• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Acute Cholecystitis

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Last updated: July 23, 2019
Years published: 1989, 1997, 1998, 2010, 2019


Acknowledgment

NORD gratefully acknowledges Gabrielle O’Dougherty, NORD Editorial Intern from the University of Notre Dame and Barb Calhoun, MSN, RN, NP, Nurse Practitioner and Outreach Coordinator, Boler-Parseghian Center for Rare and Neglected Diseases at the University of Notre Dame, for assistance in the preparation of this report.


Disease Overview

The gallbladder is a small pear shaped organ that stores and concentrates bile used for digestion of fats. Bile is a compound composed mainly of cholesterol, bile salts and bilirubin, produced by the liver and stored in the gallbladder during fasting states. When food is consumed, it is partially digested by the stomach and enters the small intestine, where bile is released by the gallbladder to aid in the breakdown of fats. Gallstones develop when the components of bile, such as cholesterol and bilirubin, remain in the gallbladder and solidify into “pebble-like” material. Gallstones may lodge in the bile ducts and block the release of bile causing a backup. Up to 80% of all gallstones do not cause symptoms but obstruction within the bile ducts can cause gallbladder swelling (distension) and severe pain and tenderness of right side of abdomen and/or back (biliary colic). If the obstruction persists, it results in inflammation, infection, and even lack of blood flow (ischemia), a common condition known as acute cholecystitis, or acute calculous cholecystitis (ACC). Repeated mild episodes of acute cholecystitis may result in chronic cholecystitis, causing thickening and shrinking of the gallbladder wall resulting in an inability to store bile.

Another form of cholecystitis, acute acalulous cholecystitis (AAC) is an inflammatory disease of the gallbladder without evidence of gallstones or obstruction of the cystic ducts. Approximately 2-15% of cases of cholecystitis are acalculous and usually occur in very sick hospitalized patients. The exact causal mechanism is not clear. Acalculous cholecystitis is associated with a higher mortality rate (~45%) due in part to serious underlying medical conditions and delayed diagnosis.

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Synonyms

  • acute acalculous cholecystitis (AAC)
  • acute calculous cholecystitis
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Signs & Symptoms

Acute Calculous Cholecystitis

The specific symptoms associated with cholecystitis vary among patients. Upper abdominal pain, often localized to the right upper quadrant, is the most common symptom. In acute calculous cholecystitis, the pain is often sudden and intense but it can be described as cramping, dull, or steady. Pain can become excruciating. Upper abdominal pain usually lasts longer than six hours, often beginning a few hours after a meal or at night. It can worsen with deep breaths and may radiate into the back and right shoulder blade (scapula). The right upper quadrant will likely be tender and 25% of patients have a perceptible mass there after 24 hours of symptoms.

In addition to pain, many affected individuals experience nausea, vomiting and shortness of breath when inhaling (due to pain). Additional symptoms of cholecystitis include stiffening of the muscles on the right side of the abdomen, bloating of the abdomen, chills, and fever. Blood testing may show an increase in white blood cell count and C-reactive protein (elevation indicates inflammation). If serum amylase levels are elevated, the patient may also have gallstone pancreatitis or gangrenous cholecystitis. Although bilirubin may be elevated, development of frank jaundice in the absence of other complications is rare. If jaundice does occur, persistent yellowing of the skin, mucous membranes, and whites of the eyes will be present. In rare cases, symptoms such as dark urine and clay colored stools are indicative of common bile duct obstruction.

Older individuals with cholecystitis may not develop pain or fever. Their only symptoms may be tenderness of the upper right portion of the abdomen, altered mental status, or decreased food intake.

Affected individuals may develop a bacterial infection preceding or during a gallbladder attack. In most patients, a gallbladder attack will last one to four days and then subside. In rare severely affected patients, the gallbladder wall may rupture (perforate) or pus may build up within the gallbladder (empyema). In these patients, surgery may be necessary.

Acute Acalculous Cholecystitis (AAC)

AAC is generally distinguishable from calculous cholecystitis because it usually occurs in association with other serious conditions requiring hospital admission. As in calculous cholecystitis patients, AAC often presents with pain in the upper right quadrant of the abdomen that radiates into the back. It is also characterized by fever, nausea, and vomiting. Increased white blood cell count (leukocytosis), decreased intestinal muscle contraction (paralytic ileus), gallbladder abscess and/or gangrene are all signs of AAC. A palpable mass or Murphy’s sign are sometimes present. Nonspecific symptoms include diarrhea, upset stomach, fatigue, altered mental status, and jaundice.

