Biochemical Investigation of Liver Function Flashcards

1
Q

What is the functional unit of the liver?

A

A liver lobule

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2
Q

How are liver lobules arranged?

A

Hexagonal shape composed of: hepatocytes (parenchymal cells) arranged in plates, in contact with bloodstream on one side and bile canaliculi (little canals) on the other

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3
Q

What are between the plates of liver lobules?

A

Vascular spaces (sinusoids) containing Kupffer cells (phagocytic macrophages)

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4
Q

What are the functions of the liver?

A
  • Metabolic - carbohydrates, hormones, lipids, drugs and proteins
  • Storage - glycogen, vitamins, iron
  • Protective - detoxification and elimination of toxic compounds, Kupffer cells ingest bacteria and other foreign material from blood
  • Bile production - formed in biliary canaliculi, emulsifies fats and provides route for waste removal
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5
Q

What are the classifications of liver disease?

A
  • Infection - viral (HepA-E, CMV), bacterial, parasitic
  • Toxic / drug induced
  • Autoimmune
  • Biliary tract obstruction - tumours, gallstones
  • Vascular
  • Metabolic - haemochromatosis, Wilson’s, hereditory hyperbilliruninaemias
  • Neoplastic
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6
Q

What can the causes be of acute hepatitis?

A
  • Poisoning (paracetamol)
  • Infection (Hep A-C)
  • Inadequate perfusion
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7
Q

What cacn the outcome be of acute hepatitis?

A
  • Resolution - majority of cases
  • Progression to acute hepatic failure
  • Progression to chronic hepatic damage
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8
Q

What are the common causes of chronic liver disease?

A
  • Alcoholic fatty liver
  • Chronic active hepatitis
  • Primary biliary cirrhosis
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9
Q

What are some unusual causes of chronic liver disease?

A
  • alph-1 AT deficiency
  • Haemochromatosis
  • Wilson’s disease
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10
Q

What is cholestasis?

A

Failure to produce or excrete bile - result is accumulation of (conjugated) billirubin in the blood leading to jaundice

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11
Q

What can cause jaundice other than hepatic causes?

A

Excessive haemolysis - bilirubin is unconjugated and does not appear in the urine

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12
Q

What does liver failure lead to?

A
  • Inadequate synthesis of albumin leading to oedema and ascites
  • Inadequate synthesis of clotting factors resulting in bruising
  • Inability to eliminate bilirubin causing jaundice
  • Inability to eliminate nitrogenous waste e.g amonia, giving rise to hepatic encephalopathy, a poorly defined neuro-psychiatric disorder
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13
Q

What are the 4 current liver function tests?

A
  • Albumin: for synthetic function
  • ALT: (&AST) aminotransferases for hepatocellular damage
  • ALP: (& gama-GT) for biliary epithelial damage and obstruction
  • Billirubin: for cholestasis (bile flow blockage)
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14
Q

What are advantages of LFTs?

A
  • Cheap, widely available, interpretable

- \direct subsequent investigation (e.g imaging)

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15
Q

What are the disadvantages of LFTs?

A
  • Do not assess liver “function”
  • Lack of complete organ specificity
  • Lack of disease specificity
  • May be “over-sensitive”
  • > 40 years old, many newly discovered diseases for which they have no diagnostic value
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16
Q

What can albumin be used as an assessment of?

A

Liver synthetic function

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17
Q

What can low albumin also be found in?

A
  • Post-surgical/ITU patients due to redistribution
  • Significant malnutrition
  • Nephrotic syndrome
18
Q

What are ALT and AST markers of?

A
  • Sensitive, non specific markers of acute damage to hepatocytes
  • Cytoplasmic enzymes also found in cardiac muscle and erythrocytes
19
Q

What is ALP a marker of?

A
  • Increased liver disease due to increased synthesis in response to cholestasis
  • Biliary epithelial damage and obstruction
  • Also present in bone, gut and placenta
20
Q

What can y-GT be a marker of?

A
  • Raised in cholestasis, also affected by ingestion of alcohol and drugs such as phenytoin
  • Also present in bone, biliary tract, pancreas and kidney
21
Q

What is bilirubin a breakdown product of?

A

Haemoglobin

22
Q

Explain how bilirubin is excreted

A
  • Breakdown product of haemoglobin
  • Unconjugated bilirubin taken up by liver and conjugated
  • Conjugated bilirubin excreted in bile
  • Attacked by bacteria in colon and excreted in faeces
  • Small amounts reabsorbed and excreted in urine as urobilinogen
23
Q

What is cholestasis?

A
  • The consequences of failure to produce and excrete bile
24
Q

What is intrahepatic cholestasis?

A

Failure by hepatocytes

25
Q

What is extrahepatic obstruction?

A

Obstruction to bile flow

26
Q

What does cholestasis result in?

A

Accumulation of bilirubin in circulation and jaundice

27
Q

Why is mild jaundice extremely dangerous in children?

A
  • Weak blood brain barrier

- Billirubin can penetrate into brain more easily and therefore cause death

28
Q

What is the likely cause of hyperbilirubin, normal ALT and ALP but increased conjugated billirubin?

A

Dubin Johnson Roctor syndrome

29
Q

What is the likely cause of hyperbilirubin, normal ALT and ALP and normal levels of conjugated billirubin?

A

Haemolysis Gilberts Crigler-Najjar syndrome

30
Q

What can increased bilirubin in an asysmptomatic patient be due to?

A

Haemolysis, Gilberts syndrome

31
Q

What can increased ALP be due to in an asymptomatic patient?

A

Physiological e.g pregancy, childhood

32
Q

What cna increased ALT be due to in an asymptomatic patient?

A

Skeletal muscle disorders, MI

33
Q

What can increased y-GT be due to in an asymptomatic patient?

A
  • Alcohol, drugs
34
Q

What are the other lab tests should be done after LFTs?

A
  • Hepatitis serology
  • alp-1 antitrypsin deficiency
  • alph-fetoprotein - tumour marker (hepatocellular carcinoma)
  • Caeruloplasmin / copper studies - Wilson’s disease
  • Iron studies - Haemochromatosis (genetic)
  • Autoantibodies - chronic active hepatitis, PBC
  • Radiology - obstruction, hepatomegaly
  • Liver biopsy
35
Q

When can LFTs be normally or mildly increased even when the patient is quite unwell?

A

Chronic disease e.g. cirrhosis

36
Q

Where does liver disease rank in terms of causes of death in men?

A
  • 3rd < 65 yrs

- Likely to rise further due to alcohol consumption and obesity

37
Q

What is iLFT?

A
  • Intelligent Liver Function Test
  • Patients with abnormal LFTs in whom the cause is unclear (patients with jaundice excluded)
  • A combination of biochemistry, haematology and serology in conjunction with liver ultrasound
38
Q

What are the elemants included in the iLFT?

A
  • Patient specific data
  • LFT and FBC performed
  • ALT, ALP and yGT all normal: no further tests
  • Any of ALT, ALP and yGT abnormal:
  • Aetiology screen - Hepatitis serology, liver immunology, ferritin, alph-1 antitrypsin, caeruloplasmin, AST, yGT, platelet count and
  • Fibrosis staging - FIB4 score
  • NAFLD fibrosis score
39
Q

What percentage of the population have Gilbert’s syndrome?

A

7%

40
Q

What is Gilbert’s disease?

A
  • Fluctuating hyperbilirubinaemia
  • Characterised by intermittent mild jaundice evident during periods of fasting and illness
  • Due to conjugating defect in liver