Presentation on theme: "Evaluation of Liver Function"— Presentation transcript:
1Evaluation of Liver Function Dr. Baghbanian M.GastroenterologistShaheed Sadoughi hospital / 2012
2liver 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
3Liver tests Can be normal in serious liver disease Can be abnormal in non hepatic diseasesRarely suggest a specific diagnosisThey suggest a general category of liver disease, such as hepatocellular or cholestatic
4liver carries out thousands of biochemical functions most cannot be easily measured by blood tests.Laboratory tests measure only a limited number of these functions.
5Aminotransferases /Alkaline phosphatase do not measure liver function at all.Rather, they detect:liver cell damageinterference with bile flow.Thus, no one test FOR assess the liver's total functional capacity.
6Liver test Bilirubin aminotransferases alkaline phosphatase albumin prothrombin time tests.
7USE MULTIPLE TEST for detection of liver disease probability of liver disease is high When :more than one of these tests are abnormaltests persistently abnormal on serial determinationsprobability of liver disease is lowWhen:all test results are normal
8Tests Based on Detoxification and Excretory Functions Serum BilirubinBlood AmmoniaSerum Enzymes
9Serum Bilirubinbreakdown product of the porphyrin of heme-containing proteinstwo fractions:Conjugated = directwater solubleexcreted by the kidney.Unconjugated = indirectinsoluble in waterbound to albumin in the blood.
10Normal Serum Bilirubin Total = mg/dL.Direct <15% of the total → considered indirectupper limit of normal for conjugated = 0.3 mg/dL.
11Isolated unconjugated hyperbilirubinemia is rarely due to liver diseaseCauses:hemolytic disordersgenetic conditions such as :Crigler-NajjarGilbert's syndromes
12bilirubin elevated but <15% direct should prompt a workup for hemolysisIn the absence of hemolysis, an isolated, unconjugated hyperbilirubinemia in an otherwise healthy patient can be attributed to Gilbert's syndrome, and no further evaluation is required.
13conjugated hyperbilirubinemia always implies liver or biliary tract disease.In most liver diseases, both conjugated and unconjugated fractions of the bilirubin tend to be elevated
14rate-limiting step in bilirubin metabolism transport of conjugated bilirubin into the bile canaliculinot conjugation
15Fractionation of the bilirubin rarely helpful in determining the cause of jaundiceExcept : purely unconjugated hyperbilirubinemia,.
16Degree of elevation of bilirubin not as a prognostic markerBut is important in :viral hepatitis: higher bilirubin→ greater hepatocellular damage.alcoholic hepatitis: Total serum bilirubin correlates with poor outcomescomponent of the Model for End stage Liver Disease (MELD)drug-induced liver disease: elevated total serum bilirubin indicates more severe injury.
17Urine BilirubinUnconjugated bilirubin binds to albumin in the serum and is not filtered by the kidney.any bilirubin in 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.
18Blood Ammonia is produced during normal protein metabolismintestinal bacteriain the colon.liver plays : detoxification of ammonia by converting it to urea→ excreted by the kidneysStriated muscle →detoxification of ammonia(combination with glutamic acid )
19Elevated ammonia levels Has very poor correlation with:presence or severity of acute encephalopathyhepatic function.
20Elevated ammonia levels occasionally useful for occult liver disease in 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.
21Serum Enzymes The liver contains thousands of enzymes These enzymes have no known functionprobably cleared by reticuloendothelial cellsliver cells damage → entrance of Enzymes into serum
223 type of LIVER enzyme tests enzymes whose elevation reflects damage to hepatocytes2) enzymes whose elevation reflects cholestasis3) enzyme tests that do not fit either pattern.
23Enzymes that Reflect Damage to Hepatocytes include:aspartate aminotransferase (AST) =serum glutamic oxaloacetic transaminase (SGPT)alanine aminotransferase (ALT) =serum glutamic pyruvic transaminase(SGPT)sensitive indicators of liver cell injurymost helpful in recognizing acute hepatocellular diseases (hepatitis)
24AST is found in Liver cardiac muscle skeletal muscle kidneys brain pancreaslungsleukocytes, and erythrocytes
25ALT is found primarily in the liver and is more specific for liver injury. The aminotransferases are normally present in the serum in low concentrations.
26Aminotransferasesdamage to the liver cell → enzymes release into bloodLiver cell necrosis is not requiredpoor correlation with degree of liver cell damagenot prognostic in acute hepatocellular disorders.
27Levels of aminotransferases normal : 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.
28Aminotransferases >1000 U/L Extensive hepatocellular injury such:viral hepatitisischemic liver injury (prolonged hypotension or acute heart failure)toxin- or drug-induced liver injury.
29The pattern of the aminotransferase acute hepatocellular disorders: ALT ≥ AST.chronic viral hepatitis : ALT ≥ ASTcirrhosis : AST ≥ ALT
30Alcoholic liver disease AST/ALT >2:1 is suggestiveAST/ALT >3:1 is highly suggestiveThe AST is rarely >300 U/LALT is often normal.A low level of ALT in the serum is due to an alcohol-induced deficiency of pyridoxal phosphate.
31Aproach to asymptomatic elevation of serum aminotransferase
32Obstructive jaundice Aminotransferases not greatly elevated Exception: passage of a gallstone into the common bile duct → acute biliary obstruction → aminotransferases 1000–2000 → decrease quickly → liver-function tests rapidly evolve typical of cholestasis.
34Enzymes that Reflect Cholestasis Are usually elevated in cholestasisAlkaline phosphatase5'-nucleotidaseGama glutamyl transpeptidase (GGT)
35Gama glutamyl transpeptidase (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.
