Liver Key points Flashcards
5 points on hepatitis
Irritation or inflammation of the liver
Acute or chronic forms, chronic form can be persistent or active
Causes including viral and non viral infections, drugs and toxins, alcoholism, ischemia, autoimmune conditions or genetic disorders
Can be a symptom of disease such as hepatic hyperbilirubinaemia. Increase in AST and ALT may be seen due to hepatocyte damage
Hepatitis can lead to acute liver failure when the rate of damage is greater than capacity to regenerate
5 points on gamma glutamyl transferase
One of the enzymes measured in a liver panel where it can be used to help diagnose a patient
GGT is located in the cell membranes and it is expressed in the liver, kidneys, pancreas and intestines
GGT elevation is a classic marker of alcoholism
GGT, ALP and bilirubin elevation indicate obstructive patterns such as cholestasis in the liver
GGT can be used to determine whether a raised ALK is due to liver diseases or diseases of the bone
What is cholestasis?
(2)
Any condition in which the flow of bile from the liver is slowed or blocked
Indicated by raised alkaline phosphatase and gamma glutamyl transferase
5 marks on markers of hepatocellular damage
Alanine transferase and aspartate aminotransferase are good markers for hepatocellular damage
They are very sensitive but they are not specific i.e. very small amount of damage needed to raise levels but they are found in other tissues
ALT and AST are used for monitoring of liver diseases as they can quickly indicate worsening or improvement early on
Both ALT and AST are found in tissues other than the liver such as the heart, muscle and red blood cells
ALT has less activity outside of the liver so it is considered to be more specific for liver damage
GGT may also be increased in hepatocellular damage but this is moreso seen in biliary tree obstruction
5 marks on alkaline phosphatase
An enzyme measured in the liver enzyme panel to help determine the cause of any determined liver damage/disease
ALP is found in both liver and bone tissue where it is used as a marker for damage in both tissues
ALP is often elevated in young children due to growing bones
ALP is released from hepatocytes when there is biliary tree damage/obstruction such as cholestasis
ALP is often measured alongside GGT to determine whether an elevated ALP is due to hepatic disease or bone disease
5 marks on aspartate aminotransferase
One of the markers for hepatocellular damage measured in the liver function panel
When hepatocytes are damaged they release enzymes such as AST which can then be measured in serum
AST is a sensitive biomarker of hepatocyte damage but it is not specific i.e. it is found in other tissues such as heart, muscle and red blood cells
Aspartate aminotransferase can be used as a cardiac biomarker along with other biomarkers such as Lactate dehydrogenase to detect myocardial infarction
For this reason AST is measured alongside alanine transferase to determine whether the cause for increased AST is due to cardiac or hepatic conditions
5 marks on bilirubin
A toxic end product of the breakdown of haemoglobin in red blood cells
The liver detoxifies bilirubin by incorporating it into bile which is then excreted from the body through the GIT in faeces
Bilirubin is formed from the breakdown of haemoglobin: haem is converted into biliverdin by haem oxygenase and biliverdin is converted into bilirubin through biliverdin oxidase
Two forms: conjugated/direct or unconjugated/indirect
Unconjugated is fat soluble and can cross the blood brain barrier when in excess while conjugated is water soluble
Hyperbilirubinaemia is elevated bilirubin and it causes jaundice in patients
10 marks on hyperbilirubinaemia
Increased levels of bilirubin in plasma which results in yellowing of the skin and eyes due to bilirubin deposition i.e. jaundice
Need to measure bilirubin fractions to determine if conjugated or unconjugated bilirubin is high which will help us determine the cause of the jaundice
Hyperbilirubinaemia can be pre-hepatic, hepatic or post-hepatic
Raised unconjugated bilirubin indicates a pre-hepatic issue e.g. haemolysis or low plasma labumin
Raised unconjugated and conjugated bilirubin indicates a hepatic issue e.g. hepatitis, malignancy, drug interactions or an excretion defect
Raised conjugated bilirubin indicates a post-hepatic issue e.g. obstruction in the bile ducts such as gallstones or pancreatic carcinoma
Elevated unconjugated bilirubin is fat soluble and can cross the blood brain barrier where it can cause kernicterus in neonates
5 marks on unconjugated bilirubin
Bilirubin is formed from the breakdown of haemoglobin, it is hydrophobic and insoluble in blood so it must be complexed with albumin to be transfered to the liver
Bilirubin complexed with albumin is known as unconjugated bilirubin
Unconjugated bilirubin is taken up by hepatocytes where it is conjugated by attachment to glucaronic acid
Conjugated bilirubin is then incorporated into bile for excretion into the GIT
In the GIT bacteria deconjugate the bilirubin, some of this unconjugated bilirubin is reabsorbed but the rest is excreted
Measurement of bilirubin
Diazo method - determines bilirubin spectrophotometrically
Diazotised sulfanic acid + bilirubin -> two azodipyrroles which produce a reddish-purple colour at neutral pH and a blue colour at low/high pH
This measures the direct/conjugated bilirubin
An accelerant can be added to measure the total bilirubin
Unconjugated bilirubin is then determined by subtracting the direct from the total
Total bilirubin is usually carried out first and fractionation is only done if elevated
Fractionation is important to determine the cause of the hyperbilirubinaemia
Bilirubin may be elevated in liver disease - in obstructive patterns of disease such as cholestasis
What might raised unconjugated bilirubin indicate?
Raised unconjugated bilirubin indicates a pre-hepatic issue e.g. haemolysis or low plasma labumin
What might raised unconjugated and conjugated bilirubin indicate?
Raised unconjugated and conjugated bilirubin indicates a hepatic issue e.g. hepatitis, malignancy, drug interactions or an excretion defect
What might raised conjugated bilirubin indicate?
Raised conjugated bilirubin indicates a post-hepatic issue e.g. obstruction in the bile ducts such as gallstones or pancreatic carcinoma
What is conjugated bilirubin?
Bilirubin bound to glucaronic acid
How is bilirubin formed?
Bilirubin is formed from the breakdown of haemoglobin: haem is converted into biliverdin by haem oxygenase and biliverdin is converted into bilirubin through biliverdin oxidase
