Definition and Classification

Cholecystitis is characterized by inflammation of the gallbladder wall. It is broadly classified into:

1. Acute Cholecystitis:

   • Sudden onset of inflammation, typically developing over hours.

   • Usually caused by temporary or prolonged obstruction of the cystic duct, most commonly by a gallstone (calculous cholecystitis).

   • Acalculous cholecystitis, occurring in the absence of gallstones, is less common but often more severe and seen in critically ill patients.

2. Chronic Cholecystitis:

   • Results from repeated episodes of acute cholecystitis or chronic irritation of the gallbladder wall.

   • Characterized by chronic inflammation and thickening of the gallbladder wall, often associated with gallstones.

   • May cause recurrent episodes of pain or be relatively asymptomatic between acute exacerbations.

Etiology and Risk Factors

The vast majority of acute cholecystitis cases (90-95%) are calculous, meaning they are caused by gallstones obstructing the cystic duct.

Causes of Calculous Cholecystitis:

• Gallstones (Cholelithiasis): The presence of stones in the gallbladder. Gallstones are formed from hardened deposits of digestive fluid. The two main types are:

  • Cholesterol stones: The most common type, often yellow-green in color.

  • Pigment stones: Dark brown or black, formed from bilirubin.

• Obstruction of the Cystic Duct: A gallstone becomes lodged in the cystic duct, preventing bile flow from the gallbladder. This leads to distension, increased intraluminal pressure, and inflammation of the gallbladder wall.

Causes of Acalculous Cholecystitis:

• Occurs in the absence of gallstones.

• More common in critically ill patients, such as those with:

  • Severe trauma or burns.

  • Major surgery.

  • Prolonged fasting or total parenteral nutrition (TPN).

  • Sepsis.

  • Severe heart disease or renal failure.

  • Diabetes mellitus.

  • HIV/AIDS or other immunosuppression.

• The exact mechanism is not fully understood but may involve gallbladder stasis, ischemia (reduced blood flow), reperfusion injury, and inflammation in the absence of stone obstruction.

Risk Factors for Gallstones (and thus Calculous Cholecystitis):

The “4 Fs” are a classic mnemonic for risk factors:

• Female: Women are more likely to develop gallstones than men.

• Fat: Obesity increases the risk.

• Forty: Risk increases with age, typically after 40.

• Fertile: Multiple pregnancies increase risk.

Other risk factors include:

• Family history of gallstones.

• Rapid weight loss.

• Diabetes mellitus.

• Certain medications (e.g., estrogen therapy, cholesterol-lowering drugs).

• Certain medical conditions (e.g., Crohn’s disease, cirrhosis, sickle cell anemia).

Pathophysiology

The pathophysiology of acute calculous cholecystitis begins with the obstruction of the cystic duct, usually by a gallstone.

1. Cystic Duct Obstruction: A gallstone blocks the flow of bile out of the gallbladder.

2. Bile Stasis: Bile accumulates in the gallbladder, leading to distension.

3. Increased Intraluminal Pressure: The pressure inside the gallbladder rises.

4. Chemical Inflammation: The concentrated bile, particularly lysolecithin (formed from lecithin by phospholipase A in the gallbladder wall), becomes increasingly irritating to the gallbladder mucosa. This chemical irritation initiates an inflammatory response.

5. Ischemia: Increased intraluminal pressure can compromise blood flow to the gallbladder wall, leading to ischemia and further damage.

6. Bacterial Infection: While initially a sterile chemical inflammation, bacterial invasion of the gallbladder wall is common, occurring in about 50-75% of cases. Bacteria typically ascend from the duodenum or reach the gallbladder via the portal vein or lymphatic system. Common bacteria include Escherichia coli, Klebsiella, Streptococcus faecalis, and Clostridium.

7. Inflammation and Edema: The combination of chemical irritation, ischemia, and bacterial infection leads to acute inflammation, edema, and thickening of the gallbladder wall.

8. Progression: If the obstruction persists and inflammation is severe, complications can develop, such as gallbladder necrosis (gangrene), perforation, or fistula formation.

In acalculous cholecystitis, the initial trigger is not stone obstruction. Instead, factors like ischemia, stasis (due to lack of enteral feeding or reduced contractility), and inflammation related to critical illness are believed to play a role, leading to a similar inflammatory cascade in the gallbladder wall.

Chronic cholecystitis results from repeated episodes of acute inflammation or chronic irritation, leading to fibrosis and thickening of the gallbladder wall. The gallbladder may become shrunken and non-functional over time.

Clinical Manifestations

The clinical presentation of cholecystitis is characterized by pain and other associated symptoms.

Acute Cholecystitis:

• Right Upper Quadrant (RUQ) Pain: The hallmark symptom. The pain is typically sudden in onset, severe, constant, and located in the RUQ or epigastrium. It may radiate to the right shoulder or back. Unlike biliary colic (pain from gallstones without inflammation), the pain of acute cholecystitis does not resolve spontaneously and persists for several hours.

• Tenderness in the RUQ: Pain upon palpation of the RUQ.

• Murphy’s Sign: A classic physical examination finding. It is elicited by asking the patient to exhale and then placing the fingers or thumb on the RUQ below the costal margin. The patient is then asked to inhale deeply. A positive Murphy’s sign is a sudden inspiration halt due to pain as the inflamed gallbladder descends and touches the examiner’s fingers.

• Fever: Typically low-grade, but can be higher if there is significant infection or complications.

• Nausea and Vomiting: Common accompanying symptoms.

• Anorexia: Loss of appetite.

• Jaundice: Less common in uncomplicated acute cholecystitis, as the obstruction is usually limited to the cystic duct. Jaundice suggests obstruction of the common bile duct (choledocholithiasis) or severe liver dysfunction.

