Evaluation of Liver Function

1. Evaluation of Liver Function Dr. Baghbanian M. Gastroenterologist ShaheedSadoughi hospital / 2012

2. liver tests (1) detect the presence of liver disease (2) distinguish different types of liver disorders (3) extent of liver damage (4) follow the response to treatment

3. Livertests • Can be normal in serious liver disease • Can be abnormal in non hepatic diseases • Rarely suggest a specific diagnosis • They suggest a general category of liver disease, such as hepatocellularor cholestatic

4. liver carries out thousands of biochemical functions • most cannot be easily measured by blood tests. • Laboratory tests measure only a limited number of these functions.

5. Aminotransferases /Alkalinephosphatase • do not measure liver function at all. • Rather, they detect: • liver cell damage • interference with bile flow. • Thus, no one test FOR assess the liver's total functional capacity.

6. Livertest • Bilirubin • aminotransferases • alkaline phosphatase • albumin • prothrombin time tests.

7. USE MULTIPLE TEST for detection of liver disease • probability of liver disease is high When : • more than one of these tests are abnormal • tests persistently abnormal on serial determinations • probability of liver disease is lowWhen: • all test results are normal

8. Tests Based on Detoxification and Excretory Functions • Serum Bilirubin • Blood Ammonia • Serum Enzymes

9. Serum Bilirubin • breakdown product of the porphyrinof heme-containing proteins • two fractions: • Conjugated = direct • water soluble • excreted by the kidney. • Unconjugated = indirect • insoluble in water • bound to albumin in the blood.

10. Normal Serum Bilirubin • Total = 1 - 1.5 mg/dL. • Direct <15% of the total → considered indirect • upper limit of normal for conjugated = 0.3 mg/dL.

11. Isolated unconjugatedhyperbilirubinemia • is rarely due to liver disease • Causes: • hemolytic disorders • genetic conditions such as : • Crigler-Najjar • Gilbert's syndromes

12. bilirubin elevated but <15% direct • should prompt a workup for hemolysis • In the absence of hemolysis, an isolated, unconjugatedhyperbilirubinemia in an otherwise healthy patient can be attributed to Gilbert's syndrome, and no further evaluation is required.

13. conjugated hyperbilirubinemia • always implies liver or biliary tract disease. • In most liver diseases, both conjugated and unconjugated fractions of the bilirubin tend to be elevated

14. rate-limiting step in bilirubin metabolism • transport of conjugated bilirubin into the bile canaliculi • not conjugation

15. Fractionation of the bilirubin • rarely helpful in determining the cause of jaundice • Except : purely unconjugatedhyperbilirubinemia,.

16. Degree of elevation of bilirubin • not as a prognostic marker • But is important in : • viral hepatitis: higher bilirubin→ greater hepatocellulardamage. • alcoholic hepatitis: Total serum bilirubin correlates with poor outcomes • component of the Model for End stage Liver Disease (MELD) • drug-induced liver disease: elevated total serum bilirubinindicates more severe injury.

17. Urine Bilirubin • Unconjugatedbilirubinbinds to albumin in the serum and is not filtered by the kidney. • any bilirubinin urine is conjugated bilirubin; • the presence of bilirubinuria implies the presence of liver disease. • In patients recovering from jaundice, the urine bilirubin clears prior to the serum bilirubin.

18. Blood Ammonia • is produced • during normal protein metabolism • intestinal bacteriainthe colon. • liver plays : detoxification of ammonia by converting it to urea→ excreted by the kidneys • Striated muscle →detoxification of ammonia(combination with glutamic acid )

19. Elevated ammonia levels • Has very poor correlation with: • presence or severity of acute encephalopathy • hepatic function.

20. Elevated ammonia levels • occasionally useful for occult liver diseasein mental changes. • correlate with outcome in fulminant hepatic failure. • in severe portal hypertension and shunting around the liver even in normal or near-normal hepatic function.

21. Serum Enzymes • The liver contains thousands of enzymes • These enzymes have no known function • probably cleared by reticuloendothelial cells • liver cells damage → entrance of Enzymes into serum

22. 3 type of LIVER enzyme tests • enzymes whose elevation reflects damage to hepatocytes 2) enzymes whose elevation reflects cholestasis 3) enzyme tests that do not fit either pattern.

23. Enzymes that Reflect Damage to Hepatocytes • include: • aspartateaminotransferase (AST) = serum glutamicoxaloacetictransaminase(SGPT) • alanineaminotransferase (ALT) = serum glutamicpyruvictransaminase(SGPT) • sensitive indicators of liver cell injury • most helpful in recognizing acute hepatocellular diseases (hepatitis)

24. AST is found in • Liver • cardiac muscle • skeletal muscle • kidneys • brain • pancreas • lungs • leukocytes, and erythrocytes

25. ALT is found primarily in the liver and is more specific for liver injury. • The aminotransferases are normally present in the serum in low concentrations.

