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CLINICAL APPROACH TO THE PATIENT WITH ABNORMAL LIVER TEST RESULTS DAVID E. KATZ, MD PGY-3 WRAMC DOM INTERN LECTURE SER

CLINICAL APPROACH TO THE PATIENT WITH ABNORMAL LIVER TEST RESULTS DAVID E. KATZ, MD PGY-3 WRAMC DOM INTERN LECTURE SERIES ‘98. OBSTRUCTION INFLAMMATION SYNTHETIC ABILITY DETOXIFICATION PORTAL HYPERTENSION. OBSTRUCTION. OBSTRUCTION: TBIL, DBIL, ALK-P. INFLAMMATORY.

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CLINICAL APPROACH TO THE PATIENT WITH ABNORMAL LIVER TEST RESULTS DAVID E. KATZ, MD PGY-3 WRAMC DOM INTERN LECTURE SER

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  1. CLINICAL APPROACH TO THE PATIENT WITH ABNORMAL LIVER TEST RESULTSDAVID E. KATZ, MDPGY-3WRAMC DOMINTERN LECTURE SERIES ‘98

  2. OBSTRUCTION • INFLAMMATION • SYNTHETIC ABILITY • DETOXIFICATION • PORTAL HYPERTENSION

  3. OBSTRUCTION

  4. OBSTRUCTION: TBIL, DBIL, ALK-P

  5. INFLAMMATORY

  6. INFLAMMATORY: AST, ALT, GGT

  7. SYNTHETIC ABILITY

  8. SYNTHETIC ABILITY: ALBUMEN, PT, FACTOR LEVELS, GLYCEMIC CONTROL.

  9. DETOXIFICATION

  10. DETOXIFICTION: NH3, MS CHANGES

  11. PORTAL HYPERTENSION

  12. PORTAL HYPERTENSION: PLATELETS, WBC, SPLENOMEGALY, VARICES

  13. LIVER “FUNCTION” TEST • GALACTOSE CLEARANCE • AMINOPYRINE CLEARANCE TEST • INCIDENCE OF CLINICALLY SIGNIFICANT LIVER DISEASE =1%

  14. CLINICAL ASSESSMENT OF THE PATIENT • HEPATOCELLULAR NECROSIS/VIRAL HEPATITIS: ANOREXIA/N/V/F. • CHOLESTASIS/INAD. BILE FLOW: DEEP JAUNDICE, PRURITIS, CLAY COLORED STOOLS, DARK URINE. • CHOLESTASIS: INTRAHEPATIC/EXTRAHEPATIC (COLIC, FEVER, CHILLS-STONES/ “T”)

  15. FAMILY HISTORY • INDIRECT HYPERBIL- HEMOLYSIS OR GILBERTS SYNDROME. • DIRECT HYPERBIL- DUBIN-JOHNSON • HX OF SEVERE LIVER DZ: WILSON’S DZ, HEMOCHROMATOSIS, ALPHA-1-AT

  16. HISTORY • SEXUAL HISTORY, TRAVEL, ETOH, DRUGS, ?BLOOD TRANSFUSION, ?NEEDLE STICKS, RAW OYSTERS • HEMATOLOGIC DISEASE • CARDIAC DZ/IBD/DIABETES/SKIN PIGMENTATION/CARDIAC DZ/ARTHRITIS/HYPOGONADISM/ THYROID DISEASE.

  17. PHYSICAL EXAM GO NUTS!!!!

  18. PHYSICAL EXAM • PALPABLE GB- EXTRAHEPATIC CHOLESTASIS • BRUIT- ANUERYSM/TR • KAYSER-FLEISCHER RINGS: WILSONS DZ • MURPHY SIGN: ACUTE CHOLECYSTITIS

  19. BILIRUBIN • TBIL <1.1 MG/DL (70% INDIRECT) • UNCONGUGATED: HEMOLYSIS/GILBERTS (TBIL<6.0) • CONJUGATED: HEPATOCELLULAR DYSFUNCTION OR CHOLESTASIS • CBD OBS: STONES=15 (>30, EXTRAHEPATIC OBSTR UNLIKELY)

