Liver Function Tests PDF

Liver function tests Presented by Dr. Salwa Soliman Salman Lecturer of Medical Biochemistry & Molecular Biology  Lecture Objectives Normal liver functions Liver function tests and their interpretation Uses of liver function tests  ❖Normal liver functions 1-In Metabolism 2-Storage functio...

Liver function tests Presented by Dr. Salwa Soliman Salman Lecturer of Medical Biochemistry & Molecular Biology  Lecture Objectives Normal liver functions Liver function tests and their interpretation Uses of liver function tests  ❖Normal liver functions 1-In Metabolism 2-Storage functions 3-Excretory function 4-Detoxification 5-Hematological functions  1-In Metabolism 1. Carbohydrate metabolism: Glycogenesis Glycogenolysis Gluconeogenesis 2. Lipid metabolism: Synthesis of cholesterol Synthesis of phospholipids Synthesis of lipoproteins(VLDL, HDL) Fatty acids oxidation Ketone bodies synthesis 3. Protein metabolism:  Amino acid catabolism(deamination and urea cycle)  Synthesis of plasma proteins 2.Storage functions:  Vitamins(K, D, A, and B12)  Iron 3.Excretory functions:  Bilirubin  others 4- Detoxification Drugs Ammonia Urea Conjugation of Steroid hormone with glucuronic acid and sulphate 5.Hematological functions: Blood formation (fetal life., proerythropoietin in adults) Blood coagulation Blood volume regulation  ❖Liver Function Test Classified in 3 groups 1. Hepatocyte injury : AST, ALT 2. Synthetic function : albumin, PT 3. Cholestasis or Excretory function : bilirubin, ALP, GGT PT, albumin, bilirubin are the most common tests used as prognostic factors  Liver enzymes are grouped in two categories 1- Enzymes whose elevation reflects damage to hepatocytes. Aspartate Aminotransferase Alanine Aminotransferase 2- Enzymes whose elevation reflects cholestasis Alkaline Phosphatase Gamma Glutamyl Transpeptidase 5‘- Nucleotidase Cellular location of enzymes  Aminotransferases (Transaminases) Enzymes that catalyze the inter-conversion of A.A.s and α-keto-acids by the transfer of amino groups. Alanine amino-transferase (ALT) OR Serum glutamate pyruvate transaminase (SGPT) ALT α-ketoglutarate ALT catalyzes the transfer of amino-group from alanine to α-ketoglutarate and thus the formation of glutamate and pyruvate.  Alanine transaminase (ALT): When a cell is damaged, it leaks this enzyme into the blood, where it is measured. It is more specific to the liver than AST Tissues sources Liver > heart > kidney > skeletal muscle > spleen  Causes of increased ALT: Marked increase Acute viral hepatitis (>300 IU/L) Toxic liver necrosis Liver cirrhosis Moderate Cholestatic jaundice Increase Liver congestion secondary to cardiac failure 100-300 IU/L Alcoholic Hepatitis Malignant infiltration of the liver chronic viral hepatitis Minor increase Hemochromatosis ( liver > skeletal muscle >RBCS > kidney > pancreas  Causes of increased AST Physiological In newborns (1.5 times) Liver cirrhosis (up to 2 times) Moderate Cholestatic jaundice (up to 10 times) increase Malignant infiltration of the liver Skeletal muscle involvement Acute viral hepatitis Marked Toxic liver necrosis increase Myocardial infarction  AST/ALT ratio In acute hepatocellular disorders AST/ALT 2:1 is suggestive of chronic liver disease while AST:ALT a ratio > 3:1 is highly suggestive of alcoholic liver disease AST in alcoholic liver disease is rarely >300 U/L and the ALT is often normal. Alkaline Phosphatase (ALP):  phosphatases are enzymes that catalyze the splitting-off of a phosphate from a monophosphate ester (AMP) in alkaline ph.  Source of enzyme: present in high levels in bone, liver, biliary tract epithelium, kidney, intestine, and placenta. Causes of high ALP: Preterm infants (5 times the upper limit for adults ) Physiological Children ( high osteoblastic activity 1.5-2 times higher) pregnancy Medication induced e.g.sulfonamide Intra-hepatic Primary biliary cirrhosis Stones Malignancy (pancreatic, duodenal, cholangiocarcinoma) Extra-hepatic Pancreatitis. Primary sclerosing cholangitis Bone disease  5' nucleotidase (5'NTD) 5' nucleotidase acts only as nucleotide -5’- phosphatases (e.g. AMP) It’s is another test specific for cholestasis or damage to the intra or extrahepatic biliary system. Bone disease does not produce elevation of 5’ nucleotidase: 1. In bone disease: high ALP and normal 5’NTD 2. In liver disease: high ALP and high 5’NTD 5' nucleotidase (5'NTD)  Gamma glutamyl