The liver - liver.pdftests that are indicators of liver injury or biliary tract disease. ......

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Transcript of The liver - liver.pdftests that are indicators of liver injury or biliary tract disease. ......

  • The liver

    Presented by

    Dr. Mohammad Saadeh

    The requirements for the Clinical Chemistry

    Philadelphia University

    Faculty of pharmacy

  • Introduction

    The liver is the largest organ in the body.

    The liver is of vital importance in intermediary metabolism and in the

    detoxification and elimination of toxic substance.

  • Introduction

    Structure of liver:

    1. 60% hepatocytes

    2.30% kupffer cell (reticuloendothelial )

    3.10% Supporting tissue

  • The liver performs an astonishingly

    large number of tasks that impact all

    body systems.

    Liver have two channels that can

    supply and oxygen nutriment :

    hepatic artery and hepatic portal

    vein .

    The corresponding channels is

    hepatic vein and bile ducts.

  • Functions of liver

    Excretory function: bile pigments, bile salts and cholesterol are excreted in bile into intestine.

    Metabolic function: liver actively participates in carbohydrate, lipid, protein, mineral and vitamin metabolisms.

    Hematological function: liver is also produces clotting factors like factor V, VII. Fibrinogen involved in blood coagulation is also

    synthesized in liver. It synthesize plasma proteins and destruction of

    erythrocytes.

    Storage functions: glycogen, vitamins A, D and B12,and trace

    element iron are stored in liver.

    Protective functions and detoxification: Ammonia is detoxified to

    urea. kupffer cells of liver perform phagocytosis to eliminate foreign

    compounds. Liver is responsible for the metabolism of xenobiotic.

  • Liver function tests (LFTs)

    Liver function tests (LFTs or LFs) are groups of blood tests that give

    information about the state of a patient's liver and can contribute to making an

    accurate diagnosis of the specific liver disorder.

    LFTs are divided into:

    true tests of liver function,

    such as serum albumin, bilirubin, and Prothrombin time.

    tests that are indicators of liver injury or biliary tract disease.

    Typically the LFT comprises of:

    1. Total protein.

    2. Albumin and globulin.

    3. (Prothrombin Time).

    4. Transaminases such as AST & ALT.

    5. Alkaline phosphatase.

    6. Bilirubin.

    7. Gamma Glutamyl Transpeptidase (GGT).

    https://en.wikipedia.org/wiki/Liver

  • Liver function tests

    Most common live disease:

    Hepatitis: acute or chronic damage to and destruction of

    liver.

    Cirrhosis: fibrosis, shrinkage liver, decrease number and

    function of hepatocellular.

    Jaundice: high plasma concentration of bilirubin.

    Cholestasis is defined as a decrease in bile flow due to

    impaired secretion by hepatocytes or to obstruction of bile

    flow through intra-or extrahepatic bile ducts.

    Note: Obstruction bile duct may cause jaundice or cirrhosis.

  • Liver function tests

    These biochemical investigation can assist in differentiating the

    following:

    Obstruction to the biliary tract.

    Acute hepatocellular damage.

    Chronic liver disease.

    Liver cancer.

  • Classification of liver functions test

    Classified based on the major functions of liver:

    Excretion: Measurement of bile pigments, bile salts.

    Serum enzymes: Transaminase (ALT, AST), alkaline phosphate (ALP),

    5-nucleotidase, LDH isoenzyme.

    Synthetic function: Prothrombin time, serum albumin.

    Metabolic capacity: Galactose tolerance and antipyrine clearance

    Detoxification : urea.

  • 1. Excretion : Bilirubin

    Bilirubin is the main bile pigment that is formed from the

    breakdown of heme in red blood cells. The broken down

    heme travels to the liver, where it is secreted into the bile by

    the liver.

    Effective bilirubin conjugation and excretion depend on

    hepatobiliary function and on the rate of RBC turnover.

  • 1. Serum bilirubin:

    Small amount of bilirubin circulates in the blood. Serum

    bilirubin is considered a true test of liver function, as it

    reflects the liver's ability to take up, process, and secrete

    bilirubin into the bile.

  • Bilirubin metabolism serum bilirubin levels are reported as

    1. Total bilirubin (conjugated and unconjugated) (normal value

    = 0.3-1.2 mg/dl).

    2. Direct bilirubin (conjugated bilirubin) (normal value 0.4

    mg/dl), filtrated by glomerulurs.

    Bilirubin is released by Hb breakdown and is bound to

    albumin as water-insoluble indirect bilirubin (unconjugated

    bilirubin), which is not filtrated by glomerulurs.

