Jaundice - Liver Function Tests
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The document details laboratory investigations related to jaundice, including bilirubin production and its types, properties, and tests for bile pigments and bile salts. It outlines the classifications of jaundice, the liver enzyme panel for diagnosis, and various tests utilized to differentiate between types of jaundice. Additionally, it discusses the aspects of hyperbilirubinemia, investigation strategies, and specific conditions leading to altered bilirubin levels.
Jaundice - Liver Function Tests
- 1. Laboratory Investigations in a case of Jaundice Tapeshwar Yadav (Lecturer) BMLT, DNHE, M.Sc. Medical Biochemistry
- 2. BILE PIGMENTS Daily bilirubin production - 250-300mg% 85% heme moiety of aged RBC 5% RBC precursors destroyed in bone marrow ( ineffective erythropoiesis),Catabolism of some heme proteins – myoglobin, cytochrome, peroxidase BILIRUBIN LEVELS: Conjugated : 0.0 – 0.2 mg / dl Unconjugated : 0.2 – 0.8 mg / dl Total : 0.2 - 1.0 mg / dl – normal 1.0- 2.0 mg /dl – latent jaundice > 2.0 mg /dl – jaundice > 3.0 mg /dl – clinical jaundice
- 3. Bilirubin-types 1. Unconjugated bilirubin ( α- bilirubin )-27% 2. Mono- conjugated bilirubin (β-bilirubin )- 24% 3. Di-conjugated bilirubin (γ- bilirubin ) -13% 4. Protein-bound bilirubin ( δ- bilirubin ) -37% ( irreversible )
- 4. PROEPRTIES Un conjugated Conjugated 1. Solubility in water in alcohol 2. In bile 3. Absorption from GIT 4. Diffusion into tissues 5. In urine 6. Vandenberg’s test Insoluble Soluble Absent Absorbed Diffuses Always absent Indirect + ve Soluble Soluble Present Not absorbed Not diffused Normally absent Indirect + ve PROPERTIES OF CONJUUGATED & UNCONJUGATED BILIRUBIN
- 5. Properties of bilirubin products No. of Hatoms colour Bilirubin (BR) 36 Orange yellow Mesobilinogen (MB) 40 yellow Urobilinogen (UBG) 44 Colour less Stercobilinogen (SBG) 48 Colour less Urobilin (UB) 42 Orange brown Stercobilin (SB) 46 Dark brown Tests for bile pigments Bilirubin (BR) Fouchet’s test, Gmelin’s test, Vandenberg’s test Urobilimogen (UBG) Ehrlich’s test Urobilin (UB) Schlesinger’s test Stercobilin (SB) Schlesinger’s test
- 6. Bile salts helps in digetion and absorption of lipids by forming molecular aggregates called “ micelle “ cholesterol (27C) (+3) OH groups ( +2) OH groups Cholic acid chemodeoxy cholic (24C) acid(24C) Primary Glycocholic acid Taurochenodeoxy cholic acid Secondary deoxy cholicacid Litho cholicacid Test for bile salts - Hay’s test .
- 7. Rolleston & Mc nee (1929) classification 1. Haemolytic Jaundice (Pre hepatic) 2. Infective Jaundice (Hepatic) 3. Obstructive Jaundice (Post hepatic) Rich’s classification 1. Retention Jaundice 2. Regurgitation Jaundice
- 10. Determination Haemolytic Obstructive Hepatic (Prehepatic) (Post hepatic) Infective Cholestasis 1. Serum Total bilirubin ++++ ++++ +++ +++ Direct bilirubin N +++ + ++ Indirect bilirubin +++ N/+ ++ + 2. Feces Colour Dark Pale dark Pale Urobilin ++++ -/Absent N / + - / N Stercobilin ++++ -/Absent N / + - / N 3. Urine Color dark dark moderate Dark Bilirubin Absent +++ + ++ Urobilin +++ Absent + + - / N
- 11. GROUP II TESTS Liver enzyme panel Serum enzymes (Routinely done) 1. Transaminases ( ALT and AST) 2* Alkaline phosphatase (ALP) Serum enzymes (Research purposes ) 1* 5! - nucleotidase 2* γ- glutamyl transferase (γ-GT) 3. Lactate dehydrogenase (LDH) 4. Iso citrate dehydrogenase (ICD) 5. Ornithine trans carbamoylase (OTC) 6* Leucine aminopeptidase (LAP) 7. Cholinesterases 8. Sorbitol dehydrogenase (SDH) * Biliary tract enzymes
- 12. Serum enzymes- routinely done in the lab 1. Transaminases. SGOT(AST) 8-40 IU/L SDPT(ALT) 13-40 IU/L AST- heart muscle. ALT- Liver Liver diseases – ALT >> AST Alcoholic hepatitis – AST >> ALT Infectious hepatitis Pre icteric phase – elevations are noticed Icteric phase – peak 12-14 hrs (10-20 times) Recovery phase – normal with in 2-5 weeks Biliary obstruction elevated 3-4 times. Decreased shortly after relief of obstruction. ALT- cytosol. AST- mitochondria Normally ALT- AST ratio is 1 or <1. acute hepatitis > 1. chronic hepatitis <<1
- 13. 2. Alkaline phosphatase 3-13 KA units/ 100ml (40-125 IU/L). Rich in intestine epithelium, kidney , liver, bones, placenta. Site of production from liver –hepatocyte adjacent to biliarycanaliculi. ALP- elevated in obstructive jaundice (3 folds) (Extra hepatic > intra hepatic) ALP- elevated in infective hepatitis and obstructive jaundice , but elevation is more in obstructive jaundice dividing line 35 KA unit/100ml > 35 KA unit /100ml suggestive of obstructive jaundice < 35 KA unit /100ml infective hepatitis. Markedly elevated in biliary cirrhosis Space occupying lesions of liver –abscess, carcinomas metastasis
- 14. SERUM ENZYMES - RESEARCH PURPOSES 1. 5´- Nucleotidase- 2-17 IU/L Specific marker enzyme – Cholestasis Added advantage over ALP – Not elevated in Bone diseases. 2. γ-GT ( Gamma Glutamyl Transferase)-10-47 IU/L Elevated in Obstructive Jaundice and drug toxicity. Marker/screening enzyme for alcohol abuse. 3. LDH ( Lactate Dehydrogenase)- 70-240 IU/L Elevated in infective hepatitis, Leukemia, hemolytic anemia and megaloblastic anemia. Less specific than Amino transferase.
