2. GROSS ANATOMY
•Two lobes (falciform ligament)
• Blood supply : Hepatic artery(oxygen)& Portal vein(nutrients)
• veinous supply : hepatic veins , inferior vena ceva
•microscopic units lobules functional units of liver
•Each lobule is a hexagonal centrally located vein with portal
3. BIOCHEMICAL FUNCTIONS
The liver performs four major functions :
Excretion / secretion
1. Synthetic functions :
Plasma proteins – albumin(osmotic pressure) , carrier
proteins ( transport of elements Fe Cu) , globulins ,
Cholestrol – precursor of steroid hormones , bile acids
Bile acids- to absorb lipid nutrients from the gut , includes
fatty acids and fat soluble vitamins .
Carbohydrate metabolism :
Liver is an important homeostatic regulator of blood
It can either produce glucose or store glucose .
By the following processes :
1. Glycogenesis – by converting glucose into
glycogen for storage .
2. Glycogenolysis – ATP is required , glycogen is
again converted back into glucose .
3. Gluconeogenesis – formation of glucose from non
precursor carbohydrates such as lactate ,
glucogenic amino acid and propinyl CoA .
5. AMINO-ACID METABOLISM
PROTEINS get breakdown in the intestine into
amino acids and reach liver by portal vein ; utilized
to form different proteins like globulin , albumin ,
coagulation factors …………………..
LIPID METABOLISM :
Fatty acids catabolised to release CoA – used for TCA cycle
and ETC to release energy .
Acetyl CoA converted to ketone bodies – acetone ,
acetoacetate and hydroxybutyric acid .
Liver synthesis apoprotein part of lipoproteins –
transportation of lipids into circulation .
6. PROTECTIVE FUNCTION & DETOXIFICATION
Exogenous substances : It detoxify toxic substances –
hydrolysis , hydroxylation ,oxidation , reduction and
More soluble in water and easily excreted through
Drugs – metabolised by P450 enzyme system of liver ,
convert drugs into more soluble form which in due
course conjugate with sub. Like glycine , glucouronic
acid to get excreted in urine .
Endogenous substances – Kupffer cells perform
phagocytosis to eliminate foreign cmpds . For eg. NH3
is detoxified urea and metabolism of xenobiotics (
7. WHAT IS PURPOSE OF LFTS?
LFTs alone do not give the physician full information, but
used in combination with a careful history, physical
examination (particularly ultrasound and CT Scanning),
can contribute to making an accurate diagnosis of the
specific liver disorder.
Different tests will show abnormalities in response to
liver injury due to drugs, alcohol, toxins, viruses
Liver malfunction due to blockage of the flow of bile
8. CLASSIFICATION OF LFT’S
Synthetic function of liver-
a. Serum proteins – albumin,globulin,ceruloplasmin haptoglobin , alpha
fetoprotein , alpha 1 antitrypsin levels
b. Prothrombin time
Serum Enzymes(liver enzyme panel)
a. Indicating hepatocellular damage- ALT , AST
b. Indicating obstruction- ALP, GGT
Based on detoxification function
a. Blood ammonia
b. Hippuric acid test
Hepatic excretory function-
a. serum- bilirubin levels, conjugated and unconjugated
b. Urine – bile pigments , bile salts and urobilinogen
10. 1)SERUM ALBUMIN LEVEL
Normal Value- 3.5 to 5 g/dl
Albumin is major protein- responsible for OSMOTIC
pressure in vascular system
Half life: 20 days, low level in all chronic diseases of liver
Normal A/G ratio is 1.2 to 1.5 :1
Reverses in case of cirrhosis due to hypoalbuminemia and
11. 2) SERUM GLOBULIN
• Alpha and beta globulins synthesized by liver and immunoglobulin by
• Normal value - 2.5 to 3.5 g/dl
• Cirrhotic liver cannot clear bacteria, antibodies against intestinal
• Ig A –Inc. in alcoholic liver disease
Ig M - ↑↑ Primary biliary cirrhosis..
Ig G - ↑↑ Auto immune hepatitis.
12. 3) PROTHROMBIN TIME
Prothrombin is synthesized by liver
Half life – 6 hrs so it indicate – present function of liver
PT :blood test, time taken by blood to clot
Normal value : 10 to 15 sec.
PT is Prolonged - liver losses 80% of reserve capacity
Commonly PT is used for detecting liver coagulopathies
Note : Vit K deficiency Prolongs PT time
But In case of LIVER diseases : PT remains prolonged even after
parenteral administration of Vit. K
13. 4) 1-ANTITRYPSIN (AAT)
• Most abundant 1-globulin and acute phase reactant
• Inactivates : serum proteases
• Normal values : 90 to 200 mg/dl
• It has multiple alleles , individuals possessing PiZZ allele : deficient
activity of this enzyme : Liver cirrhosis
Low levels Neonatal cholestasis,
High levels acute trauma, infection
14. 5) HAPTOGLOBIN• Another major 2 protein synthesised in liver.
