Presentation on theme: "Jaundice – For the practitioners"— Presentation transcript:
1 Jaundice – For the practitioners Dr.R.V.S.N.Sarma., M.D., M.Sc.,Consultant Physician & Chest SpecialistA Lucid Understanding ofJaundice – For the practitioners
2 Jaundice – Classification Normal Serum Bilirubin (SB) is 0.3 to 1.0 mg%Jaundice is increased levels of SB > 1.0 mg%Over production of Bilirubin (Hemolytic)From hemolysis of RBCLysis of RBC precursors – Ineffective erythropoesisImpaired hepatic function (Hepatitic)Hepatocellular dysfunction in handling bilirubinUptake, Metabolism and Excretion of bilirubinObstruction to bile flow (Obstructive)Intrahepatic cholestasisExtrahepatic Obstruction (Surgical Jaundice)
3 Clinical Aspects of Jaundice Clinically detectable if SB is >2.0 mg%With edema and dark skin – Jaundice is maskedWhat is special about the sclera ? – Rich ElastinDarkening of the urine – Differential DiagnosisSkin discoloration – Yellowish, - Carotinemia – Eyes NMucosa – hard palate (in dark skinned)Greenish hue of skin and sclera - due Biliverdin – indicates long standing jaundiceGeneralized Pruritus – Obstructive Jaundice – Why ?
4 Clinical History – Imp clues Duration of jaundice – Acute / ChronicAbdominal pain v/s painless jaundiceFever – Viral / bacteria /sepsisArthralgia, rash, glands; Pruritus - obstructiveAppetite – Hepatocellular / MalignancyWeight loss – Malignancy – CAHColour of stools –chalky white –obstructiveFamily history – Hemolytic – Inherited dis.H/o transfusion, promiscuity, IDUAlcohol abuse, Medications – INH, EM, Largactil
5 Coloured Urine – Differ. Diagnosis Bilirubin in urine due to Jaundice (CB)Concentrated urine in dehydrationFluid deprivation syndromesSulfasalazine use – for Ulcerative colitisRifampicin, Pyridium and Thiamine useRed urine – Porphyria,Hemoglobin & Myoglobinuria, HematuriaDark black urine in Ochranosis - HGAMelanin excretion from MelanomaRed sweat in Clofazamine, Rifampicin
6 Fate of Senescent RBC RBC life span in blood stream is 90-120 days Old RBCs are phagocytosed and/or lysedLysis occurs extravascularly in the RE system subsequent to RBC phagocytosisIntravascular Hemolysis of young RBCThis is due to hemolytic diseases of RBC
7 The Hepatobiliary & Portal System Hepatobiliary TreePortal Circulation
8 E V Pathway for RBC Scavanging Liver, Spleen &Bone marrowPhagocytosis & LysisHemoglobinGlobinHemeBilirubinAmino acidsFe2+Through LiverAmino acid poolExcreted
11 Bilirubin – And its nature PropertiesUnconjugatedConjugatedNormal serum fraction90%10%Water solubility (polarity)0 (non polar)+ (polar)Affinity to lipids (Kernicterus)+++Renal excretionNil+Vanden Berg ReactionIndirectDirectTemporary Albumin BindingIrreversible Delta Bilirubin++
12 Bilirubin in the Liver Cell 1Hepatocyte (HC) uptake of UCBAlb+UCB dissociates and UCB enters HCBy passive diffusion into HC – Ligandin boundInsoluble UCB is to be made soluble in HC2Conjugation in ER of Hepatocyte (HC)Formation of mono and di glucuronides BMG, BDGUDP Glucuronosyl transferase is energy depend.Insoluble UCB made water soluble for excretion3Excretion in into biliary canaliculiRate limiting step in metabolismCB 50% is not protein bound – no loss of albuminRemaining 50% bilirubin – Irreversibly bound
14 Blood Bile ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT ALT AlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPBile
15 X Blood Bile AlkP AlkP AlkP AlkP AlkP AlkP AlkP AlkP AlkP AlkP AlkP ALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTALTAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPAlkPXBile
16 Bilirubin in the Intestine 1. CB in bile is excreted into DuodenumCB 10% diffuses in to bloodCB excreted is not reabsorbed2. Conversion of CB into uro & stercobilinogenUrobilinogen excreted in stoolPart of the UBG enters EHC3. From gut, UBG but not CB enters EHCKidney excretes absorbed UBGIn biliary obst. UBG absent in urine
17 Bilirubin handling in Kidney Conjugated BilirubinBound (20 days)Bilirubin in urine is conjugatedUnconjugated BilirubinNot filtered or secretedNil in urineUrobilinogen in urineNormally traces↑ in Cholestaiss
18 An Approach to Jaundice Is it isolated elevation of serum bilirubin ?If so, is the↑unconjugated or conjugated fraction?Is it accompanied by other liver test abnormalities ?Is the disorder hepatocellular or cholestatic?If cholestatic, is it intra- or extrahepatic?These can be answered with a thoughtfulHistory and physical examinationInterpretation of laboratory tests andRadiological tests and procedures.
