Cholangitis John P. Cello, MD Professor of Medicine and Surgery, University of California, San Francisco Greek Symmetry of the Universe and Humanity
The Four Humors the Medieval European Concept Gentile da Foligno First autopsy diagnosis of gallstones (Padua, Italy, 1341) & the beginning of the biliary medicine (and academic servitude) Picture from: Avicenna s Canonis libri, Venice, 1520.
Definitions Choledochus Latin: bile duct (descriptive term usually reserved for common bile duct and common hepatic duct) Cholangiole Latin: bile ductule (literally: bile vessel) usually reserved for interlobular ducts, intralobular ducts and ducts of Herring Professor - Latin: teacher, one who brings forward - derived from profere v. to bring forward or to advance same root as professae n. prostitute What is Cholangitis? A Term Commonly Misunderstood Biliary suppuration Pus under pressure Abscess of the bile ducts Fever and abnormal liver function tests Dilated bile ducts with superinfection
Why is infection of the biliary tree called cholangitis and not choledochitis? Morbidity and mortality of suppuration in the biliary tree is not related to inflammation of the main bile ducts but to the consequence of purulence in the true proximal portion of the bile ducts, i.e. the cholangiole and the canaliculus. Major components: obstruction & infection Histopathologically: PMN s in and around biliary ductules, ductular proliferation, bile lakes and bile infarcts. Hepatic Histopathology - Cholangitis
Microanatomy of the Biliary System
Clinical Presentation Features - Cholangitis Age 69 + 2 yrs Fever>102 F 77% Abd pain 70% Jaundice 69% WBC 17.2 + 1.9 Bilirubin 5.8 + 0.7 Alk ptase 421 + 45 AST 165 + 26 Englisbe M. HPB 7:144-48, 2005. The Final Passageway Consequence of Counterclockwise Duodenal Rotation
The End of It All Definitions: papilla nipple Ampulla vessel inside the papilla Bacterial Organisms in Cholangitis Mostly Single Gram Negative Aerobic Organisms Enterococcus E. coli Enterobacter Klebsiella
Antibiotic Coverage 100% sensitivity for organisms: amikacin, cefotaxime (Claforan), ticar/clav.(timentin), tobramycin 90% sensitivity for organisms: aztreonam, cefotetan, gentamicin, imipenem (Primaxin), pipro/tazo (Zosyn), vancomycin Englesbe M. HPB 7: 144-48, 2005. Bacteria in Bile Gall bladder bile in patient without stones is invariably sterile. Gall bladder bile in stone patients: overall > 50 % have bacterial isolates ( cholesterol stone bile ~ 25%, pigment stone bile ~ 80%) Usually single aerobic Gram negative organisms: E. coli 55%, P. aeruginosa 24%, Enterococcus sp. 13 %, Klebsiella sp. 5%) Abeysuriya V et al. Hepatobiliary Pancreat Dis Int 7:633-37, 2008.
Pathophysiology of Cholesterol Calculi Multiple simultaneous defects in three areas: Thermodynamics, Kinetics and Time Supersaturation of hepatic bile with cholesterol (vs bile salts and lysolecithin) - primary event. Deficient solubilizing or antinucleation factors in bile - nucleation and crystal growth Increased residence time - stasis Venn diagram concept Pathophysiology of Cholesterol Stones Admirand/ Small diagram
Pathophysiology of Pigment Stone Formation Conjugated bilirubin secreted at the canaliculus is deconjugated by Gram negative bacteria. Conjugated bilirubin is water soluble, unconjugated bilirubin is insoluble in water it precipitates out Bacteria polymerize bile mucin in to a matrix intrapping bilirubin precipitates providing a haven for bacterial colony growth Biliary Calculi on ERCP
Basic Principles of Treatment of Cholangitis? Drainage of purulent material is primary therapy Antibiotics are adjunctive to biliary decompression Decompression/ drainage is rapidly accomplished by ERCP stenting w/wo sphincterotomy or transhepatic decompression. Removal of stones is secondary and should likely wait until patient stabilization.
Double Pigtail Stent for Drainage Antibiotic Treatment of Biliary Infections
Antibiotic Nomenclature Translation & Dosing Piperacillin-tazobactam Zosyn 3.375 g q. 6 h. Ticarcillin-clavulanic acid Timentin 3.1 g q. 6 h. Doripenem Doribax 500 mg q. 8 h. Ertapenem Ivanz 1 g q. 24 h. Imipenem-cilastatin Primaxin 500 mg q 6 h. Meropenem Generic 1 g. 8 h. Cefazolin Ancef 1-2 g q 8 h. Cefepime Maxipime 2 g q 8-12 h. Cefotaxime Claforan 1-2 g q. 6-8 h. Cefoxitin Mefoxin 2 g q 6 h.