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DIG > Jaundice > Flashcards

Jaundice Flashcards

1
Q

List 5 liver function tests.

A

1 - Bilirubin.

2 - Liver enzymes (AST/ALT).

3 - Hepatobiliary enzymes (gGT, Alk Phos).

4 - Albumin.

5 - Total protein.

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2
Q

List the constituents of bile.

How much bile is produced per day by hepatocytes?

A

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.
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3
Q

How many times per day is bile recycled?

Why must bile be recycled?

A
  • 6-8 times per day.

- Needs to be recycled as some is used in the intestines and some is lost through faeces.

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4
Q

List 3 functions of bile.

A

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).

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5
Q

Where in the intestine is bile released?

A

At the duodenum.

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6
Q

Where in the intestine are bile salts reabsorbed?

A

At the ileum.

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7
Q

List 4 signs and symptoms of jaundice.

A

1 - Yellow discolouration of the skin, eyes and other tissues.

2 - Fatigue.

3 - Abdominal pain.

4 - Weight loss.

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8
Q

What substance causes the yellow discolouration of tissues in jaundice?

What concentration of this substance is considered to be jaundice?

A
  • A buildup of bilirubin in tissue fluid and the bloodstream.
  • In excess of 2mg/ml.
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9
Q

What causes neonatal jaundice?

A
  • 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.
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10
Q

What are the 3 causes of jaundice?

A

1 - Prehepatic.

2 - Intrahepatic.

3 - Extrahepatic.

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11
Q

How is bilirubin formed in the body?

A

It is a product of haem catabolism, e.g. catabolism of:

1 - Red blood cells.

2 - Myoglobin.

3 - Cytochromes.

4 - Peroxidases.

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12
Q

How much bilirubin is produced per day?

A

~300mg.

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13
Q

What is the mass of the body’s total bile salt pool?

A

~3.5g.

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14
Q

What is the average lifespan of an erythrocyte?

A

~120 days.

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15
Q

What happens to erythrocytes at the end of their lifespan?

A
  • 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..
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16
Q

What is the fate of the globin that is a product of haemaglobin catabolism?

A

It is broken down into amino acids, which re-enter the blood to be used for haemopoiesis again.

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17
Q

What is the fate of the haem that is a product of haemaglobin catabolism?

A
  • 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.
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18
Q

Is unconjugated bilirubin lipid soluble or water soluble?

What are the implications of this?

A
  • Lipid soluble.

- It requires a carrier protein in the blood (albumin).

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19
Q

Where is unconjugated bilirubin in the blood transported to?

A

The liver.

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20
Q

What are Kupffer cells and where are they found?

A

Kupffer cells are specialised macrophages in the liver.

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21
Q

List 2 functions of Kupffer cells.

A

1 - To break down old / damaged erythrocytes.

2 - To catabolise unconjugated bilirubin.

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22
Q

What is conjugated with unconjugated bilirubin in the liver?

A

Glucuronic acid is conjugated with unconjugated bilirubin in the liver.

23
Q

Is conjugated bilirubin lipid soluble or water soluble?

A

Water soluble.

24
Q

What is the importance of the conjugation of unconjugated bilirubin?

A

Since conjugated bilirubin is water soluble, it is able to be excreted by the liver in bile.

25
Q

Through which duct does bile enter the gallbladder?

A

Through the cystic duct.

26
Q

Through which duct does bile enter the intestine?

A

Through the common bile duct.

27
Q

Which two ducts merge at the ampulla of Vater?

A

The common bile duct and the pancreatic duct.

28
Q

What happens to conjugated bilirubin once it reaches the ileum?

A

Intestinal bacteria converts it into urobilinogen by removing the glucoronic acid via a hydrolysis-reduction reaction.

29
Q

What happens to urobilinogen in the ileum?

A
  • 10% is reabsorbed into the blood and binds to albumin.

- 90% is oxidised by other intestinal bacteria to form stercobilin.

30
Q

What gives faeces its brown colour?

A

Stercobilin.

31
Q

What happens to the urobilinogen that is reabsorbed into the blood from the ileum?

A
  • 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.
32
Q

What happens to urobilinogen during the enterohepatic urobilinogen cycle?

A

It is taken up by the liver and secreted into the bile.

33
Q

What gives urine its yellow colour?

A

Urobilin.

34
Q

Why are the eyes particularly vulnerable to yellowing in jaundice?

A
  • Scleral tissue in the eyes is high in elastin.

- Elastin binds bilirubin with high affinity.

35
Q

List 2 prehepatic disorders that increase unconjugated bilirubin in the blood.

A

1 - Extravascular haemolytic anaemias.

2 - Ineffective haematopoiesis.

36
Q

Why do extravascular haemolytic anaemias increase levels of unconjugated bilirubin in the blood?

A

Macrophages break down red blood cells earlier than they normally would, releasing unconjugated bilirubin.

37
Q

Why might ineffective haematopoiesis increase levels of unconjugated bilirubin in the blood?

A

Macrophages breakdown defective red blood cells, releasing unconjugated bilirubin.

38
Q

Why might high unconjugated bilirubin in the blood cause pigmented gallstones?

A
  • The liver converts the unconjugated bilirubin into conjugated bilirubin.
  • This is converted into conjugated bilirubin, which increases the risk of pigmented gallstones.
39
Q

Why isn’t unconjugated bilirubin excreted?

A

Because it isn’t water soluble.

40
Q

Why might neonatal jaundice be dangerous?

A
  • Unconjugated bilirubin can collect in the basal ganglia of the brain.
  • This is known as kernicterus.
  • Kernicterus can cause brain damage and death.
41
Q

How is neonatal jaundice treated?

A
  • 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.
42
Q

List 2 genetic defects that increase unconjugated bilirubin in the blood.

A

1 - Gilbert’s syndrome.

2 - Crigler-Najjar syndrome.

43
Q

How does Gilbert’s syndrome cause jaundice?

A
  • 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.
44
Q

How does Crigler-Najjar syndrome cause jaundice?

A
  • 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.
45
Q

Give an example of a genetic disorder that causes high levels of conjugated bilirubin in the blood.

A

Dubin-Johnson syndrome.

46
Q

How does Dubin-Johnson syndrome increase conjugated bilirubin in the blood?

A
  • 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.
47
Q

Which inheritance pattern does Dubin-Johnson syndrome show?

A

Autosomal recessive.

48
Q

What effect does high blood conjugated bilirubin have on the urine and the liver?

A

They become dark.

49
Q

What is obstructive jaundice?

A

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.

50
Q

List 5 symptoms and complications of obstructive jaundice.

A

1 - Pruritis (itchy skin).

2 - Cholesterolaemia.

3 - Xanthomas (yellow patches on the skin caused by deposition of fats)

4 - Steatorrhoea.

5 - Decreased vitamin absorption.

51
Q

Why might obstructive jaundice cause steatorrhoea and decreased vitamin absorption?

A

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.

52
Q

Why does viral hepatitis increase both conjugated and unconjugated bilirubin in the blood?

A
  • 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.
53
Q

Categorise the causes of jaundice in this deck into prehepatic, intrahepatic and extrahepatic.

A

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.

54
Q

List the causes of jaundice in this deck and state how they affect both conjugated and unconjugated bilirubin in the blood.

A

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.

DIG (20 decks)

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