Ascending cholangitis: Difference between revisions

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{{Infobox medical condition (new)

| name = Ascending cholangitis

| synonyms = acute cholangitis, cholangitis

| image = Cholangitis.jpg

| caption = Duodenoscopy image of pus extruding from the [[Ampullaampulla of Vater]], indicative of cholangitis

| pronounce =

| field = [[Gastroenterology]] <br> [[General surgery]]

| symptoms = [[jaundice]], [[fever]] and [[abdominal pain]]

| complications =

| onset =

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'''Ascending cholangitis''', also known as '''acute cholangitis''' or simply '''cholangitis''', is [[inflammation]] of the [[bile duct]] (cholangitis), usually caused by [[bacteria]] ascending from [[Ampulla of Vater|its junction]] with the [[duodenum]] (first part of the [[small intestine]]). It tends to occur if the bile duct is already partially obstructed by [[gallstone]]s.<ref name=Kinney/><ref name=schwartz/>

Cholangitis can be life-threatening, and is regarded as a [[medical emergency]].<ref name=Kinney/> Characteristic symptoms include [[jaundice|yellow discoloration of the skin or whites of the eyes]], [[fever]], [[abdominal pain]], and in severe cases, [[hypotension|low blood pressure]] and [[mental confusion|confusion]]. Initial treatment is with [[intravenous fluid]]s and [[antibiotic]]s, but there is often an underlying problem (such as gallstones or [[Stenosis|narrowing]] in the bile duct) for which further tests and treatments may be necessary, usually in the form of [[endoscopy]] to relieve obstruction of the bile duct.<ref name=Kinney/><ref name=Williams/> The word is from Greek ''chol''-, bile + ''ang''-, vessel + -''itis'', [[inflammation]].

==Signs and symptoms==

[[File:Charcot's cholangitis triad-en.svg|thumb|[[Charcot's cholangitis triad|Charcot's triad]]]]

A person with cholangitis may complain of [[abdominal pain]] (particularly in the [[right upper quadrant (abdomen)|right upper quadrant]] of the [[Human abdomen|abdomen]]), [[fever]], [[rigor (medicine)|rigors]] (uncontrollable shaking) and a feeling of uneasiness ([[malaise]]). Some may report [[jaundice]] (yellow discoloration of the skin and the whites of the eyes).<ref name=Kinney>{{cite journal | author=Kinney TP | title=Management of ascending cholangitis | journal=Gastrointest Endosc Clin N Am |date=April 2007 | volume=17 | issue=2 | pages=289–306 | pmid=17556149 | doi=10.1016/j.giec.2007.03.006}}</ref>

[[Physical examination]] findings typically include jaundice and right upper quadrant tenderness.<ref name=Kinney/> [[Charcot's cholangitis triad|Charcot's triad]] is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever.<ref name=Charcot>{{cite book | author=Charcot JM | title=Leçons sur les maladies du foie, des voies biliaires et des reins faites à la Faculté de médecine de Paris: Recueillies et publiées par Bourneville et Sevestre | ___location=Paris | publisher=Bureaux du Progrés Médical & Adrien Delahaye | origyearorig-year=1877 | year=2004 | isbn=978-1-4212-1387-3}}</ref> This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%.<ref name=Kinney/> [[Reynolds' pentad]] includes the findings of Charcot's triad with the presence of [[septic shock]] and [[mental confusion]].<ref name=Reynolds>{{cite journal |vauthors=Reynolds BM, Dargan EL | title=Acute obstructive cholangitis; a distinct clinical syndrome | journal=Ann Surg |date=August 1959 | volume=150 | issue=2 | pages=299–303 | pmid=13670595 | pmc=1613362 | doi=10.1097/00000658-195908000-00013}}</ref> This combination of symptoms indicates worsening of the condition and the development of [[sepsis]], and is seen less commonly still.<ref name="Kinney"/><ref name=schwartz>{{cite book |vauthors=Oddsdóttir M, Hunter JG |veditors=Brunicardi FC, Anderson DK, Billiar TR, Dunn DL, Hunter JG, Pollock RE | title=Schwartz's Principles of Surgery | edition=Eighth | year= 2005 | publisher=McGraw-Hill | isbn=978-0-07-141090-8 | chapter=Gallbladder and the extrahepatic biliary system (chapter 31) | page=1203}}</ref>

In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features.<ref name=schwartz/> Those with an indwelling stent in the bile duct ([[#Causes|see below]]) may not develop jaundice.<ref name=schwartz/>

