Evaluating Liver Enzymes & Function Flashcards
isoenzymes
structurally different enzymes from different genes that catalyze the same chemical reaction
isoforms
structurally different enzymes from the same gene, but different post-translational modifications, that catalyze the same chemical reaction
stability
how long the enzyme remains intact outside of the body (in the sample)
half life
how long the enzyme remains measurable in the blood after being released
what units are used when evaluating liver enzymes
IU/L or X increase above the upper limit of reference interval
are values lower than reference interval clinically significant for liver enzymes
no
what type of sample is used for evaluating liver enzymes
serum
what factors interfere with liver enzymes
color (hemolysis, lipemia, icterus)
causes of elevated liver enzymes
- cell injury
- induction of enzyme synthesis
- greater cell mass
- absorption
- decreased clearance
alanine transferase (ALT)
cytoplasmic enzyme (mild cell injury)
used for small animals only w/ high specificity for liver injury
sorbitol dehydrogenase (SDH)
cytoplasmic enzyme (mild cell injury)
used for large animals w/ high specificity for liver injury
lactate dehydrogenase
cytoplasmic enzyme (mild cell injury)
rarely used - low specificity for liver injury
aspartate aminotransferase (AST)
mitochondrial & cytoplasmic enzyme (severe cell injury)
used for all species
moderate specificity for liver injury - also released by muscle so check CK concurrently
glutamate dehydrogenase (GLDH)
mitochondrial & cytoplasmic enzyme (severe cell injury)
used for large animals/exotics w/ high specificity for liver injury
alkaline phosphatase (ALP)
membrane bound inducible enzyme (increased induction of enzyme synthesis)
2 isoenzymes w/ 5 isoforms
ALP isoenzymes & isoforms
- intestinal ALP (intestinal-ALP or corticosteroid-ALP in dogs)
- tissue nonspecific ALP (liver-ALP, bone-ALP, placenta-ALP)
causes of elevated ALP
- age: high B-ALP in young animals/neonates
- mechanical cholestasis: high L-ALP (dogs)
- drugs/hormones
- increased osteoblast activity
gamma-glutamyl transferase (GGT)
membrane bound inducible enzyme (increased induction of enzyme synthesis)
more sensitive than ALP in large animals
induced by cholestasis, biliary hyperplasia, drugs/hormones
enzymes that indicate cell injury
mild: ALT, SDH, LDH
severe: AST, GLDH
enzymes that indicate increased induction
ALP, GGT
pattern of cholestasis
increased ALP and GGT
- NOT functional cholestasis
hyperbilirubinemia/uria
possible hypercholesterolemia, coagulation, inc. serum bile acids
pattern of feline hepatic lipidosis
ALP increases higher/faster than GGT
pattern of feline hyperthyroid
increased ALP
normal GGT
pattern of canine cholestatic disease
significantly increased ALP
increased GGT
liver injury vs liver dysfunction
injury: increase in liver enzymes without clinical signs of decreased liver function
dysfunction: changes in liver values +/- clinical signs of decreased liver function
liver has large functional reserve –> can function if some hepatocytes are injured
liver failure
clinical syndrome due to clinical signs that could be attributes to the loss of >75% of the liver’s functional mass
causes clinical presentation of liver dysfunction
what is the primary waste product of the liver
bilirubin
how is bilirubin metabolized
RBC death –> macrophage clean up –> unconjugated bilirubin binds to albumin to travel to liver –> hepatocytes conjugate bilirubin to become water soluble –> bilirubin gets excrete in urine or feces
causes of hyperbilirubinemia
- prehepatic
- hepatic
- posthepatic
signs of prehepatic hyperbilirubinemia
hemolysis:
- regenerative anemia
- normal plasma protein
- no evidence of cholestasis (ALP/GGT)
signs of hepatic hyperbilirubinemia
decreased uptake, conjugation, or excretion:
- decreased functional liver mass
- functional cholestasis
functional cholestasis:
- pro-inflammatory cytokines
- inflammatory leukogram
- non-regenerative anemia
- mild/no increase in ALP/GGT
signs of posthepatic hyperbilirubinemia
biliary system problems:
- marked increase in ALP/GGT
- mild hypercholesterolemia
- pancreatitis (inflammatory leukogram, increased PLI, non-septic exudate)
how to test bile acids
bile acid stim test
1 sample fasting
1 sample 2 hr post prandial
should have low amount fasting and only slightly higher amount 2 hrs post prandial
cause of increased bile acids
- decreased biliary excretion (cholestasis)
- decreased bile acid clearance (liver dysfunction)
what cell is mainly responsible for detecting toxins in blood
Kupffer cells
what is the main toxin that gets detoxified by hepatocytes
ammonia
ammonia
major byproduct from protein catabolism
produced by GI microbiome
detoxified by hepatocytes to form urea & amino acids
function of urea
helps the kidneys concentrate urine
clinical signs of hyperammonemia
CNS toxicity –> hepatic encephalopathy
causes of hyperammonemia
- decreased uptake due to abnormal portal blood flow
- decreased conversation to urea due to decreased hepatic mass
- increased production of ammonia from bacteria
what 3 things does the liver synthesize (mainly)
- proteins (albumin + clotting factors)
- cholesterol (lipoprotein metabolism)
- glucose (glycogen storage and glucose production)
CBC indicators of liver dysfunction
- anemia:
- mild
- normocytic/normochromic
- poikilocytosis - thrombocytopenia
(from portal hypertension causing congestive splenomegaly –> platelet sequestration & decreased TPO production)
coag panel indicators of liver dysfunction
- prolonged PT/PTT (dec. clotting factor production)
- increased D-dimers
- decreased fibrinogen (decreased synthesis or entering DIC)
- decreased antithrombin
chemistry indicators of liver dysfunction
- increased liver enzymes (leakage and cholestatic)
- hyperglobulinemia (dec. clearance of GI antigens)
- hypoalbuminemia
urinalysis indicators of liver dysfunction
- decreased USG (dec. urea –> less concentrated/hypotonic urine)
- ammonium biurate & bilirubin crystalluria
- bilirubinuria
