Physiology: bile and enterohepatic circulation

Question 1

What are the components of bile?

Answer 1

Cholesterol
Bile salts (acids)
Lecithin
Water
Electrolytes
Bile pigments

Question 2

What is the vein that delivers blood to the liver?
What organs does it drain?
Is it nutrient rich/poor, oxygen rich/poor?
At rest, what % of blood does it supply to the liver? And meals?

Answer 2

Hepatic portal vein
Spleen, pancreas, stomach, small intestine, large intestine
Nutrient rich, oxygen poor.
75%, 90%

Question 3

Hepatic arteries:
- What specific artery supplies the liver?
- Is it nutrient rich/poor, oxygen rich/poor?
- What % of blood does it supply to the liver?

Answer 3

The superior mesenteric artery
Nutrient poor, oxygen rich
25%

Question 4

Is the liver involved in:
- Protein synthesis (clotting factors, albumin)
- Hormone production
- Glycogen storage, maintaining BGLs
- Detoxification (urea –> ammonia)
- RBC destruction
- Immunity
- Lipid emulsification
- Regulating blood lipids

Answer 4

Yes to all

Question 5

At a microscopic level, what are the functional units of the liver?

Answer 5

Lobules

Question 6

Lobules
- What is their shape?
- What is found in the centre?
- What is at each corner?
- What radiates out from the central vein to the edges?

Answer 6

Hexagon
Central vein
Portal triad - hepatic artery, hepatic portal vein, bile duct
Hepatocyte plates

Question 7

Liver capillaries:
- What are they called?
- Are they fenestrated?
- Are they continuous?
- Within the lobules, where are they found?
- What is their function?

Answer 7

Sinusoids
Yes
No - discontinuous
Between hepatocyte plates, from portal triad to central vein
Direct blood from hepatic portal vein and hepatic arteriole to the central vein

Question 8

Sinusoids
- What is the layer between endothelial cells and hepatocytes called?
- Is it usually permeable? Why?

Answer 8

Space of Disse
Yes - as endothelium is discontinuous

Question 9

Kupffer cells:
- What are they?
- Where are they found?
- What is their function?

Answer 9

Resident macrophages of the liver
Anchored to endothelium of sinusoids
Remove unwanted materials

Question 10

Sinusoids
- What is the layer between endothelial cells and hepatocytes called?
- Is it usually permeable? Why?

Answer 10

Space of Disse
Yes - as endothelium is discontinuous

Question 11

Synthesis of bile by the liver
- What components do hepatocytes make?
- What components do the epithelial cells lining bile ducts make?

Answer 11

Hepatocytes: everything but water
- Cholesterol, bile salts (acids), lecithin, bile pigments (bilirubin), HCO3- to a small extent.

Epithelial cells: synthesise a HCO3- rich electrolyte solution

Question 12

Synthesis of bile acids
- What is the chemical precursor of bile acids? What enzyme converts it to bile acids?
- Can bile acids be conjugated with taurine or glycine to increase water solubility?
- Can bile synthesis regulate itself?
- Differentiate primary vs secondary bile acids
- At a neutral pH (eg. in a hepatocyte), what form are bile acids often found in?

Answer 12

Cholesterol, cholesterol alpha 7 hydroxylase
Yes
Yes
Primary bile acids are made by hepatocytes. GIT bacteria convert primary bile acids into secondary bile acids
Ionised as bile salts - usually pair with Na+

Question 13

Synthesis of bile pigments
- They are made from the breakdown of what structure?
- Which one is the green pigment?
- Which one is the red pigment?

Answer 13

Red blood cells
Bilverdin
Bilirubin

Question 14

Describe the metabolism of bilirubin

Answer 14

Bilirubin binds to albumin, and travels in systemic circulation.
Bilirubin enters hepatocytes
Hepatocytes conjugate bilirubin with glucuronic acid, forming bilirubin glucuronide (more water soluble)
This enables bilirubin glucuronide to be secreted via bile ducts to the duodenum.
In the duodenum
- Most of it is deconjugated and converted to other forms (eg. stercobilin) and is excreted in feces; gives feces its brown colour
- Small amounts are filtered by the kidney and are excreted in urine

Question 15

Describe how bile gets from hepaticoyte to the duodenum

Answer 15

Bile goes into bile canaliculi –> bile ductule –> R/L hepatic duct –> common hepatic duct –> common bile duct –> duodenum (during a meal)

Question 16

During meals, what happens to the sphincter of Oddi?
Between meals, where is bile stored? What role does this organ have in concentrating bile?

Answer 16

Opens - to let bile mix with food
The gall bladder. It actively transports sodium out of the gall bladder, leading to water diffusing out and the bile being concentrated

Question 17

What 2 hormones regulate bile secretion?

Answer 17

CCK
Secretin

Question 18

Secretin’s role in bile secretion:
- What is the stimulus?
- Where is secretin released?
- Where does secretin go int?
- What is the response?

Answer 18

Acidic, fatty chyme entering the duodenum
Duodenal wall enteroendocrine cells
Blood stream
Stimulates liver to produce bile more rapidly

Question 19

Cholecystokinin’s role in bile secretion:
- What is the stimulus?
- Where is secretin released?
- Where does secretin go int?
- What is the response?

Answer 19

Acidic, fatty chyme entering the duodenum
Duodenal wall enteroendocrine cells
Blood stream
Causes gall bladder to contract and Sphincter of Oddi to relax –> bile enters the duodenum

Question 20

Role of PNS in bile secretion?

Answer 20

Vagal stimulation causes weak contraction of the gall bladder.

Question 21

Enterohepatic circulation
- Describe the pathway of circulation (at a macro level)

Answer 21

Liver –> bile ducts –> duodenum (sphincter of Oddi) –> distal ileum –> hepatic portal vein –> liver

Question 22

Enterohepatic circulation
- Describe conjugation in liver vs duodenum. What 2 aa’s can be used as conjugates?
- What protein is responsible for transporting bile salts from hepatocyte into bile duct?
- What proteins are responsible for resorting bile salts from distal ileum to hepatic portal vein? Consequence of ileitis?

Answer 22

Liver: conjugated with glycine or taurine. Duodenum: deconjugated
Bile salt export pump
Carriers. INflammation can lead to bile salt malabsorption - lost in feces; in severe cases, malabsorption of fat

Question 23

Does enterohepatic circulation enable recycling of bile salts?
Why do bile salts need to be recycled?
What % of bile salts are recycled vs passed into ileum?

Answer 23

Yes
Because we produce much less bile slats than we need.
95%, 5%

Question 24

Functions of bile
- Does it neutralise gastric acid secretions via bicarbonate?
- Does it assist with the emulsification of fats?
- Does it assist with the absorption of fat soluble vitamins?

Answer 24

Yes to all

Question 25

Describe the emulsification process
Why is emulsification important?

Answer 25

Question 26

Describe the process of fat absorption

Answer 26