==Causes==

Bile duct obstruction, which is usually present in acute cholangitis, is generally due to [[gallstone]]s. 10–30% of cases, however, are due to other causes such as [[benign]] stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an [[anastomosis]] (surgical connection), various tumors ([[cholangiocarcinoma|cancer of the bile duct]], [[gallbladder cancer]], cancer of the [[ampulla of Vater]], [[pancreatic cancer]], [[small intestine cancer|cancer of the duodenum]]), [[anaerobic organism]]s such as [[Clostridium]] and [[Bacteroides]] (especially in the elderly and those who have undergone previous surgery of the [[biliary system]]).<ref name=Kinney/>

Parasites which may infect the liver and bile ducts may cause cholangitis; these include the [[roundworm]] ''[[Ascaris lumbricoides]]'' and the [[liver flukes]] ''[[Clonorchis sinensis]]'', ''[[Opisthorchis viverrini]]'' and ''[[Opisthorchis felineus]]''.<ref>{{cite journal |author=Lim JH |title=Liver flukes: the malady neglected |journal=Korean J Radiol |volume=12 |issue=3 |pages=269–79 |year=2011 |pmid=21603286 |pmc=3088844 |doi=10.3348/kjr.2011.12.3.269 }}</ref> In people with [[AIDS]], a large number of opportunistic organisms has been known to cause ''AIDS cholangiopathy'', but the risk has rapidly diminished since the introduction of [[Antiretroviral drug|effective AIDS treatment]].<ref name=Kinney/><ref name=Kimura2007>{{cite journal |vauthors=Kimura Y, Takada T, Kawarada Y | title=Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines | journal=J Hepatobiliary Pancreat Surg | year=2007 | volume=14 | issue=1 | pages=15–26 | pmid=17252293 | doi=10.1007/s00534-006-1152-y | pmc=2784509|display-authors=etal}}</ref> Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.<ref name=Williams/><ref>{{cite journal|last1=Brand|first1=M|last2=Bizos|first2=D|last3=O'Farrell P|first3=Jr|title=Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography.|journal=The Cochrane Database of Systematic Reviews|date=6 October 2010|issue=10|pages=CD007345|doi=10.1002/14651858.CD007345.pub2|pmid=20927758|pmc=12305484}}</ref>

The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.<ref name=Kinney/>

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The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 [[centimetre of water|cmH₂O]])<ref>{{cite book | author=Dooley JS | title=Oxford textbook of clinical hepatology | publisher=Oxford University Press | year=1999 | isbn=978-0-19-262515-1 | page=1650 }}</ref> and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile&mdash;[[bile salt]]s<ref name=Kinney/> and [[immunoglobulin]]<ref name=schwartz/> secreted by the [[epithelium]] of the bile duct also has a protective role.

Bacterial contamination alone in absence of obstruction does not usually result in cholangitis.<ref name=schwartz/> However increased pressure within the biliary system (above 20 cmH₂O)<ref name=Huang>{{cite journal |vauthors=Huang T, Bass JA, Williams RD |title=The significance of biliary pressure in cholangitis |journal=Arch Surg |volume=98 |issue=5 |pages=629–632 |date=May 1969 |pmid=4888283 |doi=10.1001/archsurg.1969.01340110121014}}</ref> resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of [[Kupffer cells]], which are specialized [[macrophage]] cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of [[IgA]] immunoglobulins in the bile.<ref name=Sung2>{{cite journal |vauthors=Sung JY, Costerton JW, Shaffer EA |title=Defense system in the biliary tract against bacterial infection |journal=Dig Dis Sci |volume=37 |issue=5 |pages=689–96 |date=May 1992 |pmid=1563308 |doi= 10.1007/BF01296423|urls2cid=21258760 }}</ref> This results in [[bacteremia]] (bacteria in the blood stream) and gives rise to the [[systemic inflammatory response syndrome]] (SIRS) comprising fever (often with [[Rigor (medicine)|rigors]]), [[tachycardia]], increased [[respiratory rate]] and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called [[sepsis]].<ref name=Kinney/> Biliary obstruction itself disadvantages the [[immune system]] and impairs its capability to fight infection, by impairing the function of certain immune system cells ([[neutrophil granulocyte]]s) and modifying the levels of immune hormones ([[cytokine]]s).<ref name=Kinney/>

In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi.<ref name=Kinney/> Other theories about the origin of the bacteria, such as through the [[portal vein]] or transmigration from the [[colon (anatomy)|colon]], are considered less likely.<ref name=Kinney/>

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The [[gold standard (test)|gold standard]] test for biliary obstruction is still [[endoscopic retrograde cholangiopancreatography]] (ERCP). This involves the use of [[endoscopy]] (passing a tube through the mouth into the [[esophagus]], [[stomach]] and thence to the [[duodenum]]) to pass a small cannula into the bile duct. At that point, [[radiocontrast]] is injected to opacify the duct, and [[X-ray]]s are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as [[Cholangiography|cholangiograms]]), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.<ref name=Kinney/>

