LFT

By Abebe Y.(BSc, MSc in Clinical Chemistry)

Contact : [email protected]

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 Chapter Objectives

Upon completion of this chapter, the student will be able to:

 Describe the anatomy and physiological role of the liver
 About liver enzymes and their activities including formation of
bilirubin.
 Discuss the metabolic processes and organs involved in the
formation & excretion of forms of bilirubin
 Explain the clinical significance of bilirubin
 Describe methods of analysis of serum bilirubin (Direct & total),
sources of errors, and interpretation of bilirubin results

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 Outline

 Introduction
 Anatomy of the liver
 Physiological role of the liver
 Tests for liver function
 Bilirubin
 Formation & excretion of bilirubin
 Clinical significance of bilirubin
 Determination of serum Bilirubin (Direct & total)
 Interpretation of bilirubin results

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 Anatomy of the Liver
Right lobe Left lobe

Gall bladder Bile duct

11/27/2024 Pancreas 4
 I. Gross Anatomy

• Liver weighs about 1.5 kg & is the largest organ

• Located beneath the diaphragm in the right upper quadrant of
the abdomen
• Divided into left & right anatomical lobes
• 2 smaller lobes are found on the posterior (caudate lobe) &
inferior surface (quadrate lobe) of the right lobe.

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 Liver blood circulation

• The liver has dual blood supply:

1.The portal vein (75% of blood
supply)= carries nutrient rich and
toxin-laden blood from the capillary
bed of the alimentary tract
2.The hepatic artery (25% supply) =
carries oxygenated blood from
central circulation to the liver.

• Venous drainage from the liver is via hepatic veins which enter into
the inferior vena cava.

• https://www.youtube.com/watch?v=SjWrloqmMVE

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• The portal triad = bile ducts + hepatic artery + portal vein all of
which bound together
• Bile flows from the hepatocytes into the bile canaliculi and
ductules, to the larger intrahepatic bile ducts, and finally to the left
& right hepatic bile ducts, which emerge from the liver and form
the common hepatic duct.
• Hepatic duct join cystic duct from gallbladder to form common bile
duct
• The gallbladder stores, modifies and concentrates bile.

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 Liver cell types
• The primary cell type of the liver is the hepatocyte
(parenchymal cell), w/c form the liver lobules.
• Metabolic factory of …
• The parenchymal cell (hepatocyte) is the main functional unit
of the liver, constituting 60% of the liver cell population and
80% of the total liver volume.
• The other 40% of the cells are the non parenchymal cells
lining the sinusoidal wall, which constitute endothelial cells,
Kupffer cells, hepatic stellate cells, and pit cells (liver-specific
natural killer cells).

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 Conti…
Hepatocytes contain the following structures
1.Numerous mitochondria (energy generation from oxidative
phosphorylation & fatty acid oxidation)
2.Lysosomes, w/c contain proteolytic enzymes & have specific
degradative functions
3.The Endoplasmic Reticulum , the site of many functions
• smooth ER = bilirubin conjugation, drug detoxification, &
cholesterol synthesis.
• Rough ER = protein synthesis such as albumin, coagulation factors,
& various enzymes.
4.The Golgi complex, w/c produce VLDL & involved in
glycosylation of proteins & albumin secretion
5.Microtubules & microfilaments = maintain cell shape & provide
contractile force.
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• The liver is a multifunctional organ, categorized into :
 Excretory
 Synthetic and
 Metabolic functions
• Major functions of the liver include
Central Receiving & recycling center for the Body
 constantly monitors, recycles, modifies, & distributes cords
absorbed from the GIT & delivered to the liver.
 removes many of the toxic cords that are ingested or produced in
the body (e.g. bilirubin) and targets them for excretion in the urine
or the bile.

