Lecture 6 Flashcards
(24 cards)
Functions of the liver
- remove toxic by-products
- prevent nutrient shortages
- metabolises nutrients –> energy production
- produces protein
- removes bacteria from blood
- produces blood clotting substances
- produces bile
What are Kupffer cells?
- resident macrophages of the liver
- located at the luminal side of sinusoids
Canal of Hering
- The junctional region between hepatocytes and bile ducts
Cholangiocyte
Other predominant cell type of the liver (alongside hepatocytes)
Describe the blood flow of the liver
Blood from the portal vein and hepatic artery flows towards the central vein between hepatocytes through the sinusoids
Describe the bile transport
- Bile, produced by hepatocytes, is collected into bile ducts via the bile canaliculi (hepatocytes sit on top of canaliculi).
- Then transported to gallbladder
What type of cells are sinusoids lined with?
- Endothelial cells
How does the liver regenerate?
–> 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
How are genetic liver diseases caused?
- Blood proteins (e.g. clotting factors)
- Inborn errors of metabolism (Amino acid, carbohydrate, lipid metabolism)
NAFLD
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
NASH
Non-alcoholic steatohepatitis
- type of NAFLD
—inflammation,
—liver cell damage
—fatty liver
Liver disease progression
healthy liver –> NAFLD (fat accum.) –> NASH (fat accum. & inflam.) –> Cirhosis (scar tissue replaces hepatic) –either –>liver transplant/death –or–> Hepatocellular carcinoma
Early Stage Liver disease treatment
- Resection
–> needs early diagnosis
This process allows healthy part of liver to regrow
End Stage liver disease treatment
- Liver transplant = only current treatment
o Demand for organ is inc.
o donor rates = poor
o many donated liver unsuited for transplanted
Liver Cancer treatment
- partial hepatectomy
- transplantation
- radiofrequency, cryoblation, radiotherapy
- Sorafinib (5yr survival rate 17%)
What is extracorporeal liver-assist device (ELAD) bioartificial liver?
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
Adult Stem cells
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)
Characteristics of stem cells in adult liver under injured conditions
Liver progenitor cells emerge a& expand
–> contribute to regeneration process due to their bi-lineage differentiation potential to both hepatocytes & cholangiocytes
What are oval cells?
- 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
Cholangiocytes
- 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
What is the portal triad?
Portal vein
Hepatic artery
Bile duct
Describe important features of the liver lobule
- 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
What enables and inhibits hepatocyte synthesis?
Enables:
insulin, EGF, norepinepherine, T3 from adrenal glands, stellate cells (hepatocyte growth factor; HGF)
Inhibits:
Transforming growth factor (TGF)
What are iPSC?
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.