If other causes rather than gallstones are suspected (such as a [[tumor]]), [[computed tomography]] and [[endoscopic ultrasound]] (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain [[biopsy]] (tissue sample) of suspicious masses.<ref name=Kinney/> EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.<ref name=Williams>{{cite journal |vauthors=Williams EJ, Green J, Beckingham I, Parks R, Martin D, Lombard M | title=Guidelines on the management of common bile duct stones | journal=Gut | year=2008 | volume=57 | pages=1004–1021 | pmid=18321943 | doi=10.1136/gut.2007.121657 | url=http://gut.bmj.com/cgi/content/full/57/7/1004 | issue=7| s2cid=206945855 | url-access=subscription }}</ref>

==Treatment==

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The definitive treatment for cholangitis is relief of the underlying biliary obstruction.<ref name=Kinney/> This is usually deferred until 24–48&nbsp;hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment,<ref name=Kinney/> or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).<ref name=schwartz/><ref name=Williams/>

[[Endoscopic retrograde cholangiopancreatography]] (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a [[fiberoptic]] tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the [[common bile duct]]; alternatively or additionally, the common bile duct orifice can be dilated with a balloon.<ref name=Heo>{{cite journal |vauthors=Heo JH, Kang DH, Jung HJ |title=Endoscopic sphincterotomy plus large-balloon dilation versus endoscopic sphincterotomy for removal of bile-duct stones |journal=Gastrointest Endosc |volume=66 |issue=4 |pages=720–6; quiz 768, 771 |date=October 2007 |pmid=17905013 |doi=10.1016/j.gie.2007.02.033|display-authors=etal}}</ref> Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical [[lithotriptor]] in order to crush the stone prior to removal.<ref name=Caddy>{{cite journal |vauthors=Caddy GR, Tham TC |title=Gallstone disease: Symptoms, diagnosis and endoscopic management of common bile duct stones |journal=Best Pract Res Clin Gastroenterol |volume=20 |issue=6 |pages=1085–101 |year=2006 |pmid=17127190 |doi=10.1016/j.bpg.2006.03.002}}</ref> Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by [[extracorporeal shock wave lithotripsy]]. This technique uses acoustic shock waves administered outside the body to break down the stones.<ref name=Hochberger>{{cite journal |vauthors=Hochberger J, Tex S, Maiss J, Hahn EG |title=Management of difficult common bile duct stones |journal=Gastrointest Endosc Clin N Am |volume=13 |issue=4 |pages=623–34 |date=October 2003 |pmid=14986790 |doi= 10.1016/S1052-5157(03)00102-8|url=}}</ref> An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone.<ref name=Arya>{{cite journal |vauthors=Arya N, Nelles SE, Haber GB, Kim YI, Kortan PK |title=Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones |journal=Am J Gastroenterol |volume=99 |issue=12 |pages=2330–4 |date=December 2004 |pmid=15571578 |doi=10.1111/j.1572-0241.2004.40251.x |pmid=15571578 |s2cid=6147693 }}</ref> Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with [[laparoscopy]], is required to remove the stone.<ref name=Karaliotas>{{cite journal |vauthors=Karaliotas C, Sgourakis G, Goumas C, Papaioannou N, Lilis C, Leandros E |title=Laparoscopic common bile duct exploration after failed endoscopic stone extraction |journal=Surg Endosc |volume= 22|issue= 8|pages= 1826–31|date=December 2007 |pmid=18071799 |doi=10.1007/s00464-007-9708-8 |urls2cid=2347888 }}</ref>

Narrowed areas may be bridged by a [[stent]], a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent [[Self-expandable metallic stent|self-expanding metal stents]] with a longer lifespan are used if the obstruction is due to pressure from a tumor such as [[pancreatic cancer]]. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a [[nasogastric tube]], but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment.<ref name=Kinney/> Certain treatments may be unsafe if [[coagulation|blood clotting]] is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as [[clopidogrel]] (which inhibits [[platelet]] aggregation) or if the [[prothrombin time]] is significantly prolonged. For a prolonged prothrombin time, [[vitamin K]] or [[fresh frozen plasma]] may be administered to reduce bleeding risk.<ref name=Kinney/>

=== Percutaneous biliary drainage ===

In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a [[percutaneous transhepatic cholangiography|percutaneous transhepatic cholangiogram]] (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD).<ref name="García-García 663–670">{{Cite journal|lastlast1=García-García|firstfirst1=Lorenzo|last2=Lanciego|first2=Carlos|date=2004-03-01|title=Percutaneous Treatment of Biliary Stones: Sphincteroplasty and Occlusion Balloon for the Clearance of Bile Duct Calculi|journal=American Journal of Roentgenology|volume=182|issue=3|pages=663–670|doi=10.2214/ajr.182.3.1820663|pmid=14975967|issn=0361-803X}}</ref><ref name="Williams" /> This is often necessary in the case of a proximal stricture or a bilioenteric [[Anastomosis#Medicine|anastomosis]] (a surgical connection between the bile duct and small bowel, such as the [[duodenum]] or [[jejunum]]).<ref name="schwartz" /> Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum.<ref name="García-García 663–670"/> Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance,<ref name="schwartz" /> a retrograde approach via ERCP remains first-line therapy.<ref name="Kinney" />