• Normal values: 30- 200 mg/dl
• Function – transports free Hb in the plasma to reticuloendothelial system
• Low levels – lead to ppt of free Hb in kidneys and cause damage
• Turnover rates are less than albumin – used to Identify recent changes in
Low levels Severe hepatocellular diseases (deficient synthesis),
hemolytic disease(rapid degradation)
High levels Inflammatory processes , myocardial infarction
15. 6) -FETOPROTEIN
Normal component of fetal blood., disappears after few weeks
Normal range-up to 1 year of age < 30ng/ml
adults(M and non pregnant F) < 15ng/ml
Maternal serum AFP level Inc. in fetal open tube neural
defect and dec. in foetal down syndrome
Mild Inc. Chronic hepatitis or cirrhosis
Drastic Inc. hepatocellular carcinoma, germ cell
tumour and teratoma of ovary
16. 7) CERULOPLASMIN
Synthesized by Hepatic parenchymal cells and small part by
Transport : Cu
Normal levels: males 22- 40mg/dl
pregnancy 30-120 mg/dl
Wilson's hepatolenticular degeneration
Acute Hepatitis, hemochromatosis,
obstructive biliary disease
18. TEST BASED ON SERUM ENZYMES
A. Enzymes indicating Hepatocellular Damage
Alanine amino transferase (ALT)
Serum Glutamate Pyruvate transaminase (SGPT)
Source - liver, cardiac muscle , skeletal muscle.
Increased – when cells of the liver have been inflamed or necrosed.
Normal serum level : male- 13-35 U/L
female – 10-35 U/L
19. Abnormal levels
Only ALT are elevated in:-
1. AMI rise within 6-8 hrs and remain upto 5 days
2. Pulmonary embolism
Aspartate amino transferases (AST)
Serum glutamate oxaloacetate transaminase (SGOT)
Source- more liver specific
Moderate 50 - 100 Chronic liver diseases,hepatitis C,
Very high 300-1000 Acute hepatitis , toxic or viral in
20. Normal level : 8-20 U/L
Normal AST: ALT ratio – 0.8
ratio > 2
AST is higher
Alcoholic hepatitis, hepatitis with cirrhosis ,
NASH , erythromycin treatment
Ratio < 0.8
ALT is higher
Acute hepatocellular injury, toxic exposure
,extra hepatic obstruction
elevated liver diseases, myocardial infarct,
21. B. Markers of obstructive liver disease
Alkaline Phosphatase (ALP)
Source: liver, bone, placenta and intestine.
ALP is a hydrolase enzyme responsible for removing phosphate
groups from many types of molecules, including nucleotides and
phosphomonoester ALP alcohol + phoshate ion
Normal level: 40-125 U/L
Levels are significantly higher in children and pregnant women.
Moderate increase 2-3 times Hepatic diseases includes
Very high levels 10-12 times Obstructive jaundice (gall stones)
More than 12
Not related to liver disease but
Bones disease such as rickets,
22. ISOENZYMES OF ALP
Iso enzyme location Increased in
Alpha 1 ALP Epithelial cells of
Alpha 2 heat labile
Alpha 2 heat stable
Placental origin (regan
Pre beta ALP Bone origin Pagets disease,
Gamma ALP Intestinal cells Ulcerative colitis
Normal range 2-17 U/L
Function ; hydrolysis of nucleoside 5’ phosphate esters
Sensitive and specific for hepatobiliary disorders (HBD), obstructive biliary diseases
Normal pregnancy, bone growth and bone diseases do not affect 5' NT
In pts with HBD, changes in ALP are usually followed by similar changes in 5' NT
23. GAMMA GLUTAMYL TRANSFERASE
1. Function –
Glutathione + amino acid GGT glutamyl peptide +
regulate glutathione levels
2.Source - liver, kidney, pancreas, intestinal cells absent in bone
3.Normal serum levels : 10-30 U/L
4. Diagnostic signicficance
hepatic microsomal enzyme
GGT elevation differentiate ALP increase levels ,seen in
biliary tract diseases
In alcoholic liver disease GGT levels may be parallel to alcohol
intake , even when other LFT’s are in Normal range.
diseases pancreatic disease , MI ,pulmonary disease
Drugs warfarin , antidepressants
25. TEST BASED ON DETOXIFICATIOM
Blood ammonia level
Normal level: 10-50 mcg/dl
Index of urea synthesis by liver, marker of hepatic encaphlopathy
Ammonia is converted to urea by liver
Increased levels 1. cirrhosis
2. portocaval anastomoses
Hippuric acid test
Reaction benzoic acid+glycine = hippuric acid
Ingestion of sodium benzoate thn hourly excretion hippuric acid is
Decreases when the liver fails to detoxify
26. Oral Glucose tolerance test
Glucose tolerance: ability of person to metabolise a given
load of glucose
Glucose load : 75g in 250-300ml of water. Urine samples
34. EXCRETION OF BILIRUBIN
Water soluble bilirubin
Mixed with the bile
Reaches the Intestine
Deconjugated by the bacterial flora
Urobilinogen (UBG) (Tetrapyrrole structure)
reduction of vinyl substituent groups
36. NORMAL VALUES
Total Bilirubin 0.2 to 0.8 mg/dl
Conjugated bilirubin 0 to 0.2 mg/dl
Unconjugated Bilirubin 0.2 to
42. 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
Urine urobilinogen - normally trace amounts is
In obstructive jundice no urobilinogen is present in
43. because bilirubin cannot enter intestine.
