1

ROLE OF LIVER ENZYMES IN DIAGNOSIS OF

VARIOUS LIVER DISEASES

PRESENTATIONON

PREPARED BYADITYA GIRI

AALOK KUMARCHANCHAL KUMAR

GUIDED BYDR. SUSHMA B J

MAM

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

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

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

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

6

GROUP I -TEST OF HEPATIC EXCRETORY FUNCTION

i. SERUM- BILIRUBIN;TOTAL ,CONJUGATED,UNCONJUGATED

URINE-BILE PIGMENTS, BILE SALTS AND UROBILINOGEN

GROUP II-LIVER ENZYME PANELALT

AST

ALP

GGT

CLASSIFICATION OF LIVER FUNCTION TESTA.CLASSIFICATION BASED ON LABORATORY FINDING

GROUP IV-SPECIAL TEST

CERULLOPLASMIN

FERITTIN

ALFA-1-ANTITRYPSIN

ALFA-FETOPROTEIN

GROUP III-PLASMA PROTEINS (TEST FOR SYNTHETIC FUNCTION OF LIVER)

TOTAL PROTEINS

SERUM ALBUMIN, GLOBULIN,A/G RATIO

PROTHROMBIN TIME

8

GROUP I:MARKERS OF LIVER DYSFUNCTION

SERUM BILIRUBIN, TOTAL,CONJUGATED

URINE;BILE PIGMENTS ,BILE SALTS AND UBG

TOTAL PROTEIN,SERUM ALBUMIN & A/G RATIO

PROTHROMBIN TIME

BLOOD AMMONIA WHEN INDICATED

B.CLASSFICATION BASED ON CLINICAL ASPECTS

9

GROUPII:MARKERS OF HEPATOCELLULAR INJURY

ALTASTGROUPIII:MARKERS OF

CHOLESTASIS

ALP

GGT

10

TEST MEAN VALUE RANGENORMAL VALUE

TOTAL BILIRUBIN(mg/DL)

8.5 1.5-15 0.2-0.9

SGOT(U/L) 159.6 63-204 5-35SGPT(UI/L) 229.2 76-394 5-45ALKALINE PHOSPHATASE (UI/L)

432.8 226-792 250

γ GTP(UI/L) 694.9 352-1455 5-30UNCONJUGATED BILIRUBIN (mg/dl)

4 3-5 0.2-0.7

CLINICAL STUDY OF CASE OF A 19 YEAR OLD FEMALE HAVING FOLLOWINGDIAGNOSIS

UROBILINIGEN(mg/dL

4.5 3.5-6 0.2-1

11

WHAT COULD BE THE PROBABLE CAUSE?

12

SERUM ENZYMES THATREFLECT DAMAGE TO HEPATOCYTES

13

ALKALINE PHOSPHATASE

SERUM TRANSFRASEALT AST

GGT5’NT

ENZYMES IN DIAGNOSIS OF LIVER DISEASE

14

LOCATION OF ENZYMES IN LIVER

15

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

16

ENZYMES THAT DETECT HEPATOCELLUAR NECROSIS• ALT• AST

ENZYMES THAT DETECT CHOLESTASIS• ALKALINE PHOSPHATASE• Y-GLUTAMYL

TRANSPEPTIDASE• 5 NUCLEOTIDASE• LEUCINE AMINOPEPTIDASE

SERUM ENZYMES REFLECT DAMAGE TO HEPATOCYTES

17

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)

18

Acute hemolytic anemia Cirrhosis of the liver Hepatitis Acute pancreatitis or inflammation of

pancreas Acute renal failure or loss of kidney function. Heart attack Primary muscle disease Recent surgery

Elevated levels of AST may indicate

19

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)

20

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

21

• 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

22

CLINICAL SIGNIFICANCE OF AST:ALT RATIO

23

• 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

24

ALKALINE PHOSPHATASEY-GLUTAMYL TRANSPEPTIDASE

5-NUCLEOTIDASE

ENZYMES THAT DETECT CHOLESTASIS

25

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 - 115 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

26

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)

27

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

28

29

TEST MEAN VALUE RANGENORMAL VALUE

TOTAL BILIRUBIN(mg/DL)

8.5 1.5-15 0.2-0.9

SGOT(U/L) 159.6 63-204 5-35SGPT(UI/L) 229.2 76-394 5-45ALKALINE PHOSPHATASE (UI/L)

432.8 226-792 250

γ GTP(UI/L) 694.9 352-1455 5-30UNCONJUGATED BILIRUBIN (mg/dl)

4 3-5 0.2-0.7

CLINICAL STUDY OF CASE OF A 19 YEAR OLD FEMALE HAVING FOLLOWINGDIAGNOSIS

UROBILINIGEN(mg/dL

4.5 3.5-6 0.2-1

30

Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice

Total bilirubin Normal / Increased Increased

Conjugated bilirubin Normal Increased IncreasedUnconjugated 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 PaleAlkaline 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

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.

32

Vital liver enzymes normal Serum level of the enzymes Diseases associated with the liver Elevated level of enzymes in liver diseases

TAKE HOME MESSAGE

33

REFERENCES FROM ◦ TEXTBOOK OF BIOCHEMISTRY (for medical students)

– DM Vasudevan◦ TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN

Chatterjee

BIBLIOGRAPHY

34