36Serum alkaline phosphatase found in :LiverBonePlacentaSmall intestine
37ALKP non pathologically elevated Age > 60Blood 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 )
38Elevation of liver-derived alkaline phosphatase Not specific for cholestasis< 3 fold occur in :any type of liver disease.>4 fold occur in:cholestatic liver disordersinfiltrative liver diseases such as cancer and amyloidosis
39If an elevated ALKP is only finding First aproach : ALKP electrophoresis.Second approach : inactivation by heatheat-stable : placenta or a tumor is the source.heat –unstable: intestinal, liver, and bonemeasurement of serum 5'-nucleotidase or GGT
40In the absence of jaundice or elevated aminotransferases, an elevated ALKP of liver origin Often: early cholestasisless often: hepatic infiltration by tumor or granulomata.
41isolated elevations of the alkaline phosphatase Hodgkin's diseasediabeteshyperthyroidismcongestive heart failureamyloidosisinflammatory bowel disease.
42Level of ALKP IS NOT helpful in distinguishing between intrahepatic and extrahepatic cholestasisobstructive jaundice due to cancer, common duct stone, sclerosing cholangitis, or bile duct stricture.
43Alkaline phosphatase increased in : intrahepatic cholestasis due to drug-induced hepatitisprimary biliary cirrhosisrejection of transplanted liversrarely, alcohol-induced steatohepatitis.
44Serum alkaline phosphatase Greatly elevated in hepatobiliary disorders in AIDSAIDS cholangiopathy due to cytomegalovirus or cryptosporidial infectiontuberculosis with hepatic involvement
46Serum Albumin Synthesized exclusively by hepatocytes. Long half-life: 18–20 daysNot a good indicator of acute or mild hepatic dysfunction (slow turnover)
47HypoalbuminemiaCommon in chronic liver disorders such as cirrhosis than in acute liver diseaseReflects severe liver damage and decreased albumin synthesis.is not specific for liver disease and occur in:protein malnutritionprotein-losing enteropathiesnephrotic syndromechronic infections that inhibit albumin synthesis.
48Serum Globulins Immunoglobulins produced by B lymphocytes Globulins are increased in chronic hepatitis and cirrhosis.
49increased 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.
50Specific globulins are helpful in recognition of certain liver diseases Diffuse polyclonal IgG ↑ in autoimmune hepatitisIgM ↑in primary biliary cirrhosisIgA ↑ in alcoholic liver disease.
51Coagulation Factors Are made exclusively in hepatocytes. Exception: factor VIII,(which is produced by vascular endothelial cells)
52Coagulation Factors Half-lives are shorter than albumin 6 h for factor VII to 5 days for fibrinogen.Single best acute measure of hepatic synthetic function FOR diagnosis and assessing the prognosis of acute parenchymal liver disease.
53Coagulation FactorsProthrombin time : measures factors II, V, VII, and X.(25710)Depends on vitamin K: synthesis of factors II, VII, IX, and X(29710)
54Prothrombin time May be elevated in : hepatitis cirrhosis vitamin K deficiencyobstructive jaundicefat malabsorption
55prothrombin time >5 s above control If not corrected by parenteral vitamin Kis a poor prognostic sign in acute viral hepatitis and other acute and chronic liver diseases.
56MELD (model of end stage liver disease) Allocate for liver transplantation.Has 3 component:INR,Total serum bilirubinCreatinine
57Percutaneous Liver Biopsy Is a safe procedureEasily performed at the bedsideWith local anesthesia and ultrasound guidance.
58Percutaneous Liver Biopsy Indication Hepatocellular disease of uncertain causeProlonged hepatitis (chronic active hepatitis)(3) Unexplained hepatomegaly(4) Unexplained splenomegaly(5) Hepatic filling defects IN imaging(6) Fever of unknown origin(7) Staging of malignant lymphoma
59Liver biopsyis most accurate in disorders causing diffuse changes IN liverSampling error in focal infiltrative disorders such as hepatic metastases.Should not be the initial procedure in cholestasis.
60Liver biopsy Contraindications Significant ascitesProlonged INRUnder these circumstances, the biopsy can be performed via the transjugular approach
61Ultrasonography First diagnostic test in cholestasis: dilated intrahepaticextrahepatic biliary treegallstones.space-occupying lesions IN liver, →distinguish between cystic and solid masses, and helps direct percutaneous biopsies.
62Ultrasound with Doppler Detect the patency of the :portal veinhepatic arteryhepatic veinsFirst test in patients suspected Budd-Chiari syndrome.
63Abnormal in...Liver TestCirrhosis, severe hepatocellular injuryAlbuminCholestasis, hepatocellular enzyme induction, canalicular injury, children during bone growth, bone disease, pregnancy (placenta origin)Alkaline phosphataseHepatocellular injury (ethanol, drug-induced hepatitis, hepatitis B and C, ischemic injury, chronic liver disease, NAFLD, chronic viral hepatitis, alcoholism, nonspecific viral injury, and cholestatic or replacement disease); acute biliary obstruction; rarely in hyperthyroidism, celiac disease, skeletal muscle diseaseAminotransferases (AST, ALT)Any acute or chronic liver disease; congenital disorders of bilirubin metabolism.BilirubinCholestasis5′ nucleotidaseCholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism, myotonic dystrophyGGTImpaired synthesis of vitamin K-dependent coagulation factorsINRIschemic injury, Epstein-Barr virus infection, hemolysis, solid tumorLactate dehydrogenaseAlcohol consumption, goutUric acid