Week 3 Flashcards
2 ways the liver can fail
○ Hepatocytes are little factories in the body (“coolest cells”) that make all kinds of things. If enough hepatocytes get sick or die, the liver can’t do it’s job which leads to liver failure.
○ The stuff that the liver cells make has to get to where it’s going. Some of it has to get into the blood, and some has to get to the gut thru the bile duct system. If stuff can’t move around in the liver, this will also cause your liver to fail.
In septic shock which liver cells die first
- what about with low glucose?
- cells in zone 3 because you already have very little O2 to that area
- also zone 3 because the cells in zone 1 and two have already picked up the sugar by the time the blood makes it to zone 3
Reversible liver damage
- fatty liver and accumulation of bilirubin
Fatty liver
- divsions
- Microvesicular: A lot of foamy little bubbles; more reversible because a small bubble is more in contact with the cytoplasm-has to reabsorb the fat.
- Macrovesicular: 1-2 really big bubbles that push the nucleus over
- It is not the liver’s job to store fat, so when there is fat in a hepatocyte, something ain’t right.
Accumulation of bilirubin
- Obstruction: If you block the bile duct, bile can’t move
- Metabolic causes: You end up with this brown pigment. Bile starts going into a little caliniculus–>canals of Hering–>bile duct. In cholestasis, bile gets stuck and cells get sicky
hemochromatosis
- what is it?
- what does it look like?
- stain?
- how to get rid of iron in liver?
- liver cells are accumulating iron
- golden brown stuff in licer
- Prussian blue stain
- females have menstruation, but you need to make more blood or use chelate
Ways that liver cells dies
- apoptosis and necrosis
Apoptosis
- what is it?
- final fate?
- depends on? importance?
- stain?
- programmed cell death-cell is getting old or it’s damaged
- Phagocytosed by a Kupffer cell with an intact cell membrane
- caspase; pathogens when they infect a hepatocyte go after caspase so cell can’t turn itself off
- red
Necrosis
- Ultimate fate
- Oncotic
ballooning degeneration–>cell lysis and cell contents get out (cytosol, organelles, cytokines, etc.)
- programmed cell death; cytokines released, put on cell members, macrophages gather and are ready, cell deactivates cell membrane functions–>burst
cell type in liver to give rise to fibrosis?
- stelate cell
fibrosis
- pericellular
- portal/peri portal
- bridging
- cirrhosis
- Fibrosis around the cells, fence pattern or chicken wire pattern b/c it surrounds each individual cell, classic for fatty liver disease- starts at central vein
- scarring happens in portal area so portal area gets bigge and stellate cells are activated causing fibrosis
- fibrosis connects two major structures making a wall so the products are unable to get into the blood
- liver cells completely walled in and none of the stuff it makes can get to where it is supposed to be
pathway of fibrosis in liver cells
• Hepatocyte dies–>releases cytokines–>activates kupffer cells–>kupffer cells release cytokines–>activate stellate cells (normally involved in retinol metabolism)–>once activated, they proliferate and divide and recruit more cells. They change their phenotype to myofibroblasts–>myofibroblasts have processes that wrap around sinusoids (squeeze/relax them) and control blood flow–>unfortunately, when overwhelmed can cause more damage–>also lay down collagen b/c they’re trying to repair a gap so start creating fibrosis
Matrix Metalloproteinase
- enzyme that uses a metal for its MOA (generally use zinc, some use cobalt, etc) and lyses proteins
- specialized to reabsorb ECM
PBC: florid duct lesion
- primary biliary cirrhosis
- labs?
- Body’s immune system (cytotoxic lymphocytes) is destroying bile ducts, and this bile duct is getting chewed on. It’s half gone
- has anti mitochondrial AB
- elevated bili, alk phos, GGT, and positive anti-mito antibodies
AIH
- auto-immune hepatits
- Looks like portal hepatitis (HBV, HCV) except there’s A LOT of plasma cells.
- Regenerative rosettes-plasma cells dividing to replenish themselves
- has anti-smooth muscle anti-bodies
- elevated AST/ALT, positive ANA, anti- smooth muscle anti-bodies
