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Liver function tests-tests for evaluation of liver enzymatic activity

Liver function tests-tests for evaluation of liver enzymatic activity


Liver function tests-tests for evaluation of liver enzymatic activit
y

The liver function tests are important to determine

1. Presence of liver diseases

2. Type of liver diseases

3. Extent and progression of liver diseases

Tests to assess liver function: 

The liver function tests can be divided into:

A. Tests for evaluation of liver enzymatic activity

B. Tests for evaluation of hepatic synthetic function

C. Tests for evaluation of hepatic excretory function

A. Tests for evaluation of liver enzymatic activity

Evaluation of liver enzymes involve measurement of serum enzymes derived from liver such as alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transpeptidase(GGT), 5' -nucleotidase and lactate dehydrogenase(LDH). 

The liver diseases result in damage of liver and elevation of serum enzymes.

1. Alanine transaminase(ALT)

ALT belong to transaminase enzymes which are part of transferase enzymes. The transferase enzymes catalyze transfer functional group. Alanine transaminase(ALT) is a recent name for serum glutamate pyruvate transaminase (SGPT). ALT is found in the liver, skeletal muscle Kidney and heart (minor activity). Transaminases (AST and ALT) catalyze transfer of amino group from amino acid to keto acid.

Raised ALT activities occur in the following cases:

 a-Viral hepatitis.

 b-Circulatory failure with shock and hypoxia. 

c- Liver cirrhosis. 

d-Obstructive jaundice. 

e- Skeletal muscle disease 

F- Infectious mononucleosis (due to liver involvement). Note: ALT is more specific for liver disease than AST. 

2-Apatate transaminase(AST)

AST belong to transaminase enzymes. Aspartate transaminase(AST) is also called serum glutamate oxaloacetate transaminase (SGOT). Aspartate transaminase(AST) is a recent name. The ALT is found in heart, liver, skeletal muscle, Kidney and erythrocytes. AST 

Raised AST activities occur in the following cases:

a. Viral hepatitis

b. Myocardial infarction

c. Toxic hepatitis

d. Circulatory failure with shock and hypoxia.

e. Liver cirrhosis.

F. Cholestatic jaundice.

g. Skeletal muscle disease and cardiac surgery.

h. Malignant infiltration of liver.

i. Infectious mononucleosis (due to liver involvement). Note: AST is not specific for hepatic disease.

3.      ALP (Alkaline phosphatase)

The ALP family of enzymes which catalyze hydrolysis of phosphate group at alkaline pH. Alp has highest activity liver, bone, intestine, kidney, and placenta. The clinical utility of ALP lies in its ability to differentiate hepatobiliary disease from osteogenic bone disease.

ALP isoenzymes

The major ALP isoenzymes which are found in the serum are those derived from the liver, bone, intestine, and placenta which are separated by electrophoresis technique. In electrophoresis technique, the liver fraction migrates the fastest, followed by bone, placental, and intestinal fractions.

Serum ALP increases in:

1.      In the liver, the enzyme ALP is localized to the microvilli of the bile canaliculi, and therefore it increases in:

Ø  Extrahepatic biliary obstruction, such as a stone in bile duct.

Ø  Intrahepatic cholestasis, such as drug cholestasis.

Ø  Primary biliary cirrhosis.

Ø  Hepatocellular disorders such as hepatitis and cirrhosis.

2.      Bone-related disorders.

Ø  Paget’s disease.

Ø  Bony metastases, diseases associated with an increase in osteoblastic activity.

Ø   Osteomalcia.

Ø  Rickets.

Ø  Osteogenic sarcoma.

Ø  In healing bone fracture

3.      Hyperparathyroidism.

4.      Physiologically

Ø  Rapid bone growth during puberty.

Ø  In pregnancy due to its release from the placenta.

4.      GGT (gamma glutamyl transferase, gamma glutamyl transpeptidase)

γ-Glutamyltransferase (GGT) is involved in the transfer of the γ-glutamyl residue from γ-glutamyl peptides to amino acids and small peptides. In most biologic systems, glutathione serves as the γ-glutamyl donor.

 

Tissue Source

GGT activity is found in the kidney, brain, prostate, pancreas, and liver. Serum GGT activity determination is used   mainly to evaluation of liver and biliary system disorders. Elevated serum level of GGT is indication of liver disease and biliary tract. In the liver, GGT is located in the canaliculi of the hepatic cells and particularly in the epithelial cells lining the biliary ductules. In conjunction with ALP, GGT differentiates between bone and liver disease.

The GGT levels are increased in following cases:

a.      Enzyme-inducing drugs such as warfarin, phenobarbital, and phenytoin.

b.      Alcoholism, particularly chronic alcoholism.

c.      Diabetes mellitus.

d.      Cholesteric liver disease

e.      Infectious hepatitis.

f.       Alcoholic hepatitis

g.      Acute pancreatitis.

h.      Bile duct cancer.

i.        Biliary tract Obstruction.

5.      Lactate dehydrogenase

LDH consists two different polypeptide chains H (heart) and M (muscle) which combine to yield the five major isoenzymes. Each isoenzyme consists of four polypeptide chains.

1.      LDH-1 (HHHH)

2.      LDH-2 (HHHM)

3.      LDH-3 (HHMM)

4.      LDH-4 (HMMM)

5.      LDH-5 (MMMM)

Tissue Source

LDH is found in the heart, liver, skeletal muscle, kidney, and erythrocytes; lesser amounts are found in the lung, smooth muscle, and brain.

LDH enzyme consists of four polypeptide subunits. There are two types of subunits namely M (for muscle) and H (for heart).

The highest levels of total LDH are seen in

a.       Pernicious anemia and hemolytic disorders.

b.      Liver disorders, such as viral hepatitis and cirrhosis.

c.       Myocardial infarction and pulmonary infarct.

d.      Skeletal muscle disorders.

Some leukemias e.g. acute lymphoblastic leukemia.

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