2. Battery of tests
Liver function tests are useful for
• the diagnosis
• assessment of prognosis
• monitoring of liver diseases.
Liver carries out diverse functions
So a battery of tests are needed.
3. Liver functions
1. Excretory function
Liver is involved in the uptake, conjugation
and excretion of bilirubin derived from
degradation of heme in reticuloendothelial
system.
The conjugated bilirubin is excreted via bile.
Liver also detoxifies ammonia, drug
metabolites and xenobiotics.
4. 2.Metabolic functions
carbohydrate metabolism- glycogen metabolism,
gluconeogenesis, blood glucose maintenance.
Lipid metabolism
Cholesterol metabolism, bile acid synthesis,
metabolism of lipoproteins, VLDL synthesis, synthesis
of triacyglycerol .
Protein metabolism
Catabolism of proteins, synthesis of non- essential
amino acids, formation of urea from ammonia
5. 3 . Synthesis of plasma
proteins
Liver synthesizes albumin,
coagulation factors such as
prothrombin.
4. Storage function
Vitamin A, D, K, B12 , Iron as
Ferritin are stored in liver.
6. Serum Enzymes
Serum enzymes
In liver cell damage, liver tissue enzymes
leak into circulation and their levels are
increased in plasma.
Aspartate transaminase (AST)
Alanine transaminase (ALT)
Alkaline phosphatase(ALP)
Gamma glutamyl transpeptidase (GGT)
7. Bilirubin metabolism
Heme is degraded in reticuloendothelial system
Iron is reutilized.
Globin protein – catabolized into amino acids
The bilirubin is formed from porphyrin ring of
heme which is water insoluble
It is called unconjugated bilirubin.
Unconjugated bilirubin is transported by albumin
to liver.
8. Role of liver
It is involved in the uptake of
unconjugated bilirubin and conjugates
them to bilirubin diglucuronide by the
enzyme UDP-glucuronyl transferase
using UDP- glucuronic acid, the active
donor of glucuronyl units. The
conjugated bilirubin is water soluble
and excreted in bile.
9. In the intestine- Conjugated bilirubin
gets deconjugated by bacterial beta-
glucuronidase enzyme in the terminal
ileum and large intestine.
The pigment is further reduced by fecal
flora to a group of colorless, tetra pyrrolic
compounds known as urobilinogens.
A small fraction of urobilinogens is
absorbed in the terminal ileum and re-
excreted by liver.
This is called enterohepatic circulation.
10. Then some of the urobilinogens being
water soluble, escape into urine normally.
In the intestine, further reduction of
urobilinogens form stercobilinogen which
is excreted in feces.
Some Urobilinogen gets back to liver
and reexcreted into intestine via bile . This
is enterohepatic circulation.
Oxidized products form urobilin and
stercobilin which are yellow colored.
11. Jaundice is the yellowish discoloration of
skin , mucous membrane and sclera.
It is due to hyperbilirubinemia. Normal
serum bilirubin level is 0.2 - 1 mg/dl.
Hyperbilirubinemia may be of conjugated or
unconjugated or both.
Normal serum unconjugated bilirubin level
is 0.2-0.8 mg/dl and conjugated bilirubin
level is 0.2-0.4 mg/dl.
Jaundice clinically appears when the serum
bilirubin level goes beyond 3 mg/dl.
12.
13. Vanden bergh test
Bilirubin reacts with diazotized sulfanilic acid to form
purple colored complex azobilirubin.
Conjugated bilirubin gives color in aqueous medium
immediately and is direct positive.
Unconjugated bilirubin, in methanol only color develops
and is indirect positive.
If both fractions are there, the color developed in aqueous
medium deepens on adding methanol and is called
biphasic.
Van den Bergh test is indirect positive in hemolytic
jaundice, direct positive in obstructive jaundice and
biphasic in hepatic jaundice.
14. Hemolytic Jaundice
Hemolytic jaundice or pre-hepatic jaundice or
unconjugated hyperbilirubinemia
Investigations
Serum unconjugated bilirubin is increased.
Urine bile salts and bile pigments will be negative.
So it is called as acholuric jaundice.
Urine urobilinogen will be excess.
Motion is high colored (dark brown).
Causes
Hemolytic anemia, hemoglobinopathies, mismatched
blood transfusion.
15. Inborn errors
Gilbet’s syndrome (GS): is the most common
hereditary cause of increased bilirubin
characterized by elevated levels of unconjugated
bilirubin in the bloodstream.
Enzyme glucuronyltransferase deficiency.
Crigler Najjar syndrome: It is a rare , AR disorder
with high levels of unconjugated
hyperbilirubinemia affecting brain.
UDP- glucuronyl transferase enzyme is defective.
16. Obstructive jaundice or post hepatic jaundice
or conjugated hyperbilirubinemia
Serum conjugated bilirubin is increased.
Urine bile salts, bile pigments will be positive.
Urine urobilinogen will be less or absent.
Motion is clay colored.
Causes
Biliary duct obstruction - due to gall stones,
tumor in the bile duct, carcinoma head of
pancreas, lymph node enlargement in porta
hepatis,
17. Inborn errors
Dubin Johnson syndrome : AR disorder
Increase of conjugated bilirubin in the serum without
elevation of liver enzymes (ALT, AST).
