Approach to Abnormal Liver Tests Anne Larson, MD Hepatology University of Washington

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Transcript of Approach to Abnormal Liver Tests Anne Larson, MD Hepatology University of Washington

  • Slide 1
  • Approach to Abnormal Liver Tests Anne Larson, MD Hepatology University of Washington
  • Slide 2
  • Anne Larson MD Case 1 65 y/o woman comes to you to establish care complaints fatigue pruritis dry eyes past history hysterectomy for fibroids 10 years ago no alcohol, tobacco or drug use
  • Slide 3
  • Anne Larson MD Case 1 65 y/o woman exam spider angiomata mild splenomegaly otherwise normal
  • Slide 4
  • Anne Larson MD Case 1 65 y/o woman screening labs reveal platelets 90,000-alk phos 4x uln bilirubin normal-albumin 3.3 (nl >3.5) AST/ALT normal-PT normal what do you want to do next? be thinking about this
  • Slide 5
  • Anne Larson MD Case 2 43 y/o female complaining of 4 days of prolonged, severe RUQ pain fever, severe nausea, some vomiting worse after eating Past History 20 yr ago began periodic attacks evening RUQ pain, fluctuating intensity, no fevers lasting 1-4 hours with residual RUQ tenderness
  • Slide 6
  • Anne Larson MD Case 2 43 y/o female Past History (cont) during last 8 years, continued episodes pain more intense and prolonged, accompanied by penetrating pain to back below scapula marked tenderness in RUQ persisting days told in the past she had gallstones
  • Slide 7
  • Anne Larson MD Case 3 Exam temp 38.5C pulse 100 uncomfortable/sweating marked tenderness in RUQ with splinting (+) Murphy's sign icterus bilirubin 6 mg/dl-alk phos 3x nl (~400 U/L) ALT 100 mg/dl-normal albumin, PT WBC 28,000-GGT 150 U/L (nl
  • Anne Larson MD Tests Reflecting Cell Injury Aminotransferases - cont aspartate aminotransferase (AST) in cytosol and mitochondria liver > heart > skeletal muscle > kidneys > brain > pancreas > lungs > WBCs > RBCs alanine aminotransferase (ALT) in cytosol predominantly liver more sensitive and specific than AST
  • Slide 15
  • Anne Larson MD Tests Reflecting Cell Injury Aminotransferases cont. elevated in nearly all liver diseases (ALT > AST) marked is usually hepatocellular disease levels may/may not reflect extent of damage do not correlate with eventual outcome usually ALT with EtOH, fulminant, and pregnancy
  • Slide 16
  • Anne Larson MD Tests Reflecting Cell Injury Alkaline Phosphatase catalyzes organic phosphate esters the enzyme is bound to hepatic canalicular membrane elevation may be due to induction of enzyme synthesis rather than inability of liver to secrete it into the bile increases seen with cell injury or obstruction slight to moderate (1-2x) usually hepatocellular large increases (3-10x) obstruction or cholestasis
  • Slide 17
  • Anne Larson MD Tests Reflecting Cell Injury Alkaline Phosphatase cont. isolated elevations infiltrative disease tumor, abscess, granuloma, amyloid Non-liver causes of elevations: bone diseasediabetes chronic renal failureintestinal disease renal cancergenetic (pseudoelevation) pregnancyosteitis deformans sepsis (esp. GNRs)multiple bone fractures Hodgkin's diseaseintraabdominal infections hypothyroidismpernicious anemia congenital hypophosphatasia zinc deficiency
  • Slide 18
  • Anne Larson MD Tests Reflecting Cell Injury -glutamyl transpeptidase (GGT) catalyzes transfer of -glutamyl groups high concentrations in bile ductule epithelial cells useful to exclude bone source for Alk Phos correlates with alk phos levels in liver disease sensitive but not specific in renal failure, MI, pancreatitis, diabetes
  • Slide 19
  • Anne Larson MD Tests Reflecting Cell Injury GGT cont. Causes of elevations: liver diseasepancreatic disease alcoholrenal disease cardiac diseaseobesity radiotherapy diabetes drugs GGT is inducible phenobarbital anticoagulants dilantin oral contraceptives acetaminophen tricyclic antidepressants
  • Slide 20
  • Anne Larson MD Tests Reflecting Cell Injury 5-Nucleotidase ( 5NT ) hydrolyzes 5 phosphates from nucleotides associated with canalicular and sinusoidal membranes physiologic function unknown only hepatobiliary tissue can release 5-NT specific for hepatic disease highest in cholestatic conditions
  • Slide 21
  • Anne Larson MD Tests Measuring Transport Efficiency Hepatic clearance reflects: 1.delivery to hepatocyte (blood flow) 2.uptake by hepatocyte
  • Slide 22
  • Anne Larson MD Tests Measuring Transport Efficiency Hemoglobin(1) Heme B-Alb (2) Other Tissue Cytochromes, etc. Alb
  • Slide 23
