LIVER FUNCTION TEST (ENZYME PART)

LIVER FUNCTION TEST (ENZYME PART)

1. ROLE OF LIVER ENZYMES IN DIAGNOSIS OF VARIOUS LIVER DISEASES PRESENTATION ON PREPARED BY ADITYA GIRI AALOK KUMAR CHANCHAL KUMAR GUIDED BY DR. SUSHMA B J MAM 1

2. FUNCTION OF THE LIVER INDICATION OF THE LIVER FUNCTION TEST CLASSIFICATION OF THE LIVER FUNCTION TEST CLINICAL CASE SERUM ENZYME THAT REFLECT DAMAGE TO HEPATOCYTES LOCATION OF ENZYMES IN LIVER ENZYME INDICATING HEPATO CELLULAR DAMAGE ASPARTATE TRANSAMINASE (AST/SGOT) ELEVATED LEVELS OF AST CONTENTS 2

3. ALANINE TRANSAMINASE(ALT/SGPT) ELEVATED LEVELS OF ALT AST:ALT RATIO CLINICAL SIGNIFICANCE OF THIS RATIO ENZYME THAT DETECT CHOLESTASIS ALKALINE PHOSPHATASE(ALP) Υ-GLUTAMYL TRANPEPTIDASE(GGT) 5’-NUCLEOTIDASE ABNORMAL LIVER ENZYME PROFILE TABLE OF DIAGONOSTIV TESTS CLINICAL CASE OBSTRUCTIVE JAUDICE DIFFERENTIAL DIAGNOSIS OF JAUNDICE TAKE HOME MESSAGE BIBLIOGRAPHY 3

4. Synthetic functions : synthesis of plasma proteins, cholesterol, triacyl glycerol, lipoprotein Metabolic function: protein metabolism, ketogenesis , TCA cycle, production of ATP Detoxification & excretion: ammonia to urea, bilirubin , cholesterol, drug metabolites. Homeostasis : blood glucose regulation Storage function: Vitamin A,D,K,B12 Production of bile salts FUNCTIONS OF THE LIVER 4

5. Jaundice Suspected liver metastasis Alcoholic liver disease Any undiagnosed chronic illness Annual checkup of diabetic patients Coagulation disorders Therapy with statins to check hepatotoxicity INDICATIONS OF THE LIVER FUNCTION TESTS 5

6. 6 CLASSIFICATION OF LIVER FUNCTION TEST A. CLASSIFICATION BASED ON LABORATORY FINDING

7. 8 B.CLASSFICATION BASED ON CLINICAL ASPECTS

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9. TEST MEAN VALUE RANGE NORMAL VALUE TOTAL BILIRUBIN(mg/DL) 8.5 1.5-15 0.2-0.9 SGOT(U/L) 159.6 63-204 5-35 SGPT(UI/L) 229.2 76-394 5-45 ALKALINE PHOSPHATASE (UI/L) 432.8 226-792 250 γ GTP(UI/L) 694.9 352-1455 5-30 UNCONJUGATED BILIRUBIN (mg/dl) 4 3-5 0.2-0.7 CLINICAL STUDY OF CASE OF A 19 YEAR OLD FEMALE HAVING FOLLOWING DIAGNOSIS 10 UROBILINIGEN (mg/ dL 4.5 3.5-6 0.2-1

10. 11 WHAT COULD BE THE PROBABLE CAUSE?

11. SERUM ENZYMES THAT REFLECT DAMAGE TO HEPATOCYTES 12

12. ENZYMES IN DIAGNOSIS OF LIVER DISEASE 13

13. L OCATION OF ENZYMES IN LIVER 14

14. A large number of enzyme estimations are available which are used to ascertain liver function. They are be divided into two groups: A). Enzymes indicating hepatocellular damage. B). Enzymes indicating cholestasis (obstruction). In liver cells injury , damage to the membrane of cells & organelles allows intracellular enzymes to leak into the blood SERUM ENZYMES – REFLECT DAMAGE TO HEPATOCYTES 15

15. SERUM ENZYMES REFLECT DAMAGE TO HEPATOCYTES 16

16. Normal range: 5 -35 U/L. AST is found in both cytoplasm & mitochondria AST/GOT also reflects damage to the hepatic cells & is less specific for liver disease. It is a cardiac marker. AST help diagnose various heart, muscle or brain disorders, such as a myocardial infarct (heart attack). ASPARTATE TRANSAMINASE(AST/SGOT ) 17

17. Acute hemolytic anemia Cirrhosis of the liver Hepatitis Acute pancreatitis or inflammation of pancreas Acute renal failure or loss of kidney function. H eart attack P rimary muscle disease Recent surgery Elevated levels of AST may indicate 18

