ChemPath: Liver Disease Flashcards
How may the causes of high bilirubin be categorized?
Pre-hepatic: Liver is OK but something beforehand is increasing the through put and that is haemolysis. Haemolytic anaemia is a good cause. Do a FBC and film. Film you can see if any RBCs are lysing and FBC may show anaemia.
Hepatic disease: Repeat the LFT, gamma GT, all the enzymes the liver makes will leak out into the circulation
Post-hepatic: Liver is fine but there’s something blocking the bile duct. Commonly either a gallstone and cancer of the head of the pancreas. Block the bile duct, end up with bilirubin in the circulation.
Where is bilirubin conjugated?
The liver
How do you measure conjugated and unconjugated bilirubin?
Van de Bergh Reaction
A direct reaction measures conjugated bilirubin
An indirect reaction measures unconjugated bilirubin
When may paediatric jaundice be normal and when may it be pathological?
Paediatric jaundice is usually normal, but the bilirubin should be unconjugated as the cause is usually liver immaturity coupled with a fall in the haemoglobin early in life. If it doesn’t settle, other rare causes should be looked for including hypothyroidism, other causes of haemolysis (including a Coombes test or DAT), and the unconjugated bilirubin will be useful.
What therapy may be used to help bilirubin conjugation?
Phototherapy - skin may also conjugate bilirubin. Converts bilirubin into two other compounds, lumirubin and photobilirubin which are isomers that do not need conjugation for excretion.
What type of inheritance pattern does Gilberts syndrome have?
Recessive
How prevalent is Gilbert’s syndrome?
About 6% of people will have it (1 in 20) 50% carry the gene.
What would you expect to see on LFTs for Gilberts?
Normal LFTs and high bilirubin. No need for liver biopsy.
What may exacerbate a high bilirubin level in Gilberts?
Fasting will increase bilirubin.
Describe the pathology of Gilberts.
UDP glucuronyl transferase activity reduced to 30%. This causes a slightly raised unconjugated bilirubin but this does not enter the urin and cause bilirubinurea.
What does it mean if you have urobilinogen in the urine?
That the enterohepatic circulation is intact. Urobilinogen is always present in the urine of normal people. It comes from the entero-hepatic circulation. If you have a normal GIT, the bilirubin that you make goes into the biliary tree, into the bowel, then bacteria in the bowel converts a small amount of bilirubin into stercobilinogen which is the same as urobilinogen and is reabsorbed and you poo it out.
What does a lack of urobilinogen in the urine suggest?
Blockage of the biliary tree. If you block the biliary tree then the bacteria cannot see the bilirubin, you get pale stools, don’t make any urobilinogen which means urine becomes negative. If urine is negative for urobilinogen but they are jaundice, suggests physical obstruction to biliary tree.
What is the best measure of Liver Function?
- Prothrombin time (clotting factors PT, PTTK)
- Albumin
- Bilirubin
What do raised levels of all liver enzymes suggest?
Hepatitis
What does a high AST and ALT suggest?
Hepatocyte damage
What would an extremely high Alk phos suggest?
- Obstructive Jaundice
- Obstructive jaundice normally causes alk phos to rise a lot. Alk phos will increase by the greatest of the enzymes with obstructive jaundice.
What are prehepatic causes of hyperbilirubinaemia?
- Gilberts
- Haemolysis
What is intra-hepatic shunting of blood?
Normally:
Blood enters portal tract via the portal vein and hepatic artery –> travels through sinusoids (past hepatocytes) –> hepatic vein
Here the patient develops scarring between the portal tract and the central vein
Blood only passes by collagen carring tissue not hepatocytes, it bypasses them completely, it comes in and then comes out. Nothing is done to the blood.
This is called intra-hepatic shunting of the blood.
seen in alcoholic cirrhosis