  • Anne Larson MD Tests Measuring Transport Efficiency Hepatic clearance reflects: 1.delivery to hepatocyte (blood flow) 2.uptake by hepatocyte 3.transport within hepatocyte 4.molecular alterations within hepatocyte
  • Slide 24
  • Anne Larson MD Tests Measuring Transport Efficiency Hemoglobin(1) Heme B (3) Conjugated (4) B-Alb (2) Other Tissue Cytochromes, etc. Alb
  • Slide 25
  • Anne Larson MD Tests Measuring Transport Efficiency Hepatic clearance reflects: 1.delivery to hepatocyte (blood flow) 2.uptake by hepatocyte 3.transport within hepatocyte 4.molecular alterations within hepatocyte 5.secretion by hepatocyte into bile 6.passage down bile ducts into duodenum
  • Slide 26
  • Anne Larson MD Tests Measuring Transport Efficiency Hemoglobin(1) Heme B (3) Conjugated (4) Secreted(5) B-Alb (2) Other Tissue Cytochromes, etc. (6) Feces99% Urine1% Alb
  • Slide 27
  • Anne Larson MD Tests Measuring Transport Efficiency Hemoglobin(1) Heme B (3) Conjugated (4) Secreted(5) B-Alb (2) Other Tissue Cytochromes, etc. (6) Feces99% Urine1% Alb
  • Slide 28
  • Anne Larson MD Tests Measuring Transport Efficiency Remember, hepatic clearance reflects: 1.delivery to hepatocyte hemolysis 2.uptake by hepatocyte shunts, drugs ( i.e., sulfa ) 3.transport within hepatocyte drugs, genetics 4.molecular alterations within hepatocyte genetics 5.secretion into bile cell damage, genetics 6.passage down bile ducts obstruction
  • Slide 29
  • Anne Larson MD Transport Efficiency Bilirubin derived mainly from hemoglobin ( 95% ) continuous production (300 mg daily) normal liver reserve can rev up 2-3 times normal values of total bilirubin = 0.1-1.0 mg/dL conjugated plus unconjugated direct plus indirect jaundice evident with levels >3.0 mg/dL
  • Slide 30
  • Anne Larson MD Tests Measuring Transport Efficiency Types of Bilirubin Direct BilirubinIndirect Bilirubin conjugatedunconjugated water solublelipid soluble polarnon-polar seen in urinenot in urine
  • Slide 31
  • Anne Larson MD Tests Measuring Synthetic Function Prothrombin Time (PT) Albumin Number Connection Tests / mental status The liver is the only source of albumin and the prothrombin group of clotting factors
  • Slide 32
  • Anne Larson MD Tests Measuring Synthetic Function Prothrombin Time (PT) sick liver cant make clotting factors factors 2, 5, 7, 9, 10 (made only in the liver) prolonged PT reflects failure of liver synthesis Other causes of prolongation: congenital deficiencies consumptive coagulopathies (i.e., DIC) drugs (i.e., warfarin) vitamin K deficiency (i.e., dietary, bile output)
  • Slide 33
  • Anne Larson MD Tests Measuring Synthetic Function Albumin most important plasma protein made by the liver accounts for 65% of protein in serum half-life ~17-21 days useful indicator of liver function Other causes of decrease : sepsis or multiple organ failure acute liver failure dietary
  • Slide 34
  • Anne Larson MD Tests Measuring Synthetic Function Number Connection Test liver is site of detoxification failure leads to toxins in blood toxins unknown encephalopathy is sign of liver synthetic failure
  • Slide 35
  • Anne Larson MD The Approach Important questions to address: acute vs. chronic ( 6 months, ?cirrhosis) hepatocellular vs. cholestatic asymptomatic vs. symptomatic ?impaired function recent insults to the liver? EtOH, medications, pregnancy, hepatitis, herbs, gallstones, hypotension, toxins
  • Slide 36
  • Anne Larson MD The Approach Hepatocellular Injury mainly AST & ALT +/- AP, GGT, bilirubin 2 enzyme elevations high likelihood of liver dz guides: Mild (10x normal; usually >1,000) ischemic, viral, toxic (e.g., acetaminophen, herbs)
  • Slide 37
  • Anne Larson MD The Approach Cholestatic Liver Disease mainly alkaline phosphatase & GGT +/- bilirubin determine source of AP determine fraction of bilirubin elevated if all indirect, generally not liver ultrasound and/or CT scan to rule out obstructive disease, tumors, gallstones
  • Slide 38
  • Anne Larson MD The Approach Chronic Liver Disease 6 months of abnormal liver tests symptoms asymptomatic majority of cases fatigue arthralgias pruritis jaundice
  • Slide 39
  • Anne Larson MD The Approach Chronic Liver Disease cont. Common Causes 95% of cases: Hepatitis C - (+) HCV-Ab and HCV-PCR Hepatitis B (+) HBsAg and HBV-DNA Alcoholic liver disease Hemochromatosis fasting Fe/TIBC >50%; ferritin Autoimmune hepatitis (+) ANA, (+) ASMA, IgG
  • Slide 40
  • Anne Larson MD The Approach Chronic Liver Disease cont. Less Common Causes Primary Biliary Cirrhosis (PBC) - (+) AMA; IgM Primary Sclerosing Cholangitis (PSC) abnormal ERCP Wilsons Disease ( ceruloplasmin) 1 -Antitrypsin Deficiency ( 1 AT level) Drugs (i.e., MTX, INH, amiodarone, met