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Laboratory Investigations in a case of Jaundice
Tapeshwar Yadav(Lecturer)BMLT, DNHE, M.Sc. Medical Biochemistry
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
Bilirubin-types 1. Unconjugated bilirubin ( - bilirubin )-27%
2. Mono- conjugated bilirubin (-bilirubin )- 24%
3. Di-conjugated bilirubin (- bilirubin ) -13%
4. Protein-bound bilirubin ( - bilirubin ) -37% ( irreversible )
PROEPRTIES Un conjugated Conjugated
1. Solubility in water in alcohol2. In bile3. Absorption from GIT4. Diffusion into tissues5. In urine6. 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
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
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 .
Rolleston & Mc nee (1929) classification1. Haemolytic Jaundice (Pre hepatic)2. Infective Jaundice (Hepatic)3. Obstructive Jaundice (Post hepatic)
Rich’s classification1. Retention Jaundice2. Regurgitation Jaundice
Determination Haemolytic Obstructive Hepatic
(Prehepatic) (Post hepatic) Infective Cholestasis
toxic
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 bile salts ++ Absent + Absent
GROUP II TESTSLiver enzyme panel
Serum enzymes (Routinely done)
1. Transaminases ( ALT and AST)2* Alkaline phosphatase (ALP)
Serum enzymes (Research purposes )
1* 5!- nucleotidase 2* - glutamyl transferase (-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
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
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 lymphoma and granuloma.
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. -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.
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.
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.
Determina- pre-hepatic Hepatic post-tions (haemolytic)
SGPT(ALT) N ++++ +++ + ++
SGOT(AST) N ++ +++ + ++
ALP N + + ++ ++++
viral toxic cholestatichepatic(obstructive)
GROUP II TEST liver enzyme panel - interpretation interpretation
differentiation between hepatic and obstructive jaundice. differentiation between hepatic and obstructive jaundice.
Groups III tests plasma protein panel – differentiation between acute, chronic
hepatites and cirrhosis liver
Determinatios Pre- haepatic
HepaticViral hepatitis
Acute chroniccirrhosis
Post hepatic
Total proteins N N / – N / – – N
Albumin N N / – – – – N
Globulin N N + + + N
A/G ratio N N / – N / – – – N
(reverse)
Other TestsOther Tests
Thymol turbidity testProthrombin testBSP ( Bromo Sulphthalin) retention testRose bengal dye testMEGX (Mono ethyl glycine xylidine) testAnti pyrine breath test
How do you investigate a How do you investigate a case of case of JaundiceJaundice
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
Hyper BilirubinemiaHyper Bilirubinemia
Unconjugated
(Haemolysis)
Conjugated
(Hepatobiliary damage)
Urine - Hb Haemosederine
+ ve - veIntra vascular haemolysis
Extra vascular haemolysis (Resorption of large haemotoma)Auto immune,
hemoglobino pathies,Micro angio pathic
Conjugated hyper bilirubinemiaConjugated hyper bilirubinemiaLiver 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
Conjugated hyper bilirubinemiaConjugated hyper bilirubinemia
Alkaline phosphatase (Hepato biliary obstruction)5’ NT, 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 - VePrimary Sclerosing Cholengitis Primary biliary cirrhosis
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
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
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.