Liver Function Tests

Question 1

Describe the blood supply of the liver

Answer 1

• Has a “double” blood supply o Hepatic artery – oxygenated blood o Portal vein – nutrient rich blood

Question 2

What is the functional unit of the liver

Answer 2

• Functional unit = liver lobule

Question 3

Describe a liver lobule

Answer 3

• Each lobule is hexagonal in shape and composed of: hepatocyte (parenchymal cells) arranged in plates, in contact with bloodstream on side and bile canaliculi (“little canals”) on the other

Question 4

What is between plates within the liver?

Answer 4

• Between the plates are vascular spaces (sinusoids) containing Kupffer cells (phagocytic macrophages)

Question 5

What are the main functions of the liver?

Answer 5

• Metabolic Functions – 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 and excretion – formed in biliary canaliculi, emulsifies fats and provides route for waste removal

Question 6

What is the main types of disease of the liver?

Answer 6

• Infection – viral (hepatitis A-E, CMV), bacterial, parasitic - Toxic/Drug induced - Autoimmune - Biliary tract obstruction – tumours, gallstones - Vascular - Metabolic – hemochromatosis, Wilson’s, hereditary hyperbilirubinemias

Question 7

What are the main causes of acute hepatitis?

Answer 7

o Poisoning (paracetamol) o Infection (hepatitis A-C) o Inadequate perfusion

Question 8

What are the main outcomes of acute hepatitis ?

Answer 8

o Resolution – majority of cases o Progression to acute hepatic failure o Progression to chronic hepatic damage

Question 9

What are the common causes of chronic liver disease?

Answer 9

o Alcoholic fatty liver o Chronic active hepatitis o Primary biliary cirrhosis

Question 10

What are the unusual causes of chronic liver disease?

Answer 10

o -1 AT deficiency o Haemochromatosis o Wilson’s disease

Question 11

Cholestasis =

Answer 11

failure to produce or excrete bile

Question 12

What is the result of cholestasis?

Answer 12

• Result is accumulation of (conjugated) bilirubin in the blood leading to jaundice

Question 13

Give another cause of jaundice except cholestasis

Answer 13

excessive haemolysis – bilirubin is unconjugated and does not appear in the urine

Question 14

What are the main classifications for liver failure?

Answer 14

• 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. ammonia, giving rise to hepatic encephalopathy, a poorly defined neuro-psychiatric disorder

Question 15

What are the 4 main current liver functions tests

Answer 15

Albumin - For synthetic function ALT (& AST) - Aminotransferases for hepatocellular damage ALP (& -GT) - for biliary epithelial damage & obstruction Bilirubin - For cholestasis (bile flow blockage)

Question 16

What are the advantages of LFTs?

Answer 16

o Cheap, widely available, interpretable o Direct subsequent investigation (e.g. imaging)

Question 17

What are the disadvantages of liver function tests?

Answer 17

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

Question 18

What is albumin?

Answer 18

main plasma protein

Question 19

When can low albumin be found?

Answer 19

o Post-surgical/ITU patients’ due redistribution o Significant malnutrition o Nephrotic syndrome

Question 20

What do ALT and AST indicate?

Answer 20

non-specific markers of acute damage to hepatocytes

Question 21

Where are ALT and AST found outside the liver?

Answer 21

Cytoplasmic enzymes also found in cardiac muscle & erythrocytes

Question 22

When is ALP increased in liver disease?

Answer 22

increased in liver disease due to increased synthesis in response to cholestasis

Question 23

Where is ALP also present?

Answer 23

Also present in bone, gut and placenta

Question 24

When is -GT raised?

Answer 24

raised in cholestasis, also affected by ingestion of alcohol and drugs such as phenytoin

Question 25

Where is gamma-GT also present?

Answer 25

Also present in bone, biliary tract, pancreas and kidney

Question 26

What is bilirubin >?

Answer 26

• Breakdown product of haemoglobin

Question 27

How is bilirubin excreted?

Answer 27

• 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

Question 28

Cholestasis =

Answer 28

describes consequences of failure to produce and excrete bile

Question 29

Failure by hepatocytes

Answer 29

“intrahepatic cholestasis”

Question 30

Obstruction t bile flow

Answer 30

“extrahepatic obstruction”

Question 31

Draw a flow chart showing how you would consider a patient with hyperbilirubinemia

Answer 31

Question 32

Indicate how tests distinguish vetween hepatocllular damage and colestasis

Answer 32

Question 33

What does raised bilirubin indicate in a patient with no liver symptoms?

Answer 33

haemolysis, Gilberts syndrome

Question 34

What does raised ALP indicate in a patient with no liver symptoms?

Answer 34

physiologucal - pregannacym childhood

Question 35

What does raised ALT indicate in a patient with no liver symptoms?

Answer 35

skeletal muscle disorders, MI

Question 36

What does raised gamma-GT indicate in a patient with no liver symptoms?

Answer 36

alcohol, drugs

Question 37

Give some rare liver aetiologys

Answer 37

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

Question 38

What is an iLFT?

Answer 38

• Patient specific data: age, gender, BMI< features of metabolic syndrome (diabetes, high BP), alcohol intake
• LFT and FBC performed: ALT, albumin, bilirubin, alk phos, gGT and platelets
• Any of ALT, Alk Phos and gGT abnormal:
  
  • Aetiology screen – hepatitis serology, liver immunology, ferritin, alpha-1 antitrypsin, caeruloplasmin, AST, gGT platelet count and;
  • Fibrosis staging – FIB4 score (Age, BMI, impaired fasting glucose/frank diabetes, AST, ALT, albumin, platelets)