Cholecystitis

Cholecystitis
Classification and external resources
Micrograph of a gallbladder with cholecystitisand cholesterolosis.

Cholecystitis (Greek, -cholecyst, "gallbladder", combined with the suffix -itis, "inflammation") is inflammation of the gallbladder, which occurs most commonly due to obstruction of the cystic duct with gallstones (cholelithiasis). Blockage of the cystic duct with gallstones causes accumulation of bile in the gallbladder and increased pressure within the gallbladder. Concentrated bile, pressure, and sometimes bacterial infection irritate and damage the gallbladder wall, causing inflammation and swelling of the gallbladder. Inflammation and swelling of the gallbladder can reduce normal blood flow to areas of the gallbladder, which can lead to cell death due to insufficient oxygen. Not everyone who has gallstones will go on to develop cholecystitis.

Risk factors for cholelithiasis and cholecystitis are similar and include increasing age, female sex, pregnancy, certain medications, obesity, rapid weight loss, and Native American or Mexican American ethnicity. Females are twice as likely to develop cholecystitis as males. Uncomplicated cholecystitis has an excellent prognosis; however, more than 25% of patients require surgery or develop complications. Delayed diagnosis of acute cholecystitis increases morbidity and mortality. Cholelithiasis and cholecystitis may present as a single episode or may recur on multiple occasions.

Signs and symptoms 

Cholecystitis usually presents as a pain in the right upper quadrant or epigastric region. The gallbladder may be tender and distended. Symptomatically it differs from biliary colic by the presence of an inflammatory component (fever, increased white cell count). Pain is initially intermittent, but later usually presents as constant and severe. The pain may be referred pain that is felt in the right scapula rather than the right upper quadrant or epigastric region (Boas' sign). It may also correlate with eating greasy, fatty, or fried foods. Diarrhea, vomiting, and nausea are common. The Murphy sign is sensitive, but not specific for cholecystitis.^[1] Elderly patients and those with diabetes may have vague symptoms that may not include fever or localized tenderness.

More severe symptoms such as high fever, shock and jaundice indicate the development of complications such as abscess formation, perforation or ascending cholangitis. Another complication, gallstone ileus, occurs if the gallbladder perforates and forms a fistula with the nearby small bowel, leading to symptoms of intestinal obstruction.

Chronic cholecystitis manifests with non-specific symptoms such as nausea, vague abdominal pain, belching, and diarrhea.

Causes 

The majority of cases of cholecystitis are caused by gallstones impacting or impinging on the flow of bile in the biliary tree. Gallstone impaction, called cholelithiasis, most commonly occurs at the neck of the gallbladder or in the cystic duct.^[2]:979

This leads to inspissation (thickening) of bile, bile stasis, and secondary infection by gut organisms, predominantly E. coli and Bacteroides species. The gallbladder's wall becomes inflamed. Extreme cases may result in necrosis and rupture. Inflammation often spreads to its outer covering, thus irritating surrounding structures such as the diaphragm and bowel.^{[citation needed]}

Less commonly, the gallbladder may become inflamed in the absence of a gallstone, known as acalculous cholecystitis. This is more common in debilitated patients, such as those in intensive care units, and also in patients with hemolytic anaemias such as sickle cell disease and diabetes mellitus.^[2]:979

Stones in the gallbladder may cause obstruction and the accompanying acute attack. The patient might develop a chronic, low-level inflammation which leads to a chronic cholecystitis, where the gallbladder is fibrotic and calcified.

Diagnosis

Cholecystitis is usually diagnosed by a history of the above symptoms, as well as examination findings:

• Fever (usually low grade in uncomplicated cases)
• Tender right upper quadrant with or without Murphy's sign
• Ortner's sign — tenderness when hand taps the edge of right costal arch. Named for Norbert Ortner (1865 – 1935), an Austrian Surgeon.
• Georgievskiy-Myussi's sign (phrenic nerve sign) — pain when press between edges of sternocleidomastoid. Named for Konstantin Kirelei Georgievskiy (1885 – 1922) and Vitali Lev Myussi (1886 – 1919), Russian Internists.
• Boas' sign — Increased sensitivity below the right scapula (also due to phrenic nerve irritation)

Subsequent laboratory and imaging tests are used to confirm the diagnosis and exclude other possible causes.

Ultrasound is paramount in differential diagnosis.^[3][4] Ultrasound findings suggestive of acute cholecystitis include pericholecystic fluid, >4 mm gallbladder wall thickening, andMurphy's sign. Visualization of gallstones on ultrasound helps confirm the diagnosis of cholecystitis. Computed tomography (CT) scan, magnetic resonance imaging (MRI), and hepatobiliary scintigraphy (HBS) are also useful in the detection of cholecystitis. Endoscopic retrograde cholangiopancreatography (ERCP) may be useful to visualize the anatomy.

