Jaundice Flashcards
List 5 liver function tests.
1 - Bilirubin.
2 - Liver enzymes (AST/ALT).
3 - Hepatobiliary enzymes (gGT, Alk Phos).
4 - Albumin.
5 - Total protein.
List the constituents of bile.
How much bile is produced per day by hepatocytes?
Bile is made up of:
1 - Bile acids.
2 - Cholesterol.
3 - Phospholipids.
4 - Bile pigments such as bilirubin and biliverdin.
5 - Electrolytes.
6 - Water.
- Hepatocytes produce ~0.5L bile per day.
How many times per day is bile recycled?
Why must bile be recycled?
- 6-8 times per day.
- Needs to be recycled as some is used in the intestines and some is lost through faeces.
List 3 functions of bile.
1 - Emulsification of fat (micelle formation).
2 - Fat soluble vitamin uptake (ADEK).
3 - Excretion of substances that can’t be cleared by the kidneys (cholesterol and bilirubin).
Where in the intestine is bile released?
At the duodenum.
Where in the intestine are bile salts reabsorbed?
At the ileum.
List 4 signs and symptoms of jaundice.
1 - Yellow discolouration of the skin, eyes and other tissues.
2 - Fatigue.
3 - Abdominal pain.
4 - Weight loss.
What substance causes the yellow discolouration of tissues in jaundice?
What concentration of this substance is considered to be jaundice?
- A buildup of bilirubin in tissue fluid and the bloodstream.
- In excess of 2mg/ml.
What causes neonatal jaundice?
- Low levels of the liver enzyme UGT, which is involved in the conjugation of bilirubin.
- The breakdown of fetal haemaglobin (as it is replaced with adult haemaglobin).
- These processes occur naturally but not at excessively high rates.
What are the 3 causes of jaundice?
1 - Prehepatic.
2 - Intrahepatic.
3 - Extrahepatic.
How is bilirubin formed in the body?
It is a product of haem catabolism, e.g. catabolism of:
1 - Red blood cells.
2 - Myoglobin.
3 - Cytochromes.
4 - Peroxidases.
How much bilirubin is produced per day?
~300mg.
What is the mass of the body’s total bile salt pool?
~3.5g.
What is the average lifespan of an erythrocyte?
~120 days.
What happens to erythrocytes at the end of their lifespan?
- Macrophages in the spleen and bone marrow engulf and degrade them.
- The erythrocytes release their haemoglobin molecules, which are broken down into haem and globin..
What is the fate of the globin that is a product of haemaglobin catabolism?
It is broken down into amino acids, which re-enter the blood to be used for haemopoiesis again.
What is the fate of the haem that is a product of haemaglobin catabolism?
- It is broken down further into unconjugated bilirubin and Fe2+.
- The Fe2+ re-enters circulation to be used for haemopoiesis again.
- The unconjugated bilirubin is not recycled as it is toxic, and must therefore be excreted.
Is unconjugated bilirubin lipid soluble or water soluble?
What are the implications of this?
- Lipid soluble.
- It requires a carrier protein in the blood (albumin).
Where is unconjugated bilirubin in the blood transported to?
The liver.
What are Kupffer cells and where are they found?
Kupffer cells are specialised macrophages in the liver.
List 2 functions of Kupffer cells.
1 - To break down old / damaged erythrocytes.
2 - To catabolise unconjugated bilirubin.
What is conjugated with unconjugated bilirubin in the liver?
Glucuronic acid is conjugated with unconjugated bilirubin in the liver.
Is conjugated bilirubin lipid soluble or water soluble?
Water soluble.
What is the importance of the conjugation of unconjugated bilirubin?
Since conjugated bilirubin is water soluble, it is able to be excreted by the liver in bile.
Through which duct does bile enter the gallbladder?
Through the cystic duct.
Through which duct does bile enter the intestine?
Through the common bile duct.
Which two ducts merge at the ampulla of Vater?
The common bile duct and the pancreatic duct.
What happens to conjugated bilirubin once it reaches the ileum?
Intestinal bacteria converts it into urobilinogen by removing the glucoronic acid via a hydrolysis-reduction reaction.
What happens to urobilinogen in the ileum?
- 10% is reabsorbed into the blood and binds to albumin.
- 90% is oxidised by other intestinal bacteria to form stercobilin.
What gives faeces its brown colour?
Stercobilin.
What happens to the urobilinogen that is reabsorbed into the blood from the ileum?
- It is carried by albumin back to the liver by the portal system.
- Half of this urobilinogen participates in the enterohepatic urobilinogen cycle.
- The other half is transported in the blood to the kidneys, where it is converted to urobilin and excreted.
What happens to urobilinogen during the enterohepatic urobilinogen cycle?
It is taken up by the liver and secreted into the bile.
What gives urine its yellow colour?
Urobilin.
Why are the eyes particularly vulnerable to yellowing in jaundice?
