6. Liver

Question 1

What are the main functions of the liver?

Answer 1

• Metabolic and catabolic
• Secretory and excretory
• Detoxification and immunological

Question 2

What is bile secreted by the liver used for?

Answer 2

• Emulsification and absorption of fats
• Cholesterol homeostasis
• Toxin excretion - endogenous e.g. bilirubin, and exogenous
• Secondary absorption of lipid-voluble vitamins (ADEK)

Question 3

Describe the macroanatomy of the liver

Answer 3

• 2 lobes (left and right)
- separated by falciform ligament
• Dual blood supply - hepatic artery and hepatic portal vein
• Each lobe is split into segments
- I => VIII
- IV split into a and b (upper and lower)
• Each subsection drains into its own vein
• Left, middle and right hepatic vein => Vena Cava

Question 4

What is the hepatic lobule?

Answer 4

• Structural unit
• Hexagonal
• Each corner = portal triad (linkage of 3 adjacent lobules)
• Central vein runs through the centre
- collects blood from hepatic sinusoids
• Rows of hepatocytes within lobules
- sinusoid and canaliculi facing side

Question 5

What does the portal triad consist of?

Answer 5

• Branch of hepatic portal vein - 80% of blood
- mixed venous blood from GI organs and spleen
- hepatocytes process nutrients, detoxify blood and excrete waste
• Branch of hepatic artery
- 20% of perfusion
- oxygen-rich blood
- supports hepatocyte high energy demands
• Bile ducts
- bile produced by hepatocytes
- bile canaliculi => cholagiocyte-lined bile ducts

(blood flows towards centre, bile flows towards perimeter)

Question 6

What are sinusoids?

Answer 6

• Specialised capillaries
• Wider than normal
• Allow blood to flow slower
• Fenestrated
• Space of Disse - extravascular space of plasma between sinusoids and hepatocytes

Question 7

What are Kuppfer cells?

Answer 7

• Sinusoidal macrophages
• Phagocytose bacteria
• Release cytokines to activate hepatic stellate cells in the Space of Disse
• Stellate shaped and high in number
• Attached to endothelial cells

Question 8

What are hepatic stellate cells?

Answer 8

• Quiescent state (dormant)
• Store Vitamin A in liver cytosolic droplets when inactive
• Activated via liver damage or Kuppfer cells => fibroblasts
• Proliferate and deposit collagen in ecm
• Too much => fibrosis/cirrhosis

Question 9

Describe the function hepatocytes (including what they produce and contain)

Answer 9

• 80% of liver mass
• Cubical
• Synthesise:
- albumin
- clotting factors
- bile salts
• Contain:
- glycogen
- lysozymes
- cytoplasmic enzymes
- peroxisomes
• Drug metabolism
• Receive nutrients
• Secrete bile into bile canuliculi

Question 10

What are cholangiocytes?

Answer 10

• Secrete bicarbonate and water to form bile

Question 11

Describe the anatomy of the biliary system in the liver?

Answer 11

• Bile canaliculi
• Small ductules
• Small bile ducts
• Larger bile ducts
• Right/left hepatic ducts
• Common hepatic duct
• • cystic duct => common bile duct
• Pancreatic duct (at the Ampulla of Vater)
• Duodenal papilla

Question 12

What is bile made up of?

Answer 12

• Cholesterol
• Bile salts
• Bilirubin and drug metabolites

Question 13

Summarise the production of bile?

Answer 13

• Hepatocytes 
- 60% of bile
- primary secretion
• Cholangiocytes
- 40% of bile
- secondary modification
- reabsorption and secretion
- pH alteration, HCO3- secretion, sugar/acid reabsorption
- IgA exocytosed into bile

Question 14

Describe the structure of a micelle

Answer 14

• Hydrophilic bile salts face out
• Hydrophobic bile salts face in
- reduce surface tension
• Phospholipids on outside
• Water and soluble fats condensed in lipid core

Question 15

What are the bile acids?

Answer 15

• 2 primary acids
- cholic acid
- chenodeoxycholic acid
• 2 secondary acids (made from primary acids via cut bacteria)
- deoxycholic acid
- lithocholic acid

Question 16

What is the function of the gall bladder?

Answer 16

• Small muscular storage organ
• Can store 50ml of bile
• Modifies bile - reabsorption via endothelial cells
• Concentrates bile - reabsorbes water

Question 17

What is eneterohepatic circulation?

Answer 17

• Substances cycling between gut and liver
• Continuous reabsorption in gut
• Recycling of bile salts

Question 18

Outline carbohydrate metabolism in the liver

Answer 18

• Liver stores carbohydrates as glycogen
• Glycogen => glucose when glucose drops
• 24hr fast - lactate => pyruvate => glucose to muscle (6ATP)
• Gluconeogenesis via deamination and triglycerides too

Question 19

Outline protein metabolism in the liver

Answer 19

• Transamination (switching amine group to a ketoacid)
• Makes a ketoacid - usually pyruvic acid
• Glutamic acid made - common intermediate for many amino acids
• Deamination - carbohydrate skeleton as an energy source, muscle liberates alanine and liver converts it into glucose
• Liver convert ammonia (NH3) to urea
- NH3 is highly toxic to CNS
- urea is water soluble and non-toxic

Question 20

Outline fat metabolism in the liver

Answer 20

• Stored in adipose tissue and liver
• Full glycogen - glucose => fat storage
• Metabolism - fatty acids => acetyl CoA (TCA cycle)
• Triglyceride in adipose tissue => fatty acids
• Fatty acids enter liver => acetyl CoA via beta-oxidation
• Can become ketone body or TCA cycle
• 2 acetyl-CoA => acetoacetate
• Thiophorase in skeletal muscle and brain (not liver) allows it to be used there

• Liver also synthesises lipoproteins, cholesterol and phospholipids
• Lipoprotein synthesis allows for easy transport in blood
- VLDL - lots of triglyceride
- LDL - high cholesterol and phospholipids
- HDL - high protein

Question 21

What does a lack of vitamin B12 cause?

Answer 21

• Pernicious anaemia

* Nerve demyelination

Question 22

How does synthesis of cholesterol occur?

Answer 22

• In liver

* Begins with 2x acetyl-CoA in the mevalonate pathway