42 Hepatobiliary physiology

Question 1

Which of the following is/are not the functions of liver?

1. Clotting e.g. fibrinogen
2. Storage of irons and vitamins B12, A, D
3. Carbohydrate, fat and protein metabolism
4. Endocrine bile secretion
5. Maintain plasma oncotic pressure
6. Secrete renin (endocrine function)
7. Excretion and degradation (e.g. drugs, roxic products and hormones)

Answer 1

4. should be exocrine bile secretion
5. should be angiotensinogen (precursor of Ang II that reacts with ACE and renin to become Ang II)

5 is a function, Plasma proteins e.g. produce albumin and globulins to maintain plasma oncotic pressure if not, edema :(

Question 2

What is the function of the reticuloendothelial system (RES) in the liver lobules?

Answer 2

For degrading ageing RBC and contains macrophage capable of phagocytizing bacteria/ foreign matter

Question 3

What are in between the hepatocytes and the Kupffer cells?

Answer 3

Bile canaliculi

Question 4

Describe the route of the bile secretion

Answer 4

Left and right hepatic ducts > common hepatic duct > common bile duct

CBD then joins the pancreatic duct before the bile juice is released into the duodenum, and bind to fatty acids

Question 5

What hormone relaxes the sphincter of Oddi and contracts with smooth muscle of the gallbladder wall?

Answer 5

CCK

Question 6

What do hepatic sinusoids contain? What is the final destination of the substance contained?

Answer 6

Portal blood; central vein

Question 7

List the 3 functions of bile.

Answer 7

1. Emulsification
   - Emulsify fat into droplets for lipase to digest
2. Formation of micelles
   - Form the micelles with fat to aid absorption of fat
3. Excretion of waste from blood
   - Elimination of bilirubin and excess cholesterol

Question 8

What does bile contain?

Answer 8

Bile acids (70%, from cholesterol);

phospholipids (20%; primary lecithins = FA + glycerol; water insoluble, thus take part in micelle formation);

cholesterol (4%)

and bile pigments (2%)
(mainly bilirubin derived from RBC metabolites, do not participate in micelle formation as it is water soluble)

Question 9

What does it mean by bile salt is “amphipathic”?

Answer 9

Contains a hydrophobic part (cholesterol nucleus)

and a hydrophilic part (OH-, peptide bonds, determine the hydrophilicity of the bile salt)

Question 10

How are the substances arranged in a micelle?

Answer 10

Hydrophobic substances face inwards, e.g. fat digestion products, fat-soluble vitamin and cholesterol

while hydrophilic side faces outward

Question 11

_______ bile acids are newly synthesized within the liver. They are temporarily stored in the _______, respond to _______ and release bile to duodenum then perform emulsification and formation of micelles.

Answer 11

Primary;
gallbladder;
CCK

Question 12

After _______ by bacteria in the gut and _________ within the GI lumen, they become secondary bile acids.

Answer 12

dehydrolyzation;

deconjugation

Question 13

Conjugation occurs in both primary and secondary bile acids.
What is the significance of conjugation in the liver? (2 reasons)

Answer 13

increase the number of peptide bonds can make it more water soluble

1. increase the micelle forming properties
2. Decrease passive uptake in upper intestine: when it is more water soluble, it is not absorbed back right after being released in the duodenum.

Question 14

Conjugation occurs in both primary and secondary bile acids.
What is the significance of deconjugation in the lower intestine?

Answer 14

In the lower intestine, dehydroxylation and deconjugation reduces water solubility/ increases fat solubility

> increase passive uptake by distal ileum

Question 15

What is difference in terms of composition of primary and secondary bile acids?

Answer 15

Primary:

• Cholic acid (most water soluble, with 3 -OH groups)
• Chenodeoxycholic acid (2 OH-, less water soluble)

Secondary:

• Deoxycholic acid ( 2 OH- , less water soluble)
• Lithocholic acid (least water soluble)

Question 16

What is used for conjugation in the liver?

