LIVER FUNCTION TESTS - PSAU Liver Function Tests: Albumin The liver also makes albumin, an essential

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Transcript of LIVER FUNCTION TESTS - PSAU Liver Function Tests: Albumin The liver also makes albumin, an essential

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    A- Metabolic Functions of the Liver:

    1. The liver plays a major role in carbohydrate, lipid and protein homeostasis,

    with the processes of glycolysis, the Krebs cycle, gluconeogenesis, glycogen synthesis and glycogenolysis, lipogenesis, ketogenesis, amino acid synthesis and degradation, and protein synthesis; all taking place in the hepatocytes.

    2. Hepatocytes also metabolize and detoxify endogenous (haem) and exogenous

    products (drugs), which are then excreted via the biliary tree.

    B- Importance and Classification of Liver Function Tests: Importance:

     Liver function test are valuable for:

    1. Diagnosis of liver disease. 2. Categorize the liver disease into its appropriate category. 3. Following the progress of liver disease.

    Classification:  Liver function tests can be classified according to many categories:

    A- According to its function of the test:

    1. Basic Metabolic function tests: include estimation of serum levels of liver

    enzymes e.g. sGPT (ALT) and sGOT (AST).

    2. Excretory function tests: include estimation of serum levels of total and direct


    3. Synthetic function tests: include estimation of serum levels of albumin and


    B- According to the type of variables:

    1. Hepatic anion transport tests: as bilirubin excretion and plasma bile acid


    2. Plasma protein abnormalities: they include

    a) Determination of plasma albumin: (see section No. 3).

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    Clinical Chemistry of Liver

    b) Determination Coagulation factors: Through estimation of:  Vit. K (fat soluble vitamin): where the decrease in the level of this

    vitamin (as in cholestasis) leads to increase the tendency of the patient to bleeding and failure of lipids absorption.

     Prothrombin time: due to deficiency of one or more coagulation factors

    as in hepato cellular damage.

    c) Plasma Ig: they not have large clinical significance but important in

    chronic cases as in liver cirrhosis ↑↑ IgA, ↑IgM and ↑IgG

    d) Ceruloplasmin: it is metalo-protein formed if Cu bind with protein and

    act as α1–protease inhibitor.

    3. Plasma enzyme tests:

    a) Estimation of the soluble enzymes released from cytoplasm and


    b) Estimation of the enzymes released from membrane where they are bind

    to it. They include: o γ-glutamyl transferase (GGT). o Alkaline phosphatase (ALP).

    c) Certain enzymes that their synthesis is impaired when hepato cellular

    function is greatly impaired e.g. cholinesterase enzyme

    4. Metabolic capacity tests:

     Galactose clearance.  Caffeine clearance.

    C- According to type of liver disease:

    1. Tests of hepatic fibrosis:

     Collagen: that deposited in space on basement membrane.  N-terminal peptide.

    2. Liver cirrhosis induced by alcoholic drink: estimation of desialated


    3. Cholestasis tests: e.g. Estimation of total and direct bilirubin.

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    Some of routine liver function test group:

    Clinical Chemistry of Liver

    4. Liver tumors: e.g. Estimation of alpha-fetoprotein as liver tumor marker.

    Liver Function Tests: Albumin

     The liver also makes albumin, an essential protein that circulates in blood.

     Albumin levels are low in people with severe chronic liver disease,

    because the liver does not make normal amounts of albumin.

     However, albumin levels also may fall in a variety of medical conditions.

     A low albumin level is often temporary, so it is not a reliable way to

    diagnose liver disease.

    Liver Function Tests: Bilirubin

     Bilirubin is a waste product from the breakdown of red blood cells. The liver

    processes bilirubin so it can be excreted in stool. Bilirubin flows through the liver's

    bile ducts, dissolved in bile.

     Bilirubin blood levels may be elevated in people with impaired bile flow. This can

    occur in severe liver disease, gallbladder disease, or other bile system conditions.

