Cholecystitis

Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis (calculous cholecystitis) but inflammation without gallstones (acalculous cholecystitis) can occur in a minority of patients. The acute type usually presents with right upper quadrant (RUQ) pain, fever, and leukocytosis. The diagnosis is made clinically and confirmed via ultrasound (US). The definitive management is cholecystectomy, preferred to be performed within 72 hours. This condition can present as a mild condition or as a severe disease (with complications such as gallbladder gangrene, perforation, empyema) which require emergent intervention.

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Overview

Definition

Cholecystitis is the inflammation of the gallbladder (GB).
Types:

  • Calculous cholecystitis: GB inflammation as a complication of gallstones or cholelithiasis 
    • Acute: cystic duct obstruction/GB inflammation of sudden onset, associated with intense pain
    • Chronic: chronic inflammation and fibrosis of the GB, associated with:
      • Less pain intensity
      • Mechanical irritation from gallstones
      • Recurrent attacks of acute cholecystitis
  • Acalculous cholecystitis: GB inflammation due to GB stasis and ischemia
    • Gallstones are absent.
    • Usually in critically ill and/or immunocompromised patients

Epidemiology

  • Women > men
  • Peak incidence: 40–50 years
  • Develops in 6%–11% of patients with symptomatic gallstones
  • Risk factors:
    • Pregnancy or hormone therapy
    • Older age
    • Native American or Hispanic
    • Obesity; rapid weight gain/loss
    • Diabetes

Etiology and Pathophysiology

  • Etiology: most commonly due to obstructing gallstones in the GB, causing symptoms
  • Pathophysiology:
    • Gallstone migrates to the cystic duct → obstruction
    • Obstruction leads to distention and inflammation of the gallbladder.
    • Other contributing factors to GB inflammation:
      • Prostaglandins (↑ GB contraction)
      • Lysolecithin, an inflammatory mediator which is normally absent but is produced in cases of GB wall trauma
      • May or may not be associated with bacterial infection (Escherichia coli, Enterococcus, Klebsiella, Enterobacter)
Biliary Tree Anatomy

Anatomy of the biliary tree: gallbladder in relation to other organs

Image by Lecturio.

Clinical Presentation

History

  • Right upper quadrant (RUQ) pain
    • Prolonged (> 6 hours)
    • After a fatty meal
    • Radiation to the right scapula (Boas’s sign)
  • Fever
  • Anorexia, nausea, vomiting
Typical pressure-zone in cholelithiasis

Boas’s sign is hyperesthesia below the right scapula (noted in acute cholecystitis).

Image by Lecturio.

Examination

  • Positive Murphy’s sign:
    • Examiner palpates GB area while patient takes a deep inspiration.
    • Inflamed GB descends and comes in contact with the examiner’s hand, causing pain/discomfort.
  • Abdominal guarding, rebound: local peritoneal inflammation
Murphy sign

Murphy’s sign: Examiner places hand on the gallbladder area (right subcostal area). Patient is instructed to take a deep breath. On inspiration, the inflamed gallbladder descends, coming in contact with the examiner’s hand and causing pain.

Image by Lecturio.

Diagnosis

  • Physical examination:
    • Tenderness to palpation in RUQ/epigastric area
    • Murphy’s sign
    • Fever, tachycardia
  • Laboratory tests:
    • Liver function tests (LFTs):
      • Elevation of bilirubin and alkaline phosphatase (but can be normal in uncomplicated cases)
      • Mild elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
    • CBC: leukocytosis (with left shift)
  • Imaging:
    • Ultrasound (US): test of choice
      • GB wall thickening > 4 mm
      • GB wall edema (double-wall sign)
      • Sonographic Murphy’s sign (elicited with US probe pressing on the abdomen) 
      • Pericholecystic fluid
      • Presence of gallstones 
    • Hepatobiliary iminodiacetic acid (HIDA) scan:
      • Performed if US reveals equivocal results
      • Intravenous injection of radioactive tracer that gets excreted in the bile
      • If the cystic duct is not obstructed, the tracer will be seen in the gallbladder.
      • Abnormal if gallbladder not visualized within 30–60 minutes
    • Computed tomography (CT) scan:
      • Not a first-choice test for suspected cholecystitis as most gallstones will not be visualized on CT
      • Will show GB inflammation
      • Used if patient presents with peritonitis, bowel obstruction, or sepsis
    • Magnetic resonance cholangiopancreatography (MRCP): utilized if choledocholithiasis is suspected

Management

General considerations

  • Supportive therapy:
    • Analgesia: nonsteroidal anti-inflammatory drugs (NSAIDs) (preferable), opioids
    • Intravenous fluid hydration + electrolyte correction
    • Antiemetics
  • Intravenous antibiotics:
    • Adjunctive therapy
    • Can be used as primary treatment if surgery is contraindicated (in high-risk patients)
    • Single-agent regimen:  
      • Low-risk abdominal infection: piperacillin-tazobactam or ertapenem
      • High-risk abdominal infection: imipenem, meropenem, piperacillin-tazobactam
    • Double-agent regimen: 
      • Low-risk abdominal infection: cefazolin/ceftriaxone/ciprofloxacin/levofloxacin + metronidazole
      • High-risk abdominal infection: cefepime/ceftazidime + metronidazole

