Evaluation of liver function tests ppt
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The document discusses liver function tests used to evaluate liver disease. It provides details on various tests including: - Serum bilirubin, which detects liver cell damage and cholestasis. Elevated levels suggest viral or alcoholic hepatitis. - Liver enzymes like ALT and AST reflect hepatocyte damage, while alkaline phosphatase, GGT, and 5'NT indicate cholestasis. - Prothrombin time evaluates synthetic function and is a marker of severity in acute liver disease. - Albumin reflects synthetic capacity but has a long half-life. Prealbumin and coagulation factors are more sensitive markers. - Transient elastography can stage fibrosis non-invasively
Evaluation of liver function tests ppt
- 1. EVALUATION OF LIVER FUNCTION TESTS Guide - Dr. Manohar Lal Prasad Presenter - Dr. Dhiraj Kumar Source - Harrison’s principles of internal medicine 19th edition. Sleisenger and Fortrans textbook of gastrointestinal and liver disease.
- 2. LIVER FUNCTION TEST USED TO: Detect presence of liver disesase To know the extent of known liver diseases Distinguish among different types of liver diseases Follow the response to treatment
- 3. Liver function tests Can be normal in pt. with serious liver diseases Rarely suggests specific diagnosis rather suggest general categories of liver disease Hepatocellular Cholestatic , or infiltrative They detect – liver cell damge, interference with bile flow
- 5. Tests based on detoxification function: Blood ammonia level
- 6. Tests based on excretory functions: Sr. bilirubin Urine bilirubin Urine and fecal urobilinogen Urine bile salts
- 7. Tests based on synthetic functions: Plasma protein Prothrombin time
- 8. Tests based on metabolic functions Carbohydrate metabolism • Galactose tolerance test Lipid metabolism • Sr Cholesterol Protein metabolism • Sr Protein • Aminoaciduria
- 9. Enzymes in diagnosis of liver diseses ENZYMES •AST(SGOT) •ALT(SGPT) ENZYMES •ALP •GGT •5’NT
- 10. Tests used in clinical practice Sr . Bilirubin ALT(SGPT) AST(SGOT) Alkaline phosphatase Serum Albumin Prothrombin time
- 11. Sr. Bilirubin • Breakdown product of porphyrin ring of heme containing protein( myoglobin, cytochrome, peroxidase) • Two fractions: • Conjugated(Direct)(water soluble)(excreted by kidney) • Unconjugated (indirect)(water insoluble) (bound to albumin) • Normal value- 1- 1.5mg/dl • In case of hyperbilirubinemia, if direct fraction <15% - Unconjugated hyperbilirubinemia • Direct fraction- Upper limit of normal range is 0.3mg/dl
- 14. CAUSES OF HYPERBILIRUBINEMIA Isolated increase in unconjugated bilirubin is due to – 1. Hemolytic disease 2. Genetic disorders – crigler najjar and gilbert’s syndrome 3. Neonatal jaundice/physiological jaundice Isolated increase in conjugated bilirubin is due to – 1. Cholestasis 2. Genetic disorders – Dubin johnson syndrome and rotor’s syndrome Increase in both conjugated and unconjugated bilirubin is due to – 1. Intrahepatic /liver disorders
- 17. Degree of elevation of Sr bilirubin significant in: Viral hepatitis Alcoholic hepatitis Drug induced liver disease
- 18. Model for End Stage Liver Disease(MELD) Score • Criteria for listing a pt. for liver transplantation • Range of MELD score is 6 to 40 • Liver tansplantation done in those pt who have >15 MELD score • MELD score – bilirubin, creatinine, PT as INR • MELD score >= 21 high mortality in alcoholic hepatitis
- 19. Urine Bilirubin: Any bilirubin in urine- Conjugated bilirubin Unconjugated fraction is water insoluble and albumin bound, hence not filtered Phenothiazine give false positive Recovering from jaundice urine bilirubin clears prior to Sr bilirubin
- 20. Bile salts: • Are products of cholesterol metabolism • Facilitate absorption of fat from intestine • Primary bile salts- cholate & chenodeoxycholate, produced in liver • Metabolised by bacteria in intestine • Produces secondary bile salts-lithocholate & deoxycholate
- 21. Bile salts In cirrhosis- decreased ratio of primary to secondary bile salts In cholestasis - secondary bile salts not formed – increased ratio of primary to secondary bile salts Normally renal excretion of bile salt is negligible Cholestasis increase renal excretion of bile salt Measured by- Hay’s test, HPLC