- 15. 4. ICD (Isocitrate Dehydrogenase)- 0.9-4.0 IU/L Markedly elevated in infectious hepatitis and rug toxicity. Normal in obstructive Jaundice. 5. OTC ( Ornithine transcarbomylase)- 8-20 mIU/L Elevated in acute viral hepatitis, obstructive jaundice and cirrhosis liver. Sensitive and specific measure of Hepato Cellular injury. 6. LAP (Leucine amino peptidase)- 15-56 mIU/L Moderately elevated in Viral hepatitis and Cirrhosis liver. Markedly elevated in malignant obstruction of bile duct and liver cancer. Added advantage over ALP is not elevated in osseous involvement.
- 16. 7. Cholinesterase- 2.17-5.17 IU/L Decrease in liver cell injury, cirrhosis liver Normal in obstructive jaundice. 8. SDH ( Sorbitol Dehydrogenase)- 0.2 mIU/L Strikingly elevated in acute viral hepatitis and CCl4 poisoning. Normal in chronic hepatitis and obstructive jaundice.
- 17. Determina- pre-hepatic Hepatic post- tions (haemolytic) SGPT(ALT) N ++++ +++ + ++ SGOT(AST) N ++ +++ + ++ ALP N + + ++ ++++ viral toxic cholestatic hepatic (obstructive) GROUP II TEST liver enzyme panel - interpretationinterpretation differentiation between hepatic and obstructive jaundice.differentiation between hepatic and obstructive jaundice.
- 18. Groups III tests plasma protein panel – differentiation between acute, chronic hepatites and cirrhosis liver Determinatios Pre- haepatic Hepatic Viral hepatitis Acute chronic cirrhosis Post hepatic Total proteins N N / – N / – – N Albumin N N / – – – – N Globulin N N + + + N A/G ratio N N / – N / – – – N (reverse)
- 19. Other TestsOther Tests Thymol turbidity test Prothrombin test BSP ( Bromo Sulphthalin) retention test Rose bengal dye test MEGX (Mono ethyl glycine xylidine) test Anti pyrine breath test
- 20. How do you investigate a case ofHow do you investigate a case of JaundiceJaundice
- 21. Patient with history and clinical features suggest jaundice URINE Dark color urine, UBG positive with out Bilirubin- Haemolysis Dark color urine, H/o Pruritis & UBG negative with high bilirubin - Obstruction Pale color stools
- 22. Hyper BilirubinemiaHyper Bilirubinemia Unconjugated (Haemolysis) Conjugated (Hepatobiliary damage) Urine - Hb Haemosederine + ve - ve Intra vascular haemolysis Extra vascular haemolysis (Resorption of large haemotoma) Auto immune, hemoglobino pathies, Micro angio pathic
- 23. Conjugated hyper bilirubinemiaConjugated hyper bilirubinemia Liver enzymesLiver enzymes Elevated Normal Amino transferases (Hepato cellular damage) (Hepato biliary obstruction) ALP Serological tests Abnormal Normal (Viral hepatitis) Acute Chronic Liverbiopsy •Drug toxicity •Obstruction of hepatic veins •Cirrhosis CT Scan, Doppler study Hepato biliary image Liver biopsy Pregnancy Sepsis H/o recent surgery Dubin-Johnson, Rotor syndromes
- 24. Conjugated hyper bilirubinemiaConjugated hyper bilirubinemia Alkaline phosphatase (Hepato biliary obstruction) 5’ NT, γ GT Elevated Normal (Bone disease) US/CT scan Dilated ducts Normal ducts •Gall stones •Ca. Pancreas PTC ERCP BIOPSY * Intra hepatic obstruction (Cholestasis, drugs) * Extra hepatic obstruction + Ve - Ve Primary Sclerosing Cholengitis Primary biliary cirrhosis
- 25. Neonatal Jaundice Bilirubin levels (mg/ dl) Premature Full term Cord < 2.0 < 2.0 0 – 1 day < 8.0 1.4 – 8.7 1 – 2 day < 12.0 3.4 – 11.5 3 – 5 days < 16.0 1.5 – 12.0 •Urobilinogen & Stercobilinogen abscent - Incomplete development of intestinal bacterial flora •Phototherapy trans - cis bilirubin
- 26. Isolated Hyper bilirubinemiaIsolated Hyper bilirubinemia Conjugated * Dubin –Johnson * Rotor Syndromes * Gilberts ( < 3 mg/dl) * Crigler _Najjar II ( 5 – 20 mg/dl) * Crigler _Najjar I ( > 25 mg/dl) * Lucey –Driscoll ( ~ 5 mg/dl) Un conjugated
- 27. Bilirubin - analysisBilirubin - analysis Sample collection – Transport : Precautions Fasting sample is preferred to avoid lipemia Hemolysis – falsely low values ( absorbance) Photo oxidation – exposure to sunlight or UV light Sensitive to high temperature.