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 Cont’….
Physiological Functions of the Liver
 Synthesis
 Detoxification
 Storage
 Immunologic
 Excretion/Secretion

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 Synthesis
 Synthesize many biological compounds

1. Carbohydrate metabolism
 Uses glucose for its own cellular energy

 Circulates glucose to peripheral tissue

 Stores glucose as glycogen

 Major player in maintaining stable glucose concentration due to

glycogenesis, glycogenolysis and gluconeogenesis

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2. Lipids
Liver gathers free fatty acids from diet and breaks them
down to Acetyl- CoA to form triglycerides, phospholipids,
or cholesterol
 Converts insoluble lipids to a soluble form
 70% of cholesterol produced by the liver

3. Proteins
 Almost all proteins made in the liver
 Exceptions are immunoglobulins and Hgb
4. Ketone body formation
5. Nucleotide biosynthesis
6. Synthesis and export of cholesterol and triacylglycerol
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Liver serves as a gatekeeper between the circulation
and absorbed substances
First pass: every substance absorbed in GI tract passes
through liver
Detoxification includes drugs and poisons, and
metabolic products like ammonia, alcohol, and bilirubin
 3 mechanisms
 Binds material reversibly to inactivate
 Chemically modify compound for excretion
 Drug metabolizer for detox of drugs and poisons

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• Glycogen
• All fat-soluble vitamins (A, D, E, K) and some water
soluble vitamins (B12)
• Iron
• Blood
Immunologic/protective function
• Kupffer cells ingest bacteria or other foreign material from the
blood
• IgA secretion

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 Hematological function:

 Liver participates in formation of blood (particularly in

embryo)
 Liver is also produces clotting factors like
factor V, VII.
 Fibrinogen involved in blood coagulation is
also synthesized in liver.
 It synthesize plasma proteins & destruction
of erythrocytes.

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• Liver processes and excretes bile
 3L produced/day, 1L excreted/day
Begins at the bile canaliculi, enters hepatic ducts, then to
common hepatic & bile duct
 Bilirubin is the principal pigment in bile

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 Liver disease
 Diseases of liver classified by aetiology
– Clinically also defined by stage of disease process
• Acute, subacute, chronic
– And also by pathological state of the liver
• Assessed clinically, radiologically or histologically
• E.g. A patient with alcoholic liver disease
– Acute alcoholic hepatitis
– Alcoholic cirrhosis

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 Aetiology of liver disease
• Viral • Toxic/drug-induced • Autoimmune
– Hep viruses A-E – Alcohol – AlI hepatitis
– EBV – Drugs – Primary biliary cirrhosis
– Cytomegalovirous – Poisons • Neoplastic
– Arboviruses • Biliary tract obstruction – Primary
– Arenaviruses – Gallstones – Secondary
• Parasitic – Strictures • Vascular
– Schistosomes – Sclerosing cholangitis – Budd-Chiari syndrome
– Liver flukes – Biliary atresia – Portal vein thrombosis
– Toxocara sp – Tumours – Veno-occlusive disease
– Tapeworms • Genetic/metabolic • Miscellaneous
– Leptospira sp – Haemochromatosis – Polycystic liver disease
• Protozoal – Wilson disease – Congenital liver fibrosis
– Amoebiasis – Inherited
– Kala-azar hyperbilirubinaemias
– Malaria – Cystic fibrosis
• Bacterial – Hepatic porphyria
– TB
– Pyogenic liver disease

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 Acute Liver disease
 Occurs for one of 3 reasons
 Poisoning
 Infection
 Inadequate perfusion
 Biochemical markers such as ALT and AST indicate
hepatocyte damage
 Elevated serum bilirubin, ALP, GGT and 5'- nucleotidase
show the presence of cholestasis

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 Poisoning
 The most well documented poisons that affect liver are
 Paracetamol and Carbon tetrachloride
– These are metabolized by intact liver in small
amounts, but when present at high concentrations
they give rise to toxic metabolites, leading to
destruction of hepatocytes
 Some plants and fungal toxins can also cause fatal liver
damage within 48 hrs
 3rd group of toxins are those that cause damage on
susceptible individuals
 Sodium valproate (anticonvulsant drug)
 Halothane (anaesthetic agent)
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 Liver infection
 Include
 Parasitic infection
• Helminthic = e.g. schistosomes, liver flukes
• Protozoal = e.g. plasmodial, amoebiasis
 Bacterial infection
• TB
 Viral infection
• HAV, HBV, HCV, HEV
 Acute liver damage can progress in 3 ways
 It may resolve
 It may progress to acute hepatic failure
 It may lead to chronic hepatic damage
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 Hepatic failure

 Acute hepatic failure is a major medical emergency b/c

the failure of the complex metabolic functions of the
liver cannot be compensated for by any other organ.

