Acute cholecystitis overview

# Overview
Cholecystitis is the inflammation of the gallbladder. Acute cholecystitis may be classified according to causes into two major subtypes: Acute calculous cholecystitis and acute acalculous cholecystitis. Gallstones are found in 3500 years old Egyptian mummies during the autopsies. Common risk factors in the development of acute calculous cholecystitis include advanced age, female gender, obesity, and positive family history. Long periods of fasting, total parental nutrition (TPN), and weight loss are the common risk factors for the development of acute acalculous cholecystitis. Acute calculous cholecystitis is usually caused by the mechanical obstruction of the gallbladder due to gallstones. Acute acalculous cholecystitis is caused predominantly by the gallbladder stasis. Gallstones are the most common cause of physical obstruction of the gallbladder usually at the neck or in the cystic duct. Cholesterol gallstones are the most common type of gallstones. The obstruction causes an increased pressure as the gallbladder mucosa continues to produce mucus. This raised pressure may cause the venous congestion which is followed by the arterial congestion. Eventually, the raised pressure and stasis leads to the gallbladder ischemia and necrosis. Mechanical obstruction of the gallbladder as a result of polyps, malignancy, an infestation of the gallbladder with parasites, foreign bodies, and trauma may also lead to the acute cholecystitis. Acute cholecystitis is more common in siblings and first degree relatives of affected persons. Lith gene is involved in the pathogenesis of cholecystitis. Acute cholecystitis is associated with diabetes, insulin resistance, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and gastrointestinal malignancies. Microscopic histopathology shows edematous and hemorrhagic gallbladder wall, mucosal necrosis with neutrophil infiltration. Bile infiltration of the gallbladder wall and bile and leukocyte margination of blood vessels are specific findings for acalculous cholecystitis. Acute cholecystitis must be differentiated from other diseases that cause right upper quadrant abdominal pain and nausea/vomiting such as biliary colic, acute cholangitis, viral hepatitis, alcoholic hepatitis, acute pancreatitis, acute appendicitis, and irritable bowel syndrome. The incidence of acute cholecystitis is approximately 6,300 per 100,000 in individuals under 50 years age and 20,900 per 100,000 in individuals over 50 years age worldwide. The prevalence of acute cholecystitis is approximately 369 per 100,000 individuals in the United states. It is estimated from the population-based statistics, based on a comprehensive survey in the U.S. Acute cholecystitis is comparatively less prevalent in the developing countries. The mortality rate of acute cholecystitis is approximately 0.6%. Acute Cholecystitis most commonly occurs as a result of the prolonged obstruction of the cystic duct leading to inflammation of the gallbladder. The obstruction further contributes to the development of the complications associated with acute cholecystitis such as gangrene, empyema, perforation, cholecysto-enteric fistula, emphysematous cholecystitis, and gallstone ileus. Prognosis is generally good if the patient receives treatment.  Acute cholecystitis occurs as a result of prolonged gallstone obstruction in the bile duct, one to four patients develop biliary colic and about 20% of these patients develop acute cholecystitis annually. The hallmark of acute cholecystitis is biliary colic. A positive history of biliary colic, nausea and vomiting is suggestive of acute cholecystitis. Patients with acute cholecystitis usually appear ill. Physical examination of patients with acute cholecystitis is remarkable for right upper quadrant abdominal tenderness, positive murphy's sign, and fever. The presence of murphy's sign on physical examination is highly suggestive of acute cholecystitis. Laboratory findings consistent with the diagnosis of acute cholecystitis include leukocytosis and elevated CRP. Transabdominal ultrasound is the initial test of choice for the diagnosis of acute cholecystitis. Findings on an ultrasound diagnostic of acute cholecystitis include thickened gallbladder, gallstones or sludge, and pericholecystic fluid. CT scan is usually used for the diagnosis of the complications of acute cholecystitis. These complications include emphysematous cholecystitis and gangrenous cholecystitis. Cholescintigraphy is the gold standard for the diagnosis of acute cholecystitis. Cholescintigraphy is an alternative method of imaging and uses technetium-labeled hepatic 2,6-dimethyl-iminodiacetic acid (HIDA) in difficult cases or uncertain diagnosis. Findings on a cholescintigraphy diagnostic of acute cholecystitis include lack of visualization of the gallbladder. The mainstay of treatment for acute cholecystitis (calculous and acalculous) is surgery. Laparoscopic cholecystectomy is the gold standard for the treatment of acute cholecystitis and is usually preferred over the open cholecystectomy. Percutaneous cholecystostomy (PC) is an alternative to emergency cholecystectomy in complicated cases of high-risk patients. Pharmacologic medical therapy is recommended for cases of acute cholecystitis in which surgery is delayed. Empiric pharmacologic medical therapies for acute cholecystitis include either amoxicillin-clavulanic acid, cefoxitin, cefotaxime, or ceftriaxone with metronidazole, and ciprofloxacin or levofloxacin with metronidazole. The duration of medical therapy after the cholecystectomy depends on the severity of the disease.

