Liver Key points

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

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

Any condition in which the flow of bile from the liver is slowed or blocked Indicated by raised alkaline phosphatase and gamma glutamyl transferase

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

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

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

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

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

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

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

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

Bilirubin bound to glucaronic acid

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

Alanine transferase Aspartate aminotransferase Alkaline phosphatase Gamma glutamyl-transferase Bilirubin Albumin