Liver Enzymology

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LIVER ENZYMOLOGY Omega Cantrell VMP 978

description

Presentation for senior clinical pathology rotation (VMP 978)

Transcript of Liver Enzymology

Page 1: Liver Enzymology

LIVER ENZYMOLOGY

Omega CantrellVMP 978

Page 2: Liver Enzymology

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

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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

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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

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HEPATOCYTE INJURY (“LEAKAGE”)

Alanine aminotransferase (ALT)Aspartate aminotransferase (AST)Sorbitol dehydrogenase (SDH)Glutamate dehydrogenase (GLDH)

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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

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Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 372.

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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

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Aspartate Aminotransferase (AST)Hepatocytes and myocytes all

speciesLess liver specific, but can be

more sensitiveHorses/ruminantsHalf-life

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Sorbitol Dehydrogenase (SDH)Mainly in hepatocytes liver-

specific!Not superior to ALT in dogs/catsHorses/cattleHalf-lifeStability (in vitro) less than other

enzymes

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Glutamate Dehydrogenase (GLDH)Mainly in hepatocytes liver-

specific!◦Dogs, cats, horses, ruminants

More stable than SDHAssay is difficult, not widely

available

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CHOLESTASIS (“INDUCTION”)

Alkaline phosphatase (ALP)Gamma-glutamyltransferase (GGT)

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Alkaline Phosphatase (ALP)Many sources, but some have

very short half-lifeBone originLiver originInduced by drugsSecondary to some neoplasms

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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

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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

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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

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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

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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

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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

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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

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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

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Globulins (GLOB)Most synthesized in lymphoid

tissue, but some synthesis is performed by liver

Decrease not usually as marked as albumin

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Glucose (GLUC)After SI absorption, transported

to liver and converted to glycogen

Synthesize via gluconeogenesisRelease stores via glycogenolysisConcentrations vary in animals

with hepatic failure

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Urea (BUN)Synthesized from ammonia

◦Decreased conversion in liver disease/failure

◦Causes increased [blood ammonia], decreased [BUN]

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Cholesterol (CHOL)Liver is a major site of synthesisExcreted via bile

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Coagulation FactorsMost are synthesized by the liver

◦I, II, V, IX, XNeed for bile

◦Vitamin K II, VII, IX, X

PT/APTT

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Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 372.

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ReferencesLassen, ED. (2006). Laboratory

Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 355-375.