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31 Cards in this Set
- Front
- Back
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Aminotransferases: function, location, hepatic injury
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AST (aspartate) / ALT (alanine
Function: Intracellular aminotransferring enzymes in the process of gluconeogenesis -Aspartate Aminotransferase (AST) --Aspartic acid to Oxaloacetic acid -Alanine Aminotransferase (ALT) --Alanine to Pyruvic acid Location: Present in large quantities in hepatocytes -AST is both cytosolic and a mitochondrial isoenzyme -ALT is a cytosolic enzyme Hepatic injury: “Leak” in serum secondary to hepatocyte injury / death -Elevation in many forms of liver disease -Highest in those with severe hepatocyte necrosis (rather than biliary obstruction) |
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Aminotransferases: sensitivity, specificity
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Sensitivity:
-Both abnormal in most cases of significant liver disease -Often normal in advanced cirrhosis Specificity: -AST less specific (found in skeletal and cardiac muscle too) -ALT more specific for hepatocyte necrosis (predominant location is in liver) |
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Aminotransferases: diagnostic value for liver damage
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Level of Elevation:
-Correlates poorly with extent of necrosis on biopsy and not predictive of prognosis -But serial measurements can be of value -Fulminant hepatitis: --Rapid AST & ALT fall with rising bilirubin and PT --Poor prognosis < 500 IU could be many disorders >2000 IU could be limited differential |
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Aminotransferases: very high levels
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>2000 IU/L
Acute drug- or toxin-induced hepatitis -acetaminophen -Halothane -Amanita mushrooms -CCl4 Hepatic ischemia (shock liver) Acute viral hepatitis |
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Time course of ALT elevation
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Ischemia and toxin induced liver disease
-ALT rises rapidly in several days -Often rapidly improves -No correlation between level of ALT and level of damage Viral/drug -ALT rises slowly |
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Aminotransferases: alcoholic hepatitis
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AST/ALT ratio > 2:1
-Suggestive of alcoholic liver disease - >3:1 is even more specific -Mainly reflects low ALT level -Alcohol-related deficiency of pyridoxine AST & ALT should be < 300 IU/L -If AST > 500 IU/L, rule out co-existing cause --Acetaminophen toxicity --Viral hepatitis |
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Lactate dehydrogenase: when is it elevated, specificity, uses
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LDH elevation:
-Liver, acute & chronic -Muscle injury --Skeletal --Cardiac -Hemolysis -CVA -Kidney infarction Very non-specific - Rarely useful in addition to aminotransferases Occasionally helpful - Ischemic hepatitis: massive elevation -Malignant infiltration: sustained elevation |
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Alkaline phosphatase: function, levels, tissue sources, when elevated
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Group of enzymes that function best at pH 9
Levels are age dependent Increased due to overproduction and leakage into serum Bone disease: -Bone cell production (osteoblastic) Liver disease: -Biliary tract obstruction -Infiltrating disease (tumor) -Occasionally alcoholic hepatits |
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Alkaline phosphatase: hepatic location, serum elevation, serum half life
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Location:
-Hepatocyte: canalicular membrane -Bile duct epithelium: luminal membrane Serum elevation -Increased synthesis -Increased release Serum ½ life: 1 week -Levels may take days to normalize after resolution of obstruction |
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Gamma glutamyl transpeptidase (GGT): location, inducibility
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Location:
-Liver -Not found in bone --Helpful confirming elevated alk phos to be of liver origin Microsomal enzyme -Inducible by EtOH & drugs |
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5 nucleotidase: sensitivity, associated liver disease, use
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Similar sensitivity to alkaline phos for obstructive and infiltrative processes
-Overproduction and leakage into serum Extra and intrahepatic cholestasis, diffuse infiltrating disease (tumor), occasionally alcoholic hepatitis Like GGT, can be used to confirm elevated alk phos to be of liver origin |
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Albumin: synthesis, serum half life, factors affecting levels
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Liver synthesizes 10 g/day
-Liver disease (chronic liver failure): decreased synthesis Serum ½ life is 20 day -No change in acute liver injury -Not useful to follow progress Other factors affecting albumin levels: -Nutritional status -Volume status -Vascular integrity -Increased catabolism -Urinary losses |
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Prothrombin time: hemostasis, prolongation
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Hemostasis
-Coagulation factors synthesized in the liver -Not factor VIII (vascular endo / reticuloendo) PT prolongation: -Vitamin K deficiency (malabsorption, malnutrition, antibiotics) -Warfarin (Coumadin) -DIC (will have low factor VIII levels) -Liver disease: --Synthetic: Acute or chronic liver failure --Cholestatic: Biliary obstruction |
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Child-Pugh criteria
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Predict overall function of liver
Bilirubin -1 Pt: <2 -2 Pt: 2-3 -3 Pt: >3 Albumin -1 Pt: >3.5 -2 Pt: 2.8-3.5 -3 Pt: <2.8 PT -1 Pt: 1-3 -2 Pt: 4-6 -3 Pt: >6 Ascites -1 Pt: none -2 Pt: slight -3 Pt: moderate Encephalopathy -1 Pt: none -2 Pt: 1-2 -3 Pt: 3-4 Grade A = 5-6 pts Grade B = 7-9 pts Grade C = 10-15 pts |