Surgical treatment

  • Cholecystectomy:
    • Definitive treatment
    • Approach:
      • Laparoscopic is the standard of care (lower risk of infection, shorter hospital stay).
      • Open surgery: reserved for complicated cases
    • Timing:
      • Surgery performed early (within 72 hours of presentation): better outcomes
      • Emergent surgery: may be required for emphysematous gallbladder, gallbladder perforation/gangrene, generalized peritonitis
    • Complications of surgery:
      • Bile duct injury
      • Biliary leaks 
      • Injury to nearby structures
      • Post-cholecystectomy syndrome
  • Percutaneous cholecystostomy:
    • GB is drained/decompressed with a tube placed percutaneously under radiologic guidance.
    • For patients with:
      • Contraindications to surgery
      • Cholecystitis not resolving with antibiotics/supportive management
      • Acalculous cholecystitis (especially the severely ill)
  • Endoscopic retrograde cholangiopancreatography (ERCP) prior to surgery if US showed that common bile duct (CBD) stones are present

Complications

  • Gangrenous cholecystitis
    • Most common complication
    • Severe inflammation leads to necrosis of the GB wall
    • Usually affects patients with diabetes, elderly patients, or those with delayed diagnosis
  • Emphysematous cholecystitis
    • Infection with gas-forming bacteria (Clostridium)
    • Gas in the GB wall (may manifest as abdominal wall crepitus on exam)
    • Usually in diabetic patients
  • Hydrops
    • Also called mucocele of the GB
    • Very distended GB filled with colorless mucoid fluid (white bile)
    • Prolonged impaction of a gallstone in the cystic duct → bilirubin absorption within the GB
  • Gallstone ileus
    • Fistula forms between the inflamed GB and duodenum (cholecystoenteric fistula).
    • Gallstone travels into the small bowel → small bowel obstruction
    • Rigler triad: pneumobilia (air in the biliary tree), intestinal obstruction, and an ectopic gallstone
  • Gallbladder perforation
    • 10% of acute cholecystitis
    • Leads to a pericholecystic abscess or generalized peritonitis
  • Mirizzi syndrome
    • Extrinsic compression of the common hepatic duct by the stone lodged in the cystic duct
    • Presents with jaundice, fever, and abdominal pain
    • Associated with gallbladder cancer

Differential Diagnosis

Other biliary/liver conditions

  • Biliary colic: post-prandial pain/nausea caused by brief intermittent cystic duct obstruction. Associated with normal blood tests, gallstones (no signs of inflammation) on US.
  • Biliary dyskinesia: dysfunctional motility of the gallbladder (with no stones). The clinical picture is similar to biliary colic/cholecystitis. Diagnosed by HIDA scan with cholecystokinin (CCK) injection where results show low GB ejection fraction.
  • Choledocholithiasis/cholangitis: gallstones in the common bile duct cause obstruction (choledocholithiasis), which may lead to infection (cholangitis). This condition presents with high bilirubin (> 2.0) and alkaline phosphatase, with early elevation of transaminases.
  • Gallstone pancreatitis: intermittent obstruction of junction of CBD and pancreatic duct from a migrating gallstone leads to pancreatitis. Work-up shows elevated amylase/lipase with pancreatic inflammation on US/CT scan.
  • Hepatitis: inflammation of liver parenchyma due to infectious etiology or other causes. Usually associated with very high transaminases and elevated bilirubin. Ultrasound would not show any gallstones.

Non-biliary conditions

  • Peptic ulcer disease: ulceration of gastric or duodenal mucosa. Presents with epigastric pain, nausea/vomiting. Unlike in cholecystitis, pain is often relieved by eating. Diagnosis is by upper endoscopy. 
  • Acute gastroenteritis: usually self-limited viral infection of the gastrointestinal tract. Manifestations include abdominal pain, nausea/vomiting, and diarrhea. Symptoms resolve with supportive management.
  • Acute appendicitis: an infection/inflammation of the appendix. Usual presentation includes nausea/vomiting, anorexia with pain in the right lower quadrant (RLQ). In certain cases (pregnancy, retrocecal position of the appendix), may also present with pain in RUQ.  
  • Pancreatitis: inflammation of the pancreas. Epigastric/RUQ pain is sudden in onset and typically sharp, radiating to the back, and is relieved on bending forward. Etiologies consist of gallstones and increased alcohol consumption.
  • Nephrolithiasis: also known as kidney stones. Presents with sudden onset of severe right or left flank pain. Pain is colicky in nature and associated with urinary symptoms (dysuria, hematuria). Diagnosis is by non-contrast CT scan (sometimes plain X-ray), which shows stones in the urinary tract.

References

  1. Steel, P. (2017) What are the risk factors for biliary colic and cholecystitis? In Brenner, B. Medscape. Retrieved 12 Nov 2020, from https://www.medscape.com/answers/1950020-67786/what-are-risk-factors-for-biliary-colic-and-cholecystitis
  2. Vollmer, C., Zakko, S., Afdhal, N. (2019) Treatment of acute calculous cholecystitis. In Ashley, S., Chen, W. (Eds.) UpToDate. Retrieved 11 Nov 2020, from https://www.uptodate.com/contents/treatment-of-acute-calculous-cholecystitis
  3. Zakko, S. (2018). Acute calculous cholecystitis: Clinical features and diagnosis. In Chopra, S and Grover, S (Eds). UpToDate. Retrieved 11 Nov 2020, from https://www.uptodate.com/contents/acute-calculous-cholecystitis-clinical-features-and-diagnosis?search=cholecystitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

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