1. Moderator – Dr. Saroj Jaswal
Submitted by 51-60

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
triads

3. BIOCHEMICAL FUNCTIONS
 The liver performs four major functions :
 Excretion / secretion
 Metabolism
 Detoxification
 Storage
1. Synthetic functions :
 Plasma proteins – albumin(osmotic pressure) , carrier
proteins ( transport of elements Fe Cu) , globulins ,
coagulation factors.
 Cholestrol – precursor of steroid hormones , bile acids
and 7-dehydrocholestrol.
 Bile acids- to absorb lipid nutrients from the gut , includes
fatty acids and fat soluble vitamins .

4. METABOLISM
 Carbohydrate metabolism :
 Liver is an important homeostatic regulator of blood
glucose .
 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
demethylation .
 More soluble in water and easily excreted through
urine .
 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 (
detoxification )

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 inflammation
 liver injury due to drugs, alcohol, toxins, viruses
 Liver malfunction due to blockage of the flow of bile
 Liver cancers

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
hypergammaglobulinemia.

11. 2) SERUM GLOBULIN
• Alpha and beta globulins synthesized by liver and immunoglobulin by
lymphocytes
• Normal value - 2.5 to 3.5 g/dl
• Cirrhotic liver cannot clear bacteria, antibodies against intestinal
bacteria seen.
• 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,
emphysema
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
(RES)
• 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
the liver.
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
of birth.
 Normal range-up to 1 year of age < 30ng/ml
adults(M and non pregnant F) < 15ng/ml
 Tumor marker
 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
lymphocytes
 Transport : Cu
 Normal levels: males 22- 40mg/dl
females 25-60mg/dl
pregnancy 30-120 mg/dl
Low
levels
Wilson's hepatolenticular degeneration
High
levels
Acute Hepatitis, hemochromatosis,
obstructive biliary disease

17. 8)TRANSTHYREITN (PRE-ALBUMIN)
 Produced by liver
 Transport thyroxine and triidothyronine
 Half life 2 days , hence useful parameter to assess hepatic
function early in course of liver disorders.

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
SGPT
PLP

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,
NASH(non alcoholic
steatohepatitis )
Very high 300-1000 Acute hepatitis , toxic or viral in
origin
AST
PLP

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,
muscle disease

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
proteins.
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
infective hepatitis,hepatocellular
carcinoma
Very high levels 10-12 times Obstructive jaundice (gall stones)
Drastically high
levels
More than 12
times
Not related to liver disease but
Bones disease such as rickets,
osteomalacia

22. ISOENZYMES OF ALP
Iso enzyme location Increased in
Alpha 1 ALP Epithelial cells of
biliary canaliculi
Obstructive jaundice
Alpha 2 heat labile
ALP
Hepatic cells
Alpha 2 heat stable
ALP
Placental origin (regan
iso enzyme)
Pregnancy and
inhibited by
phenylalanine
Pre beta ALP Bone origin Pagets disease,
rickets osteomalacia
Gamma ALP Intestinal cells Ulcerative colitis
5’- Nucleotidase
Normal range 2-17 U/L
Function ; hydrolysis of nucleoside 5’ phosphate esters
Clinical significance
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
(GGT)
1. Function –
 Glutathione + amino acid GGT glutamyl peptide +
cysteinylglycine
 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
 Benzoyl glycine
 Reaction benzoic acid+glycine = hippuric acid
 Ingestion of sodium benzoate thn hourly excretion hippuric acid is
constant
 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
are taken

27. EXCRETORY
FUNCTIONS OF
LIVER

28. 1.Serum bilirubin
2.Urine bilirubin
3.Urine and faecal urobilinogen
4.Urine bile salts

29. SERUM BILIRUBIN

30. What is bilirubin?
•Bilirubin is a linear tetrapyrrole structure.
•It is the end product of heme catabolism.
•It is yellowish in colour and found in bile.
•Produced by reticuloendothelial system

31.  Since the bilirubin is a waste product, hence it has
to be excreted from the body
For this it has to be first conjugated by the
hepatocytes to make it water soluble to be removed
from the body.