Differential diagnosis

Acute cholecystitis

Acute cholecysitis as seen on ultrasound. Closed arrow points to gall bladder wall thickening. Open arrow points to stones in the GB

This should be suspected whenever there is acute right upper quadrant or epigastric pain, other possible causes include:

• Perforated peptic ulcer
• Acute peptic ulcer exacerbation
• Amoebic liver abscess
• Acute amoebic liver colitis
• Acute pancreatitis
• Acute intestinal obstruction
• Renal colic
• Acute retro-colic appendicitis

Chronic cholecystitis

The symptoms of chronic cholecystitis are non-specific, thus chronic cholecystitis may be mistaken for other common disorders:

• Peptic ulcer
• Hiatus hernia
• Colitis
• Functional bowel syndrome, is defined pathologically by the columnar epithelium reaching down to the muscular layer.

Quick Differential

• Biliary colic — Caused by obstruction of the cystic duct. It is associated with sharp and constant epigastric pain in the absence of fever, and there is usually a negativeMurphy's sign, although it can be positive in some instances. Liver function tests are within normal limits since the obstruction does not necessarily cause blockage in the common hepatic duct, thereby allowing normal bile excretion from the liver. An ultrasound scan is used to visualise the gallbladder and associated ducts, and also to determine the size and precise position of the obstruction.
• Cholecystitis — Caused by blockage of the cystic duct with surrounding inflammation, usually due to infection. Typically, the pain is initially 'colicky' (intermittent), and becomes constant and severe, mostly in the right upper quadrant. Infectious agents that cause cholecystitis include E. coli, Klebsiella, Pseudomonas, B. fragilis and Enterococcus. Murphy's sign is positive, particularly because of increased irritation of the gallbladder lining, and similarly this pain radiates (spreads) to the shoulder, flank or in a band like pattern around the lower abdomen. Laboratory tests frequently show raised hepatocellular liver enzymes (AST, ALT) with a high white cell count (WBC). Ultrasound is used to visualise the gallbladder and ducts.
• Choledocholithiasis — This refers to blockage of the common bile duct where a gallstone has left the gallbladder or has formed in the common bile duct (primary cholelithiasis). As with other biliary tree obstructions it is usually associated with 'colicky' pain, and because there is direct obstruction of biliary output, obstructive jaundice. Liver function tests will therefore show increased serum bilirubin, with high conjugated bilirubin. Liver enzymes will also be raised, predominately GGT and ALP, which are associated with biliary epithelium. The diagnosis is made using endoscopic retrograde cholangiopancreatography (ERCP), or the nuclear alternative (MRCP). One of the more serious complications of choledocholithiasis is acute pancreatitis, which may result in significant permanent pancreatic damage and brittle diabetes.
• Cholangitis — An infection of entire biliary tract, and may also be known as 'ascending cholangitis', which refers to the presence of pathogens that typically inhabit more distal regions of the bowel^[5]

Cholangitis is a medical emergency as it may be life-threatening and patients can rapidly succumb to acute liver failure or bacterial sepsis. The classical sign of cholangitis isCharcot's triad, which is right upper quadrant pain, fever and jaundice. Liver function tests will likely show increases across all enzymes (AST, ALT, ALP, GGT) with raised bilirubin. As with choledocholithiasis, diagnosis is confirmed using cholangiopancreatography.

It is worth noting that bile is an extremely favorable growth medium for bacteria, and infections in this space develop rapidly and may become quite severe.^{[citation needed]}

Xanthogranulomatous cholecystitis

Xanthogranulomatous cholecystitis (XGC) is a rare form of gallbladder disease which mimics gallbladder cancer although it is not cancerous.^[6][7] It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and colleagues.^[6][8]

Investigations

Blood

Laboratory values may be notable for an elevated alkaline phosphatase, possibly an elevated bilirubin (although this may indicate choledocholithiasis), and possibly an elevation of the WBC count. CRP (C-reactive protein) is often elevated. The degree of elevation of these laboratory values may depend on the degree of inflammation of the gallbladder. Patients with acute cholecystitis are much more likely to manifest abnormal laboratory values, while in chronic cholecystitis the laboratory values are frequently normal.

Radiology

Sonography is a sensitive and specific modality for diagnosis of acute cholecystitis; adjusted sensitivity and specificity for diagnosis of acute cholecystitis are 88% and 80%, respectively. The diagnostic criteria are gallbladder wall thickening greater than 3mm, pericholecystic fluid and sonographic Murphy's sign. Gallstones are not part of the diagnostic criteria as acute cholecystitis may occur with or without them.

The reported sensitivity and specificity of CT scan findings are in the range of 90–95%. CT is more sensitive than ultrasonography in the depiction of pericholecystic inflammatory response and in localizing pericholecystic abscesses, pericholecystic gas, and calculi outside the lumen of the gallbladder. CT cannot see noncalcified gallbladder calculi, and cannot assess for a Murphy's sign.

Hepatobiliary scintigraphy with technetium-99m DISIDA (bilirubin) analog is also sensitive and accurate for diagnosis of chronic and acute cholecystitis. It can also assess the ability of the gall bladder to expel bile (gall bladder ejection fraction), and low gall bladder ejection fraction has been linked to chronic cholecystitis. However, since most patients with right upper quadrant pain do not have cholecystitis, primary evaluation is usually accomplished with a modality that can diagnose other causes, as well.

