Liver Function Tests (LFTs) Flashcards

1
Q

Why investigate LFTs?

A

LFTs are requested for two primary reasons:

  1. To confirm a clinical suspicion of potential liver injury or disease
  2. To distinguish between hepatocellular injury (hepatic jaundice) and cholestasis (post-hepatic or obstructive jaundice)
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2
Q

What blood tests are used to assess liver function?

A
  • Alanine transaminase (ALT)
  • Aspartate aminotransferase (AST)
  • Alkaline phosphatase (ALP)
  • Gamma-glutamyltransferase (GGT)
  • Bilirubin
  • Albumin
  • Prothrombin time (PT)
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3
Q

Which LFTs are used to distinguish between hepatocellular damage and cholestasis?

A

ALT, AST, ALP and GGT

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4
Q

Which LFTs are used to assess the liver’s synthetic function?

A

Bilirubin, albumin and PT

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5
Q

Briefly describe ALT

A

ALT is found in high concentrations within hepatocytes and enters the blood following hepatocellular injury. It is, therefore, a useful marker of hepatocellular injury.

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6
Q

Briefly describe ALP

A

ALP is particularly concentrated in the liver, bile duct and bone tissues. ALP is often raised in liver pathology due to increased synthesis in response to cholestasis. As a result, ALP is a useful indirect marker of cholestasis.

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7
Q

How does ALT and ALP show in hepatocellular injury?

A

Greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury.

ALT>ALP

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8
Q

How does ALT and ALP show in cholestasis?

A

Less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis.

ALT

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9
Q

Briefly describe gamma-glutamyl transferase

A

A raised GGT can be suggestive of biliary epithelial damage and bile flow obstruction. It can also be raised in response to alcohol and drugs such as phenytoin. A markedly raised ALP with a raised GGT is highly suggestive of cholestasis.

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10
Q

What may an isolated rise in ALP show? And what may cause this?

A

A raised ALP in the absence of a raised GGT should raise your suspicion of non-hepatobiliary pathology. Alkaline phosphatase is also present in bone and therefore anything that leads to increased bone breakdown can elevate ALP.

Causes:

  • Bony metastases or primary bone tumours (e.g. sarcoma)
  • Vitamin D deficiency
  • Recent bone fractures
  • Renal osteodystrophy
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11
Q

What if the patient is jaundiced but ALT and ALP levels are normal?

A

An isolated rise in bilirubin is suggestive of a pre-hepatic cause of jaundice.

Causes of an isolated rise in bilirubin include:

  • Gilbert’s syndrome: the most common cause
  • Haemolysis: check a blood film, full blood count, reticulocyte count, haptoglobin and LDH levels to confirm
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12
Q

What are the synthetic functions of the liver?

A

The liver’s main synthetic functions include:

  • Conjugation and elimination of bilirubin
  • Synthesis of albumin
  • Synthesis of clotting factors
  • Gluconeogenesis
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13
Q

What is bilirubin? And what is hyperbilirubinaemia?

A

Bilirubin is a breakdown product of haemoglobin. Unconjugated bilirubin is taken up by the liver and then conjugated. Hyperbilirubinaemia may not always cause clinically-apparent jaundice (usually visible >60 umol/l).

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14
Q

How can the colour of urine be used to differentiate between conjugated and unconjugated bilirubin?

A

Unconjugated bilirubin is water-insoluble and, therefore, doesn’t affect the colour of the patient’s urine.

Conjugated bilirubin, however, can pass into the urine as urobilinogen, causing the urine to become darker.

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15
Q

How can the colour of urine and stools indicate the cause of jaundice?

A

Normal urine + normal stools = pre-hepatic cause

Dark urine + normal stools = hepatic cause

Dark urine + pale stools = post-hepatic cause (obstructive)

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16
Q

What is albumin? And what is its function?

A

Albumin is synthesised in the liver and helps to bind water, cations, fatty acids and bilirubin. It also plays a key role in maintaining the oncotic pressure of blood.

17
Q

What can cause a fall in albumin level?

A

Albumin levels can fall due to:

  • Liver disease resulting in a decreased production of albumin (e.g. cirrhosis)
  • Inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin
  • Excessive loss of albumin due to protein-losing enteropathies or nephrotic syndrome
18
Q

What is prothrombin time (PT)? And what does it assess?

A

Prothrombin time (PT) is a measure of the blood’s coagulation tendency, specifically assessing the extrinsic pathway.

19
Q

What does a prolonged PT indicate?

A

In the absence of other secondary causes such as anticoagulant drug use and vitamin K deficiency, an increased PT can indicate liver disease and dysfunction. The liver is responsible for the synthesis of clotting factors, therefore hepatic pathology can impair this process resulting in increased prothrombin time.

20
Q

What does a ALT>AST indicate?

A

Chronic liver disease

21
Q

What does a ALT

A

Cirrhosis and acute alcoholic hepatitis

22
Q
A
23
Q

How does acute hepatocellular damage appear with regards to ALT, ALP, GGT and bilirubin?

A
24
Q

How does chronic hepatocellular damage appear with regards to ALT, ALP, GGT and bilirubin?

A
25
Q

How does cholestasis appear with regards to ALT, ALP, GGT and bilirubin?

A
26
Q

Give examples of causes of acute hepatocellular injury

A
  • Poisoning (paracetamol overdose)
  • Infection (Hepatitis A and B)
  • Liver ischaemia
27
Q

Give examples of causes of chronic hepatocellular injury

A
  • Alcoholic fatty liver disease
  • Non-alcoholic fatty liver disease
  • Chronic infection (Hepatitis B or C)
  • Primary biliary cirrhosis
28
Q

What tests are included in a typical liver function screen?

A
  • LFTs
  • Coagulation screen
  • Hepatitis serology (A/B/C)
  • Epstein-Barr Virus (EBV)
  • Cytomegalovirus (CMV)
  • Anti-mitochondrial antibody (AMA)
  • Anti-smooth muscle antibody (ASMA)
  • Anti-liver/kidney microsomal antibodies (Anti-LKM)
  • Anti-nuclear antibody (ANA)
  • p-ANCA
  • Immunoglobulins – IgM/IgG
  • Alpha-1 Antitrypsin (to rule out alpha-1 antitrypsin deficiency)
  • Serum Copper (to rule out Wilson’s disease)
  • Ceruloplasmin (to rule out Wilson’s disease)
  • Ferritin (to rule out haemochromatosis)