Liver Enzymology
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Transcript of Liver Enzymology
LIVER ENZYMOLOGY
Omega CantrellVMP 978
Disease vs. FailureFailure usually results from some
type of diseaseRecognized by failure to clear
blood of substances normally eliminated, and failure to synthesize substances normally produced
70-80% of functional hepatic mass must be lost before liver failure occurs
TestsHepatocyte injury (“leakage”)
◦ALT, AST, SDH, GLDHCholestasis (“induction”)
◦ALP, GGTLiver function
◦T. bili, bile acids, ammonia, BSP, ICG, ALB, GLOB, GLUC, BUN, CHOL, coagulation factors
Leakage vs. InductionLeakage
◦ In cytosol and/or organelles◦Damage to cell membrane/injury to organelles
Sublethal or lethal
◦No enzyme production needed = increases are seen in hours
Induction◦Attached to cell membrane◦Stimulus = increased enzyme release from
cells = increased enzyme activity in serum◦Need for enzyme production = increases
typically seen in days
HEPATOCYTE INJURY (“LEAKAGE”)
Alanine aminotransferase (ALT)Aspartate aminotransferase (AST)Sorbitol dehydrogenase (SDH)Glutamate dehydrogenase (GLDH)
Alanine Aminotransferase (ALT)Highest concentrations in dog/cat
hepatocytes◦Very liver specific, but may see
increases with severe muscle damageIncreased activity from any disease
that causes hepatocyte injury◦Membrane injury cell death◦Many potential causes
Degree of elevation◦Acute vs. chronic injury
Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 372.
ALT (cont’d)Activity vs. time
◦12 hours 1-2 days◦Recovery
Severe liver disease◦Decreased hepatic mass◦Chronic disease
Half-life◦Dogs vs. cats
Horses/ruminants◦Hepatic vs. muscle injury
Aspartate Aminotransferase (AST)Hepatocytes and myocytes all
speciesLess liver specific, but can be
more sensitiveHorses/ruminantsHalf-life
Sorbitol Dehydrogenase (SDH)Mainly in hepatocytes liver-
specific!Not superior to ALT in dogs/catsHorses/cattleHalf-lifeStability (in vitro) less than other
enzymes
Glutamate Dehydrogenase (GLDH)Mainly in hepatocytes liver-
specific!◦Dogs, cats, horses, ruminants
More stable than SDHAssay is difficult, not widely
available
CHOLESTASIS (“INDUCTION”)
Alkaline phosphatase (ALP)Gamma-glutamyltransferase (GGT)
Alkaline Phosphatase (ALP)Many sources, but some have
very short half-lifeBone originLiver originInduced by drugsSecondary to some neoplasms
γ-Glutamyltransferase (GGT)Highest concentrations in
pancreas/kidneys, but most serum GGT from liver
More specific, less sensitive than ALP (dogs)
More sensitive, less specific than ALP (cats)
Horses/ruminants: GGT superior to ALP
TESTS OF LIVER FUNCTION
Substances normally eliminated by the liverBilirubin, bile acids, CHOL, ammonia
Substances normally synthesized by the liverALB, GLOB, BUN, CHOL, coagulation factors
BilirubinBreakdown product of Hb, other
porphyrin-containing compoundsMetabolized in the liver to
conjugated formCauses of increased bilirubin
◦Increased Hb (increased RBC destruction), decreased uptake/conjugation by hepatocytes, disruption of bile flow
Species differences
Bile AcidsSynthesized in hepatocytes from
cholesterol, then secreted into biliary system◦Recirculates (via liver reuptake and secretion)
Causes of increased concentration◦Deviation of portal circulation, decreased
hepatocyte uptake, decreased excretion via biliary system
Measured pre- and post-prandiallyOnly one sample collected in horses,
ruminants, and llamas
AmmoniaProduced in digestive tract,
absorbed from intestine into blood, removed by liver
Increased concentration typically in animals with PSS, but not sensitive for diagnosis◦Can also see with loss of >60% loss
of functional hepatic massTolerance vs. concentration
Bromosulfophthalein Excretion (BSP)
Dye, given IV, removed by hepatocytes, conjugated, excreted in bile
Test of hepatic blood flow, ability of hepatocytes to remove/conjugate/excrete, patency/integrity of biliary system
No longer commercially available
Indocyanine Green Excretion (ICG)Dye, given IV, removed by
hepatocytes, excreted in bile (unconjugated)
Test assess hepatic blood flow, ability of hepatocytes to remove ICG from blood, patency/integrity of biliary system
Commercially available, but complicated
Albumin (ALB)Synthesized by liverIncreases are always affected by
extrahepatic factors (mainly dehydration)
Decreases due to hepatic factors not seen until 60-80% hepatic function is lost
Species differences in hypoalbuminemia accompanying liver disease
Globulins (GLOB)Most synthesized in lymphoid
tissue, but some synthesis is performed by liver
Decrease not usually as marked as albumin
Glucose (GLUC)After SI absorption, transported
to liver and converted to glycogen
Synthesize via gluconeogenesisRelease stores via glycogenolysisConcentrations vary in animals
with hepatic failure
Urea (BUN)Synthesized from ammonia
◦Decreased conversion in liver disease/failure
◦Causes increased [blood ammonia], decreased [BUN]
Cholesterol (CHOL)Liver is a major site of synthesisExcreted via bile
Coagulation FactorsMost are synthesized by the liver
◦I, II, V, IX, XNeed for bile
◦Vitamin K II, VII, IX, X
PT/APTT
Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 372.
ReferencesLassen, ED. (2006). Laboratory
Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 355-375.