Liver Function Tests

Question 1

What are the big 5 enzymes of the liver?

Answer 1

1. Alanine aminotransferase (ALT)
2. Aspartate aminotransferase (AST)
3. Lactate dehydrogenase (LDH/LD)
4. Alkaline phosphatase (ALK/ALP)
5. Gamma-glutamyltransferase (GGT/GGTP)

Question 2

Alanine aminotransferase (ALT)

Answer 2

Amino group transfer

Amino group of alanine –> a-ketoglutarate –> forming pyruvate & glutamate

OR

Reverse – Alanine –> glutamate –> Aspartate

Question 3

Aspartate Aminotransferase (AST)

Answer 3

Amino group transfer

Amino group of glutamate –> OAA –> froming aspartate

OR reverse

Question 4

Lactate Dehydrogenase (LDH)

Answer 4

Converts pyruvate –> lactate in anaerobic metabolism

High levels seen in liver (LDH-1) & RBCs (LDH-5)

LDH-1 – gluconeogenesis (lactate –> pyruvate –> glucose: cori cycle)

Question 5

Alkaline phosphatase (ALK/ALP)

Answer 5

Remove phosphate groups from other compounds

Question 6

Gamma-glutamyltransderase (GGT/GGTP)

Answer 6

Involved in drug metabolism through conjugation reactions involving glutathione

Makes compounds more water-soluble & easier to excrete

Question 7

Liver Enzymes are used to assess…

Answer 7

1. Hepatic cell lysis
2. Drug metabolism
3. Biliary Obstruction (Cholestasis)

Question 8

Why are the enzymes more useful when considered as a group?

Answer 8

Function of enzymes not the cirtical issue –> if enzymes are elevated & the degree of elevation indicated is useful

Question 9

Cell necrosis
1. Elevation in ALT & AST
2. Elevation of both ALT & AST

Answer 9

1. Hepatic cell lysis
2. Liver disease –> if CK also elevated possible muscle cell lysis

If AST alone elevated –> not sufficient evidence to suggest there is a liver problem

Question 10

ALT

Answer 10

Found in periportal area of the liver

Portion of liver lobule surrounding periportal space

Question 11

Alcoholic Hepatitis

AST/ALT ratio

Answer 11

AST/ALT ratio >/= 2
AST < 300 (8-20)

ETOH induced cell death in perivenous areas of liver lobule –> where drug metabolism takes place via P450 system

Question 12

Perivenous area

Answer 12

Portion of the liver lobule surrounding the central vein

Question 13

Drug Induced Hepatitis

AST/ALT ratio

Answer 13

AST/ALT ratio ~1
Both higher than ETOH hepatitis

Mechanism associated with production in ROS

Ratio will vary depending on the drug

Question 14

Acute Viral Hepatitis

AST/ALT ratio

Answer 14

AST/ALT ratio </= 1
Both > 500

Ratio is </= 1 b/c cell death is MUCH MORE Extensive –> transaminase values are usually > 500

Cell death mediated by body’s immune system

Question 15

LDH-5

Answer 15

Liver LDH –> released in response to cell lysis

Shortest half-life (10 hr) –> serum values often not elevated/ low in diseases assoc w/ hepatocellular lysis

Question 16

LDH-1

Answer 16

Erythrocytes & heart tissue

Longest half-life (100 hrs)

Question 17

Hepatic Necrosis (Hepatitis)

GGT & ALP

Answer 17

GGT: Increase less than 10-fold URL

ALP: <2.5 fold URL

Question 18

Alcohol Metabolism

GGT & ALP

Answer 18

GGT: Elevated (<5-fold URL)

ALP: Typically NOT elevated

Question 19

Alcohol & Drug Metabolism

Answer 19

Liver major site of drug metabolism

Necessary enzymes are induced in response to the type/quantity of the drug

Question 20

GGT

Answer 20

Involved in drug metabolism

Induced by alcohol & other drugs

Membrane protein localized to outer leaflet of plasma membrane & can be secreted from cells

High level of expression in Biliary Epithelial Cells

Most people w/ ETOH use disorder have an elevated GGT

Question 21

Alcohol or Drug-induced Jaundice

Answer 21

Increase in GGT, w/o increase in ALP

Question 22

Biliary Obstruction (Cholestasis)

Answer 22

Triggers proliferation of bile duct cells & expression of associated enzymes (GGT, ALP) –> release from cells w/o cell lysis

Induction of GGT & ALP @ much higher lvels

Question 23

Heme catabolism

Answer 23

Localized to: Macrophages in spleen & bone marrow

MOA: Iron taken off –> iron released for recycling

Question 24

Unconjugated bilirubin/UCB

Answer 24

Bilirubin*

Heme–>Biliverdin –> Bilirubin

Very hydrophobic, released into the blood –> binds albumin w/ high affinity

Question 25

Conjugated bilirubin (bilirubin diglucuronide)

Answer 25

Catabolized further in the liver

Bilirubin –> bilirubin diglucuronida via UGT enzyme

Makes conjugated bilirubin water soluble –> excreted in urine

Question 26

TBIL

Answer 26

Measures both conjugated & unconjugated bilirubin (UCB + CB)

Question 27

DBIL

Answer 27

Predominately a measure of conjugated bilirubin (OVERESTIMTED)

Water soluble

Test for CB

Question 28

IBIL

Answer 28

Measure of unconjugated bilirubin (UNDERESTIMATED)

Extremely hydrophobic

Hard to measure

Test for UCB

Question 29

Conjugation of bilirubin

Answer 29

Makes it more water-soluble

Question 30

Spleen & bone marrow

Answer 30

Release unconjugated bilirubin (highly hydrophobic; tightly bound to albumin)

Kidney WILL NOT filter when tightly bound to albumin (unconjugated albumin)

Question 31

Urine bilirubin

Answer 31

Test for unconjugated bilirubin

Question 32

In the liver

Answer 32

Albumin gives up bilirubin to hepatocyte

UDP-glucosyltransferase converts unconjugated bilirubin –> conjugated bilirubin –> released into bile duct –> common bile duct –> intestine

Question 33

Liver should NEVER

Answer 33

Release conjugated bilirubin into the blood

Should only be found in hepatocyte & bile duct, not in the blood –> should be really low

Unless the liver (unhealthy individual) is releasing it

Question 34

In the intestine conjugated bilirubin –>

Answer 34

Is acted on by intestinal flora –> conjugated bilirubin –> converts into urobilinogen & stercobilin