Chronic liver disease

 Three forms
 Alcoholic fatty liver
 Chronic active hepatitis
 Primary biliary cirrhosis
 All of these conditions may progress to cirrhosis, a disease
characterized by extensive liver fibrosis
fibrosis is the formation of scar tissue, and results in the
11/27/2024disorganization of liver architecture, and its shrinkage
 What is liver metastasis?
• A liver metastasis is a cancerous tumor that has spread to the liver
from another place in the body.
• It is also called secondary liver cancer.
• Primary liver cancer originates in the liver and most commonly
affects individuals who have risk factors such as hepatitis or
cirrhosis
• Most of the time, cancer in the liver is secondary, or metastatic.
• The cancer cells found in a metastatic liver tumor are not liver cells.
They are the cells from the part of the body where the primary
cancer began (for example, cancerous breast, colon, or lung cells).
• Other names for this condition include:
• liver metastases
• metastases to the liver

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 Symptoms of liver metastasis

• There may be no symptoms in the early stages of liver

metastasis.
• In later stages, cancer can cause the liver to swell or obstruct the
normal flow of blood and bile. When this happens, the following
symptoms may occur:
 loss of appetite, weight loss, dark-colored urine
 abdominal swelling or bloating
 jaundice, a yellowing of the skin or the whites of the eyes
 pain in the right shoulder, pain in the upper right abdomen
 nausea , vomiting, confusion, sweats and fever, enlarged liver
• When the liver is enlarged, a lump can be felt on the right side of
the abdomen below the ribcage.
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 Diagnosis of liver metastasis
• The doctor may suspect liver cancer if the liver is enlarged on
examination, if the liver surface is not smooth, or if any of the
symptoms above are reported.
• Various kinds of testing will be needed to confirm the diagnosis.
These tests include:
A. Liver function tests
• Liver function tests are blood tests that indicate how well the liver
is functioning.
• Liver enzyme levels are often elevated when there is a problem.
• Blood or serum markers are substances in the blood that are linked
to cancer.
• When primary liver cancer is present, there may be higher levels of
alpha-fetoprotein (AFP) detected in the blood.
• Liver function tests can help distinguish between primary liver
cancer and liver metastasis.
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AFP markers can also be used to monitor treatment effects of primary liver
27
B. CT scan of the abdomen
• A computed tomography (CT) scan is a special kind of X-ray
that takes visual images of soft-tissue organs in detail.
Cancerous tissue will have a moth-eaten appearance.
C. Ultrasound of the liver
• Also called sonography, an ultrasound transmits high-
frequency sound waves through the body. These sound waves
produce echoes. The echoes are then used to create map-like
computerized images of the body’s soft-tissue structures.
D. MRI
• Magnetic resonance imaging (MRI) creates extremely clear
images of internal organs and soft-tissue structures. It uses
radio waves, a large magnet, and a computer.
……………………etc….

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Treatments for liver cancer
• Several options are currently used for treating cancer that has
metastasized to the liver.
• In most cases treatment will be palliative. This means that it
will be used to control symptoms of cancer and prolong life
but will not likely result in a cure.
• Generally, the choice of treatments will depend on:
 the person’s age and overall health
 the size, location, and number of metastatic tumors
 location and type of the primary cancer
 the types of cancer treatment the patient had in the past

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What are the symptoms of a liver disorder?

