lft (1).pdf liver function test ,it's types

Liver function test ,it's type,diagnosis

1. LIVER FUNCTION TESTS
(LFT)
LIVER
" Liver is the largest and most complex internal
organ of the body.
" The weight of liver is about 1.5kg.
It is located below the diaphragm in the right
upper quadrant of the abdominal cavity.
" All blood flows from intestine and pancreas
and reaches liver via portal venous system.

2. FUNCTIONS OF LIVER
Liver is a multifunctional organ that is
involved in diverse body functions.
1. Metabolic Functions
Liver actively participates in carbohydrate
metabolism, lipid, protein, mineral and
vitamin metabolisms.
2. Excretory Functions
Bile pigments, bile salts and cholesterol are
excreted in bile into intestine.
3. Protective functions & detoxification
Kupffer cells of liver perform phagocytosis to
eliminate foreign compounds. For example
ammonia is detoxified to urea and
metabolism of xenobiotics (detoxification).
Clearance of hormones such as insulin,
parathyroid hormone, oestrogen, cortisol
4. Hematological and synthetic functions
Liver participates in formation of blood
(particularly in embryo)

3. Synthesis of plasma proteins (albumin and
prothrombin), hormones e.g angiotensinogen,
insulin-like growth factor and
triiodothyronine.
Destruction of erythrocytes (Bilirubin).
5. Storage functions
Glycogen, vitamins A, D and B,2
6. Production of bile salts
-Helps in digestion
Liver Function Tests (LFTS)
" It is a non-invasive methods for screening of
liver dysfunction
" Help in identifying general types of disorder
" Assess severity and allow prediction of
outcome
" Disease and treatment follow up

4. Classification of LFTS
Liver function tests are broadly classified into
following groups according to their functions:
Group -Tests of hepatic excretory function
i. Serum-Bilirubin; total, conjugated, and
unconjugated.
ii. Urine--Bile pigments, bile salts and
urobilinogen.
Group l|-Markers of liver injury
i. Alanine amino transferase (ALT)
ii. Aspartate amino transferase (AST)
iii. Alkaline phosphatase (ALP)
iv. Gamma glutamyl transferase (GGT)
Group I|-Tests for synthetic function of liver
i. Total proteins
ii. Serum albumin, globulins, A/G ratio
iii. Prothrombin time

5. 1. BILIRUBIN:
" A by-product of red blood cell breakdown.
" It is conjugated by the liver to form bilirubin
diglucuronide and excreted through bile.
" It is the yellowish pigment observed in
jaundice
" High bilirubin levels are observed in:
-Gallstones, acute and chronic hepatitis
albumin Blirubin
ligandin
Bilirubin Processing
UDP
ligandin-Bilirubin
aUDP-glucuranate
ER
Bilirubin diglucuronide
ol bumin
UDP-Glucurony!
tran sferase
bile (gall bladder)
hepatocte
direct
conjugated
post-hepatie

6. diglucuronide
Intestine
Urobilinogen
Urobilin
Fate of Bilirubin
Bilirubin
Kidney
Urobilinogen Stercobilinogen
Stercobilin > To Feces
ntero hpt iulat
Urobilinogen
Liver
PLASMA BILIRUBIN:
" Normal plasma bilirubin: 0.2-0.8 mg/dl.
Unconjugated bilirubin: 0.2-0.6 mg/dl.
Conjugated bilirubin: 0-0.2 mg/di.
" If the plasma bilirubin level exceeds 1mg/dl,
the condition is called hyperbilirubinemia.

7. Levels between 1 & 2 mg/dl are indicative of
latent jaundice.
When the bilirubin level exceeds 2 mg/dl, it
diffuses into tissues producing yellowish
discoloration of sclera, conjunctiva, skin &
mucous membrane resulting in jaundice.
lcterus is the Greek term for jaundice.
Van den Bergh Test:
" It is a specific test for identification of
increased serum bilirubin levels.
" Normal serum gives a negative van den Bergh
reaction.
Mechanism of the reaction:
Van den Bergh reagent is a mixture of equal
volumes of sulfanilic acid (in dilute HCI)&
sodium nitrite.

