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