LIVER FUNCTION TESTS

Dr. Thomas

The liver is designed to maintain bodys chemical and metabolic homeostasis

FUNCTIONS OF LIVER
1.

HEPATOCYTE : Concerned with the metabolic reactions , Protein synthesis and degradation BILIARY SYSTEM : Metabolism of Bilirubin and Bile salts RETICULOENODTHELIAL SYSTEM : Concerned with the immune system

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Uses of LFT
1.

Screening : They are a non-invasive yet sensitive

screening modality for liver dysfunction

2.

Pattern of disease : They are helpful to recognize

the pattern of liver disease. Like being helpful in differentiating between acute viral hepatitis and various cholestatic disorders and chronic liver disease

3.

Assess severity : They are helpful to assess the

severity and predict the outcome of certain diseases like primary biliary cirrhosis

4.

Follow up : They are helpful in the follow up of

certain liver diseases and also helpful in evaluating response to therapy like autoimmune hepatitis

Classification of Liver Function Tests

1.

Tests to assess the Livers metabolic capacity Tests to assess the Livers Biosynthetic capacity Tests to detect injury to hepatocytes

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To abolish liver function, over 80 % of the liver must first be destroyed CIRRHOSIS ACUTE FULMINANT HEPATIC FAILURE

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Serum Bilirubin levels - Total, Direct and Indirect Serum Total Proteins, Albumin, Globulin Prothrombin Time, INR ALT, AST ALP, GGT, 5 - Nucleotidase

METABOLIC FUNCTIONS
Bilirubin Ammonia Lipids : Cholesterol , Bile Salts

BILIRUBIN
Serum Bilirubin levels : 0.3 -1 mg/dl Indirect Serum Bilirubin / Unconjugated B : 0.2 0.7 mg/dl Direct Serum B/ Conjugated B : 0.1 0.3 mg/dl Product of Hb breakdown

Hb Heme Biliverdin Bilirubin

BLOOD STREAM
Unconjugated Bilirubin
Glucuronyl Transferase

Albumin

Conjugated Bilirubin

BLOOD STREA M

BILE CANALICULI

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Causes of Elevated Unconjugated Bilirubin

1.

Hemolytic Anemia:
Due to abnormally high levels of Hb released from RBCs The rate of bilirubin formation exceeds the rate of liver clearance in Unconjugated B / Indirect B

2.

Gilberts Syndrome

Causes of Elevated Conjugated Bilirubin

1.

Biliary Obstruction ( Cholestasis) :

Intrahepatic and extrahepatic obstruction Extra hepatic causes Gall stones, malgnancy, infection Intra hepatic causes - Cirrhosis

2.

Dubin-Johnson Syndrome : Rotor Syndrome: Misc Septicemia, drugs

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Serum Ammonia
Converted to urea in liver High ammonia levels indicates 1] Some form of liver failure 2] Valproic acid-induced

Serum Cholesterol
Liver involved in lipoprotein synthesis Cirrhosis : Cholesterol levels are Normal or Cholestasis : Cholesterol

Bile Salts
In Cholestasis : Excretion of Bile Salts in urine

SYNTHETIC FUNCTIONS
Synthesis of the plasma proteins except Immunoglobulins and von Willebrands Factor Total Proteins Serum Albumin Prothrombin Time

Total Serum Proteins

6 7.8 gm/dl

Serum Albumin
3.5 - 5 g/dl Decreased in Liver diseases like cirrhosis Renal Disease Malnutrition Protein-losing enteropathies Chronic Inflammatory Diseases In cirrhosis, there is reversal of A:G ratio

Prothrombin Time (PT)

PT assesses the extrinsic clotting cascade in which Factor VII is a part of Normal PT is 10 14 s Prolongation of PT Cirrhosis, Cholestasis Reasons -Cirrhosis : Decreased Synthesis Cholestasis : No fat-soluble vitamin K ( II, VII, IX, X)

Tests of Liver Injury

Plasma Enzyme levels Enzymes reflecting hepatocyte injury: - Transaminases ALT, AST - LDH Enzymes reflecting canalicular injury: - ALP - GGT - 5-N

Transaminases
AST = SGOT ALT = SGPT 10 40 U/L Both require Pyridoxal Phosphate (Vit B6) to function and ALT synthesis depends on it AST : Heart, muscle , liver ALT : Liver, kidney

 AST , ALT :

Alcoholic Liver Disease Viral Hepatitis Drug induced liver damage

Location of AST enzyme in hepatocyte:

80 % is present inside the mitochondria 20 % in the cytoplasm of the cell ALT : Cytosolic enzyme In Mild Liver Injury : Cytoplasmic AST and ALT released In More severe Injury : Mitochondrial AST released

In Alcoholic Liver Disease : AST >> ALT (3:1) Reason : Alcohol mitochondrial toxin ( severe damage) Pyridoxine is deficient in alcoholics ( ALT synthesis impaired) AST: ALT

ALT > AST in Viral Hepatitis

Lactate Dehydrogenase (LDH)

Vital cytosolic enzyme needed in glycolysis 5 iso enzymes - LDH1 to LDH5 LHD4 is the major isoenzyme in liver Raised in any injury to liver : ALD, Hepatitis

ALKALINE PHOSPHATASE (ALP)

Liver, Bone, Kidney, Intestine, Placenta Normal : 40 125 U/L In liver : Canalicular surface of hepatocytes Biliary system Obstruction of Biliary tract from stones in ducts or ductules cholangitis - Ascending

Gamma Glutamyl Transferase (GGT)

Regulates the transport of amino acids across cell membranes by catalyzing the transfer of a glutamyl group from glutathione to a free amino acid Present - on the canalicular surface of hepatocytes - in microsomes Raised in Cholestasis - Drugs that induce microsomal enzymes : Alcohol, Acetaminophen, Phenytoin,

Other Tests
5I Nucleotidase enzyme :
Alpha Fetoprotein : NTD, HCC Antimitochondrial Antibody : Primary Biliary Cirrhosis p-ANCA : Primary Sclerosing Cholangitis Serological markers in Viral Hepatitis Radiological Imaging CT,MRI,ERCP Liver Biopsy in Cholestasis