  20. TRANSAMINASES • ENZYMES INVOLVED IN THE TRANSFER OF AMINO GROUPS OF ASPARTATE AND ALANINE TO KETOGLUTARIC ACID.

  21. TRANSAMINASES • AST: GLUTAMIC-OXALOACETIC TRANSAMINASE: • CARDIAC • SKELETAL • KIDNEY • BRAIN • LIVER

  22. TRANSAMINASE • ALT: GLUTAMATE PYRUVATE TRANSAMINASE • ALMOST EXCLUSIVELY IN LIVER • AST W/O ALT • CARDIAC DZ • MACRO-AST

  23. AST/ALT RATIO • AST: BOTH CYTOSOL AND MITO • ALT: CYTOSOL • ETOH: DAMAGE TO MITOCHONDRIA • ETOH LIVER DZ/PYRIDOXINE DEF • AST NOT >250 U/L • RATIO LESS USEFUL IN CHRONIC LIVER DZ • VIRAL DZ: ALT>AST

  24. TRANSAMINASES • CHOLEDOCHOLITHIASIS: AST EARLIEST ABNORMALITY, TRANSIENT • DRUG/VIRAL: RISE TO LOW 1000’S IN 1-2 WEEKS. • ISCHEMIC HEPATITIS: ACUTE INCREASE (10K IU/L) RETURN WITHIN A WEEK

  25. TRANSAMINASES • >10,000 IU/L: ACETAMINOPHEN AND IN HERPES SIMPLEX VIRUS. • MEDS THAT INC AST:

  26. MEDS • ACET/ NSAIDS • ACE’I • NICOTINIC ACID • ABX: INH, SULFA, E-MYCIN • ANTIFUNGAL: GRISEOFULVIN/FLUCONAZOLE

  27. TRANSAMINITIS • NASH • THYROID DZ

  28. ALKALINE PHOSPHATASE • FAMILY OF ENZYMES THAT CATALYZE HYDROLYSIS OF PHOSPHATE ESTERS AT AN ALKALINE PH. • BONE, PLACENTA, INTESTINE, KIDNEY AND LIVER. • 80% (BONE/LIVER)

  29. ALK PHOS • CHOLESTASIS • INTRAHEPATIC • EXTRAHEPATIC (GALLSTONES/TUMOR) • LOCALIZED (HEPATOMA) • PATCHY (GRANULOMATOUS DZ) • CHF, HYPERTHYROIDISM, LYMPHOMA, HYPERNEPHROMA

  30. ALK PHOS • GAMMA-GLUTAMYLTRANSFERASE (GGT) • IF INC DISPROPORTIONATELY TO BILI INCREASE --->SARCOID, TB, FUNGAL, LYMPHOMA • PBC/PSC

  31. ALK PHOS • PITFALLS: DONE IN FASTING STATE; • PT WITH O/B BLOOD GROUP ARE SECRETORS AND CAN HAVE INC ALK-PHOS AFTER EATING A FATTY MEAL DUE TO THE RELEASE OF THE INTESTINAL ENZYME • LOW IN HYPOTHYROIDISM, WILSONS DZ, HEMOLYSIS, AND CONG. HYPOPHOSPHTEMIA

  32. ALK PHOS • INTRAHEPATIC CHOLESTASIS • PBC, DRUGS • EXTRAHEPATIC CHOLESTASIS • CBD STONES, STRICTURES, PANCREATIC CANCER

  33. ALBUMEN • SYTH. BY THE LIVER • T1/2 3 WEEKS • DEC USUALLY INDICATES LIVER DISEASE OF MORE THAN 3 WEEKS • SEPSIS

  34. PROTHROMBIN TIME • VIT K DEP CLOTTING FACTORS • VIT K NOT ABSORBED (CHOLESTASIS), HEPATOCELLULAR DISEASE. • MORE SENSITIVE THAN ALBUMEN • PROLONGATION CORRELATES WITH DISEASE

  35. OTHER TEST • IMMUNOGLOBULINS • IgM INCREASE WITH PBC • ANA >1:160 HOMGENEOUS W/ SMOOTH MUSCLE AB +. • AMA W/ PBC • WILSONS : LOW SERUM COPPER/CERULOPLASM

  36. OTHER TESTS • HEMOCHROMATOSIS: TRANSFERRIN SAT >55%, FERRITIN >1000 UG/L • A-1-AT DEF: LUNG DZ, A-1-AT LEVELS ARE <20 MG/DL • VIRAL SEROLOGIES

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