• Symptoms of a liver disorder include:

 weakness
 fatigue or loss of energy
 weight loss
 jaundice (yellow skin and eyes)
 symptoms of nephritic syndrome (swelling around the eyes,
belly, and legs)
 discolored bodily discharge (dark urine or light stools)
 nausea
 vomiting
 diarrhea
 abdominal pain

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 Tests for Liver Function

•Total and Direct bilirubin *

•Total protein *
•Albumin*
•Prothrombin time
•Cholesterol
•Triglycerides
•Urea
•Ammonia
•Liver Inflammatory Enzymes: AST*, ALT*, ALP*, GGT

* Standard liver Panel test (LFT)

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 LIVER FUNCTION TEST
• Liver function tests help determine the health of your liver by
measuring the levels of proteins, liver enzymes, or bilirubin in your
blood.
• A liver function test is often given in the following situations:
 to screen for liver infections, such as hepatitis C
 to monitor the side effects of certain medications known to affect the
liver
 if you already have a liver disease, to monitor the disease and how
well a particular treatment is working
 to measure the degree of scarring (cirrhosis) on the liver
 if you’re experiencing the symptoms of a liver disorder
 if you’re planning on becoming pregnant

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 Liver function tests cont’d
• Non-invasive methods for screening of liver
dysfunction

• Help in identifying general types of disorder

• Asses severity and allow prediction of outcome
• Diseases and treatment follow up

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 What are the most common liver function tests?
• Liver function tests are used to measure specific enzymes and
proteins in your blood. Depending on the test, either higher- or
lower-than-normal levels of these enzymes or proteins can
indicate a problem with your liver.
• Classified in 4 groups:
 Synthetic function: Total protein, albumin,
• prothrombin time

 Hepatocyte injury: AST, ALT

 Metabolic activity: bilirubin

 Cholestasis: ALP, Gamma Glutamyl Transferase (GGT)….

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Bilirubin(C33H36N4O6)
 An organic anion
It is mainly (80 %) derived from the degradation of ageing
erythrocytes in the spleen, liver (hepatocytes, kupffer
cells), kidneys and bone marrow
Approximately 36.2 mg bilirubin are produced from 1g
haemoglobin
 The daily output of bilirubin is 250-350 mg (3.8 ± 0.6 mg/kg
BW)
An apolar, water-insoluble lipophile substance, is
potentially toxic
Serum bilirubin level is an important clinical marker
of hepatobiliary excretory function

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 Bilirubin metabolism

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 Cont’…..
(Liver, Bone marrow,
& Spleen)

Phagocytosis & Lysis

Hemoglobin(80%)
Haem-containing proteins(20%)

Globin Heme Bilirubin

Amino acids Fe2+

Amino acid pool Recycled Excreted

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 Cont’…..

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• Majority of conjugated blirubin passes via
bile ducts to the intestine where it’s
transformed through bacterial action
into Urobilinogen which is highly soluble

• Small amount is deconjugated and

absorbed by the small intestine into the
portal blood to the liver where it is
extracted by the liver cells and conjugate
again and excreted in the bile
(enterohepatic circulation of bile pigments)

• Small portion returns to plasma and bound

less tightly to albumin & is excreted in the
urine

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 Bilirubin Metabolism
1. Hemoglobin released from red cells
2. Iron and globin are conserved
3. Insoluble albumin- bound unconjugated bilirubin
4. Albumin removed and conjugated to glucuronic acid by
hepatocytes
5. Conjugated bilirubin excreted in bile (via the gallbladder and
common bile duct)
6. Enters sm. intestine as component of bile
7. Bacteria convert to urobilinogen (UBG)
8. ~15% UBG is reabsorbed by intestinal mucosa

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 Urobilinogen
1. Conjugated bilirubin enters the high pH of small intestine

2. ß-glucoronidase converts bilirubin back to unconjugated form

3. Bacteria reduce biliribin to three compounds known as

urobilinogen (UBG), UBG is colorless

4. 15% UBG is reabsorbed and returns to the liver

5. All re-excreted into bile except 2-5% via kidneys

6. Most (85%) UBG is oxidized into urobilin, the brown

pigment of feces

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Types of Bilirubin
 Unconjugated bilirubin (indirect)

 Conjugated bilirubin (direct)