Hemorrhagic AAC has been reported in patients with end-stage renal disease (ESRD).

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Causes

Acute Calculous Cholecystitis

The medical term for the presence of a gallstone is cholelithiasis. Approximately 90 percent of cases of cholecystitis are associated with the presence of a gallstone obstructing the cystic duct (calculous cholecystitis), often resulting in buildup of cholesterol- saturated bile in the gallbladder. The cystic duct is a short tube that carries bile from the gallbladder to the common bile duct. Severity of the cholecystitis depends on the length of time the cystic duct is blocked. If brief, it may result in short term pain. If longer than a couple of hours, the cholelithiasis results in inflammation. The gallbladder becomes enlarged, tense, and reddened with thickened walls that may exude pericholecystic fluid. This is often accompanied by secondary infections that can cause necrosis, gangrene, or gas buildup in the wall of the gallbladder which may result in perforation if left untreated. Perforation can cause inflammation of the abdominal inner lining (peritonitis) or the upper right quadrant of the liver.

Acute Acalculous Cholecystitis (AAC)

AAC is not associated with the presence of gallstones, but an underlying medical condition or clinical trauma such as major burns, end-stage renal disease, post-hemorrhagic shock resuscitation, surgery, polytrauma or leukemia that can produce systemic inflammation. In addition, viral, bacterial, and parasitic infectious diseases have been associated with AAC. The exact cause of AAC is unknown but thought to be induced by reduced blood flow to the gallbladder (ischemia), infectious disease or lack of gallbladder stimulation (not eating) causing biliary stasis (bile immobility)

Although gallstones do not obstruct the bile duct in this form of cholecystitis, there may be other physical barriers present. These barriers may be infectious or noninfectious. For example, bile duct blockages may be caused by cysts full of parasitic Echinococcus eggs, ascariasis (intestinal infection from roundworm), hemophilia, generic cysts, and narrowing of bile duct (ampullary stenosis).

Additionally, infections can kill gallbladder tissue (gangrene), causing AAC. Other medical conditions such as diabetes mellitus, inflammation of blood vessels (vasculitis), opioid use, sickle cell anemia, dehydration, positive pressure ventilation, and blockage of oxygenated blood from getting to gallbladder (cystic artery obstruction). The following is a list of diseases associated with acute acalculous cholecystitis:

Bacterial:
○ Most commonly gram-negative intestinal (enteric) bacteria like Escherichia Coli
○ Candidiasis (fungal)
○ Leptospirosis
Coxiella Burnett
Salmonella (rarely)
Lactococcus garvieae (rarely)
○ Typhoid fever and non- Typhoid Salmonella Typhoid (impacting the biliary tract)
○ Cholera (diarrheal)
○ Campylobacter enteritis (diarrheal)
○ Tuberculosis

Parasitic:
Cryptosporidium parasite
Plasmodium falciparum (Malaria)

End-stage renal disease (ESRD)

Viral:
○ Hepatitis A
○ Hepatitis B
○ Cytomegalovirus
○ Chickenpox (varicella zoster virus)
○ HIV- AIDS
○ Dengue fever
○ Epstein-Barr virus
■ In the presence of viral infections, portal lymphadenitis with extrinsic cystic duct obstruction

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Affected populations

Although the incidence of acute cholecystitis is unknown, about 120,000 Americans are treated for acute cholecystitis annually. At age 65, 25% of women and 12% of men will have gallstone disease. Approximately 10% of all patients with symptomatic gallstones will develop cholecystitis. If the gallbladder is not removed after acute cholecystitis, there is a 29% chance of a second gallstone related event within a year. Although 60% of acute cholecystitis patients are women, the proportion of people with gallstones who develop cholecystitis is higher in men. Men also tend to have more severe symptoms. Diabetes and older age increase the risk of developing cholecystitis.

Acalculous cholecystitis has an incidence rate of 0.12% in the entire population. 80% of cases of acalculous cholecystitis are in male patients of age 50 and older.

