Liver Function Tests (LFTs)

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Liver Function Tests (LFTs). Prepared by Hamad ALAssaf a lassaf_h@yahoo.com. Routine Liver Function Tests (LFTs) . LFTs are blood tests used to diagnose & monitor disease or damage of the liver: 1- Serum Albumin 2- Blood Liver Enzymes: - Alanine amino transferase (ALT) - PowerPoint PPT Presentation

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Liver Function Tests (LFTs)

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Prepared by Hamad ALAssafalassaf_h@yahoo.com

1LFTs are blood tests used to diagnose & monitor disease or damage of the liver: 1- Serum Albumin2- Blood Liver Enzymes: - Alanine amino transferase (ALT) - Aspartate amino transferase (AST) - Gamma glutamyl transferase (GGT) - Alkaline phosphatase (ALP)3- Blood Billirubin (total, direct & indirect)4- Blood Coagulation Factors (prothrombin): Prothrombin Time (PT) 5- Markers of liver fibrosis2Routine Liver Function Tests (LFTs) Albumin is present in higher concentrations than other plasma proteins ( ~ 40 g/L in normal adults). Albumin is synthesized in the liver & has a half-life of 20 days.Very small amounts of albumin cross the glomerular capillary wall. Accordingly, no more than traces of albumin may normally appear in urine that can not be detected by ordinary laboratory means. Albuminuria : In this case, albumin can be detected in urine by ordinary laboratory means due to physiological or pathological conditions. 3Serum AlbuminCauses of hypoalbuminemia:Artifactual: Diluted samplePhysiological : Pregnancy Decreased amino acids: Reduced essential amino acids in diet & reduced synthesis of nonessential amino acids due to either Malnutrition or Malabsorption.Increased catabolism : Surgery, Trauma, Infections.Defective synthesis in liver: Chronic liver diseases (liver cirrhosis)Increased loss : From the kidney (Nephrotic syndrome) or From GIT (Protein loosing entropathies)4Serum AlbuminAminotransferases (ALT & AST) are normally intracellular enzymes.Elevated blood levels of aminotransferases indicate damage to cells rich in these enzymes (as disease to tissue or physical trauma )Blood AST & ALT are of particular diagnostic value

5Blood Aminotransferases (ALT & AST)51- Viral , toxic or alcholic hepatitis:Highly increase in ALT & AST (Up to 20 - 50 folds).In viral hepatitis, ALT is much elevated than AST2- Cirrhosis (chronic liver diseases): Moderate increase (up to 4 5 folds)In chronic cases, AST is much elevated than ALT.3- Obstructive jaundice: Moderate increase ALT & AST are increased up to 3 folds.

4- After alcoholic or drug intake: Transient slight to moderate increase.6Causes of elevated levels of blood ALT & ASTALT is more liver specific than AST. ALT rarely increases in lesions other than the liver parenchymal ALT elevations persist longer than do AST.Formerly named as Glutamate pyruvate transferase (GPT)

Blood levels of AST are increased with many diseases of various organs:1- Liver diseases 2- Myocardial infarction (MI) 3- Progressive skeletal muscular dystrophy4- Crush injury 5- Hemolytic diseases6- Artifact: in hemolysed samples or if serum separation is delayed.Formerly named as Glutamate oxaloacetate transferase (GOT)7Alanine amino transferase (ALT)Aspartate transaminase (AST)GGT present in blood originates primarily from hepatobiliary systemCauses of increased blood GGT:1- Induction of GGT synthesis by these cells occurs without cell damage by alcohol or drugs as anticonvulsants.2- Biliary obstruction: GGT is markedly increased with obstructive jaundice (5 30 folds)Increase earlier (more sensitive) than ALPPersists longer than ALP3- Viral, toxic & alcoholic hepatitis : Increase is only 2 5 folds (less sensitive than ALT & AST) 4- Primary and secondary liver tumors: GGT is elevated earlier than other enzymes in liver neoplasm.Secondary of other organ tumors in the liver can be early detected by elevated GGT. (arouse suspicious that the diseases is metastatic to liver)8Gamma glutamyl transferase (GGT)Main Sources of ALP:1- Cells of hepatobiliary tract (hepatocytes adjacent to the biliary canalculi).2- Osteoblasts of bone : 3- Other Sources: Intestine and placenta & renal tubules.

