Liver function tests
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Associate professor (Microbiology)
Dhaka Dental college , Dhaka.
Objectives
Discuss the biochemical tests which are done to assess the function of liver.
Enumerate and explain the biochemical basis of Liver Function tests.
Discuss the biochemical alterations in patients with jaundice.
LIVER:-
Largest solid organ, right upper quadrant.
Large reserve capacity.
Capable of regeneration.
Function of liver
1) Metabolic Function- Metabolism of fat, carbohydrate and protein.
2) Storage function- storage of vit. A, D, B12, folic acid, iron and glycogen.
3) Secretory function - Secretion of bile.
4) Synthetic function- synthesis of plasma protein, clotting factors-II, VII, IX, X.
5) Excretory function- excretion of certain drugs, billirubin, hormone etc.
.
Some examples of liver dysfunctions
• Hepato cellular diseases (viral hepatitis , ALD).
• Cholestatic disease (intra and extra hepatic obstruction).
• Cirrhosis.
• Cancer(secondary or primary)
• Fatty Liver
• Genetic Disorders
• Hemochromatosis (iron storage)
• Wilsons disease
Indication of liver function test
1) To assess the extent of liver damage.
2) To follow the progress of liver damage.
3) To find the possible complication.
Liver function tests can be categorized into—
i) Test based on detoxification and excretory function.
ii) Test for enzymes that reflect damage to hepatocytes.
iii)Test for enzymes that reflect cholestasis.
iv) Test that measure synthetic functions of liver.
A) Test based on detoxification and excretory function:
1) measurement of Serum billirubin level : determination of total, conjugated (direct) and
unconjugated bilirubin (indirect)
Normal value of total billirubin <1-1.5mg/dl
• Normal value of direct/conjugated : up to 15% of the total (upper limit = 0.3mg/dl
• Isolated elevation of UCB – bilirubin elevated but < 15% direct – Watch out for
hemolysis – if haemolysis is absent – Gilbert disease
• Conjugated hyper bilirubinemia – liver or biliary tract disease
• In most liver diseases both fractions are increased.
2) Urine Bilirubin :- any bilirubin found in urine is conjugated bilirubin, Bilirubinuria
implies the presence of liver disease.
3) Blood ammonia: Was used for detecting encephalopathy or for monitoring hepatic
synthetic function (poor corelation).
B) Test for enzymes that reflect damage to hepatocytes:
Aminno transferases (ALT and AST):
– AST(SGOT): Liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs,
leucocytes, and RBC - (Normal serum level 10-45 U/L ).
– ALT(SGPT): Liver-(Normal serum level 10-50U/L).
– Liver cell damage–increased permeability–increase serum levels.
– BUT poor correlation b/w liver cell damage and level of AST and ALT
– Up to 300 U/L–non specific / any type of liver disorder.
Aminno transferases (ALT and AST):
-- Levels>1000U/L extensive hepato cellular injury. (viral hepatitis, Ischemic Liver disease ,
Drug or Toxin induced).
-- In most acute hepato cellular damage ALT>AST
-- AST : ALT > 2:1 (suggestive) & > 3:1 (highly suggestive) of Alcoholic Liver Disease).
-- Amino transferases are usually not greatly elevated in Obstructive jaundice.
C) Test for enzymes that reflect cholestasis:
ALP(Alkaline phosphatase)
5’NT(Neucleotidase)
GGT (Gamma Gluteryl transferase)
ALP:- Normal level- 40-125 U/L
< 3 fold increase: not specific for cholestasis (seen in almost any type of liver disease)
>4 fold increase: cholestatic liver disorder, infilterative liver disease(Cancer), bone conditions
with rapid turnover of bone (Pagets disease)
ALP is NOT useful to distinguish b/w intra and extra hepatic obstruction.
D) Test that measure biosynthetic function of the Liver
1) Serum albumin:
– Synthesized exclusively by hepatocytes
– Half life --15-20days
– Not a good indicator of acute/mild hepatic dysfunction
– Minimum change in Viral hepatitis/drug induced hepatitis/ Obs. Jaundice
– In hepatitis Albumin levels less than 3gm/dl –suggested chronic liver disease.
– Other causes of decrease:
Protein malnutrition/ Protein losing enteropathies
Nephrotic syndrome/
Chronic infections
2) Coagulation factors:
Except for factor VIII, blood clotting factors are exclusively synthesized in hepatocytes.
T1/2 of factor VII- 6 hrs
Fibrinogen – 5days (shorter than albumin)
Rapid turnover –
(thus measurement of clotting factors is the single best acute measure of hapatic synthetic
function in the diagnosis and assessment of liver function in acute parenchymal liver
disease).
