Liver Function Tests. Dr Stephen Butler Paediatric Advance Trainee TDHB

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1 Liver Function Tests Dr Stephen Butler Paediatric Advance Trainee TDHB

2

3 Introduction Case presentation What is the liver? Overview of tests used to measure liver function

4 RJ 10 month old European girl Previously well Referred by GP Diarrhoea and vomiting for 2 weeks Rotavirus negative Stool culture negative Stopped vomiting Diarrhoea continuing

5 RJ Developed rash that morning Axilla Groin Macular papular rash Large spots up to 2cm in diameter Central pallor

6 RJ Examination Well hydrated Rash as described Otherwise unremarkable

7 Bloods 5 th th March Reference Range Sodium 140 mmol/l ( ) 145) Potassium 5.0 mmol/l ( ) 5.2) Urea 3.4 mmol/l ( ) Creatinine 40 µmol/l (20-50) Glucose 5.4 mmol/l ( ) Calcium 2.4 mmol/l ( ) 2.6) Phosphate 1.5 mmol/l ( ) 2.1) Magnesium 1.2 mmol/l ( ) CRP <5 mg/l (<5)

8 Liver Function Tests 5 th th March Reference Range T. Protein 63 g/l (51-73) Albumin Bilirubin ALP GGT AST ALT 43 g/l (30-45) 4 µmol/l (2-20) 20) 3616 U/L (50-350) 8 U/L (5-30) 50 U/L (27-80) 34 U/L (0-30)

9 Liver Function Tests 5 th th March Reference Range T. Protein 63 g/l (51-73) Albumin Bilirubin ALP GGT AST ALT 43 g/l (30-45) 4 µmol/l (2-20) 20) 3616 U/L (50-350) 8 U/L (5-30) 50 U/L (27-80) 34 U/L (0-30)

10 Liver Function Tests 5 th th March Reference Range T. Protein 63 g/l (51-73) Albumin Bilirubin ALP GGT AST ALT 43 g/l (30-45) 4 µmol/l (2-20) 20) 3616 U/L (50-350) 8 U/L (5-30) 50 U/L (27-80) 34 U/L (0-30)

11 Reviewed 10 days Later Diarrhoea resolved No vomiting Rash resolved Back to normal self Eating well Sleeping well

12 Liver Function Tests 5 th th March 15 th March Reference Range T. Protein 63 g/l 67 g/l (51-73) Albumin 43 g/l Bilirubin 4 µmol/l 10 µmol/l (2-20) 20) ALP GGT AST ALT 3616 U/L 8 U/L 50 U/L 34 U/L 48 g/l (30-45) 1277 U/L (50-350) 15 U/L (5-30) 142 U/L (27-80) 174 U/L (0-30)

13 Liver Function Tests 5 th th March 15 th March Reference Range T. Protein 63 g/l 67 g/l (51-73) Albumin 43 g/l Bilirubin 4 µmol/l 10 µmol/l (2-20) 20) ALP GGT AST ALT 3616 U/L 8 U/L 50 U/L 34 U/L 48 g/l (30-45) 1277 U/L (50-350) 15 U/L (5-30) 142 U/L (27-80) 174 U/L (0-30)

14 Reviewed 1 Month Later Well Repeat bloods taken

15 Liver Function Tests T. Protein Albumin Bilirubin ALP GGT AST ALT 5 th th March 15 th March 7 th th April Reference Range 63 g/l 67 g/l 66 g/l (51-73) 43 g/l 48 g/l 47 g/l (30-45) 4 µmol/l 10 µmol/l 14 µmol/l (2-20) 20) 3616 U/L 1277 U/L 434 U/L (50-350) 8 U/L 15 U/L 11 U/L (5-30) 50 U/L 142 U/L 43 U/L (27-80) 34 U/L 174 U/L 29 U/L (0-30)

16 Liver Function Tests T. Protein Albumin Bilirubin ALP GGT AST ALT 5 th th March 15 th March 7 th th April Reference Range 63 g/l 67 g/l 66 g/l (51-73) 43 g/l 48 g/l 47 g/l (30-45) 4 µmol/l 10 µmol/l 14 µmol/l (2-20) 20) 3616 U/L 1277 U/L 434 U/L (50-350) 8 U/L 15 U/L 11 U/L (5-30) 50 U/L 142 U/L 43 U/L (27-80) 34 U/L 174 U/L 29 U/L (0-30)

17 Liver Largest organ in the body Located in abdomen in right upper quadrant, under the ribs Blood supply Hepatic artery oxygen Portal vein newly absorbed nutrients

18

19 Liver Function Carbohydrate metabolism Regulates serum glucose Stores excess carbohydrate as glycogen Protein metabolism Makes albumin Other proteins clotting factors, transferrin, lipoproteins

20 Liver Function Lipid metabolism Makes cholesterol Makes triglycerides Biotransformation Metabolises drugs Conjugates bilirubin Converts ammonia to urea

