What is the pathophysiology of ascending cholangitis?

Pathophysiology of Ascending Cholangitis

Ascending cholangitis develops when biliary obstruction creates stasis that allows bacterial colonization, followed by increased intraductal pressure that forces bacteria across epithelial barriers into the bloodstream and lymphatics, resulting in systemic infection. 1, 2

Essential Prerequisites for Disease Development

Two fundamental conditions must coexist for cholangitis to occur 1, 2:

• Biliary obstruction with stasis – Creates an environment permitting bacterial multiplication 1, 2
• Bacterial presence in bile – Normally sterile bile becomes colonized 1, 2

Bacterial Entry Mechanisms

Bacteria reach the biliary system through two primary routes 1, 2:

• Ascending migration from the duodenum – The most common pathway, particularly after sphincter disruption or instrumentation 1, 2
• Portal venous bacteremia – Bacteria translocate from the intestinal tract via portal circulation 3, 1

Role of Biliary Obstruction

The severity and location of obstruction directly influences infection risk 3:

• High-grade strictures with bile stagnation facilitate bacterial colonization – Studies demonstrate bacterial infection in 62% of PSC patients with high-grade strictures versus only 31% without stenosis 3
• Enteric bacteria detected in 51% of patients with high-grade stenosis but never in absence of stenosis – Emphasizing the critical role of obstruction 3
• Increased biliary pressure enables bacterial penetration – Once pressure rises, bacteria breach cellular barriers and enter systemic circulation 1, 2

Common Etiologies of Obstruction

The underlying causes creating the obstructive environment include 3, 1, 4:

• Choledocholithiasis – The most common cause of acute cholangitis 3, 4
• Biliary strictures (benign or malignant) – Create focal points of stasis 1, 4
• Biliary stents and prior instrumentation – ERCP, especially with stenting, is a major risk factor for bacterial cholangitis 3
• Parasitic infestations – Important globally, causing obstruction through physical blockage, stone formation, and direct bacterial introduction 1

Microbiology Patterns

The bacterial spectrum varies based on clinical context 3, 5, 1:

• Typical enteric organisms predominate – Escherichia coli, Klebsiella, Enterococcus, Enterobacter, Pseudomonas, and anaerobes 5, 1
• Infections are often polymicrobial – Multiple organisms frequently isolated simultaneously 1
• PSC patients show different patterns – In ERCP-naive PSC patients, 75% of positive cultures are Gram-positive isolates versus 74% enteric bacteria in common duct stone controls 3
• Post-instrumentation changes microbiology – ERCP increases colonization rates from 25% to 60% in PSC patients 3

Progression to Systemic Sepsis

Once bacteria colonize obstructed bile, the pathophysiologic cascade accelerates 1, 2:

• Bacterial multiplication occurs in stagnant bile – Obstruction prevents normal clearance mechanisms 1, 2
• Elevated intraductal pressure forces bacteremia – Bacteria and endotoxins enter hepatic sinusoids and systemic circulation 1, 2
• Cholangiovenous reflux enables systemic dissemination – Direct communication between bile ducts and vascular system under pressure 2

Critical Pitfalls in Understanding Pathophysiology

Several important nuances affect clinical management 3, 1:

• Bacteria in bile do not worsen outcomes if obstruction is relieved and infection treated – The key is addressing both components 3
• Short-course antibiotics alone cannot eradicate bacteria from obstructed ducts – Drainage is mandatory for cure 3
• Candida in bile indicates poor prognosis – Often observed in late-stage disease and may necessitate urgent transplantation 3
• Portal bacteremia from active colitis may contribute – Particularly relevant in PSC-IBD patients 3