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
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