Introduction
Ascending cholangitis refers to infection of the biliary ducts most commonly seen in those >50 years old and caused by obstruction, which requires immediate diagnosis and treatment.
Approximately, 50-75% of patients present with fever, jaundice and right upper quadrant pain (Charcot's triad) ± septic shock and mental confusion (Reynold's pentad).
Common causes of ascending cholangitis include choledocholithiasis (gallstones) and strictures of the biliary tree.
Prompt intervention is required with antibiotics and drainage of the biliary tree, as ascending cholangitis can be life-threatening and result in sepsis, end-organ failure and death.
Approximately, 50-75% of patients present with fever, jaundice and right upper quadrant pain (Charcot's triad) ± septic shock and mental confusion (Reynold's pentad).
Common causes of ascending cholangitis include choledocholithiasis (gallstones) and strictures of the biliary tree.
Prompt intervention is required with antibiotics and drainage of the biliary tree, as ascending cholangitis can be life-threatening and result in sepsis, end-organ failure and death.
Epidemiology
- Incidence: 50.00 cases per 100,000 person-years
- Peak incidence: 60-70 years
- Sex ratio: 1:1
| Condition | Relative incidence |
|---|---|
| Biliary colic | 20.00 |
| Acute cholecystitis | 2.80 |
| Ascending cholangitis | 1 |
| Acute pancreatitis | 0.80 |
| Cholangiocarcinoma | 0.03 |
| <1 | 1-5 | 6+ | 16+ | 30+ | 40+ | 50+ | 60+ | 70+ | 80+ |
Aetiology
The aetiology of ascending cholangitis includes:
- Cholelithiasis (gallstones) leading to → choledocholithiasis (common bile duct stone) and biliary obstruction
- Malignant strictures
- Primary biliary tumours (cholangiocarcinoma)
- Primary gallbladder / ampullary cancer
- Pancreatic cancer
- Primary or secondary sclerosing cholangitis (20-30
- Iatrogenic biliary tract injury, commonly seen in cholecystectomy can lead to benign strictures
- Chronic pancreatitis leads to stenosis and stricture of the common bile duct
Pathophysiology
The pathophysiology of ascending cholangitis typically begins with obstruction of the common bile duct due to gallstone, stricture or malignancy → bacterial seeding of the biliary tree via the portal vein & retrograde migration of bacteria from the duodenum up the biliary tree (this is due to the interruption in flow of bile through the biliary tree that normally flushes bacteria into the duodenum).
Additionally, biliary pressure increases (>20cmH20) due the obstruction → pressure gradient that promotes bacterial extravasation into the blood stream and indirectly inhibits macrophage release from Kupffer cells → bacteraemia.
Bacteraemia gives rise to systemic inflammatory response syndrome (SIRS) comprising of:
Additionally, biliary pressure increases (>20cmH20) due the obstruction → pressure gradient that promotes bacterial extravasation into the blood stream and indirectly inhibits macrophage release from Kupffer cells → bacteraemia.
Bacteraemia gives rise to systemic inflammatory response syndrome (SIRS) comprising of:
- Fevers
- Rigors
- Tachycardia
- Tachypnoea
- Raised inflammatory markers (including WCC)
Clinical features
The most common presenting clinical feature is diffuse right upper quadrant (RUQ) abdominal pain which is present in >80% of those with ascending cholangitis. Other features include:
Charcot's triad (RUQ pain, fever and jaundice) is seen in patients with ascending cholangitis with a low sensitivity (25%) but a high specificity (95%) and can be used to differentiate ascending cholangitis from biliary colic and acute cholecystitis which also present with RUQ pain.
In addition to the clinical features described in Charcot's triad, altered mental state and septic shock may also be present. This is known as Reynold's pentad and indicates worsening of the condition and development of sepsis.
It is important to note that those with an indwelling bile duct stent may not develop jaundice as a clinical feature.
- Fever
- Rigors
- Malaise
- Jaundice
- Pruritus
- Unpleasant sensation of the skin the is perceived as an itch
- Acholic stools
- Grey / clay coloured stools due to decreased bile secretion into the small bowel
Charcot's triad (RUQ pain, fever and jaundice) is seen in patients with ascending cholangitis with a low sensitivity (25%) but a high specificity (95%) and can be used to differentiate ascending cholangitis from biliary colic and acute cholecystitis which also present with RUQ pain.
In addition to the clinical features described in Charcot's triad, altered mental state and septic shock may also be present. This is known as Reynold's pentad and indicates worsening of the condition and development of sepsis.
It is important to note that those with an indwelling bile duct stent may not develop jaundice as a clinical feature.
Investigations
Prompt diagnosis of ascending cholangitis can be achieved through history, clinical examination, laboratory findings and imaging. Those with ascending cholangitis typically have a history of gallstone calculi or previous endoscopic retrograde cholangiopancreatography (ERCP).