Answer 16

Glycine or taurine

Question 17

What do bile acid amount in the enterohepatic circulation depend on ?

Answer 17

1. Amount of bile acids returned/ absorbed from the terminal ileum (more fatty meal, more release and more reabsorption)
2. Amount of newly-synthesized bile acids
   * Return on bile acids inhibits the rate-limiting enzyme for BA synthesis from cholesterol via negative feedback (7 a-hydroxylase)

= more returning, less production

Question 18

What is that fate of bile acids after secreted?

Answer 18

Bile acids become fat soluble after deconjugation and dehydroxylation of bacteria.
95% is absorbed via passive pathway
5% is excreted in faeces, so the body will synthesize 5% to compensate the loss by negative feedback > maintain constant supply.

Question 19

What is the raw material for bile acids synthesis?

Answer 19

Cholesterol extracted from blood.

Question 20

Why are drugs that block the absorption of bile acids at the distal ileum cholesterol-lowering drugs?

Answer 20

With less bile acids reabsorbed, the liver will synthesize more new bile acids using cholesterol in blood as raw material to replenish the lost bile acids

Question 21

Name a kind of drug that lowers plasma cholesterol level.

Answer 21

Statins
It inhibits cholesterol synthesis by HMG-coenzyme A reductase in the liver, with less cholesterol level in the liver, more LDL receptors are produced in the surface of liver cells to take in more cholesterol from the blood into the liver.

Question 22

Name the 3 functions of the gallbladder.

Answer 22

1. Storage of bile
2. Concentration of bile (10 folds)
3. Expulsion of bile (in response to CCK)

Question 23

Regulation of bile flow by the gallbladder:

_____ gallbladder, tonic contraction of _______ during the _______ period.

Answer 23

Flaccid (relaxed);
the sphincter of Oddi;
interdigestive

Question 24

Regulation of bile flow by the gallbladder during the digestive period:
name 3 changes.

Answer 24

1. Increase in CCK and vagal activity
2. Contraction of gallbladder
3. Relaxation of the spincter of Oddi

Question 25

Hemoglobin is taken up by macrophages of the reticuloendothelial system, and is broken down into:

Answer 25

heme and globin

Question 26

What happens to the heme produced from the breakdown of hemoglobin?

Answer 26

Heme opens to release iron and the remaining porphyrin ring is converted into bilirubin.

Question 27

Why is the bilirubin excretory pathway important?

Answer 27

It is an important process to eliminate end product of hemoglobin (aged RBC)

Question 28

Excretion of bile pigments:

Aged RBC > Hemoglobin > bilirubin > enters liver.

What enzyme is used to conjugate the below reaction?
Bilirubin + glucuronic acid > bilirubin glucuronide (water soluble)

Answer 28

Hepatic enzyme Glucuronyl transferase

Question 29

Excretion of bile pigments can be in how many pathways?

Answer 29

2 pathways.
Bilirubin glucuronide (water soluble) 
>  degraded by bacteria to become bilirubin > Urobilinogen > Faeces (stercobilin, golden colour)
//
Urobilinogen > Urobilin > Urine

Question 30

The increase in plasma bilirubin (Hyperbilirubinemia), free or conjugated will result in?
What are the symptoms of the disease?

Answer 30

Jaundice

Yellow appearance of skin and eyeball.

Question 31

What are the types of jaundice? What are their causes and symptoms respectively?

Answer 31

1. Pre-hepatic jaundice 
Cause: increased RBC degradation 
- increase in free forms of bilirubin
- Pathological e.g. hemolysis
- Physiological jaundice in newborn

2. Post-hepatic/ obstructive jaundice
   Cause: bile duct obstruction.
   - Gallstones
   - Pale stool and dark urine

( because no bilirubin in the feces, reflux back to blood causes excess urobilin, thus dark urine)

3. Intra-hepatic jaundice
   Cause: Liver impairment (both free and conjugated forms of bilirubin increases)

• GT deficiency, cirrhosis, hepatitis