21 Liver Function Makes and excretes bile Fat emulsification and absorption Fat soluble vitamins

22 Liver Function Tests Bilirubin Total Protein Albumin AST ALT ALP GGT Prothrombin ratio

23 Liver Function Tests Bilirubin Total Protein Albumin AST ALT ALP GGT Prothrombin ratio

24 Liver Function Tests Bilirubin Total Protein Albumin AST ALT ALP GGT Prothrombin ratio

25 Others Glucose Ammonia

26 Bilirubin Waste product from the breakdown of haemoglobin in red blood cells Haemoglobin Haeme + globin Haeme is converted into bilirubin Unconjugated or indirect bilirubin

27 Bilirubin Unconjugated bilirubin is conjugated in the liver Addition of glucuronic acid Conjugated bilirubin is water soluble Conjugated (direct) bilirubin is then excreted into the bile

28

29 Bilirubin Bilirubin is yellow Jaundice is the discolouration of body tissues caused by high levels of bilirubin High levels of bilirubin result from Increased red blood cell breakdown Unconjugated hyperbilirubinaemia A defect in normal metabolism Unconjugated hyperbilirubinaemia A defect in normal excretion of bilirubin Conjugated hyperbilirubinaemia

30 Bilirubin Total bilirubin = unconjugated + conjugated

31 AST Aspartate Aminotransferase Enzyme found in very high concentrations within highly metabolically active tissue Heart muscle Liver cells Skeletal muscle Kidneys, pancreas, red blood cells

32 AST When these cells die AST is released into the blood The level of AST in the blood is directly related to the number of cells affected Level also time related Becomes elevated 8 hours after injury Peaks at hours Returns to normal in days

33 AST High serum AST levels can be caused by: Hepatitis Damage to heart muscle Damage to skeletal muscle Pancreatitis Renal disease

34 ALT Alanine Aminotransferase Enzyme found mainly in the liver Kidneys Heart muscle Skeletal muscle

35 ALT Released into the blood by liver cell death Most ALT elevations are caused by liver dysfunction More sensitive and specific to liver disease than AST Parallels AST

36 ALP Alkaline Phosphatase Enzyme found in high concentrations in: Liver cells Biliary tract epithelium Bone

37 ALP Present in cells lining the biliary collecting system Excreted into the bile Serum levels are mainly increased by both intrahepatic and extrahepatic obstruction of bile

38 ALP Bone is the main source of ALP other than the liver New bone growth in associated with elevated ALP levels Normal growth Tumours Pagets disease Healing fractures

39 GGT Gamma-Glutamyl Glutamyl Transferase Enzyme present in the cell membrane Helps to transfer amino acids and peptides across the cell membrane

40 GGT Highest concentrations found in: Liver Biliary tract Kidney, spleen, heart, intestine, brain, prostate Serum levels are increased by obstruction of bile Parallels ALP

41 PR Prothrombin Ratio (=INR) Measure of blood clotting via the extrinsic and common pathway Measures the clotting ability of: Factor I (fibrinogen) Factor II (prothrombin) Factor V Factor VII Factor X

42 PR

43 PR Factors I, II, V, VII, IX, X are produced in the liver Factors II, VII, IX, X require vitamin K

44 PR Severe liver dysfunction decreased production of clotting factors decreased serum concentration reduced clotting Biliary obstruction reduced excretion of bile fat malabsorption reduced absorption of fat reduced absorption of fat soluble vitamins (A, D, E, K) Corrects if given Vitamin K

45 PR Other causes of raised PR Hereditary factor deficiency Vitamin K deficiency Warfarin

46 Total Protein, Albumin Albumin Protein Formed in the liver 60% of total protein Maintains plasma osmotic pressure Transports drug, hormones, enzymes Severe liver dysfunction decreased production of albumin

47 Total Protein, Albumin Other causes of reduced albumin Malnutrition Protein-losing nephropathy Protein-losing enteropathy

48 Liver Function Tests Bilirubin Total Protein } Liver synthetic function Albumin AST } Liver cell damage ALT ALP } Obstruction to bile GGT Prothrombin ratio - Liver synthetic function

49 Back to the case...

50 RJ 10 month old girl Presented with vomiting, diarrhoea, rash Unremarkable examination

51 Liver Function Tests T. Protein Albumin Bilirubin ALP GGT AST ALT 5 th th March 15 th March 7 th th April Reference Range 63 g/l 67 g/l 66 g/l (51-73) 43 g/l 48 g/l 47 g/l (30-45) 4 µmol/l 10 µmol/l 14 µmol/l (2-20) 20) 3616 U/L 1277 U/L 434 U/L (50-350) 8 U/L 15 U/L 11 U/L (5-30) 50 U/L 142 U/L 43 U/L (27-80) 34 U/L 174 U/L 29 U/L (0-30)

52 Other Tests 15 March Reference Range Calcium 2.6 mmol/l ( ).26) Phosphate 1.8 mmol/l ( ) 2.1) 25-OH Vit.. D 91 nmol/l (50-150) Parathyroid hormone 3.13 pmol/l ( )

53 RJ Transient Hyperphosphatasemia of Infancy and Early Childhood Isolated raised ALP in an otherwise well child May follow viral illnesses Resolves spontaneously over months Unknown cause? Related to delayed clearance of ALP

54 RJ No treatment required Monitor liver function tests until the ALP returns to normal

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