Chronic cholecystitis overview

# Overview
Chronic cholecystitis is the chronic inflammation of the gallbladder. Chronic calculous cholecystitis is usually caused by the mechanical obstruction due to gallstones. This obstruction leads to gallbladder stasis which is the primary mechanism leading to stone formation. Lith gene is also involved in the pathogenesis of cholecystitis. Cholecystitis is more common in siblings and first degree relatives of affected persons. On gross pathology, chronic cholecystitis usually shows enlarged or distended gallbladder and serosal or mucosal exudates. Fibrosis of gallbladder may also be seen. Microscopic pathology shows lymphocytic inflammatory infiltrates, metaplasia and lipid or mucolipid accumulations in the gallbladder wall. Chronic cholecystitis may be classified according to causes into two major subtypes, acute calculous cholecystitis and acute acalculous cholecystitis. Gallstones have been 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 chronic cholecystitis. Laparoscopic cholecystectomy was developed to treat chronic cholecystitis and the change in preference from open to laparoscopic cholecystectomy occurred in the late 1980s. Common causes of cholecystitis include cholelithiasis and infections. Common risk factors in the development of calculous cholecystitis (cholelithiasis) include female gender, increasing age, obesity, pregnancy, family history, genetic factors, and oral contraceptive use.  Common risk factors in the development of acalculous cholecystitis include AIDS, diabetes mellitus, major surgery, burns, sepsis, and long term total parenteral nutrition use. It is estimated that 20 to 25 million Americans (10%15% of the population) have gallstones. However, only 1-4% experience symptomatic gallstone diseases. Gallstone disease 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. Females are more commonly affected by gallstone diseases than males for calculous cholecystitis. Males are at increased risk compared to females for acalculous cholecystitis following trauma and burns. Chronic cholecystitis must be differentiated from other conditions that affect the gallbladder and biliary tract such as biliary colic, choledocholithiasis, and cholangitis. Chronic cholecystitis must also be differentiated from colitis, functional bowel syndrome, hiatal hernia, and peptic ulcer. Cholecystitis presents with abdominal pain, which is not relieved by antacids and postural changes and lasts longer than 6 hours.  It is sometimes preceded by attacks of biliary pain (due to gallstones). Untreated cholecystitis resolves spontaneously in half of the uncomplicated cases without surgery in a span of 7 to 10 days. The complications of chronic cholecystitis include gangrenous cholecystitis, perforation of the gallbladder, Mirizzi syndrome, gallstone ileus, and gallbladder malignancies. The patients with chronic cholecystitis may have the history of recurrent episodes of biliary colic or acute cholecystitis. A positive history of biliary colic, nausea and vomiting are suggestive of chronic cholecystitis. The most common symptoms of chronic cholecystitis are right upper quadrant abdominal or epigastric pain, pain is usually prolonged and there is a positive history of pain after ingestion of heavy fatty meals. The pain is severe and steady and may radiate to the back or right shoulder. Patients with chronic cholecystitis may have malaise during the episode. The physical examination in chronic cholecystitis is remarkable for tender right upper quadrant, fever (usually low grade in uncomplicated cases), and a positive Murphy's sign. Transabdominal ultrasonography is the initial study of choice for the diagnosis of chronic cholecystitis and gallstones. Cholescintigraphy is the gold standard for the diagnosis of chronic cholecystitis. HIDA cholescintigraphy findings for chronic cholecystitis include delayed gallbladder isotope accumulation, irregular gallbladder filling, or photopenic areas and septations. Patients with acute cholecystitis are much more likely to manifest abnormal laboratory values, while in chronic cholecystitis the laboratory values are frequently normal. Laboratory findings consistent with the diagnosis of chronic cholecystitis include elevated alkaline phosphatase, leukocytosis and elevated bilirubin. Amylase may also be elevated. CT scan findings associated with chronic cholecystitis include gallbladder wall thickening, gallbladder distension or contraction and subserosal edema. The mainstay of treatment for chronic cholecystitis is surgery.  Supportive measures are instituted to prepare the patient for surgery.  These include antimicrobial therapy and fluid resuscitation. If the chronic cholecystitis is superimposed by acute cholecystitis, antibiotics can be used. Commonly used antibiotics are  Cefazolin,  Cefuroxime, and Ceftriaxone. Gallbladder removal by cholecystectomy, can be accomplished by the open surgery or a laparoscopic procedure. Laparoscopic cholecystectomy is the operation of choice in uncomplicated calculous cholecystitis. Open cholecystectomy may be performed in complicated cases or when skilled personal for laparoscopic procedure is not available. Supportive measures are instituted in the meantime to prepare the patient for surgery. These measures include fluid resuscitation and antibiotics. Antibiotic regimens usually consist of a broad spectrum cephalosporin such as ceftriaxone and an antibacterial with good cover against anaerobic bacteria, such as metronidazole.

# 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 chronic cholecystitis. Laparoscopic cholecystectomy was developed to treat chronic cholecystitis and the shift from open to laparoscopic cholecystectomy occurred in the late 1980s.

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

# Pathophysiology
Inflammation of the gallbladder is termed as cholecystitis. Chronic calculous cholecystitis is usually caused by the mechanical obstruction due to gallstones. Chronic acalculous cholecystitis is caused predominantly by the gallbladder stasis. Lith gene is also involved in the pathogenesis of cholecystitis. Cholecystitis is more common in siblings and first degree relatives of affected persons. On gross pathology, chronic cholecystitis usually shows enlarged/distended gallbladder and serosal or mucosal exudates. Fibrosis of gallbladder may also be seen. Microscopic pathology shows lymphocytic inflammatory infiltrates, metaplasia and lipid/mucolipid accumulations in the gallbladder wall.

