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.