Defective secretion of conjugated bilirubin into the
bile. Liver cell are pigmented.
Rotor syndrome . Rare , AR disorder with increase in
conjugated bilirubin
similar to Dubin Johnson syndrome except that the
liver cells are not pigmented.
18. Hepatic jaundice
Both unconjugated and conjugated bilirubin levels
are increased in serum.
Urine bile salts, bile pigments are positive.
Urine urobilinogen is lesser than normal amounts.
Motion is pale yellow colored.
Causes
Alcoholic hepatitis, viral hepatitis, drug induced
intra hepatic cholestasis.
19. Tests based on synthesis of plasma
proteins
Serum albumin level - half- life is 20 days.
In liver cirrhosis, albumin level is decreased.
Normal serum albumin level is 3.5-4.5 gm/dl
and globulin level is 2.5-3.5 gm/dl.
Normal albumin globulin ratio (AG ratio) is
1.2 to 1.8 :1 . In cirrhosis, AG ratio is reversed
Serum globulins are increased in chronic
active hepatitis and cirrhosis of liver.
20. Prothrombin time
Normal – 10-14 secs.
In liver dysfunction, it is prolonged.
It is not recovered by Vitamin K
administration.
In vitamin K deficiency due to obstructive
jaundice also, there will be prolonged
prothrombin time
But that will recover after parenteral
administration of vitamin K.
21. Tumor marker- α-feto protein (AFP) is elevated in
hepatocellular carcinoma.
Ceruloplasmin
Its level is decreased in Wilson’s disease.
Serum protein electrophoresis
In cirrhosis of liver, albumin is decreased and gamma
globulins are increased.
In biliary obstruction, α2 and β2 globulins are
increased.
22. Serum enzymes
Hepatocellular damage
Serum amino transferases- Aspartate amino transferase
(AST) and Alanine amino transferase (ALT) are
elevated.
Normally both are lesser than 40 U/L.
In acute hepatitis, may increase to more than 1000 U/L.
ALT is found in cytosol and is more liver specific.
AST/ALT ratio is lesser than 1.
But in alcoholic hepatitis, AST is increased more than ALT
and the ratio is more than 2. This is due to release of AST
from mitochondria.
23. Obstructive liver disease
Serum alkaline phosphatase (ALP) level is increased in
case of cholestasis, hepatic carcinoma and biliary tract
obstruction.
ALP is present in bone, liver, intestine and placenta.
In the absence of bone disease or pregnancy, ALP elevation
indicates cholestasis.
Gamma glutamyl transferase (γ-GT) level is increased in
obstructive jaundice.
Its level is a sensitive biomarker of alcohol abuse or
alcoholic liver disease.
5-nucleotidase enzyme is increased in hepatobiliary
disease.
24. Blood ammonia
It is increased in severe
hepatocellular damage either
acute or chronic. Normal blood
ammonia level - 15- 60 µg/dl.
Serum bile acids
They are increased in liver
disease with cholestasis.
25. Bromosulphathalein (BSP) excretion test
BSP dye (5mg/kg, 5% w/v solution ) given by
intravenous route is rapidly removed by liver and
excreted in bile.
Normally 95% of dye is cleared within 45 minutes
only less than 5% of dye is found in blood after 45
min.
In hepatic dysfunction, it is more than 5%.
Higher level of dye after 2 hours than at 45 min
due to secondary rise is diagnostic of Dubin
Johnson syndrome.
27. Unconjugated Conjugated
Hemolytic anemia Obstruction of biliary
tree
Physiological jaundice Dubin-Johnson
syndrome
Crigler-Najjar
syndrome type I & II
Rotor syndrome
Gilbert syndrome Hepatitis (Both)
-conj and unconj
Toxic
hyperbilirubinemia
28. Flow Chart - Jaundice
J (suspected)
History
Clinical examination
VD Berg test
Sr.Bili. – Total/Difference (CHB/UCHB)
Total Bili. Increased Total bili. Increased
UCHB increased CHB increased
VD Berg test VD Berg test
(indirect +ve) Direct +ve
Hemo Jaundice Obst. J. + HC.J
29. Obst. J+ HC.J
Sr.ALP (Crucial test)
>35 <35
?. Obst.J HC.J
1. Sr.Trans (<300) Sr.Trans. (>300)
2. Sr.ALP increased Sr.GGT increased
3. PT after iv vit.k – normal PT even after vit.k
abnormal
4. Urine – bilirubinuria Urine – bili. + or -
5. Urobilinogen – neglibile Serological tests
or absent
30. Bio-Chem tests
Lab tests – determined severity of J
Its type whether obstructive or HC
1. Vanden Berg reaction
- direct
- indirect
2. Bilepigments in urine
- may be detected even before clincial jaundice
is noticed
- bili is found in urine – Obstr. Jaundice
- not found in urine – hemolytic jaundice
3. Feces – bili is not found in normal
Found in children, neo mycin, meconiun
31. Urobilinogen
Faecal (50-250 mg/day)
Increased in hemo.J
Absent in Obst.J
Complete absent in maligancy
Urine (<4 mg/day)
Obstr.J - no urobilinogen
Hemolytic J – increased urobilinogen with no
bilirubin