4.05-4.06 LFT Flashcards
The five liver enzymes?
AST
ALT
LDH (least liver specific)
ALP
GGT
What enzyme is implicated in liver gluconeogensis (Cori Cycle) ?
LDH
What liver enzyme is involved in drug and xenobiotic elimination at the liver?
GGT (Gamma-glutamyltransferase)
High serum AST/ALT > 2 with Oral AST below 300 U/L
Excessive alcohol
Perivenous hepatocytes damaged (zone 3) by alcohol metabolism production of ROS especially at mitochondria (AST) while peiportal ALT spared
AST/ALT ~1 (but variable), but absolute amount of enzymes are higher
Drug induced hepatitis
AST/ALT often slightly < 1 with some variability, very high both enzymes >500 U/L in more extreme cases
Acute viral hepatitis
High sensitivity, immune system causing the damage
What LDH isoform is specific to hepatocytes ?
LDH-5
What’s the problem with blood panels of LDH?
Do not distinguish RBC (1) from liver isoforms (5) of LDH & LDH-5 has short half life = underrepresent liver damage
LOW SENSITIVITY
What happens to GGT and ALP with heptocellular damage?
Increase moderately
What damage is “induced” by alcohol and drugs and present at high levels in bile duct cells ?
GGT
What tends to result in a massive increase in both GGT and ALP?
Cholestasis (bile duct obstruction)
Note
Secreted so can increase without hepatocell lysis
Where does heme catabolism take place?
Macrophages in liver or spleen
Heme is broken down into what during catabolism at the macrophage>
Unconjugated bilirubin (UCB)
Must hitch ride on albumin to reach over *
How does bilirubin become conjugated?
1-2 glucoronic acid molecules via UGT enzyme to make conjugated bilirubin more soluble
Molecule that can’t measure becomes of its extreme hydrophobic and often underestimates truel levels?
IBL (indirect bilirubin)
A mature of CB xD often resuls in overestimation
Direct bilirubin
Total bilirubin (TBIL) ?
= UCB + CB
What can lead to massive UCB release that often exceed what even the healthiest over can tackle?
Massive RBC hemolysis/premature destruction
What conditions can cause in prehepatic jaundice or massive RBC damage?
G6PD or PK deficiencies
What kind of jaundice results in increased UCB, highly elevated IBIL, TBIL, CB BUT normal DBIL?
Prehepatic jaundice
(G6PG/PK deficiency)
Increased conjugate bilirubin production will lead to what?
Elevated urobilinogen in urine
Stools appear darker b/c stercobilin
Sky high LDH but little to no increases in other liver enzymes (jaundice)?
Prehepatic jaundice
What is the major effect of hepatic jaundice?
Impaired ability to produce conjugated bilirubin = elevated IBL** + elevated DBIL (hepatocell lysis) + elevated TBIL
Higher proportion of the urobilinogen from hepatic jaundice also goes where because of impaired enterohepatic circulation In hepatic jaundice?
Kidneys
Generally leads to moderate to significant increases in 5 hepatic enzymes?
Hepatic jaundice
Post hepatic jaundice caused most commonly by?
Bile duct obstruction (stones/tumors)
Increased DBIL, Normal IBIL, lil to no increase in urobilinogen, sometimes very dark urine from CB, with normal AST, ALT, LDH but very high ALP and GGT (jaundice kind)?
Post hepatic jaundice
Chronic obstruction of teh bile duct leads to what?
Post hepatic jaundice OR proliferation of GGT and ALP secreting cells
What molecules implies status of CB in the body/cell?
DBIL
What molecule implies the status of Unconjugated bilirubin in the body?
IBIL