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Evaluation of Liver Function. Dr. Baghbanian M. Gastroenterologist Shaheed Sadoughi hospital / 2012. 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.
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Evaluation of Liver Function Dr. Baghbanian M. Gastroenterologist ShaheedSadoughi hospital / 2012
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
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
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.
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.
Livertest • Bilirubin • aminotransferases • alkaline phosphatase • albumin • prothrombin time tests.
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
Tests Based on Detoxification and Excretory Functions • Serum Bilirubin • Blood Ammonia • Serum Enzymes
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.
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.
Isolated unconjugatedhyperbilirubinemia • is rarely due to liver disease • Causes: • hemolytic disorders • genetic conditions such as : • Crigler-Najjar • Gilbert's syndromes
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.
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
rate-limiting step in bilirubin metabolism • transport of conjugated bilirubin into the bile canaliculi • not conjugation
Fractionation of the bilirubin • rarely helpful in determining the cause of jaundice • Except : purely unconjugatedhyperbilirubinemia,.
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.
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.
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 )
Elevated ammonia levels • Has very poor correlation with: • presence or severity of acute encephalopathy • hepatic function.
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.
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
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.
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)
AST is found in • Liver • cardiac muscle • skeletal muscle • kidneys • brain • pancreas • lungs • leukocytes, and erythrocytes
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.
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.
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.
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.
The pattern of the aminotransferase • acute hepatocellulardisorders: ALT ≥ AST. • chronic viral hepatitis : ALT ≥ AST • cirrhosis : AST ≥ ALT
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.
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.
Enzymes that Reflect Cholestasis • Are usually elevated in cholestasis • Alkaline phosphatase • 5'-nucleotidase • Gama glutamyltranspeptidase (GGT)
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.
Serum alkaline phosphatase • found in : • Liver • Bone • Placenta • Small intestine
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 )
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
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
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.
isolated elevations of the alkaline phosphatase • Hodgkin's disease • diabetes • hyperthyroidism • congestive heart failure • amyloidosis • inflammatory bowel disease.
Level of ALKP ISNOT helpful in distinguishing • between intrahepatic and extrahepaticcholestasis • obstructive jaundice due to cancer, common duct stone, sclerosingcholangitis, or bile duct stricture.
Alkaline phosphataseincreased in : • intrahepaticcholestasis due to drug-induced hepatitis • primary biliary cirrhosis • rejection of transplanted livers • rarely, alcohol-induced steatohepatitis.
Serum alkaline phosphatase • Greatly elevated in hepatobiliary disorders in AIDS • AIDS cholangiopathy due to cytomegalovirus or cryptosporidial infection • tuberculosis with hepatic involvement
Serum Albumin • Synthesized exclusively by hepatocytes. • Long half-life: 18–20 days • Not a good indicator of acute or mild hepatic dysfunction (slow turnover)
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.
Serum Globulins • Immunoglobulins produced by B lymphocytes • Globulins are increased in chronic hepatitis and cirrhosis.
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.
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.