Acute Cholecystitis

Introduction

Cholecystitis is inflammation of the gallbladder that occurs most commonly because of an obstruction of the cystic duct from cholelithiasis. Uncomplicated cholecystitis has an excellent prognosis; the development of complications such as perforation or gangrene renders the prognosis less favorable.

Pathophysiology

• Ninety percent of cases of cholecystitis involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing acalculous cholecystitis.
• Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis.
• Although the exact mechanism of acalculous cholecystitis is unclear, several theories exist. Injury may be the result of retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder never receives a cholecystokinin (CCK) stimulus to empty; thus, the concentrated bile remains stagnant in the lumen.
• A study by Cullen et al demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult.[4] Endotoxin also abolished the contractile response to CCK, leading to gallbladder stasis.

Etiology

Risk factors for calculous cholecystitis mirror those for cholelithiasis and include the following:

• Female sex
• Certain ethnic groups
• Obesity or rapid weight loss
• Drugs (especially hormonal therapy in women)
• Pregnancy
• Increasing age

Acalculous cholecystitis is related to conditions associated with biliary stasis, to include the following:

• Critical illness
• Major surgery or severe trauma/burns
• Sepsis
• Long-term total parenteral nutrition (TPN)
• Prolonged fasting

Other causes of acalculous cholecystitis include the following:

• Cardiac events, including myocardial infarction
• Sickle cell disease
• Salmonella infections
• Diabetes mellitus
• Patients with AIDS who have cytomegalovirus, cryptosporidiosis, or microsporidiosis
• Patients who are immunocompromised are at increased risk of developing cholecystitis from a number of different infectious sources. Idiopathic cases exist.

Clinical Features

Signs and symptoms

1. The most common presenting symptom of acute cholecystitis is upper abdominal pain. The following characteristics may be reported:
2. Signs of peritoneal irritation may be present, and the pain may radiate to the right shoulder or scapula
3. Pain frequently begins in the epigastric region and then localizes to the right upper quadrant (RUQ)
4. Pain may initially be colicky but almost always becomes constant
5. Nausea and vomiting are generally present, and fever may be noted
6. Patients with acalculous cholecystitis may present with fever and sepsis alone, without history or physical examination findings consistent with acute cholecystitis.

Cholecystitis may present differently in special populations, as follows:

Elderly (especially diabetics) – May present with vague symptoms and without many key historical and physical findings (eg, pain and fever), with localized tenderness the only presenting sign; may progress to complicated cholecystitis rapidly and without warning

Children – May present without many of the classic findings; those at higher risk for cholecystitis include those who have sickle cell disease, serious illness, a requirement for prolonged total parenteral nutrition (TPN), hemolytic conditions, or congenital and biliary anomalies

The physical examination may reveal the following:

1. Fever, tachycardia, and tenderness in the RUQ or epigastric region, often with guarding or rebound
2. Palpable gallbladder or fullness of the RUQ (30-40% of patients)
3. Jaundice (~15% of patients)

The absence of physical findings does not rule out the diagnosis of cholecystitis.

Investigations

Laboratory tests are not always reliable, but the following findings may be diagnostically useful:

• Leukocytosis
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may be elevated in cholecystitis or with common bile duct (CBD) obstruction
• Bilirubin and alkaline phosphatase assays may reveal evidence of CBD obstruction
• Amylase/lipase assays are used to assess for pancreatitis; amylase may also be mildly elevated in cholecystitis
• Alkaline phosphatase level may be elevated (25% of patients with cholecystitis)
• Urinalysis is used to rule out pyelonephritis and renal calculi
• All females of childbearing age should undergo pregnancy testing

Diagnostic imaging modalities that may be considered include the following:

• Radiography
• Ultrasonography
• Computed tomography (CT)
• Magnetic resonance imaging (MRI)
• Hepatobiliary scintigraphy
• Endoscopic retrograde cholangiopancreatography (ERCP)