• Coagulation factors:
• What is measured
2) Prothrombin Time (PT) - collectively measures II/V/VII/X
Biosynthesis of factors II/VII/IX/X depends on Vit.K.
PT may be elevated in hepatitis, cirrhosis and disorders that result in Vit. K deficiency (eg
obstructive jaundice)
Markedly prolonged PT (>5 secs above control), not corrected by Vit. K is a poor
prognostic sign in acute viral hepatitis and other acute and chronic liver diseases.
Summary
Liver Function Clinical implication of abnormality
test
ALT Hepatocellular damage
AST Hepatocellular damage
Bilirubin Cholestasis, impair conjugation, or biliary
obstruction
ALP Cholestasis, infiltrative disease, or biliary
obstruction
PT Synthetic function
Albumin Syntheticf unction
GGT Cholestasis or biliary obstruction
5`-nucleotidase Cholestasis or biliary obstruction
Jaundice : May be defined as Yellow coloration of sclera, mucous membrane and skin due to
increased billirubin level ( above normal level – 0.3-1 mg/ml) in blood. ( more than 3 mg/ml).
Classification of jaundice-
1) predominantly UC Hyper billirubinaemia-
A) Excess production of billirubin-
a) haemolytic anaemia/
b) Resorption of blood from internal haemorrage- haematoma, post manupousal bleeding.
c) ineffective erythropoisis- thalassaemia; pernicious anaemia
B) Reduced hepatic uptake-
Gilberts Syndrome.
C) Impaired billirubin conjugation-
a) physiological jaundice
b) breast milk jaundice.
c) diffuse heoatocellular disease- viral hepatitis,drug induced hepatitis,
Pridominantly conjugated-
A) Decreased intra hepatic excreation of bile-
1) Hepatocellular damage eg viral hepatitis.
2) Dubin jonson syndrome
3) Oral contraceptives
4) Intrahepatic bile duct obstruction- primary billiary cirrhosis,
B) Extrahepatic billiary obstruction-
C) Obstruction by gall stone/
D) Carcinama head of pancrease
E) Others cyst atresia etc
Clinical classification of jaundice—
A) Haemolytic jaundice-
I. Haemolytic jaundice occurs due to excess breakdown of RBC leads to excess production
of billirubin.
II. mainly unconjugated billirubin in blood.
III. Juandice is mild ( serum billirubin level 4-6 mg/dl)
IV. unconjugated billirubin will not pass into urine.
V. urinary urobillinogen is increased.
VI. stool is dark due to presence of excess bile pigment.
VII. serum ALP, ALT, AST and albumin are normal .
Causes of Excess break down of RBC / haemolytic anaemia --
A) Intra corpuscular defect-
1) Hereditary –
a) Disorder in hemoglobin synthesis:
Thalassaemia
Haemoglobinopathies-
b) cell membrane defect—
Hereditary spherocytosis
Hereditary elliptocytosis-
c) Deficency of enzymes-
Glucose 6 phosphatase deficiency.
2) Acquired –
paroxysomal nocturnal haemoglobinuria.
B) Extra corpuscular defect—
1) immune mechanism-
i) Auto immune haemolytic anaemia
ii) Haemolytic disease of newborn.
iii) Mismatch blood transfusion.
iv) drug induced.
2) Non immune mechanism-
i) Mechanical – cardiac haemolytic anaemia , microangiopathic haemolytic
anaemia , March haemoglobinuria,
ii) Drugs and chemicals- Lead poisoning
iii) infection- malarial parasite
iv) severe burn.
2) Hepatocellular jaundice-
Occurs due to damage of hepatocytes.
Unconjugated and conjugated billirubin are increased.
causes are – Viral hepatitis.
Drugs
Chronic alcohol consumption .
Cirrhosis of liver.
3) Obstructive jaundice-- this is also called cholestasis.
A) Intra hepatic cause-
Viral hepatitis.
Drugs
Chronic alcohol consumption .
Cirrhosis of liver.
Pregnancy.
B) Extra hepatic-
Stone in CBD
Carcinoma of Head of pancrease.
Billiary stricture.
Comparison of different enzymes and level of serum billirubin in different types of jaundice---
Enzymes/ Haemolytic Hepatocellular Obstructive
billirubin jaundice jaundice jaundice
ALT(SGPT) Normal Highly Rised Low Raised
AST(SGOT) Normal Highly Rised Low Raised
ALP Normal Low Rised High
Serum Markedly Raised both Raised only
billirubin level increased mainly conjugated and conjugated
unconjugated unconjugated
W/Q --Difference between three types of jaundice -----------
