26. Liver function tests

28/11/2025

Which two blood vessels make up the liver’s dual blood supply

• Hepatic artery

• Hepatic portal vein

State 5 functions of the liver

• Converts nitrogen to urea for excretion

• Synthesises clotting factors

• Metabolises drugs

• Main site of gluconeogenesis

• Forms bile

What is jaundice?

Yellowing of the skin and eyes caused by abnormally high plasma concentrations of bilirubin

3 ways liver dysfunction can manifest

• Prehepatic

• Hepatocellular

• Cholestatic

What is pre-haptic liver disease?

A disease where the liver is not directly involved, it occurs before the liver

What is meant by hepatocellular liver disease?

Damage of the liver itself

What is meant by cholestatic liver disease?

Any condition in which substances normally excreted into the bile are retained in the liver

Summarise the metabolism and transport of bilirubin by describing what occurs in the spleen

• Hb from blood broken down into heam and globin

• The haem is further broken down into iron and bilirubin

• It then becomes bound to albumin in the plasma

What happens to bilirubin when it is in the liver?

Becomes conjugated- this form is water soluble

How does conjugated bilirubin get to the large intestine?

It is transported via the bile ducts

What happens to conjugated bile in the large intestine?

• Bacteria of the large intestine breaks it down into urobilinogen

• Urobilinogen is then broken down further into urobilin

What is prehepatic jaundice?

An increase in unconjugated bilirubin in the blood due to an increased rate of haemolysis

What happens in prehepatic jaundice?

• Increase in bilirubin production

• Which increases production of urobilinogen

• This ends up in the kidneys

• Urobilinogen in the urine

Good biomarkers for prehepatic jaundice

• Unconjugated bilirubin in blood (because a lot of bilirubin is produced)

• Urobilinogen in the urine

Why does urobilinogen end up in the urine in pre-hepatic jaundice?

• Not recycled in the liver because the system is saturated

• Urobilinogen is water soluble so ends up in the kidneys

What causes hepatocellular damage?

• Viruses such as hepatitis B

• Overuse of drugs/ consumption of poisons

• Over consumption of alcohol

What is NAFLD?

• Non alcoholic fatty liver disease

• This is where the liver is fatty without inflammation and fibrosis

What can NAFLD develop into?

• NASH- Non alcoholic steatohepatitis

• Fatty liver with inflammation and fibrosis which can lead to cirrhosis

What is liver cirrhosis

When the liver is so full of scar tissue that instead of being smooth with a dark purple colour it has a nodular surface with a yellow/green colour

What are the sequence of events that lead to liver cirrhosis?

• Injury

• Inflammation

• Cell death

• regeneration

• Regenerating cells form nodules

• Nodules become surrounded by fibrous tissue

Why is cirrhosis bad?

Block the flow of blood in the liver which reduces its own blood flow leading to further cell death

Name 3 biomarkers for hepatocellular damage

• ALT- Alanine aminotransferase

• AST- Aspartate aminotransferase

• GGT- Gamma glutamyl transferase

What is ALT?

• Alanine aminotransferase

• An enzyme found mainly in the liver and in smaller amounts in kidneys and other organs

• Biomarker of hepatocellular damage

Pros of using ALT as a biomarker for hepatocellular damage

• Very low in the serum of normal individuals

• Rises quickly when there is liver damage

• Quite tissue specific

What is AST?

• Aspartate aminotransferase

• Enzyme found in the cells throughout the body, mainly in the heart and liver but not as much in the kidneys

• Biomarker of hepatocellular damager

Pros of using AST as a biomarker of hepatocellular damage

• Very low in the serum of normal individuals

• Released when there is damage in the liver tissue

  • Good for monitoring liver damage

Cons of using AST as a biomarker for hepatocellular damage

Not very tissue specific because widely distributed in other tissues such as the heart, skeletal muscle, kidney and brain

What is GGT?

• Gamma glutamyl transferase

• Enzyme found in many organs of the body but mainly found in the hepatobiliary system

• Used as a biomarker of hepatocellular damage

Pros of using GGT as a biomarker of hepatocellular damage

• Very low in the serum of normal individuals

• Rises quickly and drastically when the liver is injured

• Sample to test for it is easily obtained- blood

Cons of using GGT as a biomarker of hepatocellular damage

• Can be elevated in many types of liver diseases

• Cannot differentiate the cause of liver damage from this biomarker

Which is the best biomarker of hepatocellular damage?

ALT- alanine aminotransferase

What is the biological half life of plasma albumin?

20 days

Which is best identified by a low plasma albumin, chronic or acute liver damage and why?

• Chronic liver damage

• Chronic liver damage develops over a long period of time meaning albumin is not produced for a very long time so there will be decreased levels of it when tested

• Acute liver disease is sudden so the liver is still producing albumin, it will still be present in the plasma with a drop after 20-40 days

Biochemical tests following hep B infection

• ELISA to capture surface antigens and to quantify how much there is

• PCR- to amplify and detect the presence of viral DNA if it is early in the infection

Cons of only using ELISA to detect surface antigens of hep B

• Takes about 1.5 months after infection to be able to detect surface antigens

• By then the infection would have gotten worse and patient will have experienced symptoms

Non-biochemical tests that can be used to identify liver damage

• Biopsy to confirm cirrhosis- punch biopsy or fine needle aspiration

• Ultrasound to confirm fatty liver

What can cause cholestatic liver disease?

• Obstruction of the gall bladder by stones or pancreatic carcinoma

• Can be drug induced such as the use of certain antibiotics

• Primary biliary cirrhosis- an autoimmune condition which attacks the bile ducts

• Primary sclerosing cholangitis- chronic autoimmune condition, common in patients with ulcerative colitis

  • bile ducts become inflamed and obstructed

State two biomarkers of cholestatic liver disease

• ALP- alkaline phosphatase

• Bilirubin in the urine

What is ALP?

• Alkaline phosphatase

• Enzyme that de-phosphorylates compounds such as toxins or lipopolysaccharides of bacteria

• Used as biomarker of cholestatic liver disease

Pros of using ALP as a biomarker of cholestatic liver disease

Secreted by the liver so is a good indicator of whether or not there is cholestatic liver disease

Cons of using ALP as a biomarker of liver disease

• It is not that tissue specific because it is found in large amounts in the kidneys and bone

• It is not easily measured because it has different isoforms specific to the liver, auto-analysers may not always be able to detect them

Why is bilirubin found in the urine in cholestatic liver disease?

• When there is an obstruction in the bile duct, bilirubin cannot go to the large intestine to be broken down into urobilin

• Conjugated bilirubin builds up in the liver and is eventually sent to the kidneys

• It is then excreted in urine via the kidneys

Why is stool pale and fatty in cholestatic liver disease?

• Urobilin makes stool dark

• If there is an obstruction then bilirubin does not become uroblilin and bile is secreted

• Bile emulsifies fat, without it fat ends up in the stool