Liver

Question 1

Give an overview of the liver (4)

Answer 1

1. Largest internal organ
2. Dual blood supply
3. Holds approx. 1 pint (1/8th) of the body’s blood supply
4. More than 500 vital functions are separated into four main groups

Question 2

What are the four main groups of the 500 vital liver functions (4)

Answer 2

1. Metabolic → hepatocytes
2. Synthetic → hepatocytes
3. Storage→ hepatocytes
4. Immune → kupffer cells

Question 3

Where is the liver located (3)

Answer 3

1. The liver is located below the diaphragm.
2. Slightly above the stomach.
3. Infront of the gallbladder

Question 4

What is the gross anatomy of the liver (5)

Answer 4

1. Two lobes - left and right
2. lobes separated by the falciform ligament
3. each lobe is made up of 8 segments
4. When viewed from the rear, the liver is seen to consist of four lobes.
5. In addition to the right and left lobes, there are the two accessory lobes: quadrate and caudate lobes.

Question 5

How is the vasculature of the liver described (4)

Answer 5

1. Dual blood supply.
2. The hepatic artery delivers oxygenated blood.
3. Each blood vessel supplying or carrying blood away from the liver has various internal branches.
4. Hepatic ducts converge on exiting the liver to form the common bile duct.

Question 6

What is the role of the hepatic artery (2)

Answer 6

1. Branches from the aorta. 2. Blood is oxygenated and carries metabolites

Question 7

What is the role of the hepatic portal vein (3)

Answer 7

1. Branches of various veins in the GI tract (except buccal)
2. Contain newly absorbed nutrients and drugs (from the oral route)
3. Partially deoxygenated.

Question 8

What is the role of the hepatic vein (3)

Answer 8

1. Returns detoxified and deoxygenated blood to general circulation and into vena cava

Question 9

What are the liver’s functional units (5)

Answer 9

1. Sinusoid
2. Kupffer cells
3. Bile canaliculus
4. Hepatocytes
5. Space of Disse

Question 10

What are sinusoids (4)

Answer 10

1. large extended capillary
2. where oxygen-rich and nutrient-rich blood mix and allow blood exchange with the hepatocytes.
3. Large gaps between endothelial cells in the hepatic sinusoids’ walls make the sinusoids permeable (or fenestrated).
4. These gaps are provided by the liver sinusoidal endothelial cells (LSECs), which have a role in the filtration and regulation of sinusoidal blood flow.

Question 11

What are kupffer cells (4)

Answer 11

1. cells that line the sinusoids (extended capillary)
2. Largest group of tissue-resident macrophages
3. First immune cells of liver
4. Take up and destroy foreign material, such as
   bacteria as well as “worn out” red blood cells

Question 12

What is the bile canaliculus (2)

Answer 12

1. a thin channel that takes bile from the hepatocytes to a bile duct at the end of an acinus
2. these ducts eventually form the common bile duct.

Question 13

What are hepatocytes (4)

Answer 13

1. Cell of main parenchymal tissue of liver
2. Make up approx. 80% of liver mass
3. Perform variety of metabolic and synthetic functions
4. contain highly developed organelles

Question 14

What is the space of Disse (3)

Answer 14

1. perisinusoidal space between hepatocyte and sinusoid.
2. Stellate cells store vitamin A and are normally quiescent (inactive), and make up 5-8% of liver cells.
3. When the liver is damaged, stellate cells activate and are the major cell type involved in fibrosis formation.

Question 15

How does blood flow in the liver acinus (4)

Answer 15

1. The centre (zone 1), which is well-oxygenated
2. The intermediate zone (zone 2) which is moderately well-oxygenated
3. To the peripheral zone (zone 3), which is the least oxygenated and more susceptible to hypoxic injury.
4. Bile flows in the opposite direction to the blood along a (thin) bile canaliculi to the bile duct.

Question 16

What are the liver’s metabolic functions (7)

Answer 16

1. Carbohydrates, lipids
2. Waste products – e.g. ammonia
3. Hormones, (e.g. Thyroxine → tri-iodothyronine, Glucagon-like peptide 1 (GLP-1) via dipeptidyl peptidase-4 (DPP4), Aldosterone, Sex hormones)
4. Drugs
5. Tri-iodothyronine is more active.
6. GLP1 – stimulates insulin production and appetite suppression.
7. Raised aldosterone levels can cause salt and water retention.

Question 17

How does carbohydrate metabolism take place in the liver (5)

Answer 17

1. Insulin enhances glucose metabolism in the liver.
2. Insulin stimulates glycogenesis (glucose → glycogen) in the liver and skeletal muscle when needed.
3. Production of glucose from amino acids also occurs in the liver.
4. Insulin reduces the amount of amino acids available to the liver and inhibits hepatic enzymes responsible for the conversion.
5. Insulin stimulates the first step of glucose metabolism and blocks the two mechanisms by which the liver releases glucose.

