Serum Liver Enzyme Tests

Question 1

Serum enzyme tests can be grouped into two categories based on:

Answer 1

Cause of elevated enzyme activity levels in the serum:

1. Generalized damage to hepatocytes
2. Cholestasis

Question 2

What is Cholestasis?

Answer 2

Any condition in which the flow of bile from the liver is inhibited or blocked

Question 3

• What are the different types of cholestasis?
  
  • Examples

long card, sorry :/

Answer 3

• Extrahepatic cholestasis (occurs outside the liver)
  
  • Strictures (narrowing of bile duct)
  • Stones in common bile duct
  • Pancreatitis
  • Primary sclerosing cholangitis (inflammation & scarring of bile duct)
  • Cysts Tumors (bile duct; nearby tumors which exert pressure on bile duct)
• Intrahepatic cholestasis (occurs inside the liver)
  
  • Alcoholic liver disease
  • Primary biliary cirrhosis
  • Viral hepatitis
• Medications
  
  • Antibiotics (e.g., penicillins)
  • Anabolic steroids
  • Birth control pills

Question 4

List the Liver Serum Enzymes:

Answer 4

1. AST (Aspartate aminotransferase) = SGOT (serum glutamic oxaloacetic transaminase)
2. ALT (Alanine aminotransferase) = SGPT (serum glutamic pyruvic transaminase)
3. ALP (Alkaline Phosphatase)
4. 5’NT (5’-Nucleotidase)
5. GGT (γ-Glutamyl Transpeptidase)

Question 5

AST & ALT catabolize “_________” amino acids

Answer 5

AST & ALT catabolize “glucogenic” amino acids

Question 6

AST (SGOT):

• Isoforms:
• Cofactor:
• Tissue distribution:

Answer 6

• Isoforms:
  
  • GOT1 = cytoplasmic form
  • GOT2 = mitochondrial form
• Cofactor: pyridoxal phosphate (PLP)
• Tissue distribution: liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lung, leukocytes, erythrocytes (liver highest, erythrocytes lowest)
  
  • note: ~80% of AST activity in human liver is due to GOT2 mitochondrial form

Question 7

ALT (SGPT):

• Cellular Location:
• Cofactor:
• Tissue distribution:

Answer 7

• Cellular Location: only in the cytoplasm
• Cofactor: pyridoxal phosphate (PLP)
• Tissue distribution: predominantly in the liver

Question 8

1. Which liver enzyme (ALT or AST) is more specific to the liver?
2. What else can elevate ALT and AST levels?

Answer 8

1. AST & ALT are not exclusively expressed in the liver:
   
   • ALT is predominantly expressed in liver
   • ALT is a more specific test of acute hepatocellular damage than AST
2. Elevated AST & ALT are NOT specific for hepatobiliary disorders:
   
   • also found in patients with severe cardiac and skeletal muscle damage
   • AST is more often increased in patients with myocardial infarction than ALT

Question 9

1. Liver Cell Necrosis
   
   1. **​ALT > AST ⇒ **
   2. AST > ALT ⇒
2. ​When use of the AST/ALT ratio most important?

Answer 9

1. Liver necrosis:
   
   • ALT > AST ⇒ viral hepatitis
   • AST > ALT ⇒ alcoholic hepatitis
2. Alcoholic hepatitis due in part to deficiency of pyridoxal phosphate (PLP) observed in these patients
   
   • Liver ALT more sensitive to PLP deficiency than liver AST.

Question 10

ALP (Alkaline Phosphatase):

1. Cellular Location
2. Function
3. Four Isoenzymes of ALP
4. Elevated serum ALP

Answer 10

1. Cellular Location: Membrane-bound metalloenzyme
2. **Function: **catalyzes the hydrolysis of phosphomonoesters at an alkaline pH
3. At least four isozymes of ALP:
   
   • non-specific liver/bone/kidney
   • intestinal
   • placental
   • germ-cell
4. Elevated serum ALP:
   
   • disorders of bone (increased osteoblastic activity)
   • growth and pregnancy

Question 11

**5’NT (5’Nucleotidase): **

1. Function
2. Tissue Distribution
3. 5’NT vs. ALP serum elevation

Answer 11

1. Function: purine catabolism
   
   • Catalyzes hydrolysis of nucleotides such as adenosine 5’-phosphate
2. Broad tissue distribution: liver, intestines, brain, heart, blood vessels, pancreas.
   
   • In liver, enzyme is associated primarily with canalicular and sinusoidal plasma membranes
3. In contrast to ALP, 5’-nucleotidase is not elevated in bone disease or during pregnancy

Question 12

GGT (γ-glutamyl transpeptidase)

1. Function:
2. Cellular Location:
3. Tissue Distribution:

Answer 12

1. Function: Catalyzes the transfer of the γ-glutamyl group from γ-glutamyl-containing peptides such as glutathione to other peptides, amino acids, or water
2. Cellular Location: cell membranes/plasma membrane
3. Broad tissue distribution: liver, kidney, brain, heart, spleen, pancreas

Question 13

What can elevate serum GGT levels?

Answer 13

• Elevated serum GGT
  
  • diseases of liver, biliary tract, and pancreas
  • certain medications (barbiturates, anticonvulsant drugs)
  • alcohol abuse (i.e., increases hepatic microsomal GGT)
• Note: Unlike alkaline phosphatase, GGT is NOT elevated in bone disease

Question 14

1. Which serum enzymes indicate hepatocellular injury?
2. Which serum enzymes indicate complications in the biliary tree?

Answer 14

1. Hepatocellular Injury:
   
   • ALT
   • AST
2. Complications in biliary tree:
   
   • ​​ALP
   • 5’NT
   • GGT