    Very high bilirubin levels cause jaundice, in which the skin and whites of

    the eyes turn yellow. Bilirubin can be a useful liver function test in people with a

    known bile flow problem. An elevated bilirubin may also be present in

    people with a type of anemia, called hemolytic anemia.

    Test Function

     Plasma albumin.  Protein synthesis.  Plasma total and direct bilirubin.  Hepatic anion transport.  Plasma enzyme activities

    ALT/AST.  Hepatocellular integrity.

     Alkaline phosphatase and GGT.  Presence of Cholestasis.

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    (Excretory and Anion Transport Hepatic Function)

    Sources of Bilirubin:  Hemoglobin;

    o RBC breakdown; 90% of RBC breakdown occurs within reticulo-

    endothelial system (RES) cells (mainly in spleen).

    o Ineffective erythropoiesis (in bone marrow).

     Other haem containing proteins e.g. myoglobin and cytochrome P450 (mainly

    in liver).

     70 to 80% of daily bilirubin production is derived from the breakdown of

    senescent red blood cells, while the remainder is derived from ineffective erythropoiesis and the breakdown of other haem-containing proteins.

     Total daily bilirubin production is 450 up to 550 µmol/day.

    Formation of Bilirubin:  Hemoglobin is broken down to globin and haem. Globin (a protein) is broken down to its constituent amino acids.

     Haem (a 4 ring structure containing Fe 2+ at its center) is broken down (via

    biliverdin) to carbon monoxide, iron and bilirubin.

     Biliverdin gives the green colour sometimes seen in a resolving bruise.  The bilirubin at this stage is termed un-conjugated bilirubin because it has not yet been processed by conjugation in the liver.

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    Clinical Chemistry of Liver

    Un-Conjugated Bilirubin (Hemo-Bilirubin, Indirect Bilirubin):

     A hydrophobic molecule.  Strongly bound (high affinity) to hydrophobic sites on albumin.  Does not appear in urine.  Free un-conjugated bilirubin normally

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    Clinical Chemistry of Liver

    Conjugation by the Liver:  The bilirubin is then conjugated with glucuronic acid by UDP-glucuronyl

    transferase (UDPGT-I) to bilirubin mono-glucuronide (BMG) and by UDPGT- II to bilirubin diglucuronide (BDG).

     Conjugated bilirubin is more water soluble and can be excreted in bile or urine .

     Under normal circumstances there is no conjugated bilirubin present in plasma.

    Excretion into Bile:  Conjugated bilirubin is transported out of the liver cells into the bile canaliculi

    by an energy-dependant carrier-mediated process which is sensitive to cell injury.

     This canalicular excretion step rather than conjugation is thought to be the rate-

    limiting step in bilirubin metabolism.

     Bile flows through the canaliculi, into the bile ducts, and finally into the


    Reticuloendothelial cells Spleen - Bone Marrow

    Biliverdin Bilirubin

    Iron Amino acids


    Systemic circulation



    on albumin


    Urobilin, brownish

    to Urine

    Old RBCs Hb Globin



    Conjugation with Glucuronic acid

    Intestine Free


    Dr. Kakul Husain Firoz 5




    Urobilin, brownish

    to feces

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    Clinical Chemistry of Liver

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     Bilirubin is usually measured by the Jendrassik Grof modification of the van

    den Bergh reaction:  conjugated bilirubin (direct-reacting) (water soluble).  unconjugated bilirubin (indirect-reacting) (water insoluble).

     Normal serum total bilirubin 40 µmol/l).

     The liver has a large reserve capacity- jaundice only appears with severe


    A. Prehepatic:  Excess bilirubin production.

    B. Intrahepatic: 

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     Decreased conjugation of bilirubin by liver cells.  Decreased excretion of bilirubin into bile canaliculi.

    C. Posthepatic:  Biliary obstruction.


    (Increased Production of Bilirubin).

    1- Haemolytic Disorders: