Acute Cholangitis

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Introduction

Acute cholangitis (a.k.a. ascending cholangitis) is an infection of the biliary tree caused by a combination of both biliary outflow obstruction and biliary infection.1 

It is an uncommon condition (1% of patients with gallstone disease) but is life-threatening with a mortality rate between 17 – 40%. Cholangitis has an equal sex distribution, and the median age of presentation is 50-60 years old.2

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Aetiology

Anatomy of the biliary system 3

The gallbladder is a pear-shaped intraperitoneal organ which lies in the right hypochondrium (right upper quadrant).

The main function of the gallbladder is to store bile.

The biliary tree is the system of ducts that transports bile (synthesised by hepatocytes) to the gallbladder for storage and then on to the duodenum.

The ducts begin in the liver parenchyma until the right and left hepatic ducts are formed (which drain bile from the left and right lobes of the liver). These two ducts then anastomose to form the common hepatic duct.

The duct which arises from the gallbladder is known as the cystic duct. The cystic duct joins the hepatic duct forming the common bile duct (CBD) which then enters the pancreas.

In the pancreatic head, the common bile duct and the pancreatic duct join to form the ampulla of Vater, which empties into the descending part of the duodenum via the major duodenal papilla (controlled by the sphincter of Oddi, a muscular valve). 

Figure 1. Anatomy of the biliary system.7

Pathophysiology

Cholangitis is caused by the combination of both biliary outflow obstruction and biliary infection. 

When the biliary system becomes obstructed, the movement of bile slows or stops. When bile remains within the gallbladder for too long, particulates within the bile begin to precipitate causing bile to thicken (known as biliary sludge). Biliary sludge provides an ideal growth medium for bacteria (typically E. coli, Klebsiella and Enterococcus). 

The pressure within the biliary system also increases as a result of obstruction increasing the risk of bacterial translocation into the bloodstream resulting in biliary sepsis.


Risk factors

Risk factors for the development of cholangitis include:1,2,8

  • Gallstone disease (e.g. Mirizzi syndrome: where a stone-containing gallbladder extrinsically compresses the common bile duct; choledocholithiasis: gallstones in the common bile duct).
  • Iatrogenic biliary injury (e.g. during cholecystectomy or ERCP)
  • Tumours (pancreatic, cholangiocarcinoma, hepatic)
  • Sclerosing cholangitis (primary and secondary)
  • Biliary strictures (benign or malignant)
  • Parasitic infections (roundworm, liver fluke)

Clinical features

History1,8 

Typical symptoms of cholangitis include:

  • Fever
  • Right upper quadrant (RUQ) pain
  • Jaundice

Other symptoms include pruritus (itching), pale stools, dark urine and nausea/vomiting.

It is also important to ask about a history of gallstone disease and any recent biliary procedures (e.g. ERCP). 

Charcot’s triad

The combination of fever, right upper quadrant pain and jaundice are known as Charcot’s triad.

Clinical examination1,8

A thorough abdominal examination should be performed. A set of basic observations should also be available.

Typical clinical findings in cholangitis include:

  • Fever
  • Jaundice
  • Right upper quadrant tenderness

Signs of a systemic infection may also be present including:

  • Rigors
  • Hypotension
  • Confusion
  • Tachycardia
Reynold’s pentad

The presence of hypotension and confusion alongside the features of Charcot’s triad may be referred to as Reynold’s pentad.

Patients with signs of systemic infection typically have a poorer prognosis.

Signs of peritonism are not typical of cholangitis. Therefore, if peritonism is present, another diagnosis should be considered. It is also essential to consider and appropriately manage the underlying cause which has lead to the development of cholangitis (e.g. gallstones).


Differential diagnoses

Right upper quadrant/upper abdominal pain with jaundice and fever has a broad differential diagnosis, including:1,2,8

  • Hepatitis
  • Hepatic abscess
  • Pancreatitis
  • Mirizzi syndrome
  • Gilbert syndrome
  • Peptic ulcer disease

Cholangitis can present with similar clinical features to other biliary conditions. The table below distinguishes the typical features of biliary colic, cholecystitis, and cholangitis.