If ALP is elevated due to a bone disease In this case, GGT is normal i.e. GGT is used to ascertain whether increased ALP is due to bone or hepatobiliary disease

9Alkaline Phosphatase (ALP)Clinical significance of increased serum ALP activities:

1- Physiological increase of ALP:During periods of active bone growth in infancy and at puberty.Preterm infants total ALP is increased to 5 times the upper reference limit of adults due to bone isoenzymes.In children under 3 years, total ALP activity is increased up to 2.5 times the upper limit.Increased twice, during the second and third trimesters of pregnancy (placental ALP).10Alkaline Phosphatase (ALP) cont.2- Pathological increase of ALP:

A- Bone causes: (due to increased osteoblastic activity):Tumors (osteogenic)Paget`s Disease of bone: Marked increase (10 25 folds) Primary osteogenic tumors Secondary malignant deposits in bone if causing osteoblastosisRickets & osteomalacia (vitamin D deficiency)Primary & secondary hyperparathyroidism (increased PTH)Healing of bone fractures 11Alkaline Phosphatase (ALP) cont.B- Hepatobiliray tract: liver diseases with involvement of biliary tract.1- Obstructive jaundice:Extrahepatic cholestiasis : (Marked increase, up to 10 12 folds)Due to obstruction of to the flow of bile through the biliary tract e.g. Gallstones, cholecystitis. Intrahepatic cholestiasis: (Moderate increase , ~ 3 -5 folds)Bile secretion from the hepatocytes into the canalculi is impaired e.g. cholangitis.

2- Viral, toxic & alcoholic hepatitis: Mild to moderate increase, less than 3 folds.12Alkaline Phosphatase (ALP) cont.The liver makes many of the proteins (clotting factors) needed to make blood clot.In certain liver disorders the liver cannot make enough of these proteins and so blood does not clot so well. Therefore, blood clotting tests may be used as a marker of the severity of certain liver disordersIn liver disease, the synthesis of prothrombin & other clotting factors is diminished prolonged prothrombin Time (PT) This may be one of the earliest abnormalities seen in hepatocellular damage, since prothrombin has a short half-life (~ 6 hours)13Coagulation factorsProcollagen type III terminal peptideHyaluronic acid (hyaluronin)14Markers of Liver Fibrosis-FetoproteinOne of the major plasma proteins in fetal life.Falls thru-out gestation and by age one yearIn acute hepatic injury AFP 10 20 folds.Used to screen and diagnose Hepatocellular carcinoma & hepatoblastoma.

1516AmmoniaAmmonia is produced by all tissues from the catabolism of amino acids Ammonia is mainly disposed is via formation of urea in liver

Blood level of ammoina must be kept very low, otherwise, hyperammonemia & CNS toxicity will occur 17Ammoniacatabolism of amino acidsWith production of In LiverUreaSmall amount excreted in urineHyperammonemia Increase of ammonia level of bloodNormal level of blood ammonia is 5-50 mmol/L Hyperammonemia : A medical emergency as ammonia has a direct neurotoxic effect on CNSAmmonia intoxication: It is defined as toxicity of the brain due to increase in ammonia level in the systemic blood. At high concentrations, ammonia can cause coma & death18Causes of Hyperammonemia1- Liver diseases: are common causes in adults i- Acute causes: viral hepatitis, ischemia, hepatotoxins ii- Chronic causes: liver cirrhosis due to alcoholism, hepatitis, biliary obstruction.

2 - Gatrointestinal Bleeding: By action of bacteria of GIT on blood urea with production of much amounts of ammonia that is absorbed to blood. 3- Ornithine transcarbamoylase deficiency (Hereditary)

19Hyperammonemia in Renal FailureRenal Failure

blood urea levels are elevated

Transfer of urea to intestine is increased

Much amounts of Ammonia is formed by bacterial urease

Absorbed to blood

Hyperammonemia20Precautions resampling, handlingA freeflowing venous (or arterial) blood sample should be collected into a specimen tube (preferably prechilled) containing either lithium heparin or EDTA As difficult venepuncture can cause a spurious increase in [ammonia].The sample should be transported on ice to the laboratory, separated within 15 minutes of collection and analyzed immediately. These precautions are necessary as the [ammonia] of standing blood increases spontaneously, due to generation and release of ammonia from red blood cells21Bilirubin and Jaundice22Formation of Bilirubin from Heme Breakdown of RBCs

Heme

Biliverdin (green) Bilirubin (red-orange) bile pigments

In Blood with albuminUNCONJUGATED BILIRUBIN (or INDIRECT BILITUBIN)

23Bilirubin Metabolism in the LiverUptake of Bilirubin by hepatocytes: Bilirubin dissociates from its carrier albumin & enters hepatocytes

Conjugation of Bilirubin: In hepatocytes, bilirubin is conjugated with two molecules of glucuronic acid by the enzyme glucuronyl transferase

Excretion of bilirubin into bile: Conjugated bilirubin (Direct bilirubin) is transported into bile canalculi & then into bile. 24Bilirubin Metabolism in the Intestine25 Conjugated bilirubin bacteria in the intestine Urobilinogen

Stercobilin Reabsorbed in stool (brown) Kidney Urine Urobi