Chronic Cholecystitis:

• May be asymptomatic between acute exacerbations.

• May present with recurrent episodes of RUQ pain, often less severe than in acute cholecystitis, and sometimes triggered by fatty meals.

• Chronic indigestion, bloating, and discomfort after eating are also common.

Diagnosis

Diagnosing cholecystitis involves a combination of clinical assessment, laboratory tests, and imaging studies.

1. Medical History and Physical Examination: A detailed history of the onset and characteristics of pain, associated symptoms, and risk factors is crucial. Physical examination focuses on assessing for RUQ tenderness and Murphy’s sign.

2. Laboratory Tests:

   • Complete Blood Count (CBC): May show leukocytosis (elevated white blood cell count), indicating inflammation or infection.

   • Liver Function Tests (LFTs): Bilirubin, ALT, AST, ALP, GGT. These are often normal in uncomplicated acute cholecystitis. Elevated bilirubin or ALP/GGT may suggest common bile duct obstruction.

   • Amylase and Lipase: May be measured to rule out pancreatitis, which can present with similar symptoms.

   • C-reactive protein (CRP): An inflammatory marker that is often elevated.

3. Imaging Studies:

   • Abdominal Ultrasound: The initial imaging modality of choice. It is non-invasive, readily available, and can visualize gallstones, gallbladder wall thickening (>3-4 mm), pericholecystic fluid (fluid around the gallbladder), and a sonographic Murphy’s sign (pain elicited by the ultrasound probe over the gallbladder). However, ultrasound may not always visualize the cystic duct or detect obstruction directly.

   • Hepatobiliary Iminodiacetic Acid (HIDA) Scan (Cholescintigraphy): A nuclear medicine scan that assesses gallbladder function and cystic duct patency. A radioactive tracer is injected intravenously and is taken up by the liver and excreted into the bile. If the cystic duct is open, the tracer will enter and fill the gallbladder. Non-visualization of the gallbladder after a certain time (usually 60-90 minutes) following tracer administration, especially after administration of cholecystokinin (which stimulates gallbladder contraction), is indicative of cystic duct obstruction and acute cholecystitis. This test is particularly useful when ultrasound findings are equivocal.

   • Computed Tomography (CT) Scan: Can be helpful in assessing for complications of cholecystitis (e.g., perforation, abscess) or identifying alternative causes of abdominal pain, but is generally less sensitive than ultrasound or HIDA scan for diagnosing acute cholecystitis itself.

   • Magnetic Resonance Cholangiopancreatography (MRCP): A non-invasive MRI technique that provides detailed images of the bile ducts and pancreatic duct. Useful if common bile duct obstruction is suspected, but not the primary test for acute cholecystitis.

Management

Management of acute cholecystitis typically involves supportive care, antibiotics, and definitive treatment, which is usually surgical removal of the gallbladder (cholecystectomy).

Acute Cholecystitis:

1. Supportive Care:

   • NPO (Nil per os): Restricting oral intake to reduce gallbladder stimulation.

   • Intravenous (IV) Fluids: To maintain hydration, especially if the patient is nauseated or vomiting.

   • Pain Management: Analgesics are necessary to control severe pain. NSAIDs (e.g., ketorolac) can be effective and may also reduce inflammation. Opioids may be required for severe pain.

2. Antibiotics:

   • Antibiotics are indicated to cover potential bacterial infection, especially if there are signs of systemic infection (fever, leukocytosis) or if complications are suspected.

   • Broad-spectrum antibiotics covering common enteric bacteria (e.g., cephalosporins, piperacillin-tazobactam) are typically used.

3. Definitive Treatment (Cholecystectomy):

   • Surgical removal of the gallbladder is the definitive treatment for acute cholecystitis to prevent recurrence and complications.

   • Timing of Surgery: Early laparoscopic cholecystectomy (within 24-72 hours of symptom onset) is generally preferred in suitable candidates, as it is associated with shorter hospital stays and lower complication rates compared to delayed surgery. Delayed surgery may be considered in patients with severe inflammation or significant comorbidities, after a period of medical stabilization.

   • Laparoscopic Cholecystectomy: The minimally invasive approach, involving small incisions and the use of a laparoscope and surgical instruments. It is the standard of care.

   • Open Cholecystectomy: May be necessary in cases of severe inflammation, complications, or when laparoscopic surgery is not feasible or safe.

   • Percutaneous Cholecystostomy: In critically ill or unstable patients who are not candidates for immediate surgery, a tube can be placed through the skin into the gallbladder to drain bile and decompress the gallbladder. This provides temporary relief and allows for stabilization before definitive treatment.

Chronic Cholecystitis:

• Management is primarily surgical removal of the gallbladder (laparoscopic cholecystectomy), especially if the patient is symptomatic.

• Elective cholecystectomy is typically performed in a non-acute setting.

Complications

Complications of acute cholecystitis can be severe and include:

• Gallbladder Gangrene: Necrosis of the gallbladder wall due to severe ischemia.

• Gallbladder Perforation: Rupture of the gallbladder wall, leading to leakage of bile and pus into the peritoneal cavity, causing peritonitis.

• Gallbladder Empyema: Accumulation of pus within the gallbladder.

• Fistula Formation: Formation of an abnormal connection between the gallbladder and an adjacent organ (e.g., duodenum, colon).

• Gallstone Ileus: Obstruction of the small intestine by a large gallstone that has passed into the bowel through a cholecystoenteric fistula.

• Pericholecystic Abscess: Formation of an abscess around the gallbladder.

• Cholangitis: Infection of the bile ducts, often due to migration of a gallstone into the common bile duct.

• Pancreatitis: Inflammation of the pancreas, often caused by a gallstone obstructing the common bile duct or the ampulla of Vater.