Liver Chemistry Tests

Question 1

AST level definition & clinical implications of abnormality

Answer 1

• AST = aspartate aminotransferases
• indicates hepatocellular damage

Question 2

ALT level definition & clinical implications of abnormality

Answer 2

• ALT = alanine aminotransferase
• indicates hepatocellular damage

Question 3

Bilirubin level definition & clinical implications of abnormality

Answer 3

• bilirubin
  
  • total
  • conjugated
• elevation indicates cholestasis, impaired conjugation or biliary obstruction

Question 4

Alkaline phosphatase level definition & clinical implications of abnormality

Answer 4

• elevation indicates:
  
  • cholestasis
  • infiltrative disease
  • biliary obstruction

Question 5

Albumin level definition & clinical implications of abnormality

Answer 5

• Albulmin = blood protein produced by liver
• low level indicates synthetic liver dysfxn

Question 6

Characteristics of ALT

Answer 6

• hepatic enzyme
• located @ cytosol of hepatocytes
• released into blood from damaged hepatocytes
• elevation is relatively specific for hepatocellular injury
  
  • however, can also occur in myopathic disease

Question 7

Characteristics of AST

Answer 7

• hepatic enzyme
• located @ cytosol + mitochondria
• released from damaged hepatocytes
• abundantly expressed @ heart, skeletal muscle, blood (less specific for hepatic injury)

Question 8

AST: ALT ration

Answer 8

• normal = 0.8 (< 1)
• > 1 ==> cirrhosis
• > 2 ==> indicates alcoholic hepatitis

Question 9

Hepatic causes of Mild (<5x) AST & ALT elevation

Answer 9

–Chronic HBV and HCV
–Acute viral hepatitis (A-E, EBV, CMV)
–Steatohepatitis
–Alcohol-related liver injury (AST predominant)
–Hemochromotosis
–Autoimmune Hepatitis
–Alpha1-Antitrypsin deficiency
–Wilson’s disease
–Celiac disease
–Cirrhosis

Question 10

Non-Hepatic causes of Mild (<5x) AST & ALT elevation

Answer 10

–Hemolysis
–Myopathy
–Thyroid disease
–Strenuous exercise

Question 11

Etiology of Severe (>15x normal) of AST & ALT elevations

Answer 11

• Acute viral hepatitis (A-E, herpes)
• Medications/toxins
• Ischemic hepatitis
• Autoimmune hepatitis
• Wilson’s disease
• Acute Budd-Chiari syndrome
• Hepatic artery ligation or thrombosis

Question 12

Major patterns of liver-associated diseases (schematic)

Answer 12

Question 13

Characteristics of alkaline phosphatase

Answer 13

• Hydrolase enzyme responsible for removing phosphate groups from nucleotides, proteins and alkaloids
• Present in nearly all tissues
  
  • Liver
  • Bone
  • Placenta
  • Intestine

Question 14

Tests that clarify elevated alk phos levels

Answer 14

•5’-nucleotidease
–Significantly elevated only in liver disease, highest levels in cholestatic diseases
•g-glutamyltransferase (GGT)
–Not present in bone
–Elevated after alcohol consumption and almost all types of liver disease

Question 15

Hepatobiliary causes of elevated alkaline phosphatase

Answer 15

–Bile duct obstruction
–Primary biliary cirrhosis (PBC)
–Primary sclerosing cholangitis (PSC)
–Medications
–Hepatitis
–Cirrhosis
–Infiltrating disease of liver

Question 16

Nonhepatic causes of elevated alkaline phosphatase

Answer 16

–Bone disease
–Pregnancy
–Chronic renal failure
–Lymphoma and other malignancies
–Congestive heart failure
–Infection and inflammation

Question 17

Characteristics of Bilirubin

Answer 17

•Normal heme degradation product
•Excreted from body via secretion into bile
•Insoluble in water
•Requires conjugation (glucuronidation) into water-soluble forms before biliary excretion
–Unconjugated (indirect) bilirubin
–Conjugated (direct) bilirubin

Question 18

General pathway of bilirubin metabolism

Answer 18

• degredation of heme ==> unconjugated bilirubin
• unconjugated bilirubin ==> hepatocytes ==> bilirubin conjugated by UDP glucoronyl transferase
• conjugated bilirubin transported into bile canaliculus ==> gallbaldder w/bile

Question 19

Causes of elevated unconjugated (indirect) hyperbilirubinemia

Answer 19

–Gilbert’s syndrome
–Hemolysis (increased heme breakdown)
–Crigler-Najjar syndrome

Question 20

Causes of elevated conjugated (indirect) hyperbilirubinemia

Answer 20

–Extrahepatic obstruction of bile flow
–Intrahepatic cholestasis
–Hepatitis
–Cirrhosis