# Historical Perspective
Gallstones are found in 3500 years old Egyptian mummies during the autopsies. In 1420, Antonio Benivieni was the first to describe gallstones. Carl Langenbuch performed the first cholecystectomy of a 43-year-old man who had suffered from biliary colic for sixteen years. Historically, open cholecystectomy was the treatment employed for the treatment of acute cholecystitis. Laparoscopic cholecystectomy was developed to treat acute cholecystitis and the shift from open to laparoscopic cholecystectomy occurred in the late 1980s.

# Classification
Acute cholecystitis may be classified according to causes into two major subtypes: Acute calculous cholecystitis and acute acalculous cholecystitis.

# Pathophysiology
Acute calculous cholecystitis is usually caused by the mechanical obstruction of the gallbladder due to gallstones. Acute acalculous cholecystitis is caused predominantly by the gallbladder stasis. Gallstones are the most common cause of physical obstruction of the gallbladder usually at the neck or in the cystic duct. Cholesterol gallstones are the most common type of gallstones. The obstruction causes an increased pressure as the gallbladder mucosa continues to produce mucus. This raised pressure may cause the venous congestion which is followed by the arterial congestion. Eventually, the raised pressure and stasis leads to the gallbladder ischemia and necrosis. Mechanical obstruction of the gallbladder as a result of polyps, malignancy, an infestation of the gallbladder with parasites, foreign bodies, and trauma may also lead to the acute cholecystitis. Acute cholecystitis is more common in siblings and first degree relatives of affected persons. Lith gene is involved in the pathogenesis of cholecystitis. Mutations in the hepatic cholesterol transporter ABCG8 also predispose an individual to the develop gallstones. Acute cholecystitis is associated with diabetes, insulin resistance, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and gastrointestinal malignancies. Microscopic histopathology shows edematous and hemorrhagic gallbladder wall, mucosal necrosis with neutrophil infiltration. Bile infiltration of the gallbladder wall and bile and leucocyte margination of blood vessels are specific findings for acalculous cholecystitis.

# Causes
The most common cause of acute cholecystitis is gallstones. Less common causes of acute cholecystitis include gallbladder stasis, gallbladder polyp, gallbladder malignancy, parasites, and foreign

# Differentiating Acute cholecystitis from Other Diseases
Acute cholecystitis must be differentiated from other diseases that cause right upper quadrant abdominal pain and nausea/vomiting such as biliary colic, acute cholangitis, viral hepatitis, alcoholic hepatitis, acute pancreatitis, acute appendicitis, and irritable bowel syndrome.

# Epidemiology and Demographics
The incidence of acute cholecystitis is approximately 6,300 per 100,000 in individuals under 50 years age and 20,900 per 100,000 in individuals over 50 years age worldwide. The prevalence of acute cholecystitis is approximately 369 per 100,000 individuals in the United states. It is estimated from the population-based statistics, based on a comprehensive survey in the U.S. Acute cholecystitis is comparatively less prevalent in the developing countries. The mortality rate of acute cholecystitis is approximately 0.6%. Acute cholecystitis usually affects individuals of the North American Indian race. Females are more commonly affected by acute cholecystitis than males. Acute cholecystitis cases are reported worldwide. Acute cholecystitis accounts for 700,000 cholecystectomies and costs of $6.5 billion annually only in the United States.

# Risk Factors
Common risk factors in the development of acute calculous cholecystitis include advancing age, female gender, obesity, and family history. Long periods of fasting, total parental nutrition (TPN), weight loss are the common risk factors for the development of acute acalculous cholecystitis.

