Acute Cholecystitis

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 Acute Cholecystitis

1. Definition

Acute cholecystitis is defined as the acute inflammation of the gallbladder, most commonly caused by obstruction of the cystic duct, typically due to gallstones (cholelithiasis). The inflammation results from bile stasis and secondary bacterial infection and can lead to serious complications such as gangrene, perforation, peritonitis, or abscess formation if not managed promptly.

It is one of the most frequent causes of acute abdominal pain, and early diagnosis and treatment are essential to prevent morbidity and mortality.

2. Anatomy and Physiology

The gallbladder is a pear-shaped organ located beneath the liver, responsible for storing and concentrating bile produced by the liver. Bile enters the gallbladder via the cystic duct and exits during digestion in response to cholecystokinin (CCK), flowing into the duodenum through the common bile duct.

Normal physiology involves the rhythmic contraction of the gallbladder to aid in fat digestion. When this outflow is impaired, bile stasis leads to inflammation and potential infection.

3. Etiology

3.1. Calculous Cholecystitis

Approximately 90–95% of acute cholecystitis cases are due to gallstone-induced obstruction of the cystic duct. Gallstones are composed primarily of cholesterol, calcium bilirubinate, and calcium carbonate. Obstruction causes bile accumulation and increased intraluminal pressure, leading to inflammation and ischemia.

3.2. Acalculous Cholecystitis

Accounts for 5–10% of cases, especially in critically ill patients. This form arises without gallstones and is thought to result from bile stasis, ischemia, infection, and biliary sludge. It is associated with:

  • ICU patients
  • Sepsis or systemic infections
  • Total parenteral nutrition (TPN)
  • Major trauma or burns
  • Mechanical ventilation
  • Prolonged fasting

4. Pathophysiology

4.1. Duct Obstruction

The initial event is typically cystic duct obstruction, leading to increased pressure and distention of the gallbladder. This causes venous and lymphatic congestion and eventually ischemic injury to the gallbladder wall.

4.2. Bile Stasis and Bacterial Infection

Stagnant bile facilitates the growth of enteric bacteria (most commonly Escherichia coli, Klebsiella, Enterococcus). These bacteria ascend from the duodenum and invade the gallbladder wall, triggering inflammation.

4.3. Inflammatory Response

The combination of chemical injury from bile salts, ischemia, and bacterial infection leads to a robust inflammatory response. If unresolved, this can progress to:

  • Gangrenous cholecystitis
  • Empyema
  • Perforation
  • Peritonitis

5. Epidemiology

  • Occurs in 10–20% of patients with gallstones
  • Women are 2–3 times more likely to be affected, often due to hormonal influences on bile composition (estrogens increase cholesterol saturation).
  • Peak incidence: 40–60 years
  • Risk factors:
    • Obesity
    • Rapid weight loss
    • Female sex
    • Pregnancy
    • Diabetes mellitus
    • Prolonged fasting or TPN

6. Clinical Presentation

6.1. Symptoms

  • Right upper quadrant (RUQ) abdominal pain: Sudden, severe, lasting more than 6 hours
  • Pain may radiate to the right shoulder or scapula
  • Nausea, vomiting
  • Fever, chills
  • Anorexia
  • Aggravation after fatty meals

6.2. Physical Exam

  • RUQ tenderness
  • Murphy’s sign: Inspiratory arrest upon deep palpation of the RUQ
  • Rebound tenderness or guarding (suggests peritonitis)
  • Mild jaundice may be present

7. Diagnosis

7.1. Laboratory Tests

  • Leukocytosis
  • Elevated C-reactive protein (CRP) and ESR
  • Mild elevation in AST, ALT, ALP, and bilirubin if bile duct is involved

7.2. Imaging Studies

Abdominal Ultrasound (US)

  • First-line diagnostic tool
  • Sensitivity: 88–94%
  • Findings:
    • Gallstones
    • Gallbladder wall thickening (>3 mm)
    • Pericholecystic fluid
    • Gallbladder distention (>4 cm)
    • Sonographic Murphy’s sign

Computed Tomography (CT)

  • Better at identifying complications
  • Shows gallbladder wall edema, gas (emphysematous cholecystitis), abscess

Hepatobiliary Iminodiacetic Acid (HIDA) Scan

  • Most sensitive imaging (~97%)
  • Non-visualization of the gallbladder indicates cystic duct obstruction

8. Differential Diagnosis

  • Acute cholangitis
  • Acute pancreatitis
  • Peptic ulcer disease
  • Appendicitis
  • Liver abscess
  • Right lower lobe pneumonia
  • Myocardial infarction