 Delta Bilirubin

 Total Bilirubin

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 Increased plasma concentrations of bilirubin (>3 mg/dL) occurs
when there is an imbalance between its production and excretion

 Recognized clinically as jaundice

 Jaundice: A condition characterized by a brownish-yellow

pigmentation of skin, sclera & mucous membranes

 Icterus: A condition characterized by an increase of bilirubin in

blood

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• A symptom, not a disease or
disorder
• The yellow staining of connective
tissue from excess bilirubin
• Prominently - sclera of the eyes and
skin
• Icterus describes the dark yellow- Above photo is courtesy of the Centers
brown color of serum with for Disease Control and Prevention

increased bilirubin

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• Jaundice can be caused by:
 Over production of bilirubin

 Disturbance in the uptake and transport of bilirubin

 Defects in conjugation or excretion of bilirubin

 Obstruction of the large bile ducts

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• Jaundice is usually not noticeable to the naked eye (known as
overt jaundice) until bilirubin levels reach 3.0 mg/dL

• Jaundice is most commonly classified based on the site of the

disorder:

 Pre-hepatic jaundice

 Hepatic jaundice and

 Post-hepatic jaundice

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Prehepatic (hemolytic) jaundice

 Results from excess production of

bilirubin (beyond the livers ability
to conjugate it) following hemolysis

 Excess RBC lysis is commonly the

result of
 Autoimmune disease;
 Hemolytic disease of the newborn (rh- or
ABO- incompatibility);
 Structurally abnormal RBCs (sickle cell
disease); or
 Breakdown of extravasated blood

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 Pre-hepatic….
 High plasma concentrations of unconjugated bilirubin (normal
concentration ~0.5 mg/dL)

 rarely have bilirubin levels that exceed 5 mg/dL

 Laboratory Results: ↑serum bilirubin (mostly unconjugated),

↑urine urobilinogen, ↓ Hgb ↓ Hct ↓ MCV ↓ MCHC ↑ RDW & ↑
reticulocytes

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Neonatal jaundice

• Another Cause of Prehepatic Jaundice

• Common, particularly in premature infants

• Transient (resolves in the first 10 days)

• High levels of unconjugated bilirubin are toxic to the newborn

Due to its hydrophobicity it can cross the blood-brain
barrier and cause a type of mental retardation known as
kernicterus

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It is due to

The larger hemoglobin mass of the neonate compared with the

adult

 A lower plasma albumin level

 A lower conjugation rate because of a low conjugates content and

immaturity of the conjugating enzyme (UDP- GT)

 An immature biliary secretory apparatus

 The absence of bacterial flora

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• Phototherapy with UV light

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 Neonatal jaundice….
• If necessary, exchange blood transfusion is used to remove
excess bilirubin

• Phenobarbital is sometimes administered to mother prior to an

induced labor of a premature infant – crosses the placenta and
induces the synthesis of UDP glucuronyl transferase

• Jaundice within the first 24 hrs of life or which takes longer than
10 days to resolve is usually pathological and needs to be further
investigated

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• Liver inflammation and/ or cellular damage due to various causes -
viral hepatitis, parasites, malignancy, drug-induced hepatitis

 Clinically HAV & HBV most common

• Also, metabolic liver diseases, alcoholic cirrhosis, autoimmune

hepatitis

• Degree of bilirubin uptake varies (normal to decreased)

• Laboratory results: ↑serum bilirubin (unconjugated & conjugated),

positive urine bilirubin, liver enzymes elevated (esp. ALT and
AST)
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 Other Causes of Hepatic Jaundice
• Transport Failure
 Gilbert's disease (preconjugation transport failure)

 Dubin-Johnson syndrome (Postconjugation transport failure )

• Conjugation Failure
 Crigler-Najjar syndrome

• Intrahepatic obstruction
 Drug induced [e.g., chlorpromazine]

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• An obstruction of the bile ducts, which serve as the conduit of
bile from the liver to the duodenum

