– DR. Kiki Lukman, dr.MSc.

, SpB-KBD, FINACS
– No. Telp : +62 811237426
– E-mail : k2luk@yahoo.com

– 1982-1988 FKUNPAD
– 1992-1994 MSC in General Surgery, University of Glasgow,
United Kingdom
– 1995-1999 PPDS Ilmu Bedah FKUNPAD Bandung
– 2000-2002 Konsultan Bedah Digestif, FKUNPAD Bandung

– Kepala Departemen Ilmu Bedah FKUP/RSHS Bandung

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Pathophysiology of Acute
Cholangitis

Kiki Lukman

Division of Digestive Surgery

Department of Surgery, Medical Faculty
UNPAD/Hasan Sadikin Hospital
 OBJECTIVES

• To explain:
– The anatomy and histology of biliary
tract system
– The etiology acute cholangitis
– The mechanisms of biliary obstruction
– The pathophysiology of acute
cholangitis

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 Introduction

• Epidemiology
– potentially lethal medical emergency (used
to be 50% mortality)
Why ?
– endoscopic management & critical care
have decreased mortality
– early & accurate diagnosis, proper selection &
timing of interventions are imperative
– Knowledge of aetiology & pathophysiology are
important for early diagnosis & assessment
severity

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 Cholangitis in Bandung (1983-1998):
Lukman K., Karnadihardja W., 2000

Etiology No. of Percentage

Cases
Cholecystitis + Cholelithiasis 103 33.44%
Choledocholitihiasis +Cholecystitis+ Cholelithiasis 171 55.51%
Hepatolithiasis 9 2.92 %
Sclerosing cholangitis 3 0.97 %
helminthiasis 3 0.97 %
Stricture 4 1.29 %
Choledochal cyst 4 1.29 %
Pancreatic malignancy 2 0.64 %
Gall bladder Ca 5 1.62 %
Post ERCP 3 0.97 %
Pancreatic stones 1 0.32 %
Total 308
 Definition

• Acute Cholangitis is ascending bacterial infection

of the bile ducts associated with partial or
complete bile duct obstruction

• Cholangiohepatitis / Recurrent Pyogenic

Cholangitis is bacterial/parasites infection of the
bile duct system, mostly intra hepatal duct.
– Bacteria: E. Coli, Klebsiela spp, Bacteriodes spp,
– Worms: Chlonorchis, Ascaris

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Anatomy

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The Anatomy

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The Anatomy

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Histology

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 Quiz no 1
• Seorang pasien, laki, 36 tahun, tampak badan kuning, nyeri
perut kanan atas, dan demam menggigil. Kesadaran menurun,
serta terdapat tekanan darah 90/60 mmHg. Dilakukan drainase
ERCP pada saluran empedu, dan tampak batu serta pus pada
papilla Vater setelah sphincterotomi. Bagaimanakah terjadinya
bactibilia pada pasien ini ?
• Jawaban:

a) Bacteriemia ke dalam sistem sirkulasi liver

b) Influks bacteria dari sistem saluran limfatik peri ductal
c) Kolonisasi bakteria karena stasis obstruksi bilier komplit
d) Kolonisasi bakteria karena stasis obstruksi bilier parsial
e) Ineffective clearance bakteri oleh sel Kupffer akibat
obstruksi bilier komplit

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Physiology & immune response of
biliary tract system
 Etiology of Acute Cholangitis

Benign
Choledocholithiasis
Benign biliary stricture
Congenital abnormalities
Postoperative stricture
Pancreatitis
Malignant
Bile duct cancer
Gallbladder cancer
Pancreatic cancer
Ampullary cancer
Duodenal cancer
Other
Autoimmune/inflammatory disease
External compression (Mirizzi/Lemel syndromes)
Sump syndrome

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Degree of Biliary Obstruction

Type I: Complete Obstruction

Tumors of the head of the pancreas
Common bile duct ligation
Cholangiocarcinoma
Gallbladder cancer
Parenchymal liver tumors (primary or secondary)

Type II: Intermittent Obstruction

Choledocholithiasis
Periampullary tumors
Duodenal diverticula
Choledochal cyst
Polycystic liver disease
Biliary parasites
Hemobilia
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Degree of Biliary Obstruction

Type III: Chronic Incomplete Obstruction

Strictures of the common bile duct
Congenital biliary atresia
Traumatic (iatrogenic)
Sclerosing cholangitis
Post radiotherapy
Stenosis of biliary-enteric anastamosis
Chronic pancreatitis
Cystic fibrosis
Sphincter of Oddi stenosis
Type IV: Segmental Obstruction
Traumatic
Intrahepatic stones
Sclerosing cholangitis
Cholangiocarcinoma

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 Bile Duct Stones

Intra hepatic
Common Bile Ductstones (Primary)
Stones (Secondary)
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Mechanisms of Biliary Colic

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Metabolic causes

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Biliary stasis
Bacteria reside in porous stones

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Inflammatory Causes

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Pathogenesis

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 Pathogenesis

Stasis or obstruction with bacteria.

Decreased bile flow (predisposed to bacterial infection: through portal vein, limph.
vessels, & duodenum)

Ascending infection in hepatic ducts

Increased intrabiliary pressure

Infected biliary cannaliculi, hepatic vein & perihepatic lymph,

resulting in bacteremia (25-40%).