18. Normal Range: 5-40 U/L. ALT is a cytoplasmic enzyme. The activity of these enzymes is low in normal serum. ALT is specific for liver disease. Its elevations favor liver cell necrosis as a cholestasis . ALANINE TRANSAMINASE (ALT/SGPT ) 19

19. Alcoholic liver disease Cancer of liver Hepatitis or inflammation of the liver Noncancerous tumor of the liver Use of medicines or drugs toxic to the liver Cirrhosis or scarring of the liver Death of liver tissue. Elevated levels of ALT/SGPT may indicate 20

20. Normal ratio is 0.7 to 1.4 Useful in Wilson disease, chronic liver disease and alcoholic liver disease AST/ALT ratio of > 2:1 is suggestive of and >3:1 is highly suggestive of Alcoholic liver disease AST in Alcoholic live disease is rarely >300 U/L. ALT is usually normal in alcoholic liver disease ; can be sometimes low due to an alcohol induced deficiency of pyridoxal phosphate AST/ALT <1 is seen in viral hepatitis. AST:ALT RATIO 21

21. CLINICAL SIGNIFICANCE OF AST:ALT RATIO 22

22. mAST /total AST ratio – marker of chronic alcohol consumption This distinguishes those who consume excess alcohol from normal subjects irrespective of the presence or absence of liver disease 23

23. ENZYMES THAT DETECT CHOLESTASIS 24

24. ALP occurs in all tissues, especially liver, bone , bile duct, kidney & the placenta. The ALP used to help diagnose certain liver diseases and bone disorders. Normal range : 30 - 11 5 U/L ALP is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides & proteins. Levels are significantly higher in growing children . A rise in serum ALP , usually associated with elevated serum bilirubin is an indicator of biliary obstruction ( obstructive/post hepatic jaundice). ALP is also elevated in cirrhosis of liver & hepatic tumors. 1) ALKALINE PHOSPHATASE 25

25. Normal range: 5 -50 U/L This is a microsomal enzyme widely distributed in body tissues, including liver. Measurement of γ - glutamyl transpeptidase (GGT) activity provides a sensitive index to asses liver abnormality . Serum GGT is highly elevated in biliary obstruction & alcoholism . GGT elevation parallels than of ALP. Increased level of GGT are observed in chronic alcoholism ,pancreatic disease ,MI ,renal failure ,diabetes mellitus. Several drugs (e.g. phenytoin) induce (liver synthesis) & increase this enzyme in circulation. 2) γ – GLUTAMYL TRANSPEPTIDASE (GGT) 26

26. Normal range : 2-15 U/L The serum activity of 5'- nucleotidase is elevated in hepatobiliary disease & this parallels ALP. It is highest in post-hepatic obstructive jaundice. The 5 '- nucleotidase is normal in patients with bone disease where as serum ALP increased . 3) 5 '- NUCLEOTIDASE 27

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28. TEST MEAN VALUE RANGE NORMAL VALUE TOTAL BILIRUBIN(mg/DL) 8.5 1.5-15 0.2-0.9 SGOT(U/L) 159.6 63-204 5-35 SGPT(UI/L) 229.2 76-394 5-45 ALKALINE PHOSPHATASE (UI/L) 432.8 226-792 250 γ GTP(UI/L) 694.9 352-1455 5-30 UNCONJUGATED BILIRUBIN (mg/dl) 4 3-5 0.2-0.7 CLINICAL STUDY OF CASE OF A 19 YEAR OLD FEMALE HAVING FOLLOWING DIAGNOSIS 29 UROBILINIGEN (mg/ dL 4.5 3.5-6 0.2-1

29. Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice Total bilirubin Normal / Increased Increased Conjugated bilirubin Normal Increased Increased Unconjugated bilirubin Normal / Increased Increased Normal Urobilinogen Normal / Increased Increased Decreased / Negative Urine Color Normal Dark (urobilinogen + conjugated bilirubin) Dark (conjugated bilirubin) Stool Color Normal Normal/Pale Pale Alkaline phosphatase levels Normal Increased Alanine transferase and Aspartate transferase levels Increased Conjugated Bilirubin in Urine Not Present Present Splenomegaly Present Present Absent Table of diagnostic tests 30

30. 31 OBSTRUCTIVE JAUNDICE Conjugated bilirubin is increased in blood & it is excreted in urine. If there is complete obstruction, UBG will be decreased in urine or even absent. In total obstruction of biliary tree, the bile doesn’t enter the intestine. Since no pigments are entering the gut, the feces become clay coloured . Van den Bergh test is direct positive as conj. bilirubin is elevated.

31. Vital liver enzymes normal Serum level of the enzymes Diseases associated with the liver Elevated level of enzymes in liver diseases 32 TAKE HOME MESSAGE

32. REFERENCES FROM TEXTBOOK OF BIOCHEMISTRY (for medical students) – DM Vasudevan TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN Chatterjee 33 BIBLIOGRAPHY

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