- 22. BLOOD AMMONIA: Produced in body during normal protein metabolism & by intestinal bacteria( specially in colon) Detoxification of ammonia In liver – get converted to urea-excreted in kidney In striated muscles- combines with glutamine – glutamic acid
- 23. Advanced liver disease • Significant muscle wasting • Contributes to hyperammonemia Increased blood ammonia • Detect occult liver disease with mental status change Increased blood ammonia • In severe portal hypertension • Portal blood shunts around liver Increased arterial ammonia • Correlates with fulminant hepatic failure outcome
- 24. ENZYMES IN LIVER DISEASES • Sr transaminases • Aspartate aminotransferases (AST)(SGOT) • Alanine aminotransferases (ALT)(SGPT) • Alkaline phosphatase(ALP) • Gamma glutamyl transpeptidase(GGT) • 5’ Nucleotidase(5’NT)
- 26. Sr enzyme test grouped in two categories: Enzymes whose elevation reflect damage to hepatocytes Enzyme whose elevation reflect cholestasis Enzyme showing infiltrative pattern
- 27. Enzymes that reflect damage to hepatocytes: Aspartate aminotransfersase(AST)(SGOT) Alanine aminotransferases(ALT)(SGPT) AST(SGPT) is found in liver > cardiac muscles > skeletal muscles> kidney> brain >pancreas> lungs> WBC >RBC ALT(SGPT) is found primarily in liver.( more liver specific) Normal range is 10-40 IU/L
- 28. • Sr aminotransferases upto 300 IU/L are non specific • Minimal ALT elevation Fatty liver disease • If levels >1000 IU/L reflects extensive hepatocellular injury seen in: 1. Viral hepatitis 2. Ischemic liver injury( prolonged hypotension or acute heart failure 3. Toxin/drug induced liver injury In most acute hepatocellular disorder ALT >=AST
- 29. AST/ALT Ratio: • Normal ratio 0.7 to 1.4 • Useful in 1. Wilson disease 2. Chronic liver disease 3. Alcoholic liver disease • AST/ALT <1 seen in 1.Chronic viral hepatitis 2.NAFLD • AST/ALT >2:1 suggestive & 3:1 is highly suggestive of alcoholic liver disease • In alcoholic liver disease : ALT rarely >300 & ALT often normal( alcohol induced deficiency of PYRIDOXAL PHOSPHATE)
- 30. Aminotransf -erases not increased in obstructive jaundice except During the acute phase of biliary obstructi on Due to passage of gall stone into CBD In this aminotran- sferases 1000-2000 IU/L
- 31. AST(SGOT) • 2 forms 1. Cytosolic 2. Mitochondrial (mAST) – synthesized in precursor form( pre-mAST) converted to mature form • Account for 80% of total AST activity in liver cells • mAST/ total AST ratio- marker of chronic alcohol consumption
- 32. • Isolated rise of ALT is seen in 1. Chronic HepC infection 2. Fatty liver • Isolated AST elevation 1. Alcohol related 2. Drug induced liver injury 3. Hemolysis 4. Myopathic processes These enzymes distinguish hepatocellular from cholestatic jaundice • Increase in ALT and AST (>500 IU/L) in hepatocellular jaundice than in cholestatic jaundice(>200 IU/L) • Persistence of elevated AST & ALT beyond 6 month in case of hepatitis – chronic hepatitis
- 34. Enzymes showing cholestasis: • 3 enzymes are elevation in cholestasis 1. Alkaline phosphatase(ALP) 2. 5’Nucleotidase(5’NT) 3. Gamma glutamyl transpeptidases(GGT) ALP & 5’NT – in or near bile canalicular membrane of hepatocytes GGT located in ER & bile duct epithelial cells(less specific for cholestasis) GGT (sometimes) used to identify occult alcohol use
- 35. • ALP isoenzyme is found in 1. Liver 2. Bone 3.Placenta 4. Small intestine • Physiological rise in ALP 1. Age >60 years ( 1-1.5 times) 2. Blood type O & B (after eating a fatty meal due to influx of intestinal ALP in blood) 3. Children and adolescents ( rapid bone growth) 4. Late in normal pregnancies( placental ALP)
- 36. • ALP < 3 times – any liver disease • ALP> 4 times 1. Cholestatic liver disease 2. Infiltrative liver disease(cancer & amyloidosis) 3. Pagets disease of bone( rapid bone turnover) If ALP is raised – source of isoenzyme by: 1. Fractionation of ALP by electrophoresis 2. Measure GGT &5’NT –elevated only in liver disease 3. Different isoenzymes have different heat susceptibility i. Increased heat stable fraction – MC from placenta ii. Sensitive to heat inactivation- Bone ALP
- 38. Normal levels Sr GGT 10 to 47 IU/L Sr 5’ NT 2 to 17 IU/L Sr ALP 39 to 117IU/L
- 39. Tests based on Biosynthetic function Plasma proteins Coagulation factors(Prothrombin time P.T.)