• The most common cause is gallstones, but tumors in or near to

the bile ducts can also impede bile flow into the small intestine

• Since conjugated bilirubin is normally excreted as a component

of bile, bilirubin accumulates in circulation, leading to jaundice

• Post-hepatic jaundice includes increased conjugated bilirubin,

detected in both serum and urine

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The absence of bilirubin in bile negatively effects digestion
1. The brown pigment urobilin is not produced -feces become
pale and clay-colored

2. Causes poor absorption of fats and fat-soluble vitamins (A, D,

E, K). Deficiencies of these nutrients are possible
 affects vitamin K dependent coagulation factors

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 Clinical Correlations
**Urobilinogen = UBG; *Total Bili = (conjugated + unconjugated)

Jaundice Clinical Serum Serum Urine Urine

Type Condition Conjugated Total Bilirubin (UBG)**
Bilirubin Bilirubin
*
None Normal Normal Normal Neg Normal
level level <1 mg/dL
Pre- Hemolytic Normal or Increase Neg Increase
hepatic anemia Sl Increase
Hepatic Hepatitis Increase Increase Positive Normal
or
increase
Post- Obstruct- Increase Increase Positive Normal
hepatic ion of bile or none.
duct
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 Analysis of Bilirubin

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 Specimens for Bilirubin / UBG Analysis
• Non-hemolyzed serum or heparinized
plasma

• Fresh urine

• Protect from light (e.g., wrap collection

tube in aluminum foil)

• Light exposure will reduce bilirubin and

UBG detected

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 Semi-quantitative Analytical methodology
Icterus Index Test
• Measures the degree of icterus in plasma or serum and correlates
with a rough estimation for bilirubin concentration.

• Take absorbance at 420nm, result is expressed in icterus index

units obtained in comparison with standard potassium
dichromate solution of assigned icterus index value

• Low specificity because of interference due to presence of

hemoglobin, carotene, and different yellow pigments found in
sample.

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 Measuring Bilirubin in Serum or Plasma
 Bilirubin in serum or plasma is commonly measured by
photometric methods based upon the diazo reaction

Conjugated bilirubin + diazotized sulfanilic acid →

azobilirubin + alkaline tartrate (green to blue-green color)

Measured with photometer at 555 - 600 nm depending on

specific reagent used
 insoluble un-conjugated-bilirubin requires an accelerating agent
to react with the diazo reagent

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Principle:
Sulphanalic acid + NaNO3 diazotized sulphanalic acid (DSA)

DSA + Bilirubin “D” Azobilirubin “purple”

Bilirubin “ID”+ DSA + accelerator Total bilirubin.

Kit components
 Sulfanalic acid reagent

 Sodium nitrate reagent

 accelerator

 Bilirubin Standard

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 Two Classic Diazo Reagent Methods
Malloy and Evelyn Jendrassik-Grof
• uses a caffeine benzoate
uses methanol as an
accelerator
accelerator

Limitations: interference from • A blue-green azobilirubin

hemoglobin and turbidity due mixture is read at 600 nm
to protein precipitation by
methanol
• Caffeine is omitted for
conjugated bilirubin only

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 Calculations

Bilirubin concentration:
Abs (test) - Abs (test blank) X concentration of standard
Abs of standard

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 Modern Adaptations of Diazo Methods
• Some systems use a dimethyl sulfoxide (DMSO) accelerator,
known as the Walters and Gerarade modification

• Sodium nitrate is used to diazotize sulfanilic acid

• Enzymatic and metal binding reagents are used in some

automated analyzers

• Dry-slide system - a modification of Jendrassik-Grof

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 Reference Ranges for Bilirubin for Interpretation
of Results
• Compare patient result with reference range
• * EU = “Ehrlich unit”, is equivalent to 1 mg/dL
• Newborn range for full term,1-2 days old

Patient conjugated total Urine Urine

bilirubin bilirubin bilirubin, urobilino-
conjugated gen
Newborn Not < 12.0
(1-2 d old) applicable mg/dL
Adult 0-0.2 0.3-1.2 negative <0.8 EU*
mg/dL mg/dL
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 Sources of Interference in Bilirubin Testing

