1. Liver function tests
Lecture 3

2. ANATOMY OF LIVER

3. LIVER HISTOLOGY

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

8. BILIRUBIN

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