The lower third of the gallbladder separated from the liver bed.
  3. Only two structures (Cystic duct and Cystic artery) entering the gallbladder. [13]

3. Percutaneous Cholecystostomy

Reserved for Grade III patients or those unfit for emergency surgery. A tube is placed through the liver (transhepatic) into the gallbladder to decompress the pus. This "cools down" the sepsis, allowing for elective surgery 6–12 weeks later.

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7. Complications

• Gangrenous Cholecystitis: Occurs in ~20% of cases; high risk in elderly and diabetics.
• Gallbladder Empyema: The gallbladder fills with frank pus; requires urgent drainage.
• Perforation:
  • "Type 1: Free perforation into the peritoneum (rare, 1%)."
  • "Type 2: Localized perforation with abscess (common)."
  • "Type 3: Cholecystoenteric fistula (leads to gallstone ileus)."
• Mirizzi Syndrome: A large stone in the gallbladder neck compresses the common hepatic duct, causing jaundice.
• Bile Duct Injury: The most dreaded surgical complication (0.3-0.5%). Often due to misidentification of the CBD as the cystic duct. [14]

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8. Evidence & Landmark Trials

1. Tokyo Guidelines (TG18): The international consensus establishing the diagnostic criteria and the grading system used worldwide to guide treatment timing. [1,2]
2. ACERTA Trial (2013): A large multicenter trial demonstrating that early laparoscopic cholecystectomy (within 24 hours of admission) significantly reduced hospital stay compared to delayed surgery, with no increase in morbidity. [PMID: 24022431]
3. CHOCOLATE Trial (2018): Showed that in high-risk patients (Grade II/III), laparoscopic cholecystectomy was superior to percutaneous drainage in terms of reducing major complications and need for re-intervention. [PMID: 30297541]
4. Gurusamy et al. (Cochrane 2013): Meta-analysis confirming that early surgery (within 1 week) is as safe as delayed surgery (after 6 weeks) but carries a significant socioeconomic benefit by reducing total hospital stay. [PMID: 23813476]

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9. Single Best Answer (SBA) Questions

Question 1

A 45-year-old female presents with constant RUQ pain and fever (38.2°C). US shows gallstones, a thickened GB wall (5mm), and pericholecystic fluid. LFTs are normal. What is the most appropriate management?

• A) Discharge with elective surgery in 6 weeks
• B) Urgent ERCP followed by cholecystectomy
• C) Early laparoscopic cholecystectomy within this admission
• D) Percutaneous cholecystostomy
• E) Intravenous antibiotics for 2 weeks, then discharge
• Answer: C. Early surgery during index admission is the standard of care for Grade I/II cholecystitis.

Question 2

Which of the following defines Grade III (Severe) acute cholecystitis according to the Tokyo Guidelines?

• A) Presence of an appendicolith
• B) WCC > 18,000 /mm³
• C) Palpable gallbladder mass
• D) Serum Creatinine > 176 μmol/L
• E) Symptoms lasting more than 72 hours
• Answer: D. Grade III is defined by organ dysfunction, of which renal failure (Cr > 176) is one criterion. B, C, and E are Grade II criteria.

Question 3

During a laparoscopic cholecystectomy, the surgeon insists on achieving the "Critical View of Safety." What is the primary purpose of this technique?

• A) To reduce the risk of wound infection
• B) To identify the Phrenic nerve
• C) To prevent injury to the Common Bile Duct
• D) To facilitate faster recovery
• E) To ensure all stones are removed
• Answer: C. The CVS is a standardized method to ensure that the Common Bile Duct is not accidentally clipped or divided.

Question 4

A 70-year-old man in the ICU following a major burn develops a fever and RUQ tenderness. US shows a distended gallbladder with wall thickening but no stones. What is the most likely diagnosis?

• A) Biliary Colic
• B) Chronic Cholecystitis
• C) Acalculous Cholecystitis
• D) Mirizzi Syndrome
• E) Ascending Cholangitis
• Answer: C. Acalculous cholecystitis is common in critically ill patients due to stasis and ischaemia.

Question 5

What is "Boas' Sign"?

• A) Cessation of inspiration on RUQ palpation
• B) Pain in the RIF on palpation of the LIF
• C) Referred pain to the right scapula/shoulder area
• D) Palpable gallbladder in a jaundiced patient
• E) Bruising around the flanks
• Answer: C. Boas' sign is hyperaesthesia or pain referred to the right scapular region.

Question 6

Which organism is most commonly isolated from the bile in patients with acute cholecystitis?

• A) Pseudomonas aeruginosa
• B) Escherichia coli
• C) Staphylococcus aureus
• D) Clostridium difficile
• E) Streptococcus pyogenes
• Answer: B. E. coli is the most common aerobe isolated.

Question 7

A patient with cholecystitis has a Bilirubin of 65 μmol/L and an ALP of 450 U/L. US shows a 5mm stone in the gallbladder and a 10mm Common Bile Duct. What is the next best investigation?

• A) HIDA Scan
• B) CT Abdomen
• C) MRCP
• D) Diagnostic Laparoscopy
• E) Repeat LFTs in 24 hours
• Answer: C. Raised Bilirubin and a dilated CBD suggest choledocholithiasis, which requires MRCP for confirmation before intervention.

Question 8

What is the "Sonographic Murphy's Sign"?

• A) Visualization of a stone in the cystic duct
• B) Maximal tenderness when the US probe is pressed over the gallbladder
• C) Gallbladder wall thickening > 4mm on US
• D) The appearance of a "target sign" on US
• E) Absence of Doppler flow in the gallbladder wall
• Answer: B. It is the ultrasonic equivalent of the clinical Murphy's sign and is more specific.

