Liver

Question 1

What are the cell types in the liver?

Answer 1

Hepatocytes = 80% of cells.
Endothelial cells = line blood vessels and sinusoids, sinusoidal endothelial cells are fenestrated to allow large molecule exchange with hepatocytes.
Cholangiocytes = bile duct epithelial cells, secrete water and bicarbonate to form bile.
Kupffer cells = fixed macrophages.
Hepatic stellate cells = vitamin A storage cells, star shaped, may be activated to a fibrogenic myofibroblastic phenotype.

Question 2

Describe the dual blood supply to the liver and the proportions of the blood supply from each vessel.

Answer 2

Hepatic Portal Vein - 80%
Hepatic Artery Proper - 20%

25% of the resting cardiac output.

Question 3

Describe how the liver can produce glucose from lactate.

Answer 3

Lactate dehydrogenase is used to convert lactate to pyruvate and then the pyruvate is converted to glucose.
This is an energy-consuming process: 6 ATP used

Question 4

Describe how amino acids can be converted to glucose in the liver.

Answer 4

Amino acids can be DEAMINATED to produce pyruvate and then glucose.
E.g. alanine —> pyruvate —> glucose.
Along with pyruvate, glutamate is produced and this is converted into ammonia and then urea using 4 ATP.

Question 5

Describe how triglycerides can be converted to glucose in the liver.

Answer 5

Triglyceride —> glycerol —> glucose

Question 6

What proportion of plasma proteins are produced by the liver? What makes up the remainder?

Answer 6

90% - the remainder are gamma immunoglobulins

Question 7

How can the liver metabolise fat as an energy source?

Answer 7

The liver can convert the fatty acids to acetyl CoA, which then enters the TCA cycle
It can convert 2 x Acetyl CoA into acetoacetic acid for transport in the blood
Synthesise lipoproteins, cholesterol and phospholipids

Question 8

What can the liver convert acetyl CoA into for travel to a different tissue?

Answer 8

Acetoacetic acid (ketone bodies)

Question 9

What other lipid molecules does the liver synthesise?

Answer 9

Lipoproteins, phospholipids, cholesterol.

*Glucose entering the liver can be converted into the several components of lipoproteins.

Question 10

What is CETP?

Answer 10

Cholesterol ester transfer protein - shuttles cholesterol from HDLs to LDLs

Question 11

What is cholesterol synthesised from?

Answer 11

Acetyl CoA

Question 12

How much bile can the gallbladder store?

Answer 12

15-60 mL

Question 13

What are the two pathways that the liver uses for secretion and absorption?

Answer 13

Secreted into the canaliculi for drainage into the bile duct

Secretion into the blood sinusoids

Question 14

What are the major components of bile?

Answer 14

Cholesterol, Bilirubin, Bile Salts, Bile Pigments, Phospholipids, Bicarbonate, Water

Question 15

How are primary bile acids made?

Answer 15

Primary bile acids are made by the oxidation of cholesterol via the addition of carboxyl and hydroxyl groups to produce cholic acid and chenodeoxycholic acid (addition of carboxyl and hydroxyl groups makes it more water soluble)

Question 16

What are primary bile acids conjugated with and what do they form?

Answer 16

Primary bile acids are conjugated with taurine and glycine to form taurocholic acid and glychocolic acid (this makes it more water soluble)

Question 17

What do bacteria in the ileum do to primary bile salts?

Answer 17

They deconjugate the bile salts making them less water soluble and more lipid soluble so they are more easily reabsorbed

Question 18

What are the roles of bile?

Answer 18

Digestion/absorption of fats
Excretion of a variety of substances via the GI tract
Neutralise acid chyme from the stomach

Question 19

What stimulates the release of bile during the intestinal phase of gastric secretion?

Answer 19

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

Question 20

What circulation is used to return bile salts to the liver?

Answer 20

Enterohepatic Circulation - less that 5% of bile salts are lost

Question 21

What percentage of bile salts are reabsorbed?

Answer 21

95%

Question 22

Describe the detox and excretory functions of bile.

Answer 22

Liver breaks down/inactivates steroid and peptide hormones and then secretes them into bile for excretion.
Similarly, involved in drug metabolism and excretion
Excretory route for excess cholesterol - lecithin allows more cholesterol in the micelles. Too much cholesterol will result in it coming out of solution and forming gallstones.

Question 23

Where does the bilirubin that bile excretes come from?

Answer 23

Break down of haem from old red blood cells. Iron from the haem is removed in the spleen and conserved.
Porphoryn group is reduced to billirubin and conjugated with glucuronic acid in the liver.

Question 24

What vitamins are stored by the liver?

Answer 24

ADEK

Question 25

How does the liver store iron?

Answer 25

As Ferritin

Question 26

How is the liver involved in calcium metabolism?

Answer 26

UV light converts cholesterol to a vitamin D precursor. The precursor requires double hydroxylation to convert it to an active form - first in the liver and then in the kidneys. So liver disease can lead to rickets.

Question 27

Couinaud classification

Answer 27

Liver is split into 8 functionally independent segments which can each be resected without damaging those remaining.
Branches of portal vein, hepatic artery and the bile duct are at the centre of each segment and branches of the hepatic vein are peripheral in each segment.

Question 28

What are lobules?

Answer 28

Building blocks of the liver parenchyma consisting of a portal triad, hepatocytes arranged in linear cords between a capillary network, and a central vein.

Portal triad/tract = collection of bile duct, branch of hepatic portal vein and branch of hepatic artery - they are found around the edges of the adjoining lobules.

Question 29

Hepatic acinus

Answer 29

Functional unit where hepatocytes are divided into zones depending on proximity to arterial blood supply.

Zone 1 = nearest to entering vascular supply, least susceptible to ischaemia but most susceptible to toxins - this zone is involved in gluconeogenesis, cholesterol synthesis and fatty acid oxidation.

Zone 3 = furthest from entering vascular supply, most susceptible to ischaemia but least susceptible to toxins - this zone is involved in glycogenolysis, lipogenesis and P450 based drug detoxification.

Question 30

P450 based detoxification

Answer 30

P450 enzymes
Phase 1 - more hydrophilic.
Phase 2 - attach water soluble side chain to make it less reactive.