- Scleral tissue in the eyes is high in elastin.
- Elastin binds bilirubin with high affinity.
List 2 prehepatic disorders that increase unconjugated bilirubin in the blood.
1 - Extravascular haemolytic anaemias.
2 - Ineffective haematopoiesis.
Why do extravascular haemolytic anaemias increase levels of unconjugated bilirubin in the blood?
Macrophages break down red blood cells earlier than they normally would, releasing unconjugated bilirubin.
Why might ineffective haematopoiesis increase levels of unconjugated bilirubin in the blood?
Macrophages breakdown defective red blood cells, releasing unconjugated bilirubin.
Why might high unconjugated bilirubin in the blood cause pigmented gallstones?
- The liver converts the unconjugated bilirubin into conjugated bilirubin.
- This is converted into conjugated bilirubin, which increases the risk of pigmented gallstones.
Why isn’t unconjugated bilirubin excreted?
Because it isn’t water soluble.
Why might neonatal jaundice be dangerous?
- Unconjugated bilirubin can collect in the basal ganglia of the brain.
- This is known as kernicterus.
- Kernicterus can cause brain damage and death.
How is neonatal jaundice treated?
- Using phototherapy.
- Unconjugated bilirubin absorbs energy from light, and undergoes conformational changes that make it more soluble.
- The unconjugated bilirubin is then able to be excreted in the urine.
List 2 genetic defects that increase unconjugated bilirubin in the blood.
1 - Gilbert’s syndrome.
2 - Crigler-Najjar syndrome.
How does Gilbert’s syndrome cause jaundice?
- It causes low activity of the liver enzyme UGT.
- UGT is necessary for conjugation of unconjugated bilirubin.
- If unconjugated bilirubin cannot be conjugated, it cannot be excreted as it will remain lipid soluble, so it remains in the blood.
How does Crigler-Najjar syndrome cause jaundice?
- It causes the liver enzyme UGT to be absent.
- UGT is necessary for conjugation of unconjugated bilirubin.
- If unconjugated bilirubin cannot be conjugated, it cannot be excreted as it will remain lipid soluble, so it remains in the blood.
Give an example of a genetic disorder that causes high levels of conjugated bilirubin in the blood.
Dubin-Johnson syndrome.
How does Dubin-Johnson syndrome increase conjugated bilirubin in the blood?
- MRP2 transporter proteins that are responsible for moving the conjugated bile from the liver into the bile ducts are deficient.
- Conjugated bilirubin therefore builds up in the liver.
- MRP3 transporter proteins are upregulated when MRP2 transporters are deficient.
- MRP3 transporters move the conjugated bilirubin into the interstitial space, where it returns to the blood.
Which inheritance pattern does Dubin-Johnson syndrome show?
Autosomal recessive.
What effect does high blood conjugated bilirubin have on the urine and the liver?
They become dark.
What is obstructive jaundice?
Jaundice caused by a blockage of the bile ducts, causing conjugated bilirubin, bile salts and cholesterol to accumulate and leak through the tight junctions between hepatocytes back into the blood.
List 5 symptoms and complications of obstructive jaundice.
1 - Pruritis (itchy skin).
2 - Cholesterolaemia.
3 - Xanthomas (yellow patches on the skin caused by deposition of fats)
4 - Steatorrhoea.
5 - Decreased vitamin absorption.
Why might obstructive jaundice cause steatorrhoea and decreased vitamin absorption?
Because bile does not reach the intestine (instead it is forced back into the blood), so fats cannot be broken down and vitamins cannot be absorbed.
Why does viral hepatitis increase both conjugated and unconjugated bilirubin in the blood?
- Hepatocytes are destroyed.
- The liver loses the ability to conjugate bilirubin, increasing unconjugated bilirubin in the blood.
- Since hepatocytes line the bile ducts, when hepatocytes are destroyed, this allows bile to leak back into the blood, increasing conjugated bilirubin in the blood.
Categorise the causes of jaundice in this deck into prehepatic, intrahepatic and extrahepatic.
Prehepatic:
1 - Extravascular haemolytic anaemias.
2 - Ineffective haematopoiesis.
Intrahepatic:
1 - Gilbert’s syndrome.
2 - Crigler-Najjar syndrome.
3 - Dubin-Johnson syndrome.
4 - Viral hepatitis
Extrahepatic:
1 - Obstructive jaundice.
List the causes of jaundice in this deck and state how they affect both conjugated and unconjugated bilirubin in the blood.
1 - Extravascular haemolytic anaemias - increase unconjugated.
2 - Ineffective haematopoiesis - increase unconjugated.
3 - Gilbert’s syndrome - increased unconjugated.
4 - Crigler-Najjar syndrome - increased unconjugated.
5 - Dubin-Johnson syndrome - increased conjugated.
6 - Viral hepatitis - increased both unconjugated and conjugated.
7 - Obstructive jaundice - increased conjugated.