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Diagnosis

Acute cholecystitis has no single clinical or laboratory finding with the level of diagnostic accuracy needed for diagnosis. Instead, the recommended diagnostic technique combines clinical observations with an abdominal ultrasound. The Tokyo Guidelines require one local sign or symptom, one systemic sign, and a confirmatory image test to form a diagnosis. However, these requirements may lead to under-diagnosis in patients presenting fewer symptoms. The Murphy’s sign test is a commonly used diagnostic tool. The physician applies pressure just below the ribs on the right side and asks the patient to inhale. Inhalation will bring the gallbladder into contact with the physician’s fingers, causing pain and an arrest in inspiration if the gallbladder is inflamed. Blood tests showing elevated levels of white blood cells (leukocytosis), elevated C-reactive protein, may be signs of infection and inflammation.

Imaging techniques are used to directly observe gallstones, gallbladder wall thickness, or cystic duct obstruction. The gallbladder wall is pathologically thickened if it is >3mm or wider. The two main imaging techniques used for cholecystitis are abdominal ultrasound and hepatobiliary scintigraphy (HIDA scan). Abdominal ultrasound is often the first test due to its widespread availability, lack of invasiveness, lack of ionizing radiation, and high accuracy in detecting gallbladder stones. Ultrasound can show the presence of stones, wall thickening and pericholecystic fluid.

A hepatobiliary iminodiacetic acid (HIDA) scan tracks the production and flow of bile from the liver to the small intestine and shows blockage. This test involves the intravenous injection of HIDA, a radioactively labelled compound, secreted into bile. A specialized camera can detect the radioactivity, allowing it to trace the movement of this bile. If the gallbladder does not fill within an hour, the cystic duct is likely obstructed. Although it is the most sensitive and specific diagnostic tool, it is limited in its use because of limited availability, long testing time, and ionizing radiation exposure. It can also be inaccurate if bilirubin is elevated which is indicative of decreased ability of the liver to secrete compounds such as HIDA into bile.

Cholangiography and computed tomography (CT) may also be used to identify cholecystitis, although their diagnostic accuracy is unknown. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. During cholangiography, a contrast dye is injected into the bloodstream, which enables x-rays to create an image of the bile ducts. Additional imaging techniques include MRI.

Diagnosis is often delayed in elderly patients, as the only symptoms may be an alteration of mental state or decreased food intake.
The 2007 Tokyo Guidelines grade the severity of the disease to help guide its treatment. Cases are graded as mild, moderate, and severe as follows:

Mild (grade 1):
• Having none of the features of moderate or severe cholecystitis

Moderate (grade 2):
● Elevated white cell count
● Palpable, tender mass in upper right quadrant
● Duration longer than 72 hours
● Local inflammation (could be biliary peritonitis, pericholecystic abscess, hepatic abscess, gangrenous cholecystitis, or emphysematous cholecystitis)

Severe (Grade 3):
● Cardiovascular dysfunction
● Neurological dysfunction
● Respiratory dysfunction
● Renal dysfunction
● Hepatic dysfunction
● Hematologic dysfunction

Acute Acalculous Cholecystitis (AAC)

Diagnosis of AAC is often much more difficult than that of typical cholecystitis because it is much less common and patients often have severe concomitant medical problems that are the reason for hospital admission. The disease is generally suspected in any critically or chronically ill patient presenting with abdominal pain, fever and unexplained leukocytosis and sepsis. Blood tests may show increases in white blood cells (leukocytosis), transaminases, alkaline phosphatase, bilirubin, and amylase. As in calculous cholecystitis, ultrasound is the primary diagnostic imaging technique for AAC. Ultrasound may show gallbladder wall thickening greater than 5 mm, pericholecystic fluid, biliary sludge, gallbladder distention, gallbladder striation, mucosal peeling, air bubbles (emphysematous cholecystitis), and gallbladder perforation. Presence of at least two of the following is generally used to diagnose AAC: positive ultrasound Murphy’s sign, gallbladder wall thickening, gallbladder distension and pericholecystic fluid, in the absence of gallstones.

CT and MRI are used when ultrasounds are inconclusive. An MRI can show gallbladder wall thickening, increased bile density, air bubbles, fluid buildup, and bleeding inside the gallbladder.

