Structure and function of liver

Question 1

What is the blood supply to the liver?

Answer 1

75% from the portal vein and 25% from the hepatic artery.

Question 2

What is a lobule?

Answer 2

Hexagonal functional unit of the liver divided by connective tissue.

Question 3

What lies at the angle of each lobule?

Answer 3

Portal tract/triad - contains branch of hepatic artery, hepatic portal vein and bile duct.

Question 4

Into what structures does the blood from the hepatic artery and portal vein run in to?

Answer 4

Sinusoids - run between plates of cells to central venule and then into hepatic vein i.e. away from the portal triad

Question 5

Where does bile flow within the liver?

Answer 5

From hepatocytes to canaliculi to the bile ducts i.e. towards the portal triad.

Question 6

How are the plates of hepatocytes arranged in the liver?

Answer 6

So that each cell has access to blood supply on one side and bile on the other. Sinusoid-facing side has fenestrated endothelium.

Question 7

What lies between the endothelial cells and hepatocytes?

Answer 7

Space of Disse

Question 8

What is the most important liver cell type?

Answer 8

Hepatocyte - 60% of cells, carry out most of metabolic functions.

Question 9

What are Kupffer cells?

Answer 9

Macrophages, located within sinusoidal lining. Protect liver and phagocytose old erythrocytes.

Question 10

What are pit cells?

Answer 10

Liver-specific NK cells.

Question 11

What are hepatic stellate cells?

Answer 11

Primary site of vit. A storage. Also control turnover of connective tissue, synthesise collagen, regulate contractility of sinusoids.

Question 12

What are the functions of the liver?

Answer 12

Synthesis - CHO, lipids, protein and bile Waste management - detox of xenobiotics, removal of internal waste eg bilirubin Storage - glycogen, vit A

Question 13

What is the composition of bile?

Answer 13

Water, bicarb, bile salts, cholesterol and phopholipids.

Question 14

What is the synthesis pathway for conjugated bile acids?

Answer 14

Either:

Cholesterol -> primary bile acids eg cholic acid -> (via gut bacteria) -> secondary bile acids eg deoxycholic acid -> conjugated with glycine/taurine

Cholesterol -> primary bile acids eg cholic acid -> conjugated with glycine/taurine

Question 15

What percentage of bile salts are recirculated?

Answer 15

95%

Question 16

What is the function of Cholestyramine?

Answer 16

Binds bile acids in the gut. Prevents the recirculation of bile. Increases bile acid synthesis. Decreases blood cholesterol.

Question 17

What effect does an increased intake of dietary fibre have on cholesterol?

Answer 17

Decreases blood cholesterol.

Question 18

What causes the formation of cholesterol gallstones.

Answer 18

Bile contains free cholesterol as well as bile salts. If more cholesterol enters the bile than can be solubised by bile salts precipitation of cholesterol occurs.

Question 19

What are phase 1 reactions?

Answer 19

Oxidation, hydroxylation, hydrolysis and reduction.

Question 20

What are phase 2 reactions?

Answer 20

Conjugation, sulphation and glucuronidation.

Question 21

What properties do liver metabolites have?

Answer 21

Usually pharmacologically inactive and more hydrophilic.

Question 22

What enzymes mainly perform phase 1 reactions?

Answer 22

Cytochrome P450 (CYP) enzymes. Large family of haem proteins. Found in SER.

Question 23

What reactants are required for phase 1 reactions aside from the main?

Answer 23

NADPH -> NADP+

O₂ -> H₂O

Question 24

What is an inducible enzyme?

Answer 24

One that is present in minute quantities but dramatically increases if a substrate is present. CYP enzymes are inducible by certain drugs eg carbamazapine

Question 25

What is conjugation?

Answer 25

Addition of glucuronyl, sulphate, methyl, acetyl and gycyl groups.

Question 26

Apart from the liver, where else do conjugation reactions occur?

Answer 26

Lung and kidney

Question 27

When might detoxification reactions be a problem?

Answer 27

When drugs are given orally - first past metabolism.

Question 28

What is the first step in the ethanol metabolism pathway and where does it occur?

Answer 28

Ethanol -> acetaldehyde

Via alcohol dehydrogenase and NAD -> NADH

Occurs in the cytosol.

Question 29

What is the second stage of alcohol metabolism?

Answer 29

Acetaldehyde -> acetate

Via acetaldehyde dehydrogenase and NAD -> NADH

Occurs in the mitochondria

Question 30

What is the lifespan of a red blood cell?

Answer 30

120 days

Question 31

How are RBCs disposed of?

Answer 31

Phagocytosed mainly by Kupffer cells in liver, also in spleen and bone marrow.

Question 32

The globin part of haemoglobin is degraded. What happens to haem?

Answer 32

Heam -> biliverdin. Looses Fe3+ and CO. Also via O2 -> H2O and NADPH -> NADP+

Biliverdin -> bilirubin via NADPH -> NADP+

Question 33

What happens to bilirubin following haem metabolism?

Answer 33

Transported to liver hepatocytes attached to albumin.

Question 34

What happens to bilirubin in the liver?

Answer 34

Conjugation (glucaronic acid) and secretion into canaliculi. Active process requires ATP.

Question 35

What happens to bilirubin in the gut?

Answer 35

Further metabolised by bacteria to urobilinogen. Urobilinogen can be converted to urobilin (urine) and stercobilin (faeces).

Question 36

What is prehepatic jaundice?

Answer 36

Too much haem overloads the system (eg haemolytic anaemia) - liver can’t manage to conjugate it all

Unconjugated bilirubin levels rise.

Prehepatic as problem occurs before liver is involved.

Question 37

What is intrahepatic jaundice?

Answer 37

Problems with the conjugation process if liver is inflamed/damaged – again increase in unconjugated bilirubin.

Question 38

What is posthepatic jaundice?

Answer 38

Problem lies with secretion e.g. gallstones then raised levels of conjugated bilirubin as this leaks back into the blood if the alternative route is blocked.

Question 39

What is Gilbert’s syndrome?

Answer 39

Affects 2-7% of population – maybe 10 people in this room. Harmless inherited disorder – not enough of the conjugating enzyme present. Usually asymptomatic, picked up in routine checks. Mild jaundice can result if stressed/ill. Major risk is too much medical investigation!