Lecture 6

Question 1

Functions of the liver

Answer 1

• remove toxic by-products
• prevent nutrient shortages
• metabolises nutrients –> energy production
• produces protein
• removes bacteria from blood
• produces blood clotting substances
• produces bile

Question 2

What are Kupffer cells?

Answer 2

• resident macrophages of the liver

- located at the luminal side of sinusoids

Question 3

Canal of Hering

Answer 3

• The junctional region between hepatocytes and bile ducts

Question 4

Cholangiocyte

Answer 4

Other predominant cell type of the liver (alongside hepatocytes)

Question 5

Describe the blood flow of the liver

Answer 5

Blood from the portal vein and hepatic artery flows towards the central vein between hepatocytes through the sinusoids

Question 6

Describe the bile transport

Answer 6

• Bile, produced by hepatocytes, is collected into bile ducts via the bile canaliculi (hepatocytes sit on top of canaliculi).
• Then transported to gallbladder

Question 7

What type of cells are sinusoids lined with?

Answer 7

• Endothelial cells

Question 8

How does the liver regenerate?

Answer 8

–> After partial hepatetomy/liver injury:
o gut derived factors (lipopolysaccharides)
are upregulated & activate hepatic non-
parenchymal cells increasing prod. of TNF &
IL-6

o Other factors are released from pancreas
(insulin), duodenum, salivary gland
(epidermal GF), adrenal gland (NA), thyroid
gland (T3) and stellate cells (hepatocyte GF).

–> Allow the hepatocyte to overcome cell-cycle checkpoint controls and move through cell cycle

–> Transforming GF (inhibits hepatocyte DNA synthesis) is blocked

Question 9

How are genetic liver diseases caused?

Answer 9

• Blood proteins (e.g. clotting factors)

- Inborn errors of metabolism (Amino acid, carbohydrate, lipid metabolism)

Question 10

NAFLD

Answer 10

Nonalcoholic fatty liver disease

• affects 30% pop. in developed countries
• one of most common liver disorders
• affects ~5 million Aussies
• key point: condition is which fat builds up in the liver

Question 11

NASH

Answer 11

Non-alcoholic steatohepatitis

• type of NAFLD
  —inflammation,
  —liver cell damage
  —fatty liver

Question 12

Liver disease progression

Answer 12

healthy liver –> NAFLD (fat accum.) –> NASH (fat accum. & inflam.) –> Cirhosis (scar tissue replaces hepatic) –either –>liver transplant/death –or–> Hepatocellular carcinoma

Question 13

Early Stage Liver disease treatment

Answer 13

• Resection
  –> needs early diagnosis
  This process allows healthy part of liver to regrow

Question 14

End Stage liver disease treatment

Answer 14

• Liver transplant = only current treatment
  o Demand for organ is inc.
  o donor rates = poor
  o many donated liver unsuited for transplanted

Question 15

Liver Cancer treatment

Answer 15

• partial hepatectomy
• transplantation
• radiofrequency, cryoblation, radiotherapy
• Sorafinib (5yr survival rate 17%)

Question 16

What is extracorporeal liver-assist device (ELAD) bioartificial liver?

Answer 16

Type of cell therapy- from outside the body. Used as a bridging process waiting for liver transplant.

The patients plasma passes through 4 cartridges where it contacts human liver cells allowing appropriate two way transfer of toxins, metabolites, + nutrients… mimicking liver function

Question 17

Adult Stem cells

Answer 17

tissue-specific or somatic stem cells
–> have the potential to change into a few cell types, usually the tissue in which they’re found
(multipotent)

Question 18

Characteristics of stem cells in adult liver under injured conditions

Answer 18

Liver progenitor cells emerge a& expand
–> contribute to regeneration process due to their bi-lineage differentiation potential to both hepatocytes & cholangiocytes

Question 19

What are oval cells?

Answer 19

• grow as extensions of terminal biliary ductules from where they originate
• form ductular structures that communicate with the biliary system at one end and terminate at a hepatocyte-forming blind end
• Induced as liver damage proceeds
• In culture, produce both hepatic cells & cholangiocytes

Question 20

Cholangiocytes

Answer 20

• Act as liver SC
• cholagiocytes of ductal origin can diff. to produce hepatocytes
• exhibit: o Bipotential plasticity
  o Proliferative capacity
• Only possible when hepatocyte diff. inhibited –> severe liver injury

Question 21

What is the portal triad?

Answer 21

Portal vein
Hepatic artery
Bile duct

Question 22

Describe important features of the liver lobule

Answer 22

• Blood from the portal vein and the hepatic artery flows toward the central vein between hepatocytes through the sinusoids
• Bile produced by hepatocytes is collected into bile ducts via the bile canaliculi
• Sinusoids are lined with endothelial cells
• Kupffer cells, resident macrophages of the liver, are located at the luminal side of sinusoids
• The canal of Hering is the junctional region between hepatocytes and bile ducts

Question 23

What enables and inhibits hepatocyte synthesis?

Answer 23

Enables:
insulin, EGF, norepinepherine, T3 from adrenal glands, stellate cells (hepatocyte growth factor; HGF)

Inhibits:
Transforming growth factor (TGF)

Question 24

What are iPSC?

Answer 24

iPSC are derived from adult cells - reprogrammed back into an embryonic- like pluripotent state.

Transcription factors + turn off genes that make the cell into a somatic cell (via viral vector) cultured as hESC —>
Pluripotent iPSC line

These new cells and tissues can repair or replace damaged or diseased cells in the body.