Table 1. Differences between biliary colic, cholecystitis, and cholangitis.

 

 

Biliary colic Cholecystitis Cholangitis

RUQ pain

Fever

Jaundice

Biliary colic is caused by an impacted stone at the neck of the gallbladder and typically presents with crampy abdominal pain in the absence of infective features (e.g. fever/raised inflammatory markers). Biliary colic is typically triggered by the consumption of fatty foods.

Cholecystitis typically presents with constant RUQ pain, fever and raised inflammatory markers. However, jaundice is absent in most cases as there is no associated biliary obstruction (except if the gallbladder is compressing the common bile duct, as in Mirizzi syndrome).


Investigations

Bedside investigations

Relevant bedside investigations include:

  • ECG: should be performed in all acutely unwell patients
  • Blood gases: may show raised lactate and metabolic acidosis

Laboratory investigations1,2,8

Relevant laboratory investigations include:

  • FBC: raised white cell count suggestive of infection
  • U&Es: raised urea and creatinine can indicate systemic organ dysfunction
  • LFTs: deranged, raised bilirubin, raised ALP and/or GGT (obstructive pattern)
  • CRP: raised suggestive of an inflammatory process
  • Blood cultures: should be taken ideally before antibiotic therapy is commenced
  • Coagulation profile: this may be deranged in hepatic disease and in obstructive biliary disease, requiring correction prior to interventions
  • Amylase: this may indicate stone-related pancreatitis

Imaging1,8

Transabdominal ultrasound scan (US)

A transabdominal ultrasound may show evidence of gallstones/CBD stones and a dilated common bile duct.

CT abdomen

A contrast-enhanced CT abdomen is typically used if ultrasound is negative and there is a high clinical suspicion of cholangitis. It should be noted that non-calcified gallstones will not be visible on CT (although the other features of cholangitis will be, such as biliary tract dilatation).

If cholangitis has developed secondary to malignancy (e.g. pancreatic cancer) a CT scan can be useful to assess the primary tumour and identify evidence of metastatic spread.

Magnetic resonance cholangiopancreatography (MRCP)

An MRCP is a dedicated biliary MRI which can produce highly detailed two/three-dimensional reconstructions of the biliary tree, aiding diagnosis (e.g. identifying non-calcified gallstones) and assisting with treatment planning.

Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is the gold standard investigation and intervention for acute cholangitis.

ERCP involves the passage of an endoscope into the second part of the duodenum and cannulation of the ampulla. ERCP can determine the underlying cause of cholangitis and can also be therapeutic, by way of stone extraction and/or stent placement.

However, ERCP is invasive and therefore carries much more risk than the imaging modalities mentioned above. As a result, it is frequently preceded by MRCP where available.

The complications of ERCP include acute pancreatitis and severe haemorrhage. The complication rate of ERCP is approximately 2-3%

Percutaneous transhepatic cholangiography (PTC)

PTC is typically combined with biliary drain placement and is discussed in the management section.

Endoscopic ultrasound (EUS)

EUS is typically less readily available than transabdominal US, CT, MRCP and ERCP. It can be useful in the detection of smaller gallstones (microlithiasis) or biliary sludge where other investigations are negative.


Diagnosis

The Tokyo guidelines for acute cholangitis (2018) are used in patients presenting with suspected acute cholangitis to guide both diagnosis and management (e.g. timing and need for biliary drainage and supportive care).4


Management

Immediate1,8

Patients who present with sepsis should be managed using an ABCDE approach. This typically involves supplemental oxygen, intravenous fluids and broad-spectrum intravenous antibiotics (according to local guidelines).

The sepsis 6 bundle should be started as soon as possible with antibiotics administered within 1 hour of presentation.5

Non-surgical biliary decompression1,8

ERCP ± sphincterotomy ± placement of drainage stent

This is the first line intervention in all patients with cholangitis. A sphincterotomy involves incising the sphincter of Oddi, where the biliary system joins the duodenum. This aids drainage and passage of any CBD stones. 

Percutaneous transhepatic cholangiography (PTC) and percutaneous transhepatic biliary drainage (PTBD)

PTC is considered if the patient is too unwell for ERCP or if ERCP is unsuccessful.