=== Cholecystectomy ===

Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but [[cholecystectomy]] (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones.<ref name=Kinney/><ref name=schwartz/><ref name=Williams/> Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased.<ref>{{cite journal |vauthors=McAlister VC, Davenport E, Renouf E |title=Cholecystectomy deferral in patients with endoscopic sphincterotomy |journal=Cochrane Database Syst Rev |issue=4 |pages=CD006233 |year=2007 |volume=2010 |pmid=17943900 |doi=10.1002/14651858.CD006233.pub2 |url=http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD006233/frame.html |archive-url=https://archive.today/20120716160957/http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD006233/frame.html |url-status=dead |archive-datepmc=2012-07-168923260 |editor1-last=McAlister |editor1-first=Vivian }}</ref>

== Biliary sepsis ==

[[Biliary sepsis]] is a systemic complication of acute cholangitis that occurs when infection spreads from the bile ducts into the bloodstream.

A systemic infection resulting from [[Intestinal permeability|bacterial translocation]] from the [[biliary tract]], most commonly due to acute [[Primary sclerosing cholangitis|cholangitis]] or [[suppurative cholecystiti]]s. It is a life-threatening complication of biliary obstruction (e.g., [[Common bile duct stone|choledocholithiasis]], strictures) and requires urgent intervention.<ref>{{Cite journal |last=Kiriyama |first=Seiki |last2=Kozaka |first2=Kazuto |last3=Takada |first3=Tadahiro |last4=Strasberg |first4=Steven M. |last5=Pitt |first5=Henry A. |last6=Gabata |first6=Toshifumi |last7=Hata |first7=Jiro |last8=Liau |first8=Kui-Hin |last9=Miura |first9=Fumihiko |last10=Horiguchi |first10=Akihiko |last11=Liu |first11=Keng-Hao |last12=Su |first12=Cheng-Hsi |last13=Wada |first13=Keita |last14=Jagannath |first14=Palepu |last15=Itoi |first15=Takao |date=2018 |title=Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos) |url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jhbp.512 |journal=Journal of Hepato-Biliary-Pancreatic Sciences |language=en |volume=25 |issue=1 |pages=17–30 |doi=10.1002/jhbp.512 |issn=1868-6982|url-access=subscription }}</ref>

==Prognosis==

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==Epidemiology==

In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten&nbsp;years, 15–26% will sufferhave one or more episodes of [[biliary colic]] (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: [[acute pancreatitis]], [[cholecystitis]] or acute cholangitis.<ref name=Williams/> Prevalence of gallstone disease increases with age and [[body mass index]] (a marker of [[obesity]]). However, the risk is also increased in those who lose weight rapidly (e.g. after [[bariatric surgery|weight loss surgery]]) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further.<ref>{{cite journal |author=Bateson MC |title=Fortnightly review: gallbladder disease |journal=BMJ |volume=318 |issue=7200 |pages=1745–8 |date=June 1999 |pmid=10381713 |pmc=1116086 |url=http://www.bmj.com/cgi/content/full/318/7200/1745 |doi=10.1136/bmj.318.7200.1745}}</ref>

==History==

Dr [[Jean-Martin Charcot]], working at the [[Pitié-Salpêtrière Hospital|Salpêtrière Hospital]] in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877.<ref name=Charcot/> He referred to the condition as "hepatic fever" (''fièvre hépatique'').<ref name=Charcot/><ref name=Kimura2007/> Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated [[Reynolds' pentad|the pentad]] that carries his name.<ref name=Reynolds/> It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968.<ref>{{cite journal |vauthors=McCune WS, Shorb PE, Moscovitz H |title=Endoscopic cannulation of the ampulla of vater: a preliminary report |journal=Ann Surg |volume=167 |issue=5 |pages=752–6 |date=May 1968 |pmid=5646296 |pmc=1387128 |doi=10.1097/00000658-196805000-00013}}</ref> ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis.<ref>{{cite journal |doi=10.1056/NEJM199206113262401 |vauthors=Lai EC, Mok FP, Tan ES |title=Endoscopic biliary drainage for severe acute cholangitis |journal=N Engl J Med |volume=326 |issue=24 |pages=1582–6 |date=June 1992 |pmid=1584258|display-authors=etal|hdl=10722/45379 |hdl-access=free }}</ref>

==See also==

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{{Gastroenterology}}

{{DEFAULTSORT:Cholangitis, ascending}}

[[Category:Inflammations]]

[[Category:Medical emergencies]]