7 LIVER FUNCTION TESTSMeasurements of the blood components that simply provide a lead to existence, the extent and the type of liver damage.Bilirubin (Total bilirubin, Direct & Indirect)Aminotransferases (AST, ALT)Alkaline phosphataseSerum albumin (serum prothrombinObstruction to biliary tract, acute hepatocellular damage, chronic liver disease
10 450 micro mole of bilirubin is formed daily. Insoluble so bound to albuminConjugation in liver hepatocytes to become soluble in water25% monoglucuronide and 75% is di glucuronide of the total bile +traces of unconjugated bilirubin.When there is block in the biliary tract bilirubin is not excreted so serum concentration rises. (Jaundice)
11 AminotransferasesInterconversion of amino acids and oxoacids by transfer of amino groups.Aspartate + a-ketoglutarateOxaloacetate + glutamateOxaloacetate + NADH + H Malate + NADAST , ALT Pyridoxal-5′-phosphate (P5′P) functions as coenzyme in the amino transfer reactions. In all amino transfer reactions, 2-oxoglutarate and l-glutamate serve as one amino group acceptor and donor pair.AST
12 Tissue sources of AST Heart Liver Skeletal muscle Kidney Pancreas SpleenLungerythrocyte.Two distinct forms have been identified: a cytoplasmic, or soluble isoenzyme, and a mitochondrial isoform.
13 Clinical significance In AMI, AST levels begin to rise within 6 to8 hours, peak at 24 hours, and generally return to normal within 5 days.AST levels are not useful in the diagnosis of AMI.Clinical utility is limited to Hepatocellular disorders and skeletal muscle involvement.5 to 35 U/L
14 Pulmonary embolism.congestive heart failure AST levels also may be increased, probably reflecting liver involvement as a result of inadequate blood supply to that organ.acute hepatocellular disorders.In viral hepatitis, levels may reach 100 times the ULN.In cirrhosis, only moderate levels—approximately four times the ULN—are detected.Skeletal muscle disorders, such as the muscular dystrophies, and inflammatory conditions also cause increases in AST levels (4 to 8× ULN).
15 ALT Tissue distribution mainly liver Alanine + a-ketoglutarate Pyruvate + glutamatePyruvate + NADH + H Lactate + NADClinical significancehepatocellular disordersALT levels are compared with levels of AST to help determine the source of an elevated AST level and to detect liver involvement concurrent with myocardial injury.7 to 45 U/LALT
16 Alkaline phosphatase Tissue Source ALP activity is present on cell surfaces in most human tissue.IntestineLiver (the enzyme is located on both sinusoidal and bile canalicular membranesBone (osteoblasts)Spleenplacenta, and kidney.
17 Clinical significance Hepatobiliary and bone disordersCholestasis CirrhosisTumours of liverBonePaget’s disease (osteitis deformans)osteomalacia, ricketsosteogenic sarcomahealing bone fracturesperiods of physiologic bone growth.Placental ALP in blood in third trimester
19 Clinical significance CholestasisAlcoholism two to three times the ULNLevels decline in abstinence but again start rising on resumption of drinking.Acute pancreatitisDiabetes mellitusMIGGT activity is useful in differentiating the source of an elevated ALP level because GGT levels are normal in skeletal disorders and during pregnancymale, 6 to 55 U/L female, 5 to 38 U/L
20 Plasma proteins Serum albumin half life 20 days Hypoalbuminemia chronic liver diseasesevere Acute liver damage.Serum globulin levelsAlpha fetoprotein ( ˂ 20 µg/ L)(hepatocellular ca, germ cell tumours)Prothrombin time
21 Jaundice Yellow discoloration of skin and sclera is known as jaundice. Hemolysis (neonatal jaundice)Failure of conjugating mechanism within hepatocytesObstruction in biliary system