Normal Liver Physiology

Question 1

Describe the bloody supply to the liver

Answer 1

70% blood via hepatic portal vein:

• Superior mesenteric vein: Small intestine, large intestine, stomach and pancreas
• Splenic vein: spleen, stomach, pancreas and large intestine

30% of blood from hepatic artery (from AA)

Question 2

Describe the venous drainage of the liver

Answer 2

Hepatic veins to the inferior vena cava

Question 3

What makes up the splanchnic circulation?

Answer 3

Blood flow through the stomach, small and large intestines, pancreas, spleen and liver.

Question 4

How are products exported by the hepatocytes?

Answer 4

Some metabolites excreted across the same membrane that they entered the hepatocyte through, into the central vein and IVC to be exported via kidneys.

Others (large drug metabolites) are excreted through the canalicula membrane into the bile duct to enter the gall bladder, small intestine and be excreted in faeces. Constituents of bile also excreted in this way.

Question 5

Describe the functional zones of liver lobules

Answer 5

Zone 1: periportal hepatocytes, most oxygenated: specialise in oxidative metabolism, gluconeogenesis and urea synthesis.

Zone 2: intermediate properties

Zone 3: pericentral hepatocytes, least oxygenated: specialise in drug metabolism, glycolysis and lipogenesis.

Question 6

What type of cell surrounds each lobule?

Answer 6

Reticuloendothelial cells

Question 7

What types of cells exist in the liver?

Answer 7

Hepatocytes
Cholangiocytes

Reticuloendothelial cell mesh:

• Endothelial cells
• Kupffer cells
• Lipocytes (stellate cells)

Question 8

What cells exist in the space of Disse?

Answer 8

Lipocytes (stellate cells)

Question 9

What are the functions of the cholangiocytes?

Answer 9

Line the bile duct

Secrete HCO3- ions and water into the bile

Question 10

What are the major functions of the liver?

Answer 10

Energy metabolism and substrate interconversion
Synthesis of plasma proteins
Drug metabolism and detoxification
Immune functions
Production of bile
Cholesterol processing
Storage of vitamins and minerals
Excretion of bilirubin

Question 11

What roles does the liver play in energy metabolism and substrate interconversion?

Answer 11

Carbohydrate metabolism

• Glycogenolysis
• Gluconeogenesis
• Glycogen synthesis
• Glycolysis, citric acid cycle and fatty acid synthesis

Lipid metabolism:

• Ketogenesis
• Triglyceride synthesis from fatty acids

Protein metabolism:

• Deamination
• Urea formation

Question 12

What plasma proteins does the liver synthesise?

Answer 12

Major plasma proteins: albumin

Factors involved in haemostasis and fibrinolysis:
Fibrinogen (coagulation), coagulation inhibitors (e.g. alpha1 anti-trypsin), plasminogen (fibrinolysis)

Carriage proteins:

• e.g. transferrin
• sex hormine bnding globulin (SHBG)
• thyroid-binding globulin (TBG)

Pro-hormones, apolipoproteins

Question 13

What is the function of albumin?

Answer 13

Maintains the osmotic pressure of the plasma

Transports substances in blood

Question 14

What is the role of Kupffer cells in the liver?

Answer 14

Tissue macrophages located in hepatic sinusoids attached to endothelial cell lining..

Ingest bacteria and inflammatory mediators by phagocytosis.

Question 15

Describe the process of production, storage and secretion of bile

Answer 15

Bile is produced by the liver and exported into the gall bladder where it is concentrated (by removing water and salts from the organic molecules in bile) and stored.
Released from the gall bladder via the bile duct into the duodenum during eating.

Question 16

What stimulates the contraction of the gall bladder to eject bile into the duodenum?

Answer 16

Cholecystokinin (CCK)

Question 17

How do cholecystokinin (CCK) and secretin work?

Answer 17

In response to the stomach emptying its contents, walls of the intestine secrete CCK and secretin.

Secretin: acts on exocrine pancreas to stimulate secretion of bicarbonate ions. Acts on the liver to stimulate bile production.

CCK: Acts on the exocrine pancreas to secrete enzymes into the small intestine. Also stimulates gallbladder contraction to release bile into the duodenum.

Question 18

What are the 6 major components of bile and their roles?

Answer 18

Bile salts conjugated with taurine (solubilise fat in small intestine)

Lecithin (a phospholipid)

HCO3- and other salts (neutralises acid in duodenum)

Cholesterol

Bile pigments and metabolic end products

Trace metals

Question 19

What are the functions of bile?

Answer 19

Solubilise dietary fat in small intestine (carried out by bile salts)

Neutralises acid in duodenum (by HCO3- secretion)

Question 20

How are bile salts formed?

Answer 20

Primary bile acids synthesised from cholesterol and conjugated with taurine or glycine.
Secondary (recycled) bile acids are conjugated with glycine. This forms bile salts which are transported out of the hepatocyte across the canalicula membrane via the bile canaliculus into the bile duct.

Question 21

Describe the enterohepatic circulation

Answer 21

Bile salts are released into the small intestine.

95% are recycled in the terminal ileum and returned to the liver via the portal circulation.
-75% are recycled as intact bile salts
-25% are deconjugated (taurine or glycine removed) by bacteria in the terminal ileum and colon to yield primary bile acids.
–Some of these are dehydroxylated by bacteria to yield secondary bile acids
(primary and secondary bile acids are both recycled- re-conjugated in the liver)

-5% are excreted in faeces - the liver synthesised new bile salts to replace them.

Question 22

What hormones are secreted into the small intestine upon the emptying of stomach contents?

Answer 22

Cholecystokinin (CCK) and Secretin

Question 23

What do hepatocytes secrete?

Answer 23

Bile salts
Cholesterol
Lecithin
Bile pigments

Question 24

How does the liver export excess cholesterol not used to make bile salts?

Answer 24

Excess cholesterol is removed from the hepatocytes and exported across the canalicula membrane to be exported in faeces

Question 25

What are the functions of bile salts?

Answer 25

Emulsification of dietary lipids, rendering them accessible to pancreatic lipases.

Elimination of cholesterol

Prevention of cholesterol precipitation in the gall bladder

Facilitation of the absorption of fat soluble vitamins

Question 26

What are the functions of cholesterol?

Answer 26

Plasma membranes
Precursor for steroid hormones
Component of bile salts
Myelin

Question 27

How is cholesterol sourced in the body? How is it transported?

Answer 27

85% made in body (mostly in liver)
15% dietary
Transported in plasma on lipoproteins

Question 28

How does the liver synthesis cholesterol?

Answer 28

From acetyl-CoA

Question 29

What vitamins and minerals does the liver store?

Answer 29

Vit A, D, E, K

Iron and copper

Question 30

What is the main bile pigment?

Answer 30

Bilirubin

Question 31

How is bilirubin formed and excreted?

Answer 31

Formed from breakdown of haem in the bone marrow and spleen, becomes bound to albumin.
Bilirubin conjugated in hepatocytes with glucoronic acid to form a polar, water soluble molecule which is exported into bile.

Conjugated bilirubin is broken down by bacterial proteases in the small intestine to form urobilinogen, 10% of which is recycled via the portal vein. The other 90% is excreted via the faeces