• Samples over-exposed to light

• Hemolysis interferes with diazo reaction
• Manual procedure requires carefully timing and pipetting to
avoid analytic error
• Outdated or poor calibration concentration curve
• Improperly maintained or operated instrument

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 Serum Albumin
• The most abundant protein synthesized by the liver
• Normal serum levels: 3.5-5g/dl
• Synthesis depends on the extent of functioning
liver cell mass
• Longer half-life:20 days
• Its level decrease in all chronic liver diseases

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 Albumin to globulin (A/G) ratio
• Normal A/G ratio: 1.2-1.5
• Globulin level increases in hypoalbuminemia as a
compensation

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 Prothrombin Time (PT)
• Prothrombin: synthesized by the liver, a marker of
liver function
• Half-life: 6 hours (indicates the present function of
the liver)
• PT is prolonged only when liver loses more than 80%
of its reserve capacity
• Vitamin K deficiency also cause prolonged PT
• -----Review Hematology - Coagulation disorder and lab.

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Prothrombin Time (PT)/INR

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 Alanine transaminase (ALT) test
• Alanine transaminase (ALT) is used by your body to metabolize
protein.
• If the liver is damaged or not functioning properly, ALT is released
into the blood.
• This causes ALT levels to increase.
• A high result on this test can be a sign of liver damage.
• According to the Mayo Clinic, •The normal range for ALT is 7–55
units per liter (U/L)
• Low ALT is not indicative of any health issues.

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 Aspartate aminotransferase (AST) test

• Aspartate aminotransferase (AST) is an enzyme found in several

parts of your body, including the heart, liver, and muscles.
• Since AST levels aren’t specific for liver damage, it’s usually
measured together with ALT to check for liver problems.
• Your doctor may use an ALT-to-AST ratio to help with their
diagnosis.
• When the liver is damaged, AST is released into the bloodstream.
• A high result on an AST test might indicate a problem with the liver
or muscles.
• The normal range for AST is 8–48 U/L.
• Low AST is not indicative of any health issues.

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 Alkaline phosphatase (ALP) test

• Alkaline phosphatase (ALP) is an enzyme found in your bones, bile

ducts, and liver.
• An ALP test is typically ordered in combination with several other
tests.
• High levels of ALP may indicate liver damage, blockage of the bile
ducts, or a bone disease.
• Children and adolescents may have elevated levels of ALP because
their bones are growing.
• The normal range for ALP is 45–115 U/L. Low ALP can also result
from a variety of conditions, including zinc deficiency,
malnutrition, and Wilson disease.

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 AST
• A Marker of hepatocellular damage
• Since AST levels aren’t specific for liver damage, it’s usually
measured together with ALT to check for liver problems.

• High serum levels are observed in:

 Chronic hepatitis

 Cirrhosis

 liver cancer

• Normal range: about 5 to 35 U/L of serum

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 ALT

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 ALT
…

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 ALT

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 ALP

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 ALP

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 ALP….

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Liver ALP…

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 GGT

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GGT…
.

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 5’ Nucleotidase (NTP)
• Raised levels of NTP activity were found in patients with
obstructive jaundice, parenchymal liver disease, hepatic
metastases and bone disease

• NTP is precise marker of early hepatic primary or

secondary tumours
• ALP levels also increased in conjugation with NTP showing
intra or extra hepatic obstruction due to malignancy
• Elevation of NTP is found in acute infective hepatitis and also
in chronic hepatitis

• In acute hepatitis elevation of NTP activity is more when

compared with chronic hepatitis

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 Ceruloplasmin
• Ceruloplasmin is synthesized in the liver and is an acute
phase protein
• It binds with the copper and serves as a major carrier for
copper in the blood
• Normal plasma level of ceruloplasmin is 200 to
600mg/L
• The level is elevated in infections, rheumatoid arthritis,
pregnancy, non Wilson liver disease and obstructive
jaundice
• In Wilson\'s disease ceruloplasmin level is depressed

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 Thank you!

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