Question 18

How is lipid metabolised in the liver (5)

Answer 18

1. Fatty acids come from the diet, breakdown of adipose tissue and synthesis by the liver.
2. Oxidation of fatty acids then yields energy for the body.
3. Triglycerides are synthesised from fatty acids, which are then stored in lipid droplets or packed into VLDLs (very low lipid density proteins) before being secreted into the circulation.
4. Cholesterol is synthesised from fatty acids (facilitated by the enzyme HMG-COA) or circulating lipoproteins (which aid the absorption of lipids in the small intestine and carry cholesterol from other tissues to the liver).
5. Cholesterol in the liver can be re-distributed throughout the body or removed by the gallbladder.

Question 19

How is ammonia metabolised in the liver (8)

Answer 19

1. The main sources are the colon and kidney; lesser amounts from RBC breakdown and metabolism in muscles.
2. Readily crosses blood-brain barrier → CNS toxicity.
3. The liver is the only organ that can facilitate the complete urea cycle (Krebs-Henseleit cycle)
4. The ammonia passes through the liver, and the majority is cleared through hepatocytes.
5. Hepatocyte mitochondria convert it to carbamoyl phosphate, which reacts with ornithine → citrulline.
6. Further cytoplasmic reactions → arginine → urea and ornithine (via dehydration)
7. Urea (small molecule) easily diffuses back into sinusoidal blood → filtration by kidneys → excretion in urine.
8. Ornithine returns to mitochondria to begin another cycle.

Question 20

How is vitamin D activated in the liver (5)

Answer 20

1. Vitamin D (cholecalciferol) obtained from the diet and synthesised by the skin is biologically inactive.
2. Needs dual hydroxylation to become active
3. The first is in the liver (in the “25-C” position)
4. The second is in the kidney (in the “1-C” position)
5. Final product is 1,25-(OH)2-vitamin D3 (or calcitriol)

Question 21

How is bilirubin processed (7)

Answer 21

1. Red blood cells are broken down by the spleen.
2. Haem (iron-containing) part of haemoglobin → bilirubin
3. Blood drains from the spleen into the hepatic portal vein.
4. Bilirubin binds to albumin.
5. Hepatocytes conjugate bilirubin to glucuronic acid (via glucuronyl transferase), which is more water-soluble.
6. Then secreted into bile via multi-drug resistance protein 2 (MRP2)
7. Bile salts are released into the circulation by active transport in the terminal ileum. Then, they returned to the liver, where they were re-secreted into bile.
   Recycling of bile salts is referred to as enterohepatic recirculation.

Question 22

How is bile produced (6)

Answer 22

1. Bile acids (another component of bile):
2. Synthesised by hepatocytes from cholesterol–cholic acid and chendoxycholic acid
3. Secondary bile acids are produced by gut bacteria action and enter bile via enterohepatic recirculation.
4. Bile acids are conjugated with taurine or glycine to make them more hydrophilic.
5. After aiding fat digestion, most are reabsorbed back into the blood and returned to the liver (enterohepatic recirculation)
6. Blood from the hepatic portal vein contains bile acids produced in the gut.

Question 23

How is albumin synthesised (5)

Answer 23

1. The most significant (quantitatively) plasma protein synthesised by the liver
2. Binds to Bilirubin, Hormones, Drugs.
3. Responsible for the majority of plasma oncotic pressure
4. Keeps fluid in circulation
5. Quantitatively, albumin is the most significant plasma protein synthesised by the liver,

Question 24

What are the effects of albumin on blood clotting (6)

Answer 24

1. Procoagulant factor synthesis
2. Factors II (thrombin), V, VII, IX, X, XI
3. Fibrinogen - Anticoagulant factor synthesis, e.g.
4. Antithrombin
5. Protein C - Secretes thrombopoietin (stimulates platelet production)
6. A healthy liver maintains the balance of these factors to avoid “unexpected” bleeds or clots.

Question 25

What are other plasma synthesis (9)

Answer 25

1. Acute phase proteins 2. Release stimulated by IL-1, IL-6 and TNF 3. Effects involving inflammatory process, tissue repair and immune cell activities (e.g. C-reactive protein (CRP)) 4. Proteins that bind to and transport thyroid hormones and cholesterol 5. Angiotensinogen – part of RAAS responsible for BP regulation 6. The liver does not synthesise immunoglobulin proteins. 7. The three cytokines listed stimulate the release of the acute phase proteins. 8. The collection of acute phase proteins is yet to be fully sorted out by scientists and has a wide range of effects. 9. Lipoproteins carry cholesterol and triglycerides around the body.

Question 26

What are the storage functions (4)

Answer 26

1. Glycogen 2. Fats 3. Minerals - copper, iron 4. Vitamins – A, D, E, K

Question 27

How is iron stored in the liver (5)

Answer 27

1. The liver produces proteins (e.g. ferritin, hepcidin) that maintain iron balance 2. Hepatocytes are the major storage site 3. Free intracellular iron is toxic; the majority is stored as ferritin 4. If excess iron → liver increases storage (but if prolonged, it can  damage the liver) 5. Mobilises iron from hepatocytes to circulation to meet metabolic needs

Question 28

What are the liver’s main functions relating to iron homeostasis (3)

Answer 28

1. Hepatocytes are the main site of ferritin production. 2. High hepcidin levels reduce duodenal iron absorption – explains why we now only give iron supplements once a day. 3. If patients are iron deficient, hepcidin levels are suppressed to allow iron to be transported from the enterocyte to the serum.