19 Bilirubin testing Van den Berg Reaction SB + SAA Diazo compound formedDiazo is chromogenic – ColourimertyReaction in H2O medium – Direct – CBReaction in ethnol medium – IndirectIndirect includes CB and UCB = Total BTime is the essence of the direct testFoam test, Ictotest for urine – CB only
20 Normal values for LFT Features Healthy Normal Total Bilirubin Less than 1.00 mgConjugated BilirubinLess than 0.15 mgAST (SGOT)Less than 31 i.u/LALT (SGPT)Less than 35 i.u/LAlkaline phosphataseLess than 112 i.u /LGGT and 5’ Nucleosidase, CDTSignificantly ↑ in ALDUrine BilirubinAbsentUrine UrobilinogenIn trace quantityUrine Bile Salts
21 Lab Diagnosis of Jaundice – D.D FeaturesPrehepatic(Heamolytic)Intrahepatic(Hepatocellular)Posthepatic(Obstructive)Unconjugated↑NormalConjugatedAST or ALT↑ ↑Alkaline phos.and GGTUrine bilirubinAbsentPresentIncreasedUrobilinogen
22 Liver Function Tests (LFT) Normal RangeValueBilirubinTotalConjugated0.1 to 1.0 mg< 0.2 mgDx. Of Jaundice, SeverityAlkaline phosphataseiu/LDx of Obstructive JaundiceAspartate transaminase(AST/SGOT)5-31 iu/LEarly Dx and follow upAlanine transaminase(ALT/SGPT)5-35 iu/LAST/ALT > 1 in ALDAlbuming/dLAssess severity of diseaseProthrombin time (PT)12-16 s
23 Utility of Liver Function Tests LFTUtility of the testALT/SGPTALT ↓than AST in alcoholismAlbuminAssess severity / chronicityAlk. phosphataseCholestasis, hepatic infiltrationsAST/SGOTEarly Dx. of Liver disease, F/upBilirubin (Total) /Conjug.Diagnose jaundiceGamma-globulinDx. F/up Chronic hepatitis & cirrhosisGGTDx alcohol abuse, Dilantin toxicity
29 Third Step : If CSB is increased Do - AST and ALT (SGOT and SGPT)Elevated AST and ALTHepatocellular jaundiceAKP, 5N, GGT will be normalDo - Alkaline Phosphatase and GGTAKP, GGT ↑↑ in Obstructive JaundiceAST and ALT will be normal
30 Fourth Step : Hepatocellular Hepatocellular – Features and D.DConjugated SB is increasedAST and ALT are increasedAKP, 5NS, GGT are normalHepititis – A,B,C,D,E, CMV,EBVToxic Hepatitis – Drugs, AlcoholMalignancy – Primary CaCirrhosis – ALD, NAFLD
31 What imaging we need Ultrasonography – 98% Sp, 90% Sen. For GB stones USG better than CTFor duct stones –only 40% seen in USGPTC – Extrahepatic obstr. – drainageERCP – Distal biliary obstruction Dx.Rx.MRCP – Most useful for duct stones
32 Neonatal Jaundice Neonatal jaundice is common 50% healthy term infants Re-emergence of kernicterusIn utero bilirubin is handled by placenta andmother’s liverAfter birth, neonate to has cope with increase inbilirubin production and the immature liver cannothandle for a few days
34 Basis of photo therapy ? UCB is not water soluble in its form Blue light confrontational change in UBGIts Photo Isomers are water solubleBlue light converts the UCG into its photo isomersThe soluble photo isomers pass through the Glomerular filter and get excretedThus conjugation in liver is by passed.
35 Post hepatic Obstructive Jaundice Painful v/s painlessObstruction can beLuminal (stone)Stricture (benign v/s cholangiocarcinoma)Extra luminal pancreatic cancer, Sec. lymph nodesInvestigate & treat withRadiology (US, CT, MRCP)ERCP / PTC
52 When to refer to GE Specialist Unexplained jaundiceSuspected biliary obstructionAcute hepatitis - severe or fulminantUnexplained abnormal LFTs persisting (for 6 months or greater)Unexplained cholestatic liver diseaseCirrhosis (in non-alcoholic) for consideration of liver transplantSuspected hereditary hemochromatosisSuspected Wilson's diseaseSuspected autoimmune hepatitisChronic hepatitis C for consideration of antiviral therapy
53 Conclusions Jaundice and liver injury are very common Careful history and physical examination are a mustAcute hepatocellular diseases with jaundiceChronic hepatocellular jaundice (CLD)Cholestasis and obstructive jaundiceLFT – SB, CB, – AST. ALT, AKP, 5’NS, GGT, Alb, PTUltasonography, MRCP, ERCP, PTCLaparoscopy and liver biopsyTreatment as per the cause
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