# Screening
There is insufficient evidence to recommend routine screening for acute cholecystitis.

# Natural History, Complications, and Prognosis
Acute Cholecystitis most commonly occurs as a result of the prolonged obstruction of the cystic duct leading to inflammation of the gallbladder. The obstruction further contributes to the development of the complications associated with acute cholecystitis such as gangrene, empyema, perforation, cholecysto-enteric fistula, emphysematous cholecystitis, and gallstone ileus. Prognosis is generally good if the patient receives treatment. The majority of the patients undergo cholecystectomy.

# Diagnosis

## Diagnostic Study of Choice
Cholescintigraphy is the gold standard for the diagnosis of acute cholecystitis. Transabdominal ultrasonography is the initial study of choice for the diagnosis of acute cholecystitis and gallstones. Thickened gallbladder, gallstones or sludge, and pericholecystic fluid are the findings associated with transabdominal ultrasound in patients with acute cholecystitis.

## History and Symptoms
The majority of patients with cholelithiasis are asymptomatic. Acute cholecystitis occurs as a result of prolonged gallstone obstruction in the bile duct, one to four patients develop biliary colic and about 20% of these patients develop acute cholecystitis annually. The hallmark of acute cholecystitis is biliary colic. A positive history of biliary colic, nausea and vomiting is suggestive of acute cholecystitis.

## Physical Examination
Patients with acute cholecystitis usually appear ill. Physical examination of patients with acute cholecystitis is remarkable for right upper quadrant abdominal tenderness, positive murphy's sign, and fever. The presence of murphy's sign on physical examination is highly suggestive of acute cholecystitis.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of acute cholecystitis include leukocytosis and elevated CRP.

## Electrocardiogram
There are no ECG findings associated with acute cholecystitis. However, acute cholecystitis presents with pain in the epigastrium, which can be confused with an acute myocardial infarction. ECG can be useful in excluding an MI.

## X-ray
Abdominal X-Ray (AXR) does not aid diagnosis of acute cholecystitis. AXR is performed as an initial evaluation to diagnose the complicated gallbladder disease.

## Ultrasound
Transabdominal ultrasound is the initial test of choice for the diagnosis of acute cholecystitis. Findings on an ultrasound diagnostic of acute cholecystitis include thickened gallbladder, gallstones or sludge, and pericholecystic fluid.

## CT scan
CT scan is usually used for the diagnosis of the complications of acute cholecystitis. These complications include emphysematous cholecystitis and gangrenous cholecystitis.

## MRI
Abdominal MRI may be helpful in the diagnosis of acute cholecystitis. Findings on MRI suggestive of acute cholecystitis include thickening of the gallbladder and pericholecystic fluid.

## Other Imaging Findings
Cholescintigraphy is the gold standard for the diagnosis of acute cholecystitis. Cholescintigraphy is an alternative method of imaging and uses technetium-labeled hepatic 2,6-dimethyl-iminodiacetic acid (HIDA) in difficult cases or uncertain diagnosis. Findings on a cholescintigraphy diagnostic of acute cholecystitis include lack of visualization of the gallbladder.

## Other Diagnostic Studies
The histopathological analysis may be helpful in the diagnosis of acute cholecystitis. Findings suggestive of acute cholecystitis include edematous and hemorrhagic gallbladder wall, mucosal necrosis with neutrophil infiltration, eosinophilic infiltration of the gallbladder mucosa, and bile infiltration and leucocyte margination of blood vessels.

# Treatment

## Medical Therapy
The mainstay of treatment for acute cholecystitis (calculous and acalculous) is surgery. Pharmacologic medical therapy is recommended for cases of acute cholecystitis in which surgery is delayed. Empiric pharmacologic medical therapies for acute cholecystitis include either amoxicillin-clavulanic acid, cefoxitin, cefotaxime, or ceftriaxone with metronidazole, and ciprofloxacin or levofloxacin with metronidazole. The duration of medical therapy after the cholecystectomy depends on the severity of the disease.

## Surgery
Surgery is the mainstay of treatment for acute cholecystitis (calculous and acalculous).Laparoscopic cholecystectomy is the gold standard for the treatment of acute cholecystitis and is usually preferred over the open cholecystectomy. Percutaneous cholecystostomy (PC) is an alternative to emergency cholecystectomy in complicated cases of high-risk patients.

## Primary Prevention
Administration of NSAIDs in the patients with biliary colic prevents the progression to acute cholecystitis.

## Secondary Prevention
There are no established measures for the secondary prevention of acute cholecystitis.