Question 9

A 78-year-old woman with severe CCF presents with Grade III cholecystitis and septic shock. She is unfit for general anaesthesia. What is the most appropriate management?

• A) Immediate Laparoscopic Cholecystectomy
• B) Open Cholecystectomy
• C) Percutaneous Cholecystostomy
• D) High-dose oral antibiotics only
• E) Comfort care only
• Answer: C. Percutaneous drainage is the treatment of choice for patients with Grade III disease or those too frail for surgery.

Question 10

In the ACERTA trial, what was the primary benefit of early versus delayed cholecystectomy?

• A) Lower rate of bile duct injury
• B) Reduced conversion rate to open surgery
• C) Reduced total hospital stay
• D) Improved survival at 5 years
• E) Reduced incidence of post-cholecystectomy syndrome
• Answer: C. The primary proven benefit is a shorter total length of stay and reduced overall costs.

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12. Hepatobiliary Dynamics: The Murphy's Sign Mechanics

Why does it "stop breathing" when pressed?

A. The Mechanical Trigger

• The Anatomy: The gallbladder sits directly beneath the liver. When it is inflamed, the peritoneal covering (the lining) is extremely sensitive.
• The Mechanics: As the patient breathes in, the diaphragm pushes the liver and the inflamed gallbladder downward. If a doctor presses their hand in that specific spot, the inflamed gallbladder is "trapped" between the doctor's hand and the patient's descending liver.
• The Reflextive "Catch": The sudden pain causes the patient to reflexively stop their breath (the respiratory catch). This is "Murphy's Sign."

B. Acalculous Mechanics

• In critically ill patients (ICU/Trauma), the gallbladder can become inflamed even without stones. This is due to bile stasis and ischemia. The bile becomes thick ("sludge"), and because the patient isn't eating, the gallbladder never contracts, leading to pressure build-up and wall death.

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13. Molecular Diagnostics: HIDA and Procalcitonin

Going deeper than just a simple Ultrasound.

A. HIDA Scan (Cholescintigraphy)

• The Gold Standard: If Ultrasound is unclear, a HIDA scan is the most sensitive test.
• The Logic: A radioactive tracer is injected. If the gallbladder is not seen after 60 minutes, it proves the "cystic duct" is blocked (the definition of cholecystitis).

B. Procalcitonin as a Severity Marker

• New studies suggest that Procalcitonin levels are better than CRP at predicting which patients have a "gangrenous" (black/dead) gallbladder, which requires more urgent surgery and has a higher risk of complications.

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14. Surgical Nuances: The "Safety Zone"

The secret to avoiding the "Surgeon's Nightmare" (Bile Duct Injury).

A. The Critical View of Safety (CVS)

• To safely remove the gallbladder, the surgeon must clearly see two—and only two—structures entering the gallbladder: the Cystic Duct and the Cystic Artery. The lower part of the gallbladder must be "peeled" away from the liver to reveal the "windows" behind these structures. Only then is it safe to cut.

B. Subtotal Cholecystectomy

• When the inflammation is so severe that the anatomy is "frozen" or dangerous, the surgeon may perform a Subtotal surgery. Instead of removing everything, they cut the gallbladder open, remove the stones, and leave the back wall attached to the liver. This is a "safety first" approach to avoid injuring the main bile duct.

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15. Future Trends: EUS-Guided Drainage

The end of the "Percutaneous Drain"?

A. EUS-Guided Gallbladder Drainage (EUS-GBD)

• Traditionally, frail patients got an external drain through their skin into the gallbladder.
• The Innovation: Using an Endoscopic Ultrasound (EUS) scope through the stomach, a doctor can place a "stunt" directly from the gallbladder into the stomach or duodenum.
• The Result: Internal drainage, no external tubes, less pain, and better quality of life for the patient.

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16. Patient Explanation

"Acute cholecystitis is a sudden, painful swelling of your gallbladder, usually caused by a gallstone that has become stuck and blocked the exit. It's like a small blockage in a sink that causes the water to get stagnant and smelly. In the hospital, we use antibiotics to clear the infection, but the best permanent fix is to remove the gallbladder. This is usually done through 'keyhole surgery.' You can live completely normally without a gallbladder because your liver—the factory that makes the bile—is still working perfectly; it will just send the bile straight to your stomach instead of storing it in the 'bag' that we remove."

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17. Examination Focus: Viva & OSCE Points

The "Tokyo" Viva

• Severity Grading: Be able to classify into Grade I (Mild), Grade II (Moderate - palpable mass/WCC > 18), or Grade III (Severe - organ failure).
• The "Culture" Rule: Mention that bile cultures are positive in ~50-70% of cases, often with E. coli, Klebsiella, or Enterococcus.
• The "Window" of Surgery: Emphasize that early surgery (less than 72 hours from symptom onset) is superior to delayed surgery in terms of total hospital stay and costs.

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18. References

1. Yokoe M, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci. 2018. [PMID: 29032636]
2. Strasberg SM, et al. Rationale and use of the Critical View of Safety in laparoscopic cholecystectomy. J Am Coll Surg. 2010. [PMID: 20610259]
3. Gutt CN, et al. Acute cholecystitis: early versus delayed cholecystectomy (ACERTA). Ann Surg. 2013. [PMID: 24022431]
4. Di Saverio S, et al. WSES guidelines for the management of acute cholecystitis. World J Emerg Surg. 2020.
5. Teoh AY, et al. EUS-guided gallbladder drainage versus percutaneous cholecystostomy for acute cholecystitis in high-risk surgical patients. Gastrointest Endosc. 2020.

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Last Updated: 2026-01-05 | MedVellum Editorial Team