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Flashcards in Liver Chemistry Tests Deck (20):
1

AST level definition & clinical implications of abnormality

  • AST = aspartate aminotransferases
  • indicates hepatocellular damage

2

ALT level definition & clinical implications of abnormality

  • ALT = alanine aminotransferase
  • indicates hepatocellular damage

3

Bilirubin level definition & clinical implications of abnormality

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

4

Alkaline phosphatase level definition & clinical implications of abnormality

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

5

Albumin level definition & clinical implications of abnormality

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

6

Characteristics of ALT

  • 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

7

Characteristics of AST

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

8

AST: ALT ration

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

9

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

–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

10

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

–Hemolysis
–Myopathy
–Thyroid disease
–Strenuous exercise
 

11

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

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

12

Major patterns of liver-associated diseases (schematic)

13

Characteristics of alkaline phosphatase

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

14

Tests that clarify elevated alk phos levels


•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
 

15

Hepatobiliary causes of elevated alkaline phosphatase

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

16

Nonhepatic causes of elevated alkaline phosphatase

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

17

Characteristics of Bilirubin

•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
 

18

General pathway of bilirubin metabolism

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

19

Causes of elevated unconjugated (indirect) hyperbilirubinemia

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

20

Causes of elevated conjugated (indirect) hyperbilirubinemia

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