8. Principle:
Diazotised sulfanilic acid reacts with bilirubin
to form a purple coloured azobilirubin.
Direct and indirect reactions:
Bilirubin as such is insoluble in water while
the conjugated bilirubin is soluble.
Bilirubin shows direct, indirect and mixed
reactions according to its unconjugated and
conjugated state.
Van den Bergh reagent reacts with conjugated
bilirubin & gives a purple colour immediately
(normally within 30 seconds).
This is direct positive van den Bergh reaction.
" Addition of methanol (or alcohol) dissolves
the unconjugated bilirubin & gives the van
den Bergh reaction (normally within 30
minutes) positive.
This is indirect positive van den bergh reaction

9. If the serum contains both unconjugated and
conjugated bilirubin in high concentration, the
purple colour is produced immediately (direct
positive) which is further intensified by the
addition of alcohol (indirect positive).
This type of reaction is known as biphasic.
Van den berg test and Jaundice
" Useful in understanding the nature of
jaundice.
This is due to jaundice is characterized by
increased serum concentration of
unconjugated bilirubin (hemolytic),
conjugated bilirubin (obstructive) or both of
them (hepatic).
" Indirect positive -Hemolytic jaundice
" Direct positive-Obstructive jaundice
" Biphasic -Hepatic jaundice

10. Bilirubin in Urine:
" Normally bilirubin is absent in urine.
" Conjugated bilirubin being water soluble is
excreted in urine in obstructive jaundice.
" This can be detected by Fouchet's test
" In prehepatic jaundice, when the
unconjugated bilirubin is increased in blood, it
does not appear in urine; hence called
acholuric jaundice.
" In obstructive jaundice, urine contains
bilirubin; hence in old literature, it is called
choluric jaundice.
Urobilinogen (UBG) and bile salts
" Most UBG is metabolized in the large intestine
but a fraction is exCreted in urine (less than 4
mg/day).
" urobilinogen is detected by Ehrlich's test.
" Normally bile salts are NOT present in urine

11. Obstruction in the biliary passages causes:
-Leakage of bile salts into circulation,
Excretion in urine.
Bilirubin cannot enter intestine.
" Note: Presence of bilirubin in urine and
absence of urobilinogen in urine is seen in
obstructive jaundice.
Note: Increased urobilinOgen in urine and
absence of bilirubin in urine is seen in
hemolytic jaundice.
Fecal urobilinogen -Normal about 300mg.
" Increased in Hemolytic jaundice in which color
of feces is dark.
In Obstructive jaundice urobilinogen is not
excreted through feces and the color is the
feces is pale.

12. Jaundice:
Jaundice is yellow discolouration of
conjunctivae, mucous membrane and skin
due to increased bilirubin level.
Clinical jaundice appears when bilirubin
concentration is more than 3 mg/dl.
Levels between 1 and 3 mg/dl is sub-clinical
jaundice.
Classification of Jaundice:
Jaundice is classified into three types
1. Prehepatic or Hemolytic jaundice:
In this, there is increased breakdown of Hb,
so that liver cells are unable to conjugate all
the increased bilirubin formed.
Causes :
>Increased production of unconjugated
bilirubin from:
" hemolysis -sickle cell anemia
Rapid turnover of RBC -Neonate

13. Physiological jaundice (Bilirubin 5mg/di).
Kernicterus Bilirubin >20mg/dl.
" Brain damage due to entry of bilirubin.
" No blood brain barrier.
> Decreased uptake of bilirubin by hepatocyte -
Gilbert syndrome.
Decreased conjugation -Neonatal Jaundice,
drug inhibition, crigler -najjar syndrome,
Hepatocellular dysfunction.
2.0bstructive jaundice or Post hepatic jaundice:
In this, there is obstruction to the flow of bile in
the extrahepatic ducts.
Decreased secretion of conjugated bilirubin
into canaliculi -Hepatocellular disease,
hepatitis.
" Decreased drainage -Intrahepatic obstruction
by drugs, cirrhosis.
" Extra hepatic obstruction -stones, Carcinoma.