Note: Presence of bilirubin in urine and absence of
urobilinogen in urine is seen in obstructive jaundice.
In hemolytic jaundice increased production of bilirubin
causes increased formation of urobilinogen which
appears in urine.
Note: Increased urobilinogen in urine and absence of
bilirubin in urine is seen in hemolytic jaundice.
44. Fecal urobilinogen - Normal about 300mg.
Increased in Hemolytic jaundice in which color of feces
In Obstructive jaundice urobilinogen is not excreted
through feces and the color is the feces is pale.
46. SYNTHESIS OF BILE SALTS
Cholesterol hydroxylated at 3/7/12 positions
Removal of 3-carbon unit, to make it 24 C
Conjugation with glycine
Secretion into intestinal canal
In the intestine, deconjugation and removal of
47. Normally bile salts (sodium salts of taurocholic acid
and glycocholic acid) are present in the bile; but are
not seen in urine. Bile salts in urine are detected by
Positive Hay’s test indicates the obstruction in the
biliary passages causing regurgitation of bile salts
into the systemic circulation leading to its excretion
49. • Jaundice is yellowish discoloration of the
skin, sclera and mucous membranes due to
hyperbilirubinemia and deposition of bile
• Equilibrium between bilirubin production and
clearance is disturbed .
• Serum bilirubin level greater than 2mg/dL
• Jaundice is NOT a disease, but rather a sign
that can occur in many different diseases.
What is Jaundice?
50. TYPES OF JAUNDICE
PRE HEPATIC HEPATIC POST
of bilirubin is
presented to the
liver due to
of bilirubin by the
due to mechanical
obstruction to bile
bilirubin in serum
bilirubin may be
elevated in serum
bilirubin in serum
51. TYPES OF JAUNDICE
52. There are other types of Jaundice :
Pathologic jaundice can occur in children and adults and is diagnosed
when jaundice presents a health risk. Several forms of hepatitis,
cirrhosis of the liver and other liver diseases, bile duct blockage, along
with infections and medications, can also cause pathological jaundice.
Gilbert Syndrome Jaundice
Gilbert's syndrome is a harmless hereditary condition that
results in mild jaundice. During times of illness or stress,
people with Gilbert's syndrome will experience low levels of
some bilirubin-processing enzymes in their livers,
according to LabTestsOnline.com. Once diagnosed,
Gilbert's syndrome does not require further medical
53. Neonatal Jaundice
•Jaundice is clinically detectable in the newborn
when the serum bilirubin levels are greater than
85 μmol/L. This occurs in approximately 60% of
term infants and 80% of preterm infants.
•Neonatal jaundice first becomes visible in the
face and forehead. Blanching reveals the
underlying colour. Jaundice then gradually
becomes visible on the trunk and extremities.
55. Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice
Total bilirubin Normal / Increased Increased
Conjugated bilirubin Normal Increased Increased
Unconjugated bilirubin Normal / Increased Increased Normal
Urobilinogen Normal / Increased Increased Decreased / Negative
Urine Color Normal
Dark (urobilinogen +
Stool Color Normal Normal/Pale Pale
Alanine transferase and
Conjugated Bilirubin in
Not Present Present
Splenomegaly Present Present Absent
Table of diagnostic tests
56. VAN DEN BERGH TEST
Van den bergh test is specific for bilirubin.
Normal serum gives a positive van den
Principle of the reaction:
Bilirubin + diazotized sulphanilic acid
Purple coloured azobilirubin
57. VAN DEN BERGH TEST
conjugated bilirubin gives a purple color immediately on
addition of the reagent.
Purple color develops only when the reagent and
methanol are added.
Unconjugated bilirubin gives color only when methanol
Hence conjugated bilirubin is also called direct bilirubin
and unconjugated called indirect bilirubin
58. VAN DEN BERGH TEST
Purple color develops immediately on addition of
Addition of methanol intensifies the color.
Elevation of both unconjugated and conjugated
59. VAN DEN BERGH TEST
Indirect Positive Hemolytic jaundice
Direct Positive Obstructive jaundice
Biphasic Hepatic jaundice
60. SCHLESINGER’S TEST
The bilinogens form complexes with zinc ions
which exhibit brilliant green fluorescence.
It is negative in normal urine.