    Unconjugated bilirubin travels to the liver, where it is

    separated from albumin, conjugated with monoglucuronide

    (25%) and diglucuronide (75%) (more water soluble), and

    then actively secreted into bile as conjugated bilirubin (direct

    bilirubin), which is filtrated by Glomerulurs.

    Figure in the next slide

  • Bilirubin metabolism

  • indirect

    bilirubin

    direct

    bilirubin

    Binding with Glucuronic acid no yes

    Reacting with the diazo reagent

    Slow and indirect

    Rapid and direct

    solubility in water small large

    Discharged via kidney no yes

    Pass through the

    membrane of cell yes no

    Difference of two bilirubins

  • A. urobilinogen :

    Conjugated bilirubin is excreted via bile salts to intestine. Bacteria in

    the intestine break down bilirubin to urobilinogen for excretion in the

    feces (normal value for fecal urobilinogen = 40 - 280 mg/day)

    2. urine(/faeces)

    Normally there are mere traces of urobilinogen in the urine. average

    is 0.64mg , maximum normal 4mg/24 hours.

    B. Urobilin

    Urobilin is the final product of oxidation of urobilinogen by oxygen in

    air. The amount change with the amount of urobilinogen excretion .

  • B. bilirubinurine:

    Bilirubin is not normally present in urine and faese since bacteria in

    intestine reduce it to urobilinogen.

    The kidneys do not filter unconjugated bilirubin because of its avid

    binding to albumin. (bilirubin-albumin complex is too large)

    conjugated bilirubin can pass through glomerular filter.

    Bilirubin is found in the urine in obstructive jaundice due to various

    causes and in cholestasis.

    Note:

    Bilirubin in the urine may be detected even before clinical

    jaundice is noted.

  • Who is a candidate for the test?

    Bilirubin is used to diagnosis of jaundice.

    There are three major causes of increased serum bilirubin

    1. Hemolytic Jaundice, increases total bilirubin; direct bilirubin

    (conjugated) is usually normal. Urine color is normal, and no

    bilirubin found in urine.

    2. Hepatic Jaundice, occur in viral hepatitis; may cause an

    increase in both direct and indirect bilirubin. Urine color is dark,

    and bilirubin is present in the urine.

    3. Obstructive jaundice ( Cholestasis), may be intrahepatic or

    extrahepatic, increase direct and indirect bilirubin. Urine color is

    dark, and bilirubin is present in the urine.

  • Who is a candidate for the test? Bilirubin is used to diagnosis of jaundice.

    Abnormal bilirubin levels can be found in many disorders, including:

    blocked bile ducts

    Cirrhosis

    hepatitis

    liver diseases

    immature liver development in newborns.

  • Liver function tests

    2. Serum enzymes

    Examples:

    Increase (total bilirubin and ALP) OR (ALP and GGT) are indices of

    cholestasis (blockage of bile flow). vvi

    Increase ALT and AST measure the integrity of liver cells. vvi

    Albumin and Prothrombin time measure the liver synthetic capacity.

    Standard group of test Property being assessed

    Serum albumin, PT Protein synthesis

    Serum bilirubin (total) Hepatic anion transport

    Serum enzyme activity

    ALT, AST Hepatocellular integrity

    ALT, GGT Presence of cholestasis

  • Liver function tests

    2. Serum enzymes

    Alkaline phosphatase (ALP or GPT) (remember)

    Clinical significance:

    diagnosis of two groups of conditions; increase in hepatobiliary disease

    (obstructive jaundice, cirrhosis, hepatitis and metastic) and bone disease

    associated with increased osteoblastic activity (child's rickets with D vitamin

    deficiency, Paget's disease, hyperparathyroidism with skeletal).

    extraheptic biliary obstruction; example

    Stone in bile duct.

    Intrahepatic cholestasis.

    Biliary cirrhosis.

    ALP Physiologically increase in; Pregnancy, Childhood, Fatty meals.

  • Liver function tests; 2. Serum enzymes -Glutamyl transferase (GGT): levels are elevated in:(remember)

    Cholestasis

    liver diseases such as alcoholic cirrhosis and drug such as phenytoin.

    5' nucleotidase (5'NTD):(hydrolysis of a nucleotide into a nucleoside and a phosphate)

    5' Nucleotidase (5'NTD) is another test specific for cholestasis or damage to

    the intra- or extrahepatic biliary system

    Elevated ALP and GGT or 5'NTD suggest that the liver is the source.

    Aminotrasferases (remember)

    1. AST (GOT) increased in

    myocardial infarction.

    Acute hepatitis (cell damage) Hepatobiliary diseases such as cirrhosis.

    2. ALT (GPT) levels are el