14. 3.Hepatocellular or hepatic jaundice:
In this, there is disease of the parenchymal cell
of liver.
Causes:
Acute hepatitis is usually caused by viral
infections e.g. Hepatitis A, C, D, E
or by toxins eg: paracetamol, Carbon
tetrachloride etc.
Cass of Jaundiee
Pre-bepatic or hemolytie Abnomal red cells; antibodies; drugs and toxins;
Hepatic ar
Hepatocellular
Causes
Post-bepatie
thalessemia
Hemoglobinopathies, Gilbert's, Crigler-Najjar
syndrome
Viral bepatitis, toxic hepatitis, intrahepatie
cholestass
Extrabep cholestasis; g
carcinoma
oftones;
tumors of the
pancreas

15. Parameter
Senn bindin
Seruim enzymes
Binbn in une
Biochemial changes for the ditferential diagnosis of three types of jaundice
van den Burgh acton ndisdt posthe
Ubinogen in uine
Hemolic jaundie
(preheptic jaundice)
Urconjga blntn
AT, AST nd ALP+
Nct exceted
Eoson f
Ohstruce jundice
(posthepatie jaundice
Carigand blináin t
Diect postie
Hepate jndce
Jatralegaie jpundce
Erceled
Botasic
AP Tt, AT nd AST Nagia ATd AST 1, AP nag T
Eoted
AT: Aanine tasanihase AST: Aspatale larsanins ALP: Alaire ghoshatase T :hoas :DecR:lomal
TESTS BASED ON SYNTHETIC
FUNCTION OF LIVER
1.SERUM ALBUMIN
" The most abundant protein synthesized by the liver
Normal serum levels: 3.5 -5 g/dL.
Synthesis depends on the extent of functioning liver
cell mass
" Longer half-life: 20 days
" Its levels decrease in all chronic liver diseases

16. 2.SERUM GLOBULIN
" Normal serum levels: 2.5 -3.5g/dL
a and B-globulins mainly synthesized by the liver
" They constitute immunoglobulins (antibodies)
" High serum Y-globulins are observed in chronic
hepatitis and cirrhosis:
-IgG in autoimmune hepatitis
-IgA in alcoholic liver disease
3.Prothrombin
" synthesized by the liver, a marker of liver
function
" Half-life:6 hrs. (indicates the present function
of the liver)
" Normal Prothrombin Time = 11 to 12 seconds
" PT is prolonged only when liver loses more
than 80% of its reserve capacity
" Vitamin K deficiency also causes prolonged PT
" Intake of vitamin K does not affect PT in liver
disease

17. 4.a-Fetoprotein (AFP)
" One of the major plasma proteins in foetal life.
" In acute hepatic injury AFP T 10 -20X upper
ref limits.
" About 10% pt with viral hepatitis have T AFP
"Fibrosis post chronic liver disease, AFP ‘
" Used to screen and diagnose HCC &
hepatoblastoma
TESTS BASED ON SERUM ENZYMES
1. ALANINE AMINO TRANSFERASE
" ALT or SGPT (serum glutamate pyruvate
transaminase)
" ALT isa cytoplasmic enzyme.
" Normal Range: 10-35 U/L.
" The test is primarily used to diagnose liver
disease, to monitor the course of treatment
for hepatitis, active postnecrotic cirrhosis, and
the effect of drug therapy.

18. " Normal range: 8-20 U/L
" A marker of hepatocellular damage
High serum levels are observed in:
Chronic hepatitis, cirrhosis and liver cancer
3. Alkaline phosphatase (ALP)
" A non-specific marker of liver disease
" Produced by bone osteoblasts (for bone
calcification)
" Present on hepatocyte membrane
" Normal range: 40-125 U/L
Moderate elevation observed in:
-Infective hepatitis, alcoholic hepatitis and
hepatocellular carcinoma

19. High levels are observed in:
-Extrahepatic obstruction (obstructive
jaundice) and intrahepatic cholestasis
Very high levels are observed in:
-Bone diseases
4.y-Glutamyl transpeptidase (GGT)
It is a membrane bound glycoprotein which
catalyses the transfer of y-glutamyl group to
other peptides and AAS.
GGT is used by the body to synthesize
glutathione tri peptide.
This is a microsomal enzyme widely
distributed in body tissues, including liver.
Very useful in diagnosis of obstructive
jaundice. (not elevated in bone diseases)

20. " Normal range: 10-30U/L
" Moderate elevation observed in:
-Infective hepatitis and prostate cancers
" GGT is increased in alcoholics despite normal
liver function tests
-Highly sensitive to detecting alcohol abuse
" In liver diseases, GGT elevation parallels that
of ALP.
In alcoholic liver disease, GGT Ilevels may be
parallel to alcohol intake
OTHER TESTS:
" Tests based on metabolic capacity -Galactose
tolerance, antipyrine clearance.
Tests based on detoxification -Hippuric acid
synthesis.
Special tests:
" Blood ammonia
" al-antitrypsin
" Immunoglobulins
" Ceruloplasmin
" Ferritin