Liver Function Tests Flashcards
What are the big 5 enzymes of the liver?
- Alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
- Lactate dehydrogenase (LDH/LD)
- Alkaline phosphatase (ALK/ALP)
- Gamma-glutamyltransferase (GGT/GGTP)
Alanine aminotransferase (ALT)
Amino group transfer
Amino group of alanine –> a-ketoglutarate –> forming pyruvate & glutamate
OR
Reverse – Alanine –> glutamate –> Aspartate
Aspartate Aminotransferase (AST)
Amino group transfer
Amino group of glutamate –> OAA –> froming aspartate
OR reverse
Lactate Dehydrogenase (LDH)
Converts pyruvate –> lactate in anaerobic metabolism
High levels seen in liver (LDH-1) & RBCs (LDH-5)
LDH-1 – gluconeogenesis (lactate –> pyruvate –> glucose: cori cycle)
Alkaline phosphatase (ALK/ALP)
Remove phosphate groups from other compounds
Gamma-glutamyltransderase (GGT/GGTP)
Involved in drug metabolism through conjugation reactions involving glutathione
Makes compounds more water-soluble & easier to excrete
Liver Enzymes are used to assess…
- Hepatic cell lysis
- Drug metabolism
- Biliary Obstruction (Cholestasis)
Why are the enzymes more useful when considered as a group?
Function of enzymes not the cirtical issue –> if enzymes are elevated & the degree of elevation indicated is useful
Cell necrosis
1. Elevation in ALT & AST
2. Elevation of both ALT & AST
- Hepatic cell lysis
- Liver disease –> if CK also elevated possible muscle cell lysis
If AST alone elevated –> not sufficient evidence to suggest there is a liver problem
ALT
Found in periportal area of the liver
Portion of liver lobule surrounding periportal space
Alcoholic Hepatitis
AST/ALT ratio
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
Perivenous area
Portion of the liver lobule surrounding the central vein
Drug Induced Hepatitis
AST/ALT ratio
AST/ALT ratio ~1
Both higher than ETOH hepatitis
Mechanism associated with production in ROS
Ratio will vary depending on the drug
Acute Viral Hepatitis
AST/ALT ratio
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
LDH-5
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
LDH-1
Erythrocytes & heart tissue
Longest half-life (100 hrs)
Hepatic Necrosis (Hepatitis)
GGT & ALP
GGT: Increase less than 10-fold URL
ALP: <2.5 fold URL
Alcohol Metabolism
GGT & ALP
GGT: Elevated (<5-fold URL)
ALP: Typically NOT elevated
Alcohol & Drug Metabolism
Liver major site of drug metabolism
Necessary enzymes are induced in response to the type/quantity of the drug
GGT
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
Alcohol or Drug-induced Jaundice
Increase in GGT, w/o increase in ALP
Biliary Obstruction (Cholestasis)
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
Heme catabolism
Localized to: Macrophages in spleen & bone marrow
MOA: Iron taken off –> iron released for recycling
Unconjugated bilirubin/UCB
Bilirubin*
Heme–>Biliverdin –> Bilirubin
Very hydrophobic, released into the blood –> binds albumin w/ high affinity