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MELD Score
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Try to determine potential mortaility of patients
=3.8(log bilirubin)+11.2(log INR)+9.6(log creatinine)+6.4 |
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Sources of bilirubin
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Arises from breakdown of hemoglobin (80%)
Hepatic enzymes and other proteins (20%) Heme acted on by heme oxygenase forming biliverdin Biliverdin converted to bilirubin by biliverdin reductase Bilirubin in bloodstream is hydrophobic and isn't excreted by liver -Unconjugated Bilirubin converted by liver into conjugated bilirubin which is water soluble -Passes through biliary system into intestines |
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Bilirubin metabolism
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Bilirubin in bloodstream is hydrophobic and unconjugated
Picked up by liver and attached to ligandin (carrier protein) Brought to ER to be conjugated by UDP transferase to bilirubin monoglucuronide (20%) and bilirubin diglucuronide (80%) Excreted into canaliculus |
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Physiologic jaundice of the newborn
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Some infants born with insufficient amount of UDP transferase causing increase in unconjugated bilirubin
Transient |
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Breastmilk jaundice
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Moms have enzymes that affect UDP transferase
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Gilbert's syndrome
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Autosomal dominant
-10% of population -Caucasians Liver histology and chemistries normal Elevated unconjugated bilirubin -Not very significant In fasting states the bilirubin rises When fasting state is over, bilirubin falls to baseline May have inpairment in transport of bilirubin into liver Main problem is decreased levels of UDP transferase that manifests itself predominantly during periods of fasting |
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Crigler-najjar syndrome
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Decreased UDP transferase
Type I has not UDP transferase -Chance of survival depends on liver transplant or chronic phototherapy Type II has markedly decreased levels of UDP transferase (more than in Gilbert's) |
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Dubin-johnson syndrome
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Able to convert bilirubin but have problems excreting conjugated bilirubin into biliary system due to disorder of transport protein
Diffuse brown pigment on liver biopsy |
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Bilirubin metabolism disorders: laboratory data
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Indirect bilirubin elevated
Direct normal to slightly increased No bilirubin in urine AST/ALT normal ALP normal |
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Hepatocellular disorders: laboratory data
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Indirect and direct bilirubin elevated
Bilirubin in urine Very elevated AST/ALT ALP elevated |
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Cholestatic disorders: laboratory data
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Indirect bilirubin normal to elevated
Direct bilirubin elevated Bilirubin in urine ALP increased? |
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Disorders of bilirubin metabolism
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Increased bilirubin production
-Hemolysis, ineffective erythropoesis, massive transfusion, hematoma resorption Decreased bilirubin conjugation -Physiologic jaundice of the newborn, Gilbert’s syndrome, Crigler-Najjar syndrome Decreased bilirubin secretion -Dubin-Johnson syndrome, Rotor’s syndrome |
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Hepatocellular disorders
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Viral hepatitis (A,B,C,D,E)
Alcohol Medication-induced liver disease Ischemic liver injury Nonalcoholic Steatohepatitis (NASH) Autoimmune hepatitis Hemochromatosis Wilson’s disease Alpha-1 Antitrypsin Deficiency Acute Fatty Liver of Pregnancy |
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Cholestatic disorders
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Extrahepatic bile duct obstruction
-Choledocholithiasis -Pancreas cancer, cholangiocarcinoma Primary sclerosing cholangitis Primary biliary cirrhosis Intrahepatic cholestasis -Medication-induced, TPN, sepsis, post-op -Intrahepatic cholestasis of pregnancy Infiltrative disorders -Sarcoid, amyloid, infection, neoplasm |
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History in evaluation of abnormal liver tests
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Associated fever or weight loss
Use of alcohol Risk factors for viral hepatitis (S/D/R&R) History of jaundiced illness Prior biliary tract surgery Medications Family history of liver disease |
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Physical exam in evaluation of abnormal liver tests
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Jaundice
Spider angiomata Confusion/asterixis Gynecomastia Palpable left lobe of liver Splenomegaly Ascites |
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Clinical approach to jaundiced patient
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ALP or ALT/AST abnormal?
-No: Evaluate for hemolysis, hereditary hyperbilirubinemia If yes, evaluated clinical likelihood of biliary obstruction -If none: Biochemical studies for specific liver disease If yes, abdominal ultrasonogram (or CT scan) -If nondilated bile ducts: Biochemical studies for specific liver disease If dilated bile ducts: ERCP, MRCP, or PTC -If no biliary obstruction, biochemical studies for specific liver disease If no biliary obstruction -Therapeutic intervention |