Suppurative Cholangitis
 Quiz No 2

• Seorang perempuan, 40 tahun, dengan keluhan mata dan

badan kuning, serta demam menggigil. Ditemukan nyeri
perut kanan atas, dan jumlah leukosit 21.500/mm3. USG
Hepatobilier menunjukkan pelebaran saluran empedu intra
hepatal dan batu multipel. Ditemukan hasil kultur positif
bakteria dari darah. Apakah jenis mikroba yang paling
mungkin menjadi penyebabnya?

a) E. Coli
b) Streptococcus Spp
c) Pseudomonas Spp
d) Clostridium Spp
e) Staphylococcus

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 Bacteriology :

Bacteria Blood Bile

• E. coli 26 % 26 %
• Klebsiella spp 14 % 12 %
• Enterococci 9% 11 %
• Pseudomonas spp. 9% 5%
• Stapylococcus spp. 9% 3%
• Enterobacter spp. 1% 5%
• Bacteroides spp. 2% 4%
• Clostridium spp. 0.3 % 4%
• Might be poly-microbial
 Quiz No 3

• Seorang perempuan, 45 tahun, dengan tanda-tanda

Cholangitis berat dan pada USG hepatobilier pancreas
menunjukkan batu multipel pada vesica felea dan saluran
empedu yang tampak melebar. Apakah yang menjadi
penyebab perburukan pasien ini ?

a) Tekanan intra ductal kurang 5 cm H20

b) Tekanan intra ductal antara 5 -10 cm H2O
c) Tekanan intra ductal antara 10 -20 cm H2O
d) Tekanan intra ductal antara 20 – 25 cm H2O
e) Tekanan intra ductal lebih dari 25 cm H2O

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Pathology

Ineffective clearance
Bactibilia,
Bacteriemia,
Sepsis

Increased
Pressure > 25 cmH2O

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Biomolecular of cholestasis
Liver/Cholangiocyte injury
 Pathogenesis of
Cholangiohepatitis

• Parasitic infestation causes necrosis, inflammation,

fibrosis, strictures, and cholangiectasis
• Mechanisms:
– Result of the irritating chemical composition of the
parasite, parasitic secretions, or eggs;
– Physical obstruction of the bile ducts;
– Induction of formation of biliary stones;
– Introduction of bacteria into the biliary system
during migration from the duodenum.

Pigmented stones due to enzymatic deconjugation of bilirubin by bacteria

Carpenter HA. Mayo Clin Proc. 1998 May;73(5)
 Quiz No 4

• Seorang perempuan, 52 tahun, dengan Indeks Massa Tubuh

34 dan keluhan mata dan badan kuning. Ditemukan nyeri
perut kanan atas, dan jumlah leukosit 19.200/mm3. USG
Hepatobilier menunjukkan pelebaran saluran empedu dan
batu saluran empedu multipel. Sudah sejak 2 hari produksi
urin pasien hanya 200 ml. Apakah penyebab fenomena
oliguri tersebut?
a) Hiperbilirubinemia sistemik
b) Endotoxemia
c) Penurunan garam empedu siatemik
d) Peningkatan fibrinolysis
e) Peningkatan garam empedu pada duodenum

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 PATHOPHYSIOLOGY OF
HEPATORENAL SYNDROME
Obstructive Jaundice

↓Kuppfer Cell ↑Systemic Bile Salts ↑ Systemic bilirubin

Clearance ↓Gut Bile Salt

↓clearance of cardiotoxins Endotoxemia

Cardiovascular
system Renal System Coagulation System

Prostaglandins Peritubular fibrin

ANP & ANP & & cytokines
hypodipsia cytokines deposition

↓LV ↓Plasma ↓Pheripheral Altered Direct

function volume resistance Intrarenal Parenchyma ↑ Renal Vascular Resistance
hemodynamics toxicity ↓ Renal Permeability

↓Blood pressure
Renal impairment or
acute renal failure
Complications

• Sepsis
• Septic shock
• Multiple organ failures
• Liver abscess
• Peritonitis
 Diagnostic Criteria
Clinical Problems

Tokyo Guidelines 2018

A. Systemic inflammation
- A-1. Fever higher than 38
- A-2. Laboratory evidence of inflammation (white blood cell count <4 or >10, C-
reactive
protein >1)
B. Cholestasis
- B-1. Jaundice (Total bilirubin >2 mg/dL)
- B-2. Abnormal liver function tests (elevation > 1.5 Standard deviation of alkaline
phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, or
alanine
aminotransferase )
C. Imaging
- C-1. Biliary dilation
- C-2. Evidence of etiology of obstruction
Suspected diagnosis: One item in A 1 1 item in either B or C.
Definite diagnosis: One item in A, 1 item in B, and 1 item in C.

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 SUMMARY

• Biliary stasis due to bile duct

obstruction and failed microbial
clearance in the bile ducts form the
pathophysiology of acute cholangitis,
resulting in increased bile duct
pressure and microbial colonization
and translocation to systemic
circulation and remote organs.

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 SUMMARY

• A thorough understanding of the

etiology and pathophysiology of
acute cholangitis coupled with
utilization of modern diagnostic
schema can assist the
practitioner in making this
urgent diagnosis in an accurate
and timely fashion.
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