- 40. Plasma proteins • Liver is the sole source of plasma proteins except for immunoglobulins( by plasma cells) • Sr albumin comprises 60% of all plasma proteins • Tests of plasma protein include: 1. Total Sr protein 2. Sr albumin 3. Sr globulin 4. Sr A/G ratio 5. Pre albumin 6. Pro collagen III peptide 7. Ceruloplasmin
- 41. Albumin • Synthesized exclusively by hepatocytes • Long half life 18 – 20 days; 4% is degraded per day • Slow turn over – not a good indicator of acute or mild hepatic dysfunction • In hepatitis , albumin < 3 mg/dl – Chronic liver disease like cirrhosis, reflects liver damage and decreased albumin synthesis • Non hepatic cause of low albumin: 1. Protein malnutrition 2. Protein losing enteropathy 3. Nephrotic syndrome 4. Chronic infection(increased levels of IL-1, TNF, Cytokines- inhibit albumin synthesis
- 42. Sr Globulin • Made of alpha, beta , gamma globulin • Alpha & beta globulin produced primarily in hepatocytes • Gamma globulin produced by B lymphocytes • In Cirrhosis and Chronic hepatitis – gamma globulin is increased ( Cirrhotic liver fails to clear bacterial antigen from intestine which come through hepatic circulation) • Diffuse polyclonal IgG – Auto immune hepatitis • Increased IgM – Primary biliary cirrhosis • Increased IgA- Alcoholic liver disease
- 43. • Pre Albumin 1. Level falls in liver diseases 2. Half life 2 days 3. Sensitive indicator of change in synthetic & catabolic function 4. Useful in drug induced hepato toxicity • Ceruloplasmin 1. Acute phase protein 2. Normal plasma level 0.2 – 0.4g/l • Decreased in Increased in 1. Wilson disease 1.Copper toxicity 2. Menke’s disease 2. Pregnancy 3. Aceruloplasminemia 3. OCPs 4. Copper deficiency
- 44. Pro collagen III peptide • Cleavage product of type III procollagen molecule • Radioimmuno assay • Increased when there is transformation of viable hepatic tissue into connective tissue / fibrosis • Used in evolution of liver disease like: 1. Chronic active hepatitis 2. Liver fibrosis 3. Liver cirrhosis
- 45. Coagulation factors • Except factor VIII, clotting factors synthesized in liver • Half life ranges 6 hrs( factor VII) to 5 days (fibrinogen) • Measurement is single best measure of hepatic synthetic function • Diagnosis and prognosis of acute parenchymal liver diseases • Test – Prothrombin time(PT) • PT measures II, VII, IX, X activity - Vit K dependent
- 46. PT & INR • INR- Degree of anti coagulation on warfarin therpy • International Sensitivity index(ISI): INR standardise PT measured according to thromboplastin reagent used in any lab expressed as ISI. • ISI is used to calculate INR • PT is increased in 1. Hepatitis 2. Cirrhosis 3. Vit k deficiency- obstructive jaundice, fat malabsorption 4. If PT > 5 times , not corrected by parenteral Vit k - poor prognostic sign in acute viral hepatitis & other liver disease INR is part of MELD Score
- 47. LFT in Anti TB treatment • LFT should be preferred before starting anti TB treatment • With use of rifampicin & isoniazid , onset of liver damage may be as soon as 10 days or may be upto 1yr after commencing therapy • So LFT should be repeated routinely • High risk groups are – 1. Malnourished 2. Children and elderly 3. Known liver disease - Alcoholic liver disease - Hepatitis B &C
- 48. Percutaneous liver biopsy Can be performed bedside with LA Done in • Hepatocellular disease of uncertain cause • Prolonged hepatitis with possibility of auto immune hepatitis • Unexplained hepatitis • Fever of known origin • Staging of malignant lymphoma Contradiction of percutaneous liver biopsy • Significant ascites • Prolonged INR In these conditions transjugular approach is done.
- 49. Transient Elastography (FibroScan) • Ultra sound waves to measure hepatic stiffness non invasively • Useful for early fibrosis in 1. Chronic Hep C 2. Primary Biliary Cirrhosis 3. Hemochromatosis 4. NAFLD 5. Recurent chronic hepatitis after liver transplantation
- 51. Evaluation of chronically abnormal liver tests