PTC allows placement of a biliary drain (PTBD) to decompress the biliary tree from above. This is performed by passing a needle through the skin and into the bile ducts. It is more likely to be successful when the intrahepatic bile ducts are sufficiently dilated. Contrast material is injected and the anatomy of the biliary tree is defined. A drain (the PTBD) can then be inserted and fixed to the skin.

Surgical biliary decompression1,8

Emergency surgical methods of biliary decompression are used as a last resort in patients with cholangitis.

Non-surgical intervention methods are preferred as they have a superior risk/benefit ratio.6

If surgical methods have to be used, they are usually performed laparoscopically. Options include:

  • Laparoscopic choledochotomy with T-tube placement: the CBD is cut open and a drainage tube is inserted and left in place.
  • Cholecystectomy and CBD exploration

If definitive surgery for an obstructing tumour is required, this is usually deferred until the acute cholangitis has been managed and the patient has stabilised (e.g. haemodynamically stable with improving jaundice).


Complications

Complications of cholangitis can include:1

  • Acute pancreatitis: stones in the distal common bile duct causing cholangitis can also lead to blockage of the pancreatic duct
  • Inadequate biliary drainage following endoscopy, radiology or surgery
  • Hepatic abscess formation

Complications of surgical intervention can include:

  • Infection
  • Bleeding
  • Damage to other local structures (e.g. nerves, vasculature)

Prognosis

In most patients, when adequate biliary drainage is achieved, there is usually marked clinical improvement.1

The mortality rate is around 17-40% depending on age and other co-morbidities.2

Factors which worsen prognosis include:

  • Significant comorbidities (e.g. chronic kidney disease, liver disease)
  • Delayed biliary decompression
  • Older age

Key points

  • Acute/ascending cholangitis is an infection of the biliary tree caused by the combination of both biliary outflow obstruction and biliary infection. 
  • Causes of cholangitis include gallstone disease, iatrogenic biliary injury, tumours, strictures and parasitic infections.
  • Typical symptoms of cholangitis include fever, right upper quadrant pain and jaundice (Charcot’s triad)
  • Signs of a systemic infection may be present including rigors, hypotension, confusion and tachycardia.
  • When hypotension and confusion are present alongside Charcot’s triad, this is known as Reynaud’s pentad.
  • Transabdominal ultrasound may show evidence of gallstones with a dilated CBD.
  • The gold standard investigation and management option is ERCP.
  • Emergency surgical methods are used as a last resort in patients with cholangitis as these patients are at a higher risk of surgical morbidity.
  • Complications can include acute pancreatitis, hepatic abscess formation, overwhelming infection and bleeding.
  • The mortality rate is around 17-40% depending on age and other co-morbidities.

Reviewer

Mr Christopher Hadjittofi

General Surgery Registrar


Editor

Dr Chris Jefferies


References

  1. BMJ Best Practice. Acute Cholangitis – Symptoms, Diagnosis And Treatment | BMJ Best Practice. Available from: [LINK]
  2. Knott, D., Cholangitis. What Is Cholangitis? Disease Of The Gallbladder. [online] Patient.info. Available from: [LINK]
  3. Drake, R., Vogl, A. and Mitchell, A., 2010. Gray’s Anatomy For Students. 2nd ed. London: Elsevier, pp.319, 323.
  4. Mdcalc.com. n.d. Tokyo Guidelines For Acute Cholangitis 2018 – Mdcalc. [online] Available from: [LINK]
  5. 2014. Sepsis. [ebook] Royal College of Emergency Medicine, The UK Sepsis Trust. Available from: [LINK]
  6. Mukai S, Itoi T, Baron TH, et al. Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018. J Hepatobiliary Pancreat Sci. 2017 Oct;24(10):537-49.
  7. Vishnu2011. Anatomy of the biliary system. License: [Public domain]. Available from: [LINK]
  8. Kumar, P. and Clark, M., 2009. Kumar And Clark’s Clinical Medicine. 7th ed. Saunders Elsevier, pp.326-327, 368-372.

 

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