Liver Function Tests: Bilirubin - PDF

Liver Function tests Plasma Bilirubin Bilirubin o Liver synthesises bile which contains bile acids (cholesterol metabolite) and bilirubin (a breakdown product of haemoglobin). o Principal pigment in bile. o Derived from haemoglobin when aged red blood cells are phagocytised by the...

Liver Function tests Plasma Bilirubin Bilirubin o Liver synthesises bile which contains bile acids (cholesterol metabolite) and bilirubin (a breakdown product of haemoglobin). o Principal pigment in bile. o Derived from haemoglobin when aged red blood cells are phagocytised by the reticuloendothelial system. o ~ 85% of bilirubin formed daily – from the degradation of haemoglobin, remaining comes from erythrocyte precursors destroyed in bone marrow, and degradation of haem-containing proteins (myoglobin, cytochromes, catalase). Bilirubin Metabolism Urine Bilirubin contd o200-300 mg bilirubin is produced every day. oA large proportion is excreted in faeces (conjugated form), small proportion exists in serum (both conjugated and unconjugated forms). oNormal serum contains 0.2 –1.0 mg/dL (3-17 mol/L) bilirubin of which only a small proportion (0.2 mg/dL, generally 1/5 of Total) is in the conjugated form. th oClinically evident jaundice, plasma bilirubin > 50 mol/L. oWhen bilirubin concentrations in blood rise, yellowish pigment deposits in sclera of eyes and skin –Jaundice. oJaundice occurs due to imbalance between production and removal of bilirubin. Hyperbilirubinaemia -Jaundice Jaundice Classification of Jaundice Unconjugated Bilirubin o Normally most of the bilirubin in plasma is unconjugated. Most methods measure both conjugated and unconjugated bilirubin in plasma. Causes for increased Bilirubin in Blood Jaundice oHaemolysis/ Ineffective erythropoiesis – Haemoglobin breakdown products are raised – high bilirubin oHepatic cause: Defective conjugating system in the liver Unconjugated bilirubin is not taken up efficiently oObstruction of the biliary system. Jaundice (Types and Tests) - 1 oHaemolytic jaundice – pre-hepatic – Caused by haemolysis, ineffective erythropoiesis Tests: Urinary urobilinogen? Urinary bilirubin? Stool colour? Jaundice (Types and Tests) -2 Hepatic – hepatocellular damage o Conjugation failure a) Neonatal jaundice – activity of UDP transferase is deficient or suppressed b) Crigler-Najjar – defective UDPG-transferase o Bilirubin transport disturbances a) Pre-conjugation failure – Gilbert’s disease b) Post-conjugation failure – Dubin-Johnson disease o Hepatocellular damage or necrosis by Toxins, Infections, Neoplasms, Intrahepatic obstructions (hepatitis, cirrhosis, infiltrations). Jaundice (Types and Tests) - 3 o Obstructive jaundice- post-hepatic - ― Occurs due to stones, spasms or constricture of the bile duct, carcinoma of the pancreas or biliary tree – ??? urobilinogen is formed Tests Urine ? Stools? Familial Causes of Raised Bilirubin Gilbert’s CRIGLER-NAJJAR Dubin- disease SYNDROME Johnson Syndrome Reference Ranges for Plasma Bilirubin Bilirubin (Adult) Total 0.2-1.0 mg/dl (3-17 μmol/L) Unconjugated 0.2-0.8 mg/dl (3-14 μmol/L) Conjugated 0-0.2 mg/dl (0-3 μmol/L) Total Bilirubin in infant in mg/dl 24h 48h 3-5d Premature 1-6 6-8 10-12 Full term 2-6 6-7 4-6 Interpretation of Raised Bilirubin levels! Raised Bilirubin plus: Raised liver enzymes Conjugated bilirubin fraction is raised in the plasma Bilirubin appearance in the urine sample then it reflects liver disease or biliary obstruction. If raised bilirubin but liver enzymes are normal then the following can be considered: Haemolysis Gilbert’s disease Crigler-Najjar Chronic liver disease Bilirubin Summary o Bilirubin originates from red blood cell turnover (~85%), inefficient erythropoiesis, and haemproteins (~15%). oTransported bound to proteins mainly albumin.*0% bilirubin is unconjugated and does not appear in the urine. o Liver uptake through cell membrane-receptor carrier. o Conjugates with glucuronic acid in the presence of enzyme uridine diphosphate glucuronyl transferase- conjugated form is water soluble. o Excreted via the bile duct. o Metabolised in the ileum/colon by intestinal bacteria – urobilinogen – converted to urobilin and excreted or reabsorbed into portal circulation back to liver (~10% filtered by kidney and excreted in urine)