Cholecystitis

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

X-Ray during laparoscopic cholecystectomy

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.[1] 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.[2, 3] 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.

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%.

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[5] 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.

Cholecystitis
Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site of pathology, known as referred pain. The pain is originally located in the right upper quadrant but the referred pain may occur in the right scapula region. This may also present with the above mentioned pain after eating greasy or fatty foods such as pastries, pies, and fried foods. This is usually accompanied by a low-grade fever, diarrhea, vomiting, nausea and granulocytosis. The gallbladder may be tender and distended. 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
Cholecystitis is often caused by cholelithiasis (the presence of choleliths, or gallstones, in the gallbladder), with choleliths most commonly blocking the cystic duct directly. This leads to inspissation (thickening) of bile, bile stasis, and secondary infection by gut organisms, predominantly E. coli and Bacteroides species.[citation needed] 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. Less commonly, in debilitated and trauma patients, the gallbladder may become inflamed and infected in the absence of cholelithiasis, and is known as acute acalculous cholecystitis. This can arise in patients with anorexia nervosa, as the lack of stimulation of the gallbladder leads to an infectious process. 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. Georgievskiy Myussi's sign (phrenic nerve sign) pain when press between edges of sternocleidomastoid 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 can assist in the differential.

Differential diagnosis
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.

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 9095%. 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
For most patients, in most centres, the definitive treatment is surgical removal of the gallbladder. Supportive measures are instituted in the meantime and to prepare the patient for surgery. These measures include fluid resuscitation and antibiotics. 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. Gallbladder removal, cholecystectomy, can be accomplished via open surgery or a laparoscopic procedure. Laparoscopic procedures can have less morbidity and a shorter recovery stay. Open procedures are usually done if complications have developed or the patient has had prior surgery

to the area, making laparoscopic surgery technically difficult. A laparoscopic procedure may also be 'converted' to an open procedure during the operation if the surgeon feels that further attempts at laparoscopic removal might harm the patient. Open procedure may also be done if the surgeon does not know how to perform a laparoscopic cholecystectomy. 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 an interventional 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.

Complications

Perforation or rupture Ascending cholangitis Rokitansky-Aschoff sinuses

Cholecystectomy

emphysematous cholecystitis bile leak ("biloma") bile duct injury (about 57 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.[4]

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