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ROLE OF LIVER ENZYMES IN DIAGNOSIS OF
VARIOUS LIVER DISEASES
PRESENTATIONON
PREPARED BYADITYA GIRI
AALOK KUMARCHANCHAL KUMAR
GUIDED BYDR. SUSHMA B J
MAM
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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
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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
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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
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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
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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
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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
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GROUPII:MARKERS OF HEPATOCELLULAR INJURY
ALTASTGROUPIII:MARKERS OF
CHOLESTASIS
ALP
GGT
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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
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WHAT COULD BE THE PROBABLE CAUSE?
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SERUM ENZYMES THATREFLECT DAMAGE TO HEPATOCYTES
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ALKALINE PHOSPHATASE
SERUM TRANSFRASEALT AST
GGT5’NT
ENZYMES IN DIAGNOSIS OF LIVER DISEASE
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LOCATION OF ENZYMES IN LIVER
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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
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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
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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)
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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
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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)
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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
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• 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
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CLINICAL SIGNIFICANCE OF AST:ALT RATIO
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• 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
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ALKALINE PHOSPHATASEY-GLUTAMYL TRANSPEPTIDASE
5-NUCLEOTIDASE
ENZYMES THAT DETECT CHOLESTASIS
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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
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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)
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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
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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
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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
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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.
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Vital liver enzymes normal Serum level of the enzymes Diseases associated with the liver Elevated level of enzymes in liver diseases
TAKE HOME MESSAGE
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REFERENCES FROM ◦ TEXTBOOK OF BIOCHEMISTRY (for medical students)
– DM Vasudevan◦ TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN
Chatterjee
BIBLIOGRAPHY
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