9. Treatment

9.1. Initial Management

  • NPO (nothing by mouth)
  • IV fluids
  • Analgesia: NSAIDs or opioids
  • IV antibiotics: Cover gram-negative and anaerobes
    • First-line: Ceftriaxone + Metronidazole
    • Severe: Piperacillin-tazobactam or Meropenem

9.2. Surgical Management

Laparoscopic Cholecystectomy

  • Treatment of choice
  • Ideally within 72 hours of symptom onset
  • Minimally invasive with low complication rates

Open Cholecystectomy

  • Reserved for complicated cases or failed laparoscopy

Percutaneous Cholecystostomy

  • For critically ill or inoperable patients
  • Image-guided drainage of the gallbladder

10. Complications

  • Gangrenous cholecystitis
  • Gallbladder perforation → peritonitis
  • Empyema
  • Cholecystoenteric fistula
  • Gallstone ileus (mechanical bowel obstruction)
  • Sepsis

11. Prognosis

  • With timely intervention, the prognosis is excellent
  • Mortality: <1% for uncomplicated cases, but can reach 15% in elderly or septic patients
  • Delayed treatment increases the risk of severe complications
  • The recurrence rate is low after cholecystectomy

12. Prevention and Monitoring

  • Asymptomatic gallstones do not require surgery
  • Recurrent episodes or complicated cholecystitis warrant elective cholecystectomy
  • Postoperative follow-up includes monitoring for:
    • Bile leak
    • Wound infection
    • Abscess formation

13. Severity Grading and Guidelines

Tokyo Guidelines 2018 (TG18)

These international guidelines provide a framework for diagnosis and severity classification:

Diagnostic Criteria

  • Local signs (Murphy's sign, RUQ pain)
  • Systemic signs (fever, elevated WBC)
  • Imaging findings

Severity Grading

  • Grade I (Mild):
    • No organ dysfunction
    • No local complications
  • Grade II (Moderate):
    • Elevated WBC >18,000/mm³
    • Palpable tender mass
    • Duration >72 hours
  • Grade III (Severe):
    • Associated with organ failure (cardiovascular, respiratory, renal, neurological, etc.)

Management per Grade:

  • Grade I: Early laparoscopic cholecystectomy
  • Grade II: Stabilization → surgery
  • Grade III: Drainage, ICU care, then surgery if feasible

14. Recent Advances

  • Use of percutaneous drainage as bridge therapy in high-risk surgical patients
  • Enhanced Recovery After Surgery (ERAS) protocols reduce hospital stay
  • Research into non-operative management using antibiotics alone for select cases

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Case study: 40-Year-Old Female Presenting with Right Upper Quadrant Pain and Nausea_Acute Cholecystitis

History and Imaging

  1. A 40-year-old woman presented with progressive right upper quadrant (RUQ) abdominal pain and nausea radiating to the shoulder, which began two days before her visit.

  2. Her medical history was significant for nausea, vomiting (emesis), and food intolerance.
    Food intolerance refers to a condition in which the body experiences discomfort after ingesting certain foods due to impaired digestion, not due to an immune response.

Characteristics of Food Intolerance:

  • Bloating or abdominal distention

  • Diarrhea or constipation

  • Heartburn or indigestion

  • Headaches, fatigue, and general malaise

Comparison with Food Allergy:

FeatureFood IntoleranceFood Allergy
CauseEnzyme deficiency, chemical sensitivity, etc.Immune-mediated reaction (IgE antibody response)
Onset TimeSymptoms appear hours after ingestionRapid onset within minutes to an hour
SymptomsMainly gastrointestinal (e.g., abdominal pain, gas)Systemic: may include breathing difficulty, hives, anaphylaxis
SeverityUncomfortable but not life-threateningCan be life-threatening in severe cases

Examples:

  • Lactose intolerance: Caused by lactase enzyme deficiency, leading to poor digestion of lactose in dairy products.

  • Gluten intolerance: Discomfort following ingestion of gluten found in wheat, barley, etc. (distinct from celiac disease).

  1. Physical examination revealed a positive Murphy’s sign, and laboratory tests showed markedly elevated liver enzymes: AST at 278 U/L and ALT at 221 U/L.

Murphy’s Sign Explained: Murphy’s sign is considered positive when a patient halts inspiration due to pain upon palpation of the right upper abdomen, indicating gallbladder inflammation.

