Liver Function Tests LFT Dr Aida Ahmed Lecturer

Liver Function Tests (LFT) Dr/ Aida Ahmed Lecturer of Clinical Pathology Al-Azhar University

Review: Liver � The liver is the largest organ in the body. � It is located below the diaphragm in the right upper quadrant of the abdominal cavity. � The working cells of the liver are known as hepatocytes.

� Liver regeneration can occur after surgical removal of a portion of the liver or after injuries that destroy parts of the liver. � , repetitive insults can produce liver failure & death.

Functions of liver � Metabolic � Liver function: actively participates in carbohydrate, lipid, protein, mineral & vitamin metabolisms. � Excretory � Bile function: pigments, bile salts & cholesterol are excreted in bile into intestine.

� 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.

� Storage function: � Glycogen, vitamins A, D & B 12 & trace element iron are stored in liver. � Protective function & detoxification: � Ammonia is detoxified to urea. � kupffer cells of liver perform phagocytosis to eliminate foreign compounds. � Liver is responsible for the metabolism of xenobiotics.

Bilirubin Production Hemoglobin (70 to 80%) Heme proteins myoglobin, cytochromes (20 to 25%) ferritin apoferritin Erythroid cells Heme (250 to 400 mg/day) 3 [O] Fe 3+ + CO Heme oxygenase Biliverdin NADPH + H+ Biliverdin reductase NADP+ albumin Bilirubin Indirect unconjugated pre-hepatic

Bilirubin Processing albumin-Bilirubin albumin ligandin-Bilirubin hepatocyte 2 UDP-glucuronate ER 2 UDP-Glucuronyl transferase Bilirubin diglucuronide bile (gall bladder) direct conjugated post-hepatic

Bilirubin Excretion Bilirubin diglucuronide liver 2 glucuronate Bacterial enzyme Bilirubin Intestines Intrahepatic urobilinogen cycle Bacterial enzyme Urobilinogen kidneys Urobilin Bacterial enzymes Stercobilinogen urine Feces

Plasma Bilirubin � Normal plasma bilirubin: 0. 2– 0. 8 mg/dl. � Unconjugated bilirubin: 0. 2– 0. 6 mg/dl. � Conjugated bilirubin: 0– 0. 2 mg/dl. � If the plasma bilirubin level exceeds 1 mg/dl, the condition is called hyperbilirubinemia. � Levels between 1 & 2 mg/dl are indicative of latent jaundice.

� When the bilirubin level exceeds 2 mg/dl, it diffuses into tissues producing yellowish discoloration of sclera, conjunctiva, skin & mucous membrane resulting in jaundice.

Bilirubin in urine � The conjugated bilirubin is water soluble & is excreted in urine. � The unconjugated bilirubin is not excreted.

� Major liver function tests may be classified as follows � Tests based on excretory function – Measurement of bile pigments, bile salts, � Tests based on serum enzymes derived from liver - Determination of transaminases, alkaline phosphatase, 5'-nucleotidase, γ – glutamyltranspeptidase.

� Tests based on synthetic functions – Prothrombin time, serum albumin. .

� Cholesterol mainly synthesized &metabolized in the liver � 70% estrified&30% free � Normal cholesterol 140 -240 mg/dl � Increased serum cholesterol in obstructive jaundice -Cholesterol total& estrified form decreased in chronic liver disease but increased in cholestasis or obstructive impaired metabolism jaundice due to

2. Serum enzymes � A large number of enzyme estimations are available which are used to ascertain liver function. � They are be divided into two groups: � Most commonly & routinely done in the laboratory. � AST & ALT

Aspartate transaminase (AST/SGOT) � AST or SGOT (serum glutamate oxaloacetate transaminase) SGOT

Aspartate transaminase (AST/SGOT) � Normal range: 10 -45 U/L. � AST is found in both cytoplasm & mitochondria � AST/GOT also reflects damage to the hepatic cells & is less specific for liver disease. � It can also be released with heart, muscle & brain disorders. � AST help diagnose various heart, muscle or brain disorders, such as a myocardial infarct (heart attack).

Elevated levels of AST may indicate � Acute hemolytic anemia � Cirrhosis of the liver � Hepatitis � Acute pancreatitis or inflammation of pancreas � Acute renal failure or loss of kidney function. � Heart attack � Primary muscle disease

Alanine transaminase (ALT/SGPT) � ALT or SGPT (serum glutamate pyruvate transaminase) � ALT is a cytoplasmic enzyme. � Normal Range: 5 -40 U/L. SGPT

Elevated levels of ALT/SGPT may indicate � Alcoholic liver disease � Cancer of liver � Hepatitis or inflammation of the liver � Noncancerous tumor of the liver � Use of medicines or drugs toxic to the liver � Cirrhosis or scarring of the liver � Death of liver tissue.

Alkaline phosphatase (ALP) � ALP occurs in in all tissues, especially liver, bone. bile duct, kidney & the placenta. � The ALP used to help diagnose certain liver diseases and bone disorders. � Normal range: 30 - 95 IU/L (3 -13 kings unit) Levels are significantly higher in growing children

� A rise in serum ALP (normal 3 -13 KA units/dl), usually associated with elevated serum bilirubin is an indicator of biliary obstruction (obstructive/posthepatic jaundice). � ALP is also elevated in cirrhosis of liver & hepatic tumors.

γ - Glutamyl transpeptidase (GGT) � This is a microsomal enzyme widely distributed in body tissues, including liver. � Measurement of γ - glutamyl transpeptidase (GGT) activity provides a sensitive index to asses liver abnormality. � The activity of this enzyme almost parallels that of transaminases in hepatic damage.

� Normal range: 10 -15 U/L � Serum GGT is highly elevated in biliary obstruction & alcoholism. � Several drugs (e. g. phenytoin) induce (liver synthesis) & increase this enzyme in circulation.

5'-Nucleotidase � Normal range: 2 -15 U/L � The serum activity of 5'-nucleotidase is elevated in hepatobiliary disease & this parallels ALP. � The 5'-nucleotidase is not altered in bone disease (as is the case with ALP).

4. Synthetic function � Serum albumin: � Albumin is solely synthesized by the liver. � It has a half-life of about 20 -25 days. � It is a good marker to assess chronic (& not acute) liver damage. � Low serum albumin is commonly observed in patients with severe liver damage. � Albumin is also decreased in malnutrition.

� Functional impairment of liver is frequently associated with increased synthesis of globulins. � Cirrhosis of the liver causes a reversal of albumin/globulin ratio (A/G ratio). .

Prothrombin time � The liver synthesizes all the factors concerned with blood clotting. � A decrease in the concentration of plasma clotting factors is found in the impairment of liver function. � Prothrombin time is prolonged in patients with liver damage, compared to normal. � It generally falls 10 - 15 seconds.

INTERPRETATION OF LIVER FUNCTION TESTS

Typical LFT profile in hepatocellular disease Typical LFT profile in cholestatic jaundice Marked elevation of AST and ALT (usually >500 IU) Marked elevation of ALP (>3 times normal) Mild increase of ALP (<3 times normal Elevation of GGT and 5'Nucleotidase Mild or no increase of ALT and AST (usually <200 IU). . Hyperbilirubinemia, if present, is of both conjugated and unconjugated type Elevation of conjugated bilirubin

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