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Liver function tests Lecture 3.

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1 Liver function tests Lecture 3






7 LIVER FUNCTION TESTS Measurements 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 phosphatase Serum albumin (serum prothrombin Obstruction to biliary tract, acute hepatocellular damage, chronic liver disease



10 450 micro mole of bilirubin is formed daily.
Insoluble so bound to albumin Conjugation in liver hepatocytes to become soluble in water 25% 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 Aminotransferases Interconversion of amino acids and oxoacids by transfer of amino groups. Aspartate + a-ketoglutarate Oxaloacetate + glutamate Oxaloacetate + NADH + H Malate + NAD AST , 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
Spleen Lung erythrocyte. 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 to 8 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 + glutamate Pyruvate + NADH + H Lactate + NAD Clinical significance hepatocellular disorders ALT 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/L ALT

16 Alkaline phosphatase Tissue Source
ALP activity is present on cell surfaces in most human tissue. Intestine Liver (the enzyme is located on both sinusoidal and bile canalicular membranes Bone (osteoblasts) Spleen placenta, and kidney.

17 Clinical significance
Hepatobiliary and bone disorders Cholestasis Cirrhosis Tumours of liver Bone Paget’s disease (osteitis deformans) osteomalacia, rickets osteogenic sarcoma healing bone fractures periods of physiologic bone growth. Placental ALP in blood in third trimester

18 GGT Tissue distribution Kidney Brain Prostate Pancreas Liver

19 Clinical significance
Cholestasis Alcoholism two to three times the ULN Levels decline in abstinence but again start rising on resumption of drinking. Acute pancreatitis Diabetes mellitus MI GGT activity is useful in differentiating the source of an elevated ALP level because GGT levels are normal in skeletal disorders and during pregnancy male, 6 to 55 U/L female, 5 to 38 U/L

20 Plasma proteins Serum albumin half life 20 days
Hypoalbuminemia chronic liver disease severe Acute liver damage. Serum globulin levels Alpha 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 hepatocytes Obstruction in biliary system

22 Post-hepatic Jaundice
Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice Total bilirubin Increased Conjugated bilirubin Normal Unconjugated bilirubin Urobilinogen Normal / Increased Decreased / Negative Urine Color Normal (urobilinogen) Dark (urobilinogen + conjugated bilirubin) Dark (conjugated bilirubin) Stool Color Pale Alkaline phosphatase levels Incresed Alanine transferase and Aspartate transferase levels Conjugated Bilirubin in Urine Not Present Present present

23 Acute hepatitis ALT Chronic hepatitis Albumin, globulin Cirrhosis ALP, albumin/ globulin Cholestasis Bilirubin, ALT, ALP, Malignancy ALT, ALP

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