liver function tests lecture 3. anatomy of liver
TRANSCRIPT
Liver function tests
Lecture 3
ANATOMY OF LIVER
LIVER HISTOLOGY
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
BILIRUBIN
• 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)
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
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.
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
• 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).
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
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.
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
GGT• Tissue distribution
– Kidney– Brain– Prostate– Pancreas– Liver
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
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
Jaundice• Yellow discoloration of skin and sclera is
known as jaundice.– Hemolysis (neonatal jaundice)– Failure of conjugating mechanism within
hepatocytes– Obstruction in biliary system
Function testPre-hepatic
JaundiceHepatic Jaundice
Post-hepatic Jaundice
Total bilirubin Increased Increased Increased
Conjugated bilirubin Normal Increased Increased
Unconjugated bilirubin Increased Increased Increased
Urobilinogen Normal / Increased Increased Decreased / Negative
Urine Color Normal (urobilinogen)Dark (urobilinogen + conjugated bilirubin)
Dark (conjugated bilirubin)
Stool Color Normal Pale
Alkaline phosphatase levels
Normal Normal / Increased Incresed
Alanine transferase and Aspartate transferase
levelsIncreased
Normal / Increased
Conjugated Bilirubin in Urine
Not Present Present present
• Acute hepatitis– ALT
• Chronic hepatitis– Albumin, globulin
• Cirrhosis– ALP, albumin/ globulin
• Cholestasis– Bilirubin, ALT, ALP,
• Malignancy – ALT, ALP