CHOLESTASIS

Dr I Gede Palgunadi SpPD-FINASIM FK-UNRAM/RSUP NTB

Metabolism of bilirubinLiver microsomesTissuesPlasma

Bilirubin uptake. Metabolise and secretion by hepatocyteConjugation(UGT1)

Classification and causes of jaundicePre-hepaticHepaticPost-hepatic

Bilirubin load Haemolyis ConjugationGilberts, Crigler Najjar

TransportHepatic, cirrhosis, alcohol, drugCanalicular secretion (drug, sex hormones, inhetited)Ductular disease (Primary billiary cirrhosis)Bile duct obstruction (gallstone, cancer of bile duct or pancreas)

First steps in the diagnosis of the jaundiced patientClinical history and examinationUrine, stoolsSerum biochemical tests Bil, transaminase (GOT, GPT), alkaline phophatase, GT, albumin, quantitative immunoglobulinsHaematology Hb, white celss, plateletsBlood filmProthrombine time (before and after IV Vit K)X-ray of chest

Physical signs in jaundice

The billiary secretory apparatusC = cytosceletonN - nucleus

The anatomy of the intrahepatic bilary system

Mechanism of bile formationBile salt dependen (225 ml/day)Bile salt independent (225 ml/day)Ductular flow (150 ml/day) stimulated by secretin

Major transport in bile formation

The effects of lack intestinal bile in chronic cholestatic jaundice

Diminished bile salts in intestineFailure emulsification dietary fatDiarrhoea, malnutrition, low plasma proteinsSteatorrhoeaFailure to absorb1. Vit. ANight blindness, thick skin2. Calcium & vit. DOsteomalacia (demineralize bone, kyphosis, frractures)3. Vit. KPuntura hematoma, spontaneous brushing, prolonged PT4. Vit. ENeuromuscular weakness

Extrahepatic effects of cholestasisItchingJaundiceRenal FunctionCoagulationVascular responseWound healingImmune function?Other?BilirubinBile AcidsLipidsEndotoxinOxidative stress

Diagnosis of cholestasis

USG

Dilated bile ductsNon dilated bile ductsMRCP/ERCP (PTC if ERCP fail)Depends on clinical data

? Duct disease? Intra hepatic cholestasisMRCP/ERCPLiver biopsy

Classification of intrahepatic cholestasis according to possible major sites of involvement of the billiary treePrimary billiary cirrhosisAllograft rejectionGraft versus hostBilliary AtresisIdiopathic adult ductopenia

Therapeutic option for bile duct obstrtuction

CholestasisMRCPUltrasound dilated bile ductsStone strictureERCP

successFailureEndoscopic sphincterotomy nasobilliary tube stentPTC eith drainage/stent

Surgery if appropriate

Drug treatment of pruritus

RoutineCholestyramineVariable effectAnti-histamine; ursodeoxycholic acid; phenabarbitoneCareful useRifampicinExperimentalNaloxone; nalmefene; ondansetron; S-adenosylL-methionine; propofol

Management of chronic cholestasis

1. Dietary fat (if steatorrhoea) reduce neutral fat (40g daily) add medium chain trig lycerides (up to 40g daily)2. Fat-soluble vitamins*OralK10mg/dayA25.000U/dayD400-4.000 U/dayi.v. K10mg/monthi.m. A100.000 U/3-monthlyi.m.D100.000 U/month3. Calcium extra low fat milkoral calcium