the role of clinical biochemistry in liver disease Flashcards

1
Q

what are in a liver disease blood test? 7

A
  • Serum bilirubin
  • Serum alanine amino-transferase- ALT
  • serum aspartate amino-transferase- AST
  • Serum alkaline phosphatase- ALP
  • serum gamma glutamyl transpeptidase- GGT
  • Serum albumin
  • Plasma prothrombin
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2
Q

what factors influence serum transaminase findings? 7

A
  • Serum activates of ALT and AST are based on three factors:
  • The extent of the damage to the tissues releasing transaminases
  • The amount of transaminase in that tissue
  • The rate of clearance of the enzyme from the circulation
  • The half-life for ALT= 47 hours and AST= 17 hours
  • Complicating factor= hepatocytes have two forms of AST- cytosol and mitochondrial
  • BMI can increase ALT over guideline range
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3
Q

what are the considerations for interpretations for transaminases? 3

A
  • Biological variables (diurnal variation, dietary factors, race, weight)
  • Reference range selection (population exclusion criteria, skewed distribution curve)
  • Drugs (prescribed and over the counter)
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4
Q

describe ALP? 4

A
  • Alkaline phosphatase:
    catalyses the hydrolysis of the phosphate monoesters
  • Membrane bound and mainly found in the liver and bone
  • In the liver it is found in cells which are next to the canaliculi
  • Upregulated (rather than released due to damage) in response to bile duct obstruction and infiltrative or space occupying lesions within the liver
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5
Q

describe GGT? 3

A
  • Mainly found in the hepatobiliary system
  • Increase in blood concentration due to induction/ increase
  • Synthesis by drug or alcohol, biliary obstruction, liver tumours (smaller increase seen in hepatitis)
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6
Q

what are the routine protein tests? 2

A
  • Serum albumin concentration

- Prothrombin time (INR)

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7
Q

describe the production of bilirubin from haem? 4

A
  • 80% of bilirubin is from the red cells taken up by the reticuloendothelial system for degradation
  • Haem oxygenase releases the iron from the haem molecule to form biliverdin
  • Biliverdin is then converted to bilirubin by biliverdin reductase
  • Bilirubin released is tightly bound to albumin
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8
Q

describe the two different types of bilirubin in the blood stream?

A
  • Conjugated=
  • 40% of total
  • Water soluble
  • Excreted in bile
  • If elevated, it appears in the urine giving it a dark colour
  • .
  • Unconjugated=
  • Not water soluble
  • Bound to albumin and therefore does not appear in the urine
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9
Q

describe the presenting features of liver disease? 4

A
  • Jaundice (with or without itching)
  • Pain
  • Non-specific
  • Incidental laboratory finding
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10
Q

describe the diagnosis of liver disease? 3

A
  • Clinical presentation
  • Pattern of routine liver testes
  • How these point to more specific tests including diagnostic radiology
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11
Q

what are the causes of obstructive jaundice? 7

A
  • Extrahepatic:
  • Gallstones
  • Malignancy
  • Pancreatitis
  • .
  • Intrahepatic
  • Hepatocellular disease
  • Drug induced cholestasis
  • Cholangitis
  • Cirrhosis
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12
Q

what are the markers of liver fibrosis? 3

A
  • The FIB-4 score
  • NFS
  • The enhanced liver function test- combines 3 serum markers measures by immunoassay
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13
Q

what are come causes of hepatocellular disease? 11

A
  • Infections:
  • Viral- hepatitis
  • Parasitic- malaria
  • Bacterial
  • .
  • Metabolic:
  • Alcohol
  • Drugs- paracetamol poisoning
  • NAFLD
  • .
  • Autoimmune:
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
  • .
  • Genetic:
  • A1AT deficiency
  • Hemochromatosis
  • Wilson’s disease
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14
Q

describe the investigation into persistent elevated serum ALT? 10

A
  • LFTs including GGT and AST
  • Total protein, albumin, immunoglobulins
  • Glucose
  • Full blood count
  • Autoimmune profile
  • Iron, transferrin saturation, ferritin
  • Copper
  • Viral studies
  • Carbohydrate deficient transferrin
  • Drug history
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15
Q

what are the NAFLD risk factors? 8

A
  • Present when >5% of hepatocytes are steatotic in patients who do not consume excessive alcohol
  • Age
  • Males
  • Metabolic syndrome
  • High in Hispanic people
  • Diet- saturated fat, high fructose
  • Sleep apnoea
  • Genetic
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16
Q

describe NAFLD progression? 3

A
  • 90% simple steatosis- reversible and benign
  • Of these 10-30% progress to NASH – non- alcoholic steatohepatitis
  • Of these 25-40% develop cirrhosis
17
Q

describe the causes of unconjugated hyperbilirubinemia? 3

A
  • Increased bilirubin production (haemolysis, resolution larger haematoma)
  • Impaired bilirubin uptake (poor liver perfusion, drugs)
  • Impaired bilirubin conjugation (physiological in new-born, hereditary defects of conjugation, drugs inhibiting conjugation)
18
Q

describe the role of the laboratory in liver disease? 12

A
  • Detecting liver disease:
  • Clinically overt- jaundice, pain
  • Incidental laboratory finding
  • .
  • Determining the cause of liver disease:
  • Patterns of enzymes and confirmatory tests
  • .
  • Assessing the severity of liver disease:
  • Degree of elevation of bilirubin and enzymes
  • Decrease in serum albumin concentrations
  • Prolonged plasma prothrombin time (INR)
  • .
  • Monitoring the progress of liver disease:
  • Resolution of bilirubin and enzyme activities
  • Development of fibrosis- FIB-4