Hepatobiliary scintigraphy is the best diagnostic tool for AAC because it can detect those without the disease 100% of the time. This test shows improper gallbladder filling in both AAC and calculous cholecystitis.

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Standard Therapies

Treatment
When first admitted for ACC, patients receive nothing by mouth as they may need immediate surgery. The primary treatment for the disease is usually cholecystectomy, the surgical removal of the entire gallbladder. Surgical removal of just the gallstones has a high rate of pathological recurrence within 5 years.

For patients with mild cholecystitis, immediate laparoscopic cholecystectomy is recommended. During this procedure, a small, thin tube called a laparoscope is passed through a small incision in the abdominal wall, allowing a surgeon to remove the diseased gallbladder. It can be performed openly (operative cholecystostomy/ laparotomy) or laparoscopically.

Patients with moderate cholecystitis may have immediate surgical removal of the gall bladder. Others will be put on bowel rest and receive intravenous hydration with fluids/electrolytes and pain medications followed by surgery once patient improves.

Many patients with moderate to severe disease may not undergo cholecystectomy if complicated by infection and systemic dysfunctions that make them high risk for surgery. Instead, high surgical risk patients such as the elderly or those with immunodeficiency or diabetes may have a percutaneous, transhepatic cholecystostomy drainage tube permanently placed in their gall bladder with the guidance of ultrasonography. Severely affected patients are treated with resuscitation and IV antibiotics in the intensive care unit and surgery is performed once patient improves. The 2013 Tokyo Guidelines suggest immediate use of antibiotics in all patients with cholecysititis.

Treatment for AAC is dependent on the type of underlying disease or trauma that is involved. Emergency cholecystectomy is necessary in many patients. The closed version of this surgery is usually preferred because AAC has such a high rate of tissue death (gangrene) and perforation. Conservative treatment by broad spectrum antibiotics is best when caused by Salmonella Enteritidis infection or Dengue. Gram-negative and anaerobic microorganism targeting antibiotics should be used in all patients. Treatment for any underlying conditions is also necessary.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

TEXTBOOKS
Ahmed N. Acute acalculous cholecystitis complicating major trauma: a report of five cases. South Med J. 2008;101:1146-1149.

Altun E, Semelka RC, Elias J Jr., et al. Acute cholecystitis: MR findings and differentiation from chronic cholecystitis. Radiology. 2007:244:174-83.

Stein JH., Sande MA, Zvaifler NJ, eds. Internal Medicine, 5th ed. St. Louis, MO: Mosby, Inc. 1998:2227-2230.

JOURNAL ARTICLES

Ansaloni, L., Pisano, M., Coccolini, F., Peitzmann, A., et al. World J Emerg Surg. 2016 Jun 14;11:25. doi: 10.1186/s13017-016-0082-5. eCollection 2016

Strasberg SM. Acute calculous cholecystitis. N Engl J Med. 2008;358:2804-2811.

Takada T, Kawarada Y, Nimura Y, et al. Background: Tokyo guidelines for the management of acute cholangitis and cholecystitis.. J Hepatobiliary Pancreat Surg 2007;14:78-82.

INTERNET
Bloom A A . Cholecystitis Treatment & Management. Medscape. Updated: Mar 12, 2019. https://emedicine.medscape.com/article/171886-treatment#d12. Accessed June 13, 2019.

De Oliveira SA, Jr, Lemos TE, and De Medeiras AC, Jr. Acute acalculous cholecystitis in critically ill patients: risk factors, diagnosis and treatment strategies. Journal of the Pancreas 2016:17(6), 580-586. https://pancreas.imedpub.com/acute-acalculous-cholecystitis-in-critically-ill-patients-risk-factors-diagnosis-and-treatment-strategies.php?aid=17273. Accessed June 13, 2019.

Acute cholecystitis. MedlinePlus. Review date 7/10/2017. https://medlineplus.gov/ency/article/000264.htm Accessed June 13, 2019.

Parmet S, Cassio L, and Glass RM. Acute Cholecystitis. JAMA Patient Page. 2003;289:124. Available at: https://jama.ama-assn.org/cgi/content/full/289/1/124 Accessed June 13, 2019.

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