26. Aminotransferases • damage to the liver cell → enzymes release into blood • Liver cell necrosis is not required • poor correlation with degree of liver cell damage • not prognostic in acute hepatocellular disorders.

27. Levels of aminotransferases • normal : 10-40 U/L. • <300 U/L are nonspecific and may be found in any type of liver disorder. • Minimal ALT elevations in asymptomatic blood donors rarely indicate severe liver disease; fatty liver is the most cause.

28. Aminotransferases >1000 U/L • Extensive hepatocellular injury such: • viral hepatitis • ischemic liver injury (prolonged hypotension or acute heart failure) • toxin- or drug-induced liver injury.

29. The pattern of the aminotransferase • acute hepatocellulardisorders: ALT ≥ AST. • chronic viral hepatitis : ALT ≥ AST • cirrhosis : AST ≥ ALT

30. Alcoholic liver disease • AST/ALT >2:1 is suggestive • AST/ALT >3:1 is highly suggestive • The AST is rarely >300 U/L • ALT is often normal. • A low level of ALT in the serum is due to an alcohol-induced deficiency of pyridoxal phosphate.

31. Aproach to asymptomatic elevation of serum aminotransferase

32. Obstructive jaundice • Aminotransferases not greatly elevated • Exception: passage of a gallstone into the common bile duct → acute biliaryobstruction → aminotransferases 1000–2000 → decrease quickly → liver-function tests rapidly evolve typical of cholestasis.

33. Aproach to isolated elevation of bilirubin

34. Enzymes that Reflect Cholestasis • Are usually elevated in cholestasis • Alkaline phosphatase • 5'-nucleotidase • Gama glutamyltranspeptidase (GGT)

35. Gama glutamyltranspeptidase (GGT) • GGT is more diffuse in liver→ is less specific for cholestasis than alkaline phosphatase or 5'-nucleotidase. • GGT in occult alcohol use? • lack of specificity / questionable.

36. Serum alkaline phosphatase • found in : • Liver • Bone • Placenta • Small intestine

37. ALKP non pathologically elevated • Age > 60 • Blood types O and B after fatty meal (influx of intestinal ALKP into the blood.) • Children and adolescents undergoing rapid bone growth, (bone) • Late in normal pregnancies (influx of placental )

38. Elevation of liver-derived alkaline phosphatase • Not specific for cholestasis • < 3 foldoccur in : • any type of liver disease. • >4 fold occur in: • cholestaticliver disorders • infiltrative liver diseases such as cancer and amyloidosis

39. If an elevated ALKP is only finding • First aproach : ALKP electrophoresis. • Second approach : inactivation by heat • heat-stable : placenta or a tumor is the source. • heat –unstable: intestinal, liver, and bone • measurement of serum 5'-nucleotidase or GGT

40. In the absence of jaundice or elevated aminotransferases, an elevated ALKP of liver origin • Often: early cholestasis • less often: hepatic infiltration by tumor or granulomata.

41. isolated elevations of the alkaline phosphatase • Hodgkin's disease • diabetes • hyperthyroidism • congestive heart failure • amyloidosis • inflammatory bowel disease.

42. Level of ALKP ISNOT helpful in distinguishing • between intrahepatic and extrahepaticcholestasis • obstructive jaundice due to cancer, common duct stone, sclerosingcholangitis, or bile duct stricture.

43. Alkaline phosphataseincreased in : • intrahepaticcholestasis due to drug-induced hepatitis • primary biliary cirrhosis • rejection of transplanted livers • rarely, alcohol-induced steatohepatitis.

44. Serum alkaline phosphatase • Greatly elevated in hepatobiliary disorders in AIDS • AIDS cholangiopathy due to cytomegalovirus or cryptosporidial infection • tuberculosis with hepatic involvement

45. Aproach to isolated elevation of ALKP

46. Serum Albumin • Synthesized exclusively by hepatocytes. • Long half-life: 18–20 days • Not a good indicator of acute or mild hepatic dysfunction (slow turnover)

47. Hypoalbuminemia • Common in chronic liver disorders such as cirrhosis than in acute liver disease • Reflects severe liver damage and decreased albumin synthesis. • is not specific for liver disease and occur in: • protein malnutrition • protein-losing enteropathies • nephrotic syndrome • chronic infections that inhibit albumin synthesis.

48. Serum Globulins • Immunoglobulins produced by B lymphocytes • Globulins are increased in chronic hepatitis and cirrhosis.

49. increased Serum Globulins • In cirrhosis: due to the increased synthesis of antibodies against intestinal bacteria. • Cause : cirrhotic liver fails to clear bacterial antigens that normally reach through the hepatic circulation.

50. Specific globulins are helpful in recognition of certain liver diseases • Diffuse polyclonal IgG ↑ in autoimmune hepatitis • IgM ↑in primary biliary cirrhosis • IgA ↑ in alcoholic liver disease.