Lecture 4th Year MBBS (Pathology)

Liver Function Tests

BY

Brig (R) Prof Aamir Ijaz

MCPS, FCPS, FRCP (EDIN), MCP-HPE
Professor Chemical Pathology
Modi Uddin Islamic Medical College, Mirpur AJK
 Liver Function Tests
Serum
• Bilirubin
• ALT
• Alkaline Phosphatase
• Albumin
Urine
• Bile salts
• Bile Pigments
• Urobilinogen

11/10/21 2
 Liver Function Tests

• Bilirubin---Excretory Function of Liver

• ALT --------Secretory Function
• Alkaline Phosphatase…..Cholestasis
• Albumin ---Synthetic function

11/10/21 3
 Patient NO 1
A 25 years old male complained of influenza like
illness and loss of appetite. He had following liver
function tests results:
Serum
• Bilirubin : 17 µmol/L (<18)
• ALT : 370 U/L (< 42)
• ALP : 214 U/L (78-306)
• Albumin : 43 g /L (35-50)

• What is the most probable diagnosis

Acute Viral Hepatitis

 Q. 1
What Is The Most Common Cause
Of Acute Viral Hepatitis In
Pakistan
• Hepatitis E
• Spread by oro-fecal rout
• ALT is increased may be upto 4000 U/L
 Q. 2
What is the Most Common Cause
Of Hepatitis In Children

• Hepatitis A
• May go unnoticed without jaundice
• So, almost all adults are immune to
Hep A in Pakistan
 Q. 3
What Are The Two Common
Causes Of Chronic Viral Hepatitis
In Pakistan

• Hepatitis B : the incidence is falling due

to vaccination
• Hepatitis C : Incidence is rising as no
vaccination is available
• Both spread by parentral route
Hepatic Transaminases

Two Enzymes
• ALT (Old name GPT)
• AST (Old name GST)
 ALT

• ALT is mainly a cytoplasmic enzyme

• In Acute Hepatitis, only cell membrane is
damaged while organelles remain intact
• So in Acute Hepatitis ALT is markedly increased
• ALT may be the first or only liver marker to rise
 AST

• AST has two fractions :

• Cytoplasmic AST
• Organellar AST
• In Chronic Hepatitis AST is a better marker
• AST lacks specificity
• So for diagnosis and monitoring of Chronic Hepatitis
(Hep B and C), ALT is used.
• AST has now very limited use; only for cirrhosis
 LFTs Animated

AST –The Cheater: Heart expelled AST saying “go away cheater -
you are also loyal to the liver” (AST has been removed from the list of
cardiac markers because of its non-specificity). To add to its insult
liver also gives preference to ALT on AST because of its ‘relation’ with
heart. So, poor AST is out of heart and liver, on the accusation of
cheating. Do we have a lesson here to learn?
Adapted with thanks from “Chemical Pathology for the Beginners” by Aamir Ijaz
PRESENTATION TITLE | PRESENTED
11/10/21 11
BY: NAME
(2017).
MCQ 1: Which of the following enzymes is a Membrane
Bound Enzyme :
a. Alkaline Phosphatase
b. Aspartate Aminotransferase
c. Cholinesterase
d. Glutamyl Dehydrogenase
e. Glutathione S-Transferase

a. Alkaline Phosphatase
Membrane Bound Hepatic
Enzymes
1. Alkaline Phosphatase (ALP)
2. Gamma Glutamyl Transferase (Gamma GT)
3. 5-prime Nucleotidase
ALP a marker of Cholestasis
• Increased in Cholestasis
• Bound with cell membranes of endothelial cells of bile
canaliculli
• Obstruction and stasis cause digestion of fat content of cell
membranes.
• So, ALP and other membrane bound enzymes are released in
circulation
 Q 4:
Jaundice Is A Disease Effecting
Liver Due To Viral Infection
True / False

False
Explanation:
• Jaundice is not a disease but rather a sign that can
occur in many different diseases.
• Yellowish pigmentation of the skin, conjunctival
membranes over the sclerae and other mucus
membranes
Jaundice
 Q 5:
Jaundice is caused by decreased levels
of bilirubin in the blood
True / False

False
Explanation:
• Caused by hyperbilirubinemia (increased levels
of bilirubin in the blood).
 Pathogenesis

• Normally, systemic bilirubin production is

equal to the rates of bilirubin uptake ,
conjugation, and biliary excretion.
• Jaundice occurs when the balance between
the bilirubin production and clearance is
disturbed.
 Q 6:
Symptoms of Jaundice Occurs When
the Systemic Bilirubin Level Increases
above 2 mg/dl (34 µmol/L)
True / False
True
Explanation:
• Before this level jaundice is not evident
clinically.
 Types Of Jaundice
1. Hepatocellular Damage (Hepatitis)
2. Excessive production of bilirubin (Haemolysis)
3. Obstructive (Cholestasis).
 Hepatic Jaundice
• Hepatic jaundice results from failure in the
function of hepatocytes to take up, metabolize or
excrete bilirubin.
• Conjugated Bilirubin is much higher than
Unconjugated Bilirubin
• Serum ALT / AST are increased.
 Patient No 2
A 20 hours baby has following LFT :
• Conjugated Bilirubin : 3 µmol/L (< 4)
• Unconjugated Bilirubin: 24 µmol/L (<14)
• ALT : 34 U/L (< 42)
• ALP : 715 U/L (85- 730)
• Albumin : 49 g /L (35-50)

What is the most probable diagnosis in this patient?