Management

1. Treatment of cholecystitis depends on the severity of the condition and the presence or absence of complications.
2. For acute cholecystitis, initial treatment includes bowel rest, IV hydration, correction of electrolyte abnormalities, analgesia, and IV antibiotics. Options include the following:
• Sanford guide – Piperacillin-tazobactam, ampicillin-sulbactam, or meropenem; in severe life-threatening cases, imipenem-cilastatin
• Alternative regimens – Third-generation cephalosporin plus metronidazole
• Emesis can be treated with antiemetics and nasogastric suction
• Because of the rapid progression of acute acalculous cholecystitis to gangrene and perforation, early recognition and intervention are required.
3. Supportive medical care should include restoration of hemodynamic stability and antibiotic coverage for gram-negative enteric flora and anaerobes if biliary tract infection is suspected.
4. Daily stimulation of gallbladder contraction with IV cholecystokinin (CCK) may help prevent formation of gallbladder sludge in patients receiving TPN

For cases of uncomplicated cholecystitis, outpatient treatment may be appropriate. The following medications may be useful in this setting:

• Levofloxacin and metronidazole for prophylactic antibiotic coverage against the most common organisms
• Antiemetics (eg, promethazine or prochlorperazine) to control nausea and prevent fluid and electrolyte disorders
• Analgesics (eg, oxycodone/paracetamol)

Empiric Therapy Regimens

Disease with severe physiologic disturbance, in those of advanced age or immunocompromised state, or with acute cholangitis following bilioenteric anastomosis of any severity:

1. Imipenem-cilastatin 500 mg IV q6h or
2. 1 g IV q24h or
3. 1 g IV q8h or
4. 500 mg IV q8h or
5. 3.375 g IV q6h or
6. 400 mg IV q12h plus metronidazole 500 mg IV q8h or
7. 750 mg IV q24h plus metronidazole 500 mg IV q8h or
8. 2 g IV q8-12h plus 500 mg IV q8h

Surgical and interventional procedures used to treat cholecystitis include the following:

1. Laparoscopic cholecystectomy (standard of care for surgical treatment of cholecystitis)
2. Percutaneous drainage
3. ERCP
4. Endoscopic ultrasound-guided transmural cholecystostomy
5. Endoscopic gallbladder drainage

Complications

1. Bacterial proliferation within the obstructed gallbladder results in empyema of the organ. Patients with empyema may have a toxic reaction and may have more marked fever and leukocytosis. The presence of empyema frequently requires conversion from laparoscopic to open cholecystectomy.
2. In rare instances, a large gallstone may erode through the gallbladder wall into an adjacent viscus, usually the duodenum. Subsequently, the stone may become impacted in the terminal ileum or in the duodenal bulb and/or pylorus, causing a gallstone ileus.
3. Emphysematous cholecystitis occurs in approximately 1% of cases and is noted by the presence of gas in the gallbladder wall from the invasion of gas-producing organisms, such as Escherichia coli, Clostridia perfringens, and Klebsiella species. This complication is more common in patients with diabetes, has a male predominance, and is acalculous in 28% of cases. Because of a high incidence of gangrene and perforation, emergency cholecystectomy is recommended. Perforation occurs in up to 15% of patients.
4. Other complications include sepsis and pancreatitis.

Prognosis

Uncomplicated cholecystitis has an excellent prognosis, with very low mortality. Most patients with acute cholecystitis have a complete remission within 1-4 days. However, 25-30% of patients either require surgery or develop some complication.

Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Perforation occurs in 10-15% of cases. Patients with acalculous cholecystitis have a mortality ranging from 10-50%, which far exceeds the expected 4% mortality observed in patients with calculous cholecystitis. In patients who are critically ill with acalculous cholecystitis and perforation or gangrene, mortality can be as high as 50-60%.

D/D

• Abdominal Aortic Aneurysm
• Acute Gastritis
• Acute Mesenteric Ischemia
• Acute Pyelonephritis
• Appendicitis
• Biliary Colic
• Biliary Disease
• Cholangiocarcinoma
• Cholangitis
• Gallbladder Cancer
• Gallbladder Mucocele
• Gallbladder Tumors
• Gallstones (Cholelithiasis)
• Peptic Ulcer Disease

 Courtesy : PDM