Management

X-Ray during laparoscopic cholecystectomy

For most patients diagnosed with acute cholecystitis, the definitive treatment is surgical removal of the gallbladder, cholecystectomy. Until the late 1980s surgical removal was usually accomplished by a large incision in the upper right quadrant of the abdomen under the rib cage. Since the advent of laparoscopic surgery in the early 1990s, laparoscopic cholecystectomy has become the treatment of choice for acute cholecystitis.^[9] Laparoscopic cholecystectomy is performed using several small incisions located at various points across the abdomen. Several studies have demonstrated the superiority of laparoscopic cholecystectomy when compared to open cholecystectomy. Patient undergoing laparoscopic surgery report less incisional pain postoperatively as well as having fewer long term complications and less disability following the surgery.^[10][11] Additionally, laparoscopic surgery is associated with a lower rate of surgical site infection.^[12]

During the days prior to laparoscopic surgery, studies showed that outcomes were better following early removal of the gallbladder, preferably within the first week.^[13] Patients receiving early intervention had shorter hospital stays and lower complication rates. In the era of laparoscopic surgery, a similar approach is still advocated. In a 2006 Cochrane review, early laparoscopic cholecystectomy was compared to delayed treatment. The review consisted of 5 trials with 451 patients randomized to either early (223 patients) or delayed (228) surgical management.^[14] There was no statistically significant difference in terms of negative outcomes including bile duct injury (OR 0.63, 95% CI 0.15 to 2.70) or conversion to open cholecystectomy (OR 0.84, 95% CI 0.53 to 1.34).^[14] However, the early group was found to have shorter hospital stays.^[14] For early cholecystectomy, the most common reason for conversion to open surgery is inflammation obscuring Calot's triangle. For delayed surgery, the most common reason was fibrotic adhesions.^[14]

Supportive measures are usually instituted prior to surgery. These measures include fluid resuscitation and antibiotics targeting enteric organisms, such as E coli and Bacteroides. Antibiotic regimens usually consist of a broad spectrum antibiotic such as piperacillin-tazobactam (Zosyn), ampicillin-sulbactam (Unasyn), ticarcillin-clavulanate (Timentin), or a cephalosporin (e.g.ceftriaxone) and an antibacterial with good coverage (fluoroquinolone such as ciprofloxacin) and anaerobic bacteria coverage, such as metronidazole. For penicillin allergic patients, aztreonam and clindamycin may be used. Parenteral narcotics can be used for pain control.

In cases of severe inflammation, shock, or if the patient has higher risk for general anesthesia (required for cholecystectomy), the managing physician may elect to have aninterventional radiologist insert a percutaneous drainage catheter into the gallbladder ('percutaneous cholecystostomy tube') and treat the patient with antibiotics until the acute inflammation resolves. A cholecystectomy may then be warranted if the patient's condition improves.

Homeopathic approaches to treating cholecystitis have not been validated by evidence and should not be used in place of surgery.

Complications

• Perforation or rupture
• Ascending cholangitis
• Rokitansky-Aschoff sinuses

Cholecystectomy

• emphysematous cholecystitis
• bile leak ("biloma")
• bile duct injury (about 5–7 out of 1000 operations. Open and laparoscopic surgeries have essentially equal rate of injuries, but the recent trend is towards fewer injuries with laparoscopy. It may be that the open cases often result because the gallbladder is too difficult or risky to remove with laparoscopy)
• abscess
• wound infection
• bleeding (liver surface and cystic artery are most common sites)
• hernia
• organ injury (intestine and liver are at highest risk, especially if the gallbladder has become adherent/scarred to other organs due to inflammation (e.g. transverse colon)
• deep vein thrombosis/pulmonary embolism (unusual- risk can be decreased through use of sequential compression devices on legs during surgery)
• fatty acid and fat-soluble vitamin malabsorption

Gall bladder perforation

Gall bladder perforation (GBP) is a rare but life-threatening complication of acute cholecystitis. The early diagnosis and treatment of GBP are crucial to decrease patient morbidity and mortality.

Approaches to this complication will vary based on the condition of an individual patient, the evaluation of the treating surgeon or physician, and the facilities' capability. Perforation can happen at the neck from pressure necrosis due to the impacted calculus, or at the fundus. It can result in a local abscess, or perforation into the general peritoneal cavity. If the bile is infected, diffuse peritonitis may occur readily and rapidly and may result in death A retrospective study looked at 332 patients who received medical and/or surgical treatment with the diagnosis of acute cholecystitis. Patients were treated with analgesics and antibiotics within the first 36 hours after admission (with a mean of 9 hours), and proceeded to surgery for a cholecystectomy. Two patients died and 6 patients had further complications. The morbidity and mortality rates were 37.5% and 12.5%, respectively in the present study. The authors of this study suggests that early diagnosis and emergency surgical treatment of gallbladder perforation are of crucial importance.