transpeptidase (GGT): γ Glutamyl transpeptidase (GGT) is a membrane bound glycoprotein which catalyzes the transfer of γ glutamyl group to other peptides or amino acids. Large amounts are found in the kidneys, pancreas, liver, intestine and prostate. the primary usefulness of γ glutamyl transpeptidase is limited to the exclusion of bone disease, as γ glutamyl transpeptidase is normal in skeletal disease , children and in healthy pregnant females. Gamma glutamyl transpeptidase (GGT):  Gamma Glutamyl transpeptidase A more sensitive marker for cholestatic damage, cirrhosis and carcinoma than ALP. (GGT) may be elevated with even minor, sub- clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic). There is a direct relation between alcohol intake & GGT level. Bilirubin  Plasma Bilirubin Total Bilirubin 1 mg/dl Indirect: Direct The main form 0.1-0.2 mg /dl 0.2 – 0.7 mg / dl  Bilirubin level >1 mg/dl >2 mg/dl Hyperbilirubinemia Jaundice  Urine Bilirubin And Urobilinogen Urine Bilirubin Absent Urine Urobilinogen 0 – 4 mg / 24hour (Traces) Clinical classification of Hyperbilirubinemia or jaundice 1 2 3 Prehepatic Hepatic Posthepatic Indirect bilirubin in Indirect and direct bilirubin in plasma (Obstructive) plasma Direct bilirubin in urobilinogen in Direct bilirubin in plasma(Marked ) urine. Thus, Dark urine. Thus, Dark urine on standing urine Direct bilirubin in urine. Thus, Dark stercobilinogen in urine stercobilinogen in stool. Thus, faint stool.Thus, dark stool stercobilinogen in stool stool. Thus, very faint ALT & AST in stool Anemia plasma ALP(Marked )  Plasma proteins The liver is the major source of most the plasma proteins. The parenchymal cells are responsible for synthesis of albumin, fibrinogen and other coagulation factors and most of the α and ᵦ globulins.  Total proteins: 6.5-8 gm/dl  1- Albumin It is synthesized exclusively by the liver. Represent 40-60% of total proteins. Synthesis depends on the extent of functioning liver cell mass Longer half-life: 20 days 2- globulins  Normal serum levels: 2 – 3 g/dL   and -globulins mainly synthesized by the liver  High serum -globulins are observed in chronic hepatitis and cirrhosis: › IgG in autoimmune hepatitis › IgA in alcoholic liver disease  Albumin / globulin ratio  Albumin: 3.5 - 5 gm/dl  Globulins: 2 -3 gm/dl  A/G Ratio: 2:1 In chronic liver disease: albumin decreases, globulin increases and total proteins are not affected; while A/G ratio is decreased or reversed In acute liver disease: globulins increase, albumin not affected  Prothrombin time (PT) The liver is major site of synthesis of 11 blood coagulation proteins In acute and chronic hepatocellular disease; the PT may serve as a prognostic indicator  Prothrombin time (PT) Prothrombin: synthesized by the liver, a marker of liver function Half-life: 6 hrs. (indicates the present function of the liver) PT is prolonged only when liver loses more than 80% of its reserve capacity Vitamin K deficiency also causes prolonged PT Dosage of vitamin K does not affect PT in liver disease  A single liver function test is of little value in screening for liver. The use of battery of liver function tests, however constitutes a highly sensitive procedure. Liver Function tests ALT & AST ------------------→ rises in hepatocyte damage Or necrosis of liver cell ALP (with GGT) ------------------→ rises with obstruction of bile flow (( cholestatic picture)) Albumin & PT ----------------→ low Albumin & increased PT (( synthesis is affected)) ALT 5-45 IU/L AST 0-45 IU/L ALP 30-120 IU/L 5’nucleotidase 2-17 IU/L GGT 5-50 IU/L Total Bilirubin (< 1.2 mg/dl) Total protein 6.5-8.5 gm/dl Albumin 3.5-5 gm/dl globulin 2-3 gm/dl A/G Ratio 2/1 Prothrombin Time 10.9-12.5 sec The normal range may be different from lab to lab and sex different Algorithm for Diagnosis of Liver Diseases  Various uses of Liver function tests Screening : They are a non-invasive yet sensitive screening modality for liver dysfunction. Pattern of disease : They are helpful to recognize the pattern of liver disease. Like being helpful in differentiating between acute viral hepatitis, chronic liver disease (CLD) and various cholestatic disorders.  Various uses of Liver function tests Assess severity : They are helpful to assess the severity and predict the outcome of certain diseases. Follow up : They are helpful in the follow up of certain liver diseases and also helpful in evaluating response to therapy.