Liver Function Tests (LFTs) - PowerPoint Presentation

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Liver Function Tests (LFTs)

Measurement of Serum Bilirubin (Total, direct &indirect)

T.A. Bahiya Osrah

BilirubinBilirubin is the product of heme

degradation (80% hemoglobin, 20% other hemo-protein as cytochrome, myoglobin

).

Elevated levels of

bilirubin

in blood and urine indicate certain diseases.

BilirubinBilirubin Structure:

Bilirubin consists of four open chain pyrrols, unlike heme

which consists of four rings

pyrrols

called (

porphyrin

).

Bilirubin

Heme

Types of bilirubin in serumIndirect

bilirubin: is unconjugated or water insoluble, it is called indirect because it reacts slowly, so it indicates indirect reaching to reagent. Direct

bilirubin

: is conjugated or water soluble it is called direct because it reacts faster, so it indicates direct reaching to reagent.

Note: Total

bilirubin

= D+ ID

Knowing the level of each type of bilirubin has diagnostic important

Bilirubin ProductionAfter approximately 120 days in the circulation, red blood cells are taken up and degraded by the

reticuloendothelial (RE) system, particularly in the liver, spleen and in the bone marrow. hemoglobin destroyed

to the

heme

+

globin

amino acidIron is removed from the heme molecule, porphyrin ring is opened to form bilirubin

Bilirubin Transportation Bilirubin is insoluble in water and is carried in plasma bound to albumin

On reaching the liver, the bilirubin is taken into the hepatocyte by specific carrier mechanism

Specific carrier

mechanism

Conjugation of bilirubin and secretion into bile

In the liver:Glucouronic acid + un-conjugated bilirubin

(water insoluble)

UDP-

glucuronyltransferase

Bilirubin diglucuronides (water soluble)

Bilirubin diglucuronides are water soluble and readily transported into bile.

Further metabolism of bilirubin in the gut In the intestine:

Bilirubin diglucuronides

Bacteria

Glucouronic

acid + un-conjugated bilirubin

Further metabolism of bilirubin in the gut

Reabsorption

Into the blood

SUMMARY

Measurements of plasma bilirubin: Serum

bilirubin concentration depends on the rate of removal of bilirubin from destruction of hemoglobin. A bilirubin test measures the amount of bilirubin in a blood sample. Types of Bilirubin:

Bilirubin is present in plasma as:

Indirect

Bilirubin (

unconjugated bilirubin

)

Direct Bilirubin (conjugated bilirubin) Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin.

JaundiceJaundice: • Is a term used in clinical medicine to describe a condition in which the skin and sclera appear

yellow caused by increased amounts of bilirubin in the blood

Classification of the causes of Jaundice:

1.

Prehepatic

jaundice

2. Hepatic jaundice

3. Posthepatic jaundice

Pre-hepatic (before bile is made in the liver)Jaundice

in these cases is caused by rapid increase in the breakdown and destruction of the red blood cells (hemolysis), overwhelming the liver's ability to adequately remove the increased levels of bilirubin from the blood. Examples of conditions with increased breakdown of red blood cells include:

Malaria,

sickle cell crisis,

thalassemia,

glucose-6-phosphate dehydrogenase deficiency (G6PD),

drugs or other toxins, and

autoimmune disorders

Hepatic (the problem arises within the liver)

Jaundice in these cases is caused by the liver's inability to properly metabolize and excrete bilirubin. Results from:

• Impaired cellular uptake.

• Defective conjugation.

• Abnormal secretion of bilirubin by the liver cell.

Post-hepatic (after bile has been made in the liver)

Jaundice in these cases, also termed obstructive jaundice, is caused by conditions which interrupt the normal drainage of conjugated bilirubin in the form of bile from the liver into the intestines. This may due to:

gallstones in the bile ducts, tumor

Rise in the serum conjugated bilirubin level and stool becomes clay-colored. Why?

Because of the normal drainage interruption of conjugated bilirubin in the form of bile from the liver into the intestines urine

urobilinogen

levels got decreased therefore the secretion of

sterocobilin resulted to a clay-colored stool

Physiologic jaundice of the newbornHigh

bilirubin levels are common in newborns age (1-3 days old). It is happened because after birth the newborns breaking down the excess RBCs they are born with and, because the newborn’s liver is not fully mature, it is unable to process the extra

bilirubin

, leads to elevate its level in blood and other body tissues.

This situation usually resolves itself within a few days.

Usually newborn is treated by

phototherapy

which breakdown bilirubin (ID<<<<D) and convert it to the photo isomer form which is more soluble. Very high bilirubin is danger and toxic. It may cause brain damage and affect on muscles, eyes and even death.

SUMMARY

The Lab practiceCalculationsThe absorbance of bilirubin

equivalent standard represents:Direct bilirubin=2.5 mg/dl

Total

bilirubin

= 5 mg/dl

Direct

bilirubin

after 1min= (abs test- abs test blank/abs std )* 2.5Total bilirubin after 5 min= (abs test- abs test blank/abs std )* 5To convert mg/dl into µmol/l, multiply the final results by 17.1