# Causes
Common causes of cholecystitis include cholelithiasis and infections.

# Differentiating chronic cholecystitis from Other Diseases
Chronic cholecystitis must be differentiated from other conditions that affect the gallbladder and biliary tract such as biliary colic, choledocholithiasis, and cholangitis. Chronic cholecystitis must also be differentiated from colitis, functional bowel syndrome, hiatal hernia, and peptic ulcer.

# Epidemiology and Demographics
It is estimated that 20 to 25 million Americans (10%15% of the population) have gallstones. However, only 1-4% experience symptomatic gallstone diseases. Gallstone disease 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. Females are more commonly affected by gallstone diseases than males for calculous cholecystitis. Males are at increased risk compared to females for acalculous cholecystitis following trauma and burns.

# Risk Factors
Common risk factors in the development of calculous cholecystitis (cholelithiasis) include female gender, increasing age, obesity, pregnancy, family history, genetic factors, and oral contraceptive use.  Common risk factors in the development of acalculous cholecystitis include AIDS, diabetes mellitus, major surgery, burns, sepsis, and long term total parenteral nutrition use.

# Screening
There is insufficient evidence to recommend routine screening for chronic cholecystitis. However, screening ultrasound can be used in children presenting with abdominal pain. Bile amylase concentration may also be a useful screening tool for chronic cholecystitis.

# Natural History, Complications, and Prognosis
Cholecystitis presents with abdominal pain, which is not relieved by antacids and postural changes and lasts longer than 6 hours.  It is sometimes preceded by attacks of biliary pain (due to gallstones). Untreated cholecystitis resolves spontaneously in half of the uncomplicated cases without surgery in a span of 7 - 10 days. The complications of chronic cholecystitis include gangrenous cholecystitis, perforation of the gallbladder, Mirizzi syndrome, gallstone ileus, and gallbladder malignancies.

# Diagnosis

## Diagnostic Criteria
Cholescintigraphy is the gold standard for the diagnosis of chronic cholecystitis. Transabdominal ultrasonography is the initial study of choice for the diagnosis of chronic cholecystitis and gallstones.

## History and Symptoms
The patients with chronic cholecystitis may have the history of recurrent episodes of biliary colic or acute cholecystitis. A positive history of biliary colic, nausea and vomiting are suggestive of chronic cholecystitis. The most common symptoms of chronic cholecystitis are right upper quadrant abdominal or epigastric pain, pain is usually prolonged and there is a positive history of pain after ingestion of heavy fatty meals. The pain is severe and steady and may radiate to the back or right shoulder.

## Physical Examination
Patients with chronic cholecystitis may have malaise during the episode. The physical examination in chronic cholecystitis is remarkable for tender right upper quadrant, fever (usually low grade in uncomplicated cases) and a positive Murphy's sign.

## Laboratory Findings
Patients with acute cholecystitis are much more likely to manifest abnormal laboratory values, while in chronic cholecystitis the laboratory values are frequently normal. Laboratory findings consistent with the diagnosis of chronic cholecystitis include elevated alkaline phosphatase, leukocytosis and elevated bilirubin. Amylase may also be elevated.

## Electrocardiogram
There are no associated EKG findings associated with chronic cholecystitis. However, chronic 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 does not aid diagnosis of chronic cholecystitis. It is performed as an initial evaluation to diagnose the complicated gallbladder disease.

## Ultrasound
Sonography is the most effective initial modality for the diagnosis of chronic cholecystitis. The 2 major diagnostic criteria are cholelithiasis and sonographic Murphy's sign. Other findings may include gallbladder wall thickening, and gallbladder dilatation or contraction.

## CT scan
CT scan findings associated with chronic cholecystitis include gallbladder wall thickening, gallbladder distension or contraction and subserosal edema.

## MRI
Abdominal MRI may be helpful in the diagnosis of chronic cholecystitis. Findings on MRI suggestive of chronic cholecystitis include thickening of the gallbladder and gallstones.

## Other Imaging Findings
HIDA cholescintigraphy is the most sensitive and accurate modality for the diagnosis of chronic cholecystitis. HIDA cholescintigraphy findings for chronic cholecystitis include delayed gallbladder isotope accumulation, irregular gallbladder filling, or photopenic areas and septations.

## Other Diagnostic Studies
The histopathological analysis may be helpful in the diagnosis of chronic cholecystitis. Findings suggestive of chronic cholecystitis include lymphocytic inflammatory infiltrates, metaplasia, fibrosis, lipid and mucolipid accumulation in gallbladder wall.

# Treatment

## Medical Therapy
The mainstay of treatment for chronic cholecystitis is surgery.  Supportive measures are instituted to prepare the patient for surgery.  These include antimicrobial therapy and fluid resuscitation. If the chronic cholecystitis is superimposed by acute cholecystitis antibiotics can be used. Commonly used antibiotics are  Cefazolin,  Cefuroxime, and Ceftriaxone.

## Surgery
Gallbladder removal, cholecystectomy, can be accomplished by the open surgery or a laparoscopic procedure. Laparoscopic cholecystectomy is the operation of choice in uncomplicated calculous cholecystitis. Open cholecystectomy may be performed in complicated cases or when trained/skilled personal for laparoscopic procedure is not available. Supportive measures are instituted in the meantime to prepare the patient for surgery. These measures include fluid resuscitation and antibiotics. Antibiotic regimens usually consist of a broad spectrum cephalosporin such as ceftriaxone and an antibacterial with good cover against anaerobic bacteria, such as metronidazole.

## Primary Prevention
There are no established measures for the primary prevention of acute cholecystitis.

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