Bile, Bilirubin and Jaundice

Question 1

State three roles of bile.

Answer 1

Cholesterol homeostasis
Dietary lipid/vitamin absorption
Removal of xenobiotics, drugs and endogenous waste products (e.g. steroid hormones)

Question 2

List the major components of bile.

Answer 2

Bile salts, cholesterol, bilirubin, phospholipids, bicarbonate, WATER

Question 3

How much bile is produced daily?

Answer 3

500 mL

The capacity of the gallbladder = 15-60 mL

Question 4

Which cell types produce bile? State the relative proportions of bile produced by each cell type.

Answer 4

Hepatocytes - 60%

Cholangiocytes - 40%

Question 5

What does bile flow depend on?

Answer 5

The concentration of the bile

Question 6

What regulates bile concentration?

Answer 6

The transporters in the cholangiocytes

Question 7

What channel transports bicarbonate and chloride ions into the bile?

Answer 7

CFTR

Question 8

State some of the main transporters that regulate bile concentration.

Answer 8

Bile Salt Excretory Protein (BSEP)
MDR related proteins
Multidrug Resistance Genes
Familial Intrahepatic Cholestasis gene

Question 9

What are the primary bile acids and their respective secondary bile acids? What is the difference between primary and secondary bile acids?

Answer 9

Primary bile acids are produced by the liver. They are converted to secondary bile acids by the action of colonic bacteria. Deoxycholate is reabsorbed but 99% of lithocholic acid is excreted in the stool.
Primary = Cholic Acid + Chenodeoxycholic Acid
Secondary = Deoxycholic Acid + Lithocholic Acid

Question 10

What percentage of bile is water?

Answer 10

97%

Question 11

Describe the effect of cholecystokinin on bile release.

Answer 11

Cholecystokinin causes contraction of the gallbladder and relaxation of the sphincter of Oddi

Question 12

What percentage of bile salts are reabsorbed in the terminal ileum?

Answer 12

95%

Question 13

Describe how terminal ileal disease can cause steatorrhoea.

Answer 13

Terminal ileal disease will mean that less bile salts are reabsorbed so less bile salts are released in the bile into the duodenum so there is less fat emulsification, digestion and absorption so more fat passes through the small intestines and enters the colon and leaves the body.

Question 14

What is another important consequence of fat digestion and absorption is reduced?

Answer 14

They also absorb fewer fat soluble vitamins - ADEK

Question 15

State three important roles of the gallbladder.

Answer 15

Store bile
Acidify bile
Concentrate the bile

Question 16

What are the effects of cholecystectomy?

Answer 16

The bile drips into the duodenum and you can function perfectly fine. However, you will not be able to produce a large release of bile due to gallbladder contraction so there may be some discomfort after eating a fatty meal.

Question 17

What are the main sources of bilirubin?

Answer 17

75% Breakdown of haem group in haemoglobin
22% Breakdown of other haem proteins
3% from ineffective erythropoiesis

Question 18

What plasma protein carries bilirubin to the liver?

Answer 18

Albumin

Question 19

What happens to bilirubin when it reaches the liver?

Answer 19

Bilirubin is conjugated with glucuronic acid to make it more water soluble by the action of UDPGA from smooth ER

Question 20

What two substances can bilirubin be converted to in the intestines and how are they excreted?

Answer 20

Bilirubin can be converted to urobilinogen and excreted via the kidneys. Urobilinogen is formed mainly in the intestines by bacterial action. GIT mucosa is impermeable to conjugated bilirubin but is permeable to unconjugated bilirubin and urobilinogens. So some unconjugated BR enters the enterohepatic circulation, and some forms urobilinogens.
Half of urobilinogens formed are reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidneys. 20% of urobilinogens are reabsorbed into the general circulation.
It can be converted to stercobilinogen and then to stercobilin and excreted with the stools - stercobilin is brown.

Question 21

What concentration of bilirubin is considered jaundice?

Answer 21

> 34 mcmol/L

Question 22

What are the three types of jaundice?

Answer 22

Pre-hepatic
Hepatic
Post-hepatic

Question 23

State some causes of pre-hepatic jaundice. What would be the expected conjugated: unconjugated ratio?

Answer 23

Increased unconjugated bilirubin because there is too much bilirubin being produced for the liver to conjugate it all
It is caused by haemolysis (could be autoimmune), haematoma resorption, massive transfusion, ineffective erythropoiesis

Question 24

What causes hepatic jaundice?

Answer 24

Caused by ineffective uptake, conjugation and bilirubin excretion

Question 25

What can cause post-hepatic jaundice?

Answer 25

An obstruction to the biliary system e.g. pancreatic carcinoma or a gallstone

Question 26

What are some simple clinical features of post-hepatic/obstructive jaundice?

Answer 26

Pale stools - because bile isn’t entering the intestines so there is less stercobilin being produced
Dark urine - the body is trying to excrete some of the bilirubin via the urine, which would contain a lot of urobilinogen, which is dark

Question 27

What is Gilbert’s Syndrome?

Answer 27

The most common hereditary cause of increased bilirubin
Caused by a 70-80% decrease in the glucuronidation activity of UDPGA.
Leads to elevated unconjugated bilirubin.
Autosomal recessive