Examination Method:

  1. Have the patient lie supine.

  2. The examiner palpates beneath the right costal margin (liver and gallbladder area).

  3. The patient is asked to take a deep breath.

  4. If the patient suddenly stops breathing in due to pain, the sign is positive.

Conditions Suspected When Murphy’s Sign is Positive:

  • Acute cholecystitis (most common)

  • Biliary obstruction from gallstones

  • Rarely, inflammation around the liver or bile ducts

Summary Table:

ItemDescription
Korean Term머피 징후 (Murphy's sign)
Clinical PurposeDiagnostic indicator for cholecystitis
Exam SiteRight upper abdomen (beneath liver, over gallbladder)
Positive FindingPain causes the patient to halt deep inspiration

  1. RUQ ultrasound revealed the presence of cholelithiasis (gallstones), although acute cholecystitis could not be definitively confirmed.

  2. Hepatobiliary scintigraphy (HIDA scan) images were obtained immediately after injection of the radiotracer, and at 10, 30, and 60 minutes post-injection.

  3. A time-lapse summary of these images (per minute or per frame) is also provided.




Quiz 1:

  1. What is the most important finding after 60 minutes of imaging?
    (1) Nonvisualization of the gallbladder
    (2) Nonvisualization of the liver
    (3) Nonvisualization of the bowel

  2. Which of the following is the most commonly used radiotracer in hepatobiliary scintigraphy?
    (1) Technetium (Tc) 99m mebrofenin
    (2) Technetium (Tc) 99m sulfur colloid
    (3) Technetium (Tc) 99m sodium pertechnetate
    (4) Technetium (Tc) 99m methylene diphosphonate

  3. Which of the following is the most appropriate next step in this study?
    (1) Administer morphine and acquire additional delayed images
    (2) Acquire additional delayed images for 3 more hours, completing a total imaging time of 4 hours after tracer injection
    (3) Administer cholecystokinin
    (4) Either (1) or (2) is appropriate
    (5) (1), (2), or (3) is appropriate
    (6) None of the above is appropriate

  4. Hepatobiliary scintigraphy is the best initial imaging modality for diagnosing acute cholecystitis.
    (1) True
    (2) False
    Explanation: In most cases, RUQ ultrasound is typically the initial imaging modality of choice.

Delayed Imaging

According to the institutional protocol, morphine was administered, and an additional 30 minutes of delayed imaging was performed. Images were acquired immediately after morphine injection, at 15 minutes, and at 30 minutes post-injection. A summarized image set by minute (or frame) is also provided.


Quiz 2:

  1. What is the most prominent finding on the delayed scintigraphy images?
    (1) Visualization of the gallbladder
    (2) Nonvisualization of the gallbladder

  2. Given the current clinical context, nonvisualization of the gallbladder on delayed images following morphine administration is most consistent with a diagnosis of acute cholecystitis.
    (1) True
    (2) False

Findings and Diagnosis

Findings
99mTc mebrofenin hepatobiliary scintigraphy: The radiotracer was rapidly taken up by the liver, and transit into the bowel was observed at 27 minutes. The gallbladder was not visualized during the initial 60 minutes of imaging. Even after an additional 30 minutes of delayed imaging following morphine administration, the gallbladder remained nonvisualized.

Differential Diagnosis

  • Acute cholecystitis

  • Cholangiocarcinoma

  • Primary sclerosing cholangitis

  • Choledocholithiasis

  • Pancreatitis

  • Acute hepatitis

Diagnosis: Acute cholecystitis

Discussion

Acute Cholecystitis

Pathophysiology
Most commonly caused by obstruction of the cystic duct due to gallstones (90–95%).

  • Continued mucus production leads to increased intraluminal pressure and distention.

  • Luminal distention limits blood flow to the gallbladder wall.

  • Resultant edema and ischemia lead to wall thickening and inflammation.

  • Stasis due to obstruction reduces bile clearance and increases the risk of bacterial infection.

Epidemiology
Among patients with symptomatic gallstones, the risk of developing acute calculous cholecystitis is estimated to be 6–11%.

Clinical Presentation

  • Severe, persistent right upper quadrant or epigastric pain lasting more than 4 hours, possibly radiating to the right shoulder or back

  • Associated symptoms include fever, nausea, vomiting, and anorexia

  • Physical exam may reveal a positive Murphy’s sign (sensitivity ~97%, high specificity)

Imaging Features

  • Tc-99m mebrofenin/disofenin hepatobiliary scintigraphy: Nonvisualization of the gallbladder on delayed or 4-hour images after morphine administration is a key diagnostic feature.

Treatment

  • Cholecystectomy

  • Placement of a cholecystostomy tube in critically ill patients who are not surgical candidates

References

  1. Strasberg SM, et al. "Acute calculous cholecystitis." N Engl J Med. 2008.
  2. Tokyo Guidelines 2018 (TG18) for acute cholecystitis
  3. Sabiston Textbook of Surgery, 21st edition
  4. UpToDate: Acute cholecystitis overview



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