1. LIVER ENZYMOLOGY Omega Cantrell VMP 978

2. Disease vs. Failure Failure usually results from some type of disease Recognized 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 3. Tests Hepatocyte injury (leakage) ALT, AST, SDH, GLDH Cholestasis (induction) ALP, GGT Liver function T. bili, bile acids, ammonia, BSP, ICG, ALB, GLOB, GLUC, BUN, CHOL, coagulation factors 4. Leakage vs. Induction Leakage 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 5. HEPATOCYTE INJURY (LEAKAGE) Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Sorbitol dehydrogenase (SDH) Glutamate dehydrogenase (GLDH) 6. Alanine Aminotransferase (ALT) Highest concentrations in dog/cat hepatocytes Very liver specific, but may see increases with severe muscle damage Increased activity from any disease that causes hepatocyte injury Membrane injury cell death Many potential causes Degree of elevation Acute vs. chronic injury 7. Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 372. 8. ALT (contd) 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 9. Aspartate Aminotransferase (AST) Hepatocytes and myocytes all species Less liver specific, but can be more sensitive Horses/ruminants Half-life 10. Sorbitol Dehydrogenase (SDH) Mainly in hepatocytes liver-specific! Not superior to ALT in dogs/cats Horses/cattle Half-life Stability (in vitro) less than other enzymes 11. Glutamate Dehydrogenase (GLDH) Mainly in hepatocytes liver-specific! Dogs, cats, horses, ruminants More stable than SDH Assay is difficult, not widely available 12. CHOLESTASIS (INDUCTION) Alkaline phosphatase (ALP) Gamma-glutamyltransferase (GGT) 13. Alkaline Phosphatase (ALP) Many sources, but some have very short half-life Bone origin Liver origin Induced by drugs Secondary to some neoplasms 14. -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 15. TESTS OF LIVER FUNCTION Substances normally eliminated by the liver Bilirubin, bile acids, CHOL, ammonia Substances normally synthesized by the liver ALB, GLOB, BUN, CHOL, coagulation factors 16. Bilirubin Breakdown product of Hb, other porphyrin-containing compounds Metabolized in the liver to conjugated form Causes of increased bilirubin Increased Hb (increased RBC destruction), decreased uptake/conjugation by hepatocytes, disruption of bile flow Species differences 17. Bile Acids Synthesized 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-prandially Only one sample collected in horses, ruminants, and llamas 18. Ammonia Produced 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 mass Tolerance vs. concentration 19. 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/int egrity of biliary system No longer commercially available 20. 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 21. Albumin (ALB) Synthesized by liver Increases 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 22. Globulins (GLOB) Most synthesized in lymphoid tissue, but some synthesis is performed by liver Decrease not usually as marked as albumin 23. Glucose (GLUC) After SI absorption, transported to liver and converted to glycogen Synthesize via gluconeogenesis Release stores via glycogenolysis Concentrations vary in animals with hepatic failure 24. Urea (BUN) Synthesized from ammonia Decreased conversion in liver disease/failure Causes increased [blood ammonia], decreased [BUN] 25. Cholesterol (CHOL) Liver is a major site of synthesis Excreted via bile 26. Coagulation Factors Most are synthesized by the liver I, II, V, IX, X Need for bile Vitamin K II, VII, IX, X PT/APTT 27. Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: 28. References Lassen, ED. (2006). Laboratory Evaluation of the Liver. In: Thrall, MA, et al. Veterinary Hematology and Clinical Chemistry. Ames, IA: Blackwell. 355-375.