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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
2
 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
 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
4
 Jaundice
 Suspected liver metastasis
 Alcoholic liver disease
 Any undiagnosed chronic illness
 Annual checkup of diabetic patients
 Coagulation disorders
 Therapy with statins to check hepatotoxicity
5
GROUP I -TEST OF HEPATIC EXCRETORY
FUNCTION
i. SERUM- BILIRUBIN;TOTAL ,CONJUGATED,UNCONJUGATED
URINE-BILE PIGMENTS, BILE SALTS AND UROBILINOGEN
6
GROUP II-LIVER ENZYME PANEL
ALT
AST
ALP
GGT
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
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
8
9
GROUPII:MARKERS OF HEPATOCELLULAR
INJURY
ALT
AST
GROUPIII:MARKERS OF CHOLESTASIS
ALP
GGT
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
11
12
ALKALINE PHOSPHATASE
SERUM TRANSFRASE
ALT AST
GGT
5’NT
13
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
15
ENZYMES THAT DETECT
HEPATOCELLUAR
NECROSIS
•ALT
•AST
ENZYMES THAT DETECT
CHOLESTASIS
•ALKALINE PHOSPHATASE
•Y-GLUTAMYL TRANSPEPTIDASE
•5 NUCLEOTIDASE
•LEUCINE AMINOPEPTIDASE
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).
17
 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
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.
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.
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.
21
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
•ALKALINE PHOSPHATASE
•Y-GLUTAMYL TRANSPEPTIDASE
•5-NUCLEOTIDASE
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 - 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.
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.
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 .
27
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
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
31
 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.
Vital liver enzymes
normal Serum level of the enzymes
Diseases associated with the liver
Elevated level of enzymes in liver diseases
32
 REFERENCES FROM
◦ TEXTBOOK OF BIOCHEMISTRY (for medical students)
– DM Vasudevan
◦ TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN
Chatterjee
33
34

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LIVER FUNCTION TEST (ENZYME PART)

  • 1. 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 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 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 5
  • 6. GROUP I -TEST OF HEPATIC EXCRETORY FUNCTION i. SERUM- BILIRUBIN;TOTAL ,CONJUGATED,UNCONJUGATED URINE-BILE PIGMENTS, BILE SALTS AND UROBILINOGEN 6 GROUP II-LIVER ENZYME PANEL ALT AST ALP GGT
  • 7. 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 8
  • 10. 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
  • 11. 11
  • 12. 12
  • 14. 14
  • 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 15
  • 16. ENZYMES THAT DETECT HEPATOCELLUAR NECROSIS •ALT •AST ENZYMES THAT DETECT CHOLESTASIS •ALKALINE PHOSPHATASE •Y-GLUTAMYL TRANSPEPTIDASE •5 NUCLEOTIDASE •LEUCINE AMINOPEPTIDASE 16
  • 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). 17
  • 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 18
  • 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. 19
  • 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. 20
  • 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. 21
  • 22. 22
  • 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 23
  • 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. 25
  • 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. 26
  • 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 . 27
  • 28. 28
  • 29. 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
  • 30. 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
  • 31. 31  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 32
  • 33.  REFERENCES FROM ◦ TEXTBOOK OF BIOCHEMISTRY (for medical students) – DM Vasudevan ◦ TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN Chatterjee 33
  • 34. 34