Physiological Jaundice
Physiological (Neonatal) Jaundice

• Full Term Infants jaundice lasts for about 10 days with a rapid
rise of serum bilirubin up to 204 µmol/L (12 mg/dL).
• Phase Two bilirubin levels remains at about 34 µmol/L
(2 mg/dL) for two weeks, eventually coming down to less than
17 µmol/L (2 mg/dL) i.e. the adult values.
• Preterm Infants jaundice lasts for about two weeks, with a
rapid rise of serum bilirubin up to 255 µmol/L (15 mg/dL).
 Pathological Neonatal Jaundice

Any of the following features characterizes pathological jaundice:

• Clinical jaundice (> 2 mg/dL) appearing in the first 24 hours
• Jaundice lasting more than 14 days of life (>1 month in
premature).
• Increases in the level of total bilirubin by more than 8.5 µmol/L
(0.5 mg/dL) per hour or (85 µmol/L) 5 mg/dL per 24 hours.
• Total bilirubin more than 331 µmol/L (19.5 mg/dL)
• Direct bilirubin more than 34 µmol/L (2.0 mg/dL).
Causes Of Pathological Neonatal
Unconjugated Hyperbilirubinemia

• Hemolytic Disease of the Newborn: The most

common cause of pathologic indirect
hyperbilirubinemia is increased bilirubin production
due to hemolytic disease processes
• Decreased Clearance: Congenital condition like
Crigler-Najjar syndrome and Gilbert Syndrome
• Breast Milk Jaundice: A very common cause
• Other Causes e.g. GDM
 Patient No 3
A 22 years old medical student was upset to find that her sclera sometimes
look yellow especially when she is fasting and after taking Panadol for
trivial problems. She discussed the problem with her clinical teacher who
got her LFTs. On seeing the report he assured her that this is due to a
benign liver disease which is very common. Her LFTs were:
• Conjugated Bilirubin: 5 µmol/L (<4)
• Unconjugated Bilirubin: 30 µmol/L (<14)
• ALT : 22 U/L (< 42)
• ALP : 145 U/L (85- 306)
• What is the most probable diagnosis in this patient?

Gilbert Syndrome
 Gilbert's Syndrome

• The most common inherited disorder of bilirubin glucuronidation

(9-10% of the adult population)
• Also called "constitutional hepatic dysfunction" and "familial
nonhemolytic jaundice"
• Enzyme Defect: Uridinediphosphoglucuronate
glucuronosyltransferases (UGTs) which is a family of enzymes
that mediate glucuronidation of various endogenous and
exogenous compounds
• Genetic Defect: The mutation is in the promoter region,
upstream to exon 1 of the gene encoding bilirubin-UGT
 Congenital Causes Of
Hyperbilirubinaemia
Unconjugated Bilirubinaemia
Ø Gilbert syndrome:
Ø Crigler-Najjar
Conjugated Bilirubinaemia
Ø Dubin-johnson syndrome:
Ø Rotar Syndrome
 Patient No 4
A 10 days old baby has following LFT
• Conjugated Bilirubin : 34 µmol/L (<4)
• Unconjugated Bilirubin: 378 µmol/L (<14)
• ALT : 54 U/L (< 42)
• ALP : 745 U/L (85- 730)
• Albumin : 49 g /L (35-50)
• What is the most probable diagnosis in this patient?

Haemolytic Disease of the Newborn

(HDN)
 Haemolytic Disease of the
Newborn (HDN)

• HDN is a condition in which the red cells of the fetus or

newborn are destroyed by maternally-derived
alloantibodies.
• These antibodies arise in the mother as the direct result of
a blood group incompatibility between the mother and fetus,
• For example when Rh(D) negative mother carries an Rh(D)
positive fetus
 Incidence of HDN

• In developed world very high incidence has

been reduced due to immunization of Anti D.
• In Pakistan, exact incidence is not known.
However, in a local study, ABO incompatibility
was known to be the major cause of HDN
(71%)
 Patient No 5

A 66 years old male has following LFT :

• Conjugated Bilirubin : 334 µmol/L (<4)
• Unconjugated Bilirubin : 34 µmol/L (<14)
• ALT : 62 U/L (< 42)
• ALP : 1045 U/L (85- 306)
• Albumin : 49 g /L (35-50)

Obstructive Jaundice
Causes of Obstructive Jaundice

• Intrahepatic
• Liver tumours
• Severe hepatitis
• Extrahepatic
• Carcinoma head of the pancreas
• Bile duct stones
 Summary Of Lfts In
Liver Disease
LFT Pre-hepatic Hepatic Post hepatic
Total bilirubin Increased Increased increased
Conjugated Normal increased increased
bilirubin

Unconjugated Increased Increased (Mild) Normal (Mild)

bilirubin

ALP Normal Increased Increased

(Marked)

ALT Normal Increased Increased

(Marked)
Thank You and Best Of Luck