Those suspected of cholangitis should have the following laboratory tests:
Following laboratory tests, diagnostic imaging should be requested:
Those suspected of cholangitis should have the following laboratory tests:
- FBC
- White cell count will be >10 x109/L
- Coagulation panel
- Prothrombin time will be raised with sepsis
- LFTs
- Deranged LFTs are often seen with hyperbilirubinaemia and elevated serum alkaline phosphatase
- Normal LFTs are more in keeping with acute cholecystitis
- U&Es
- Often decreased K+ and Mg2+
- CRP is almost always raised and indicative of inflammation
- Blood cultures
- Positive in 20-70% of cases
Following laboratory tests, diagnostic imaging should be requested:
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Best first intervention in patients with known history of biliary disease or index for suspicion of cholangitis is high
- Provides both diagnosis and therapy via biliary decompression
- Contraindicated in those with previous Roux-en-Y gastric bypass or stricture and so percutaneous trans-hepatic cholangiography must be used for placement of biliary catheter
- Transabdominal ultrasound of abdomen / pelvis
- Quick and accurate for detecting common bile duct (CBD) dilation is >90%
- Will highlight a thick walled gallbladder in cholecystitis or a dilated common bile duct in biliary obstruction in 38% of cases
- Magnetic retrograde cholangiopancreatography (MRCP)
- High specificity and sensitivity in diagnosis of biliary obstruction >6mm, strictures and malignancy
- Delineate biliary tree anatomy and highlight the distal part of CBD
- Contraindicated in those with metallic devices
- Endoscopic ultrasound (EUS)
Differential diagnosis
The differential diagnoses of ascending cholangitis are predominantly of surgical origin. However, it is important not to disregard medical pathology in a patient with an acute abdomen.
Differential diagnoses of ascending cholangitis include:
Other differential diagnoses to consider include:
| Biliary Colic | Acute Cholecystitis | Ascending Cholangitis |
|---|---|---|
| RUQ Pain | RUQ Pain | RUQ Pain |
| Fever | Fever | |
| Jaundice |
Differential diagnoses of ascending cholangitis include:
- Acute cholecystitis
- Both display RUQ pain and fever
- A positive Murphy's sign is predominantly seen in acute cholecystitis and diffuse RUQ pain in cholangitis
- Transabdominal ultrasound will show gallbladder wall thickening in acute cholecystitis
- Acute pancreatitis
- Pain is often more severe than cholangitis
- Amylase and lipase are elevated with pancreatitis
- Peptic ulcer disease
- LFTs are typically normal, but deranged with cholangitis
- Symptoms tend to improve with food ± antacids
- Acute pyelonephritis
- Urinalysis will demonstrate nitrites ++
Other differential diagnoses to consider include:
- Right lower lobe pneumonia
- Pulmonary embolism
- HELLP syndrome of pre-eclampsia
Management
Patients with ascending cholangitis should be managed in hospital as this considered an emergency condition and fluid resuscitation to initially stabilise the patient will be required, followed by prompt drainage of the biliary tree.
The following management has been adapted from NICE guidelines and BMJ best practice, with initial treatment including:
Biliary decompression is ultimately required to treat ascending cholangitis either non-operatively or through surgery:
The following management has been adapted from NICE guidelines and BMJ best practice, with initial treatment including:
- Intravenous antibiotics
- Broad-spectrum antibiotic therapy initially until antibiotic treatment can be guided with blood cultures
- Majority of cases are gram-negative, but gram-positive anaerobes may also be present
- Piperacillin / tazobactam (or gentamicin + metronidazole in penicillin-allergic patients) with the aim to convert to oral antibiotics once biliary drainage has been achieved
- Intravenous hydration
- Fluid status and resuscitation
- Maintenance fluids ± bolus of 0.9% sodium chloride
- Correct electrolyte imbalances + coagulation abnormalities
- Fresh frozen plasma may be required for clotting abnormalities, especially in septic patients
- Analgesia
- Using the WHO Analgesic Pain Ladder
- Initiate the Sepsis 6 protocol if suspected within 1 hour
Biliary decompression is ultimately required to treat ascending cholangitis either non-operatively or through surgery:
- Non-operative management
- ERCP ± sphincterotomy
- Insertion of biliary stent to allow drainage of bile
- Percutaneous trans-hepatic cholangiography (PTC) for those with stricture / malignancy or previous Roux-en-Y gastric bypass
- Nasobiliary drain
- Surgical management
- Non-operative procedures are preferred due to the increased risks of surgery (bleeding, infection, abscess formation)
- Cholecystectomy ± common bile duct exploration
- Choledochotomy with T-tube placement
Complications
Complications of ascending cholangitis include:
- Pyogenic hepatic or biliary abscess
- Formation of an abscess will require antibiotics or ultrasound guided drainage
- They are more common in patients with primary sclerosing cholangitis
- Acute kidney injury
- Acute pancreatitis
- Due to obstruction of the pancreatic duct or Ampulla of Vater due to a distal common bile duct stone
- Recurrent pyogenic cholangitis (Asiatic cholangitis)
- Chronic infection of bacterial cholangitis with primary hepatolithiasis
- Exclusive to those living in South-East Asia, due to the presence of calcium bilirubinate stones attributed to high incidence of E. Coli infection.
- Inadequate biliary drainage
- Symptoms will recur or worsen
- Requires further investigation of the biliary tree