33. CONJUGATION OF BILIRUBIN

34. EXCRETION OF BILIRUBIN
Water soluble bilirubin
Mixed with the bile
Reaches the Intestine
Deconjugated by the bacterial flora
Free Bilirubin
Reduced
Urobilinogen (UBG) (Tetrapyrrole structure)
reduction of vinyl substituent groups
Stercobilinogen (SBG)

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
0.6mg/dl

37. HYPERBILIRUBINEMIAS
These can be grouped in two ways
1. Conjugated or Unconjugated
2. Congenital and aquired

38. CONGENITAL HYPERBILIRUBINEMIAS
 Crigler Najjar Syndrome- Deficiency of UDP
glucuronyl transferase
 Gilbert Syndrome-Defective uptake of bilirubin by
the liver
 Dubin Johnson Syndrome-Defective excretion of
conjugated bilirubin
 Rotor Syndrome

39. AQUIRED HYPERBILIRUBINEMIAS
 Physiological Jaundice in new borns
 Breast Milk Jaundice

40. URINE UROBILINOGEN

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
present.
In obstructive jundice no urobilinogen is present in
urine.

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
is dark.
In Obstructive jaundice urobilinogen is not excreted
through feces and the color is the feces is pale.

45. BILE SALTS

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
hydroxyl groups.

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
Hay’s test.
 Positive Hay’s test indicates the obstruction in the
biliary passages causing regurgitation of bile salts
into the systemic circulation leading to its excretion
in urine.

49. • Jaundice is yellowish discoloration of the
skin, sclera and mucous membranes due to
hyperbilirubinemia and deposition of bile
pigments .
• 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
HEPATIC
Excessive amount
of bilirubin is
presented to the
liver due to
excessive hemolysis
Impaired cellular
uptake, defective
conjugation or
abnormal secretion
of bilirubin by the
liver cell
Impaired excretion
due to mechanical
obstruction to bile
flow
Elevated
unconjugated
bilirubin in serum
Both conjugated
and unconjugated
bilirubin may be
elevated in serum
Elevated conjugated
bilirubin in serum

51. TYPES OF JAUNDICE
PRE
HEPATIC
HEPATIC POST
HEPATIC
Hemolytic
Anemia
Hepatitis,
cirrhosis, Crigler-
Najjar Syndrome,
Dubin-Johnson
Syndrome,
Rotor’s
Syndrome
Gallstone,
malignancy,
inflammation

52. There are other types of Jaundice :
 Pathologic 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
treatment.

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 +
conjugated bilirubin)
Dark (conjugated
bilirubin)
Stool Color Normal Normal/Pale Pale
Alkaline phosphatase
levels
Normal
Increased
Alanine transferase and
Aspartate transferase
levels
Increased
Conjugated Bilirubin in
Urine
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
bergh reaction.
Principle of the reaction:
REACTION
Bilirubin + diazotized sulphanilic acid
Purple coloured azobilirubin

57. VAN DEN BERGH TEST
Direct Positive:
conjugated bilirubin gives a purple color immediately on
addition of the reagent.
Indirect Positive:
Purple color develops only when the reagent and
methanol are added.
Unconjugated bilirubin gives color only when methanol
is added.
 Hence conjugated bilirubin is also called direct bilirubin
and unconjugated called indirect bilirubin

58. VAN DEN BERGH TEST
BiPhasic:
Purple color develops immediately on addition of
reagent.
Addition of methanol intensifies the color.
Elevation of both unconjugated and conjugated
bilirubin.

59. VAN DEN BERGH TEST
RESULTS
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.

61. EHRLICH’S TEST
 Bilinogens react with Erlich’s aldehyde reagent i.e.
Para dimethyl amino benzaldehyde to form red
colour.

63. HAYS TEST
 Hay's test, also known as Hay's sulphur flower
test, is a chemical test used for detecting the
presence of bile salts in urine

64. THANK YOU