Liver Function Tests PDF

Liver Function Tests Dr Karan Rana Learning Outcomes  Basic structure and functions of the liver.  Conditions that can involve liver malfunction especially jaundice. Biochemical tests for hepatocellular damage  Plasma albumin.  Biological half life of albumin is 20 days so not reduced in...

Liver Function Tests Dr Karan Rana Learning Outcomes  Basic structure and functions of the liver.  Conditions that can involve liver malfunction especially jaundice. Biochemical tests for hepatocellular damage  Plasma albumin.  Biological half life of albumin is 20 days so not reduced in acute liver disease.  In chronic liver disease concentration of albumin in plasma is reduced due to reduced synthesis and loss of albumin into the extravascular compartment. Biochemical tests following hepatitis B infection  HBs Ag – surface antigen (immunoassay)  Anti HBc – antibody to core.  Anti HBs – antibody to surface. Non-biochemical tests  Biopsy to confirm cirrhosis.  Ultrasound to confirm fatty liver. Fat accumulation Cholestatic liver disease  The failure of normal amounts of bile to reach the duodenum.  Obstruction: gallstones (cholesterol/bilirubin/calcium salts); pancreatic carcinoma.  Drug-induced: many agents e.g. several antibiotics.  Primary biliary cirrhosis: chronic autoimmune condition, typically affects women in mid-life.  Progressive obstruction of bile ducts within the liver, often develop a severe pruritus (itchy skin).  Primary sclerosing cholangitis: chronic autoimmune condition common in patients with ulcerative colitis.  The ducts carrying bile within and outside the liver become inflamed, thickened, scarred (sclerotic) and obstructed. Biochemical tests for cholestatic liver disease  Alkaline phosphatase is elevated in cholestatic liver disease. p-nitrophenyl phosphate + H2O phosphate + p-nitrophenol (absorbs at 405 nm)  Specific liver isoform, but this is not detectable on a auto-analyser.  Also found in bone (osteoblasts), placenta and intestinal epithelium.  Elevated in bone disease, cholestatic and to a lesser extent hepatocellular disease. Biochemical tests for cholestatic liver disease  Mainly conjugated bilirubin is elevated in cholestatic liver disease.  Conjugation mechanism is functioning normally but conjugated bilirubin refluxes back into plasma.  Bilirubin detectable in urine.  Conjugated bilirubin is water soluble so it is filtered into the urine at the kidney.  If biliary obstruction substantial: no urobilinogen in urine and light coloured faeces with high fat content.  Bilirubin has to get into the gut before urobilinogen is formed. Metabolism and transport of bilirubin in CLD Spleen Haemoglobin Liver haem globin Bilirubin diglucuronide iron bilirubin Active transport of albumin (conjugated) conjugate across Bilirubin-albumin the canaliculus bilirubin (unconjugated) Bile duct b a Kidney bilirubin c Portal vein t bilirubin (entero-hepatic urobilinogen e in urine r circulation) i urobilin a Large Intestine Putting it all together  Combinations of tests can be much more powerful than a single test.  E.g. 21yo student returns from Asia with flu-like symptoms.  Appeared jaundiced, bilirubin in urine.  Subsequently shown to be infected with hepatitis virus type A. normal range 36 47 Albumin (g/l) 40 Alkaline 40 125 phosphatase (u/l) 190 10 40 560 alanine amino transferase (u/l) 2 17 bilirubin total 110 (µmol/l)  -glutamyl 10 35 transferase (u/l) 60  Summary  The liver can be subjected to numerous conditions and therefore a battery of tests is vital to diagnose liver abnormalities.  The use of non-biochemical tests is particularly useful to assess liver function.  ALP again is not a great biomarker but works well, in conjunction with other biomarkers.  Recommended reading:  Chapter 8 Liver Function Tests in Clinical Biochemistry ed. Nessar Ahmed (2011) or Chapter 5 The Liver in Clinical Chemistry, W J Marshall et al. 7th Edn (2012)  Any questions?? [email protected]