LIVER FUNCTION TEST

Maimun ZA
Lab Patologi Klinik
FKUB-RSSA
 Why does the liver damage?
Cause of liver damaged ?
 Viral
 Bacteria
 Parasite
 Drugs
 Alcohol
 Immunologic process
 Tumor
If the liver damaged, what will be disturb?
 Refer to anatomy and histology of the liver
From these damaged, what are the clinical
manifestations?
 What are the clinical manifestations?

The most common of clinical manifestation of liver

disorder is jaundice (icterus), but not all of the liver
disorder cause icterus
If jaundice is present, what should we do?
• Determine the type of icterus
• (Hemolytic, obstructive, parenchymatous)
• Laboratory Examination  liver disorder or not?
• Determine:
• Severity
• Acute or chronic
• etiology (example: serologic Test)
• If important, we can use USG, etc
Canaliculus
Biliaris
Sinusoid

Sel-sel hepar
Liver Lobule - Functional Unit
 Liver cell
(Conjugated)

Conjugated bilirubin

Sinusoid

Bile duct
Unconjugated bilirubin
 Laboratory Examination of
Liver Function
Examination of serum enzymes
1. SGPT Examine liver cell integrity
2. SG OT
3. ALP Examine excretion function of liver
4. Gamma GT

Examination of Synthetic Function of the liver

1. Albumin
2. Cholin esterase
3. PPT
4. Cholesterol

Examination of Excretion Function of the Liver

1. Bilirubin
2. Bile acid
3. Ammonia
Sero marker  HBs Ag, Anti HBs,
Anti HBc, HBe Ag,
Anti HBe, HBV-DNA

Tumor marker
1. Alpha fetoprotein
2. Carcinoembryonic antigen
3. PIVKA II
 Bilirubin

Fe

Heme

Porphyrin Unconjugated
Erythrocytes Bilirubin

Globin
 RES
Unconjugated
Bilirubin
Blood
Kidney
Conjugated
Liver
Bilirubin

Portal
Biliary tree Vein

Intestines Urine

Feces
 Bilirubin
• There are two kinds:
– Unconjugated
– Conjugated

• Unconjugated bilirubin unsoluble in water 

bilirubin urine is negative

• Conjugated bilirubin  water soluble  bilirubin

urine is positive.
 Serum & Urine Bilirubin

• Not sensitive test for screening, because the liver

have great capacity

• Bilirubin is important to differ the cause of liver

disorder (hemolytic, obstructive, parenchymatous)

• The presence of bilirubinuria implies the presence

of liver disease, eventhough before the jaundice is
appear

• Urine bilirubin will be negative prior to serum

bilirubin
 Hepatocyte
(Conjugation)

Conjugated bilirubin

Sinusoid

Bile duct
Unconjugated bilirubin
Prehepatic (hemolytic) jaundice

Results from excess

production of bilirubin
(beyond the livers
ability to conjugate it)
following hemolysis
Bilirubin uri neg
Urobilin pos
High plasma
concentrations of
unconjugated bilirubin
(normal concentration ~
0.5 mg/dL)
Intrahepatic jaundice
Impaired uptake,
conjugation, or secretion
of bilirubin
Reflects a generalized
liver (hepatocyte)
dysfunction
Urine: urobilin +
bilirubin +
In this case,
hyperbilirubinemia is
usually accompanied by
other abnormalities in
biochemical markers of
liver function
Posthepatic jaundice
Caused by an obstruction of the
biliary tree
Plasma bilirubin is conjugated,
and other biliary metabolites,
such as bile acids accumulate in
the plasma
Urine: Urobilin neg
Bilirubin pos
Characterized by pale colored
stools (absence of fecal bilirubin
or urobilin), and dark urine
(increased conjugated bilirubin)
In a complete obstruction,
urobilin is absent from the
urine
 SGOT - SGPT
• SGPT (ALT)
– Produced in liver
– Located in the cytoplasm of hepatocyte
– More spesific for liver disease
• SGOT (AST)
– Produced in liver and muscle
– Located both in cytoplasm and mitochondria of hepatocyte
• SGOT/SGPT ratio
– < 1  mild damage/normal
– > 1  severe damage
– Exp: SGOT =150 , SGPT = 90  ratio >1
(intracellular damage)
 SGPT

SGOT

SGOT

SGOT/SGPT RATIO < 1 mild damage

SGOT/SGPT RATIO > 1 severe damage

 Cellular Locations of Liver Enzymes
Mechanisms of Enzyme
Release

-Enzymes are released from

hepatocytes as a result of
injury to the cell membrane
 extrusion of the cytosolic
contents.
- In addition, agents like
ethanol cause release of
mitochondrial AST from
hepatocytes and its
expression on cell surfaces

- Cytoplasmic enzymes : LDH, AST, and ALT.

- Mitochondrial enzymes : mitochondrial isoenzyme of AST
- Canalicular enzymes : ALP, GGT 21
Henry Clinical Diagnosis & Management 2006
 AST ALT

catalyze transfer amino groups catalyze transfer amino groups

to form pyruvate to form oxaloacetate
cytosol (20%) and mitochondria cytosol
(80%)
T1/2 17 hr. (cytosol) T1/2 47 hr.
87 hr. (mitochondria)
liver, cardiac muscle, skeletal low concentration in other
muscle, kidneys, brain, tissues
pancreas, lungs, leucocytes, and
RBC
 Alkaline phosphatase (excretion function)
(male: 6-28U/L female: 4-18 U/L)

 Produced in:
 Liver (bile canaliculi, sinusoid)  (excretion
function)
 Pancreas, intestine, bone
 Differentiated by examining another LFT  if
another LFT increased, the increase of ALP is from
liver
 In bile duct obstruction (stone/tumor)  ALP >>
 Increasing ALP > 350 ng/ml  suspect carcinoma
 Children – puberty or pregnant woman  ALP
increase 2-2.5  normal.
 Gamma-Glutamyl Transferase

• Located in: liver, kidney, pancreas.

• Found primarily on the canalicular surface of the hepatocyte
• Increased highly in biliary tractus obstruction and
hepatocarcinoma
• Increased in liver disease due to:
– Alcohol
– Barbiturate
– Decompensatio cordis
– Infection
• In clinical practice, ALP assay combined with GGT
– ALP ↑, GGT normal  bone disorder
– ALP ↑ & GGT ↑  cholestasis
• Sensitive  early appear, lately return
 Albumin

 Decrease in severe/chronic liver disease

 Describe synthetic function of liver
 Lowering albumin will be followed by increasing
globulin and gamma globulin
 Reference range: 3.8- 5.2 g/dl
 Level < 2 g/dl  edema
 Not spesific  another disease have same
appearance:
 Renal disease, malnutrition
 Plasma cell dyscrasia.
 Coagulation Factors

• All of coagulation factor synthesized by liver

• Vit K dependent coagulation factor: II, VII, IX,
X
• Deficiency of these factors  prolonged PPT
(Extrinsic pathway)
• If abnormal PPT become normal with vit K
treatment  respect that this abnormality
not caused by liver disease (but from vit K
deficiency)