Jaundice & Liver failure

Question 1

What is jaundice?

Answer 1

Symptom of excessm bilirubin

Question 2

WHy do we make bile?

Answer 2

Cholesterol homeostasis

Lipid and vitamin absorption

Removal of waste products

• xenobiotics
• drugs
• hormones

Question 3

How much bile is produced daily? Where? Drain?

Answer 3

Half a litre

Hepatocytes - 60pc
Cholangiocytes - line biliary tree - 40pc

Drains from liver through bile ducts into DUODENUM

Question 4

WHat is the role of the biliary tree?

Answer 4

ALteration of pH and fluidity

- HCO3 added, H2O etc

Question 5

How is bile modified? Give examples

Answer 5

BIliary excretion of bile salts goverened
bu

BSEP - active transport of bile acids
MRP3
MRP2
MDR1 - mediates excretion of xenobiotics
MDR3 - phospholipid translocation

Question 6

What are the two primary bile acids?

Answer 6

Cholic acid

Chenodoxycholic acid

Question 7

How are secondary acids formed? What are they?

Answer 7

Converted by colonic bacteria

Question 8

What is the function of bile salts?

Answer 8

Reduce fat’s surface tension

Envelop fat in a micelle
- amphiphilic, so carries it in the hydrophobic core

Question 9

What are the problems of high bile salts?

Answer 9

Cytotoxic

- detergent-like actions

Question 10

How is bile flow and secretion regulated? Where and how does it drain?

Answer 10

Bile drains out of right liver from right hepatic duct

Also stored in gall bladder
- drains through cystic duct

Both vessels join above pancreas to form common bile duct, which then enters the duodenum

Regulated by sphincter of Oddi

• closes Ampulli when no food
• when food, cholecystokinin relaxes sphincter, squeezes gall bladder to pump bile. more prevalent if fatty diet

Question 11

What is enterohepatic circulation? What are the uses ?

Answer 11

Where liver cells transfer substances from plasma to bile
They are then reabsorbed by liver cells

Drugs can utilise this
Bile salts can too
- 95pc of bile salts are reabsorbed in the gut and return to liver via HPV

Question 12

Where is bile reabsorbed?

Answer 12

Terminal ileum

Question 13

What is terminal ileum disease?

Answer 13

Terminal ileum disease

• means that bile isnt reabsorbed
• bile salts continue to enter colon
• cause irritation and diarrhoea

Question 14

What might occur if there is a lack of bile in the gut?

Answer 14

Steatorrhea

Deficiency of Vit ADEK

Question 15

Give 3 functions of the gall bladder?

Answer 15

Stores
Acidifies
Concentrates bile

Question 16

Why might the gall bladder concentrate bile?

Answer 16

Store more - it is small but this means that more salts can be retained per unit^3

Question 17

What are the effects of a cholecystectomy?

Answer 17

Nothing major, healthy

• bile is still made from liver
• no store so constant drip
• however, fatty foods may lead to diarrhoea

Question 18

What is bilirubin? How is it formed?

Answer 18

Water insoluble, yellow pigment

Hb breakdown
Haem protein catabolism
Ineffective bone marrow erythropoeisis

Question 19

Where is bilirubin made and how does it get to the liver? Describe uptake

Answer 19

Made in the spleen and bound to albumin to be transported in circulation to travel to liver.

Once in the liver, it disassociates and then enters the hepatocytes.
Binds to cytoplasmic proteins and forms glucoronic acid by UDPGT
Now it is more soluble, and then transported into bile canaliculi

Question 20

How is BR metabolised and excreted? Why are faeces brown?

Answer 20

Formation of urobilinogen by bacterial action in the intestine
Urobilinogen passes into the stool as stercobilinogen

Oxidation of stercobilinogen to stercobilin

Question 21

Why does jaundice occur?

Answer 21

Increased plasma bile salts due to incomplete bile removal

Question 22

What is cholestasis?

Answer 22

Cessation of bile flow, likely cause of jaundice

Question 23

What causes jaundice? What are the group?

Answer 23

Pre-hepatic

Hepatic

Post-hepatic

Question 24

Why does pre-hepatic jaundice occur?

Answer 24

Increased BR production

• Increased haemolysis
• Massive transfusion
• Haematoma resorption - lot of dead RBCs
• Ineffective erythropoiesis

Means that too much BR for the liver to deal with

Question 25

Why does hepatic jaundice occur? Give specific examples

Answer 25

Defective uptake, normal production

• Occurs due to disease of hepatocytes
  
  • less conjugation and hence less BR excretion
• Liver failure
  
  • chronic
  • acute
  • viral hepatitis
  • autoimmune disease

Question 26

If a patient has pre-hepatic jaundice, will they have high or low conjugated BR levels? Is this the same for hepatic jaundice?

Answer 26

Low, high free BR

Yes

Question 27

How can pre-hepatic and hepatic jaundice be differentiated?

Answer 27

Liver function

- liver enzymes high as cell death leads to enzyme release

Question 28

Why does post - hepatic jaundice occur? Give specific examples

Answer 28

Defective transport of BR via biliary duct system

• physical obstruction which reduces bile flow into duodenum
• hence lower bile can flow, amount of plasma BR increases

Obstructions

• gall stones
• cancer - tumour of pancreas head

Question 29

If a patient has post-hepatic jaundice, will they have high or low conjugated BR levels? What differentiates it from the others?

Answer 29

High

Less enters gut
Hence, less stercobilin in gut
- faeces are less brown
- dark urine by BR excretion

Question 30

What is Gilbert’s syndrome?

Answer 30

Hereditary cause of increased BR, is AR
- benign

Caused by reduction in action of UDPGT - can’t conjugate BR

Hence, mild jaundice may appear in times of fasting, stress and infection

Question 31

What is liver failure? Why?

Answer 31

Amount of liver cells being destroyed is much larger than those being made

Ischaemia
Necrosis
Apoptosis