Injury And Cell Death_Pathology

Front 1

coagulative necrosis

Back 1

cytoplasmic proteins are denatured or "coagulated" and accompanied by organelle breakdown and cell swelling

Front 2

karyolysis

Back 2

fading of the normal chromatin basophilia (due to DNAse action on DNA)

Front 3

pyknosis

Back 3

Nuclear shrinkage and increased basophilia (seen in both necrotic cell death and apoptosis)

Front 4

karyorrhexis

Back 4

fragmentation and dispersion of the necrotic nucleus

Front 5

liquefactive necrosis

Back 5

main feature = enzymatic degradation of tissue

form of necrotic brain death!

what can cause this?

Hint 5

some bacterial and fungal infections (especially those that attract many neutrophils)

Front 6

gangrenous necrosis

Back 6

subtype of coagulative necrosis marked by extensive, even regional necrosis

Front 7

caseous necrosis

Back 7

subtype of coagulative necrosis that has a cheese-like appearance due to amorphous granular debris.

What does this look like on the microscopic level?

Hint 7

On the microscopic level there is fragmentation of coagulated cells and a surrounding granulomatous reaction

Front 8

fat necrosis

Back 8

areas of fat destruction from lipases.

What can this lead to?

Hint 8

saponification, as the free fatty acids released from lipases during TG breakdown combine with calcium ions to produce white, chalky regions

Front 9

where does dystrophic calcification occur?

Back 9

in degenerated or necrotic tissue

Front 10

what happens in the cell nucleus during apoptosis?

Back 10

chromatin condenses and aggregates peripherally (forms discrete dense masses) and then eventually undergoes karyorrhexis

Front 11

what happens in the cell cytoplasm during apoptosis?

Back 11

the cytoplasm condenses with resultant tight packing of organelles

Front 12

What is the extrinsic pathway of caspase activation?

Back 12

involves external signals delivered via cell membrane "death domains."
receptor-ligand interactions --> receptor multimerization --> activation of intracellular domains --> activation of caspases by proteolytic cleavage

What are some specific examples of receptor-ligand interactions involved in this pathway?

Hint 12

TNF-TNF receptor

Fas-Fas ligand (fas-fas ligand then associates with TNFR1, which in turn associates with the Intracellular Fas-associated death domain (FADD)

Front 13

What is the intrinsic pathway of caspase activation?

Back 13

the intrinsic pathway involves adjustments in the relative permeability of the mitochondrial membrane, which is dictated by members of the Bcl family.

Bcl family responds to both pro- and anti-apoptotic factors. if the mito membrane receives enough pro-apoptotic stimulation, its permeability increases such that activators of caspases (including cyt c) leak out --> activate caspases --> apoptosis

What are some specific examples of anti-apoptotic Bcl molecules?

Hint 13

Bcl-2 and Bcl-x

Front 14

nerve growth factor

Back 14

acts as a survival signal for neurons

Front 15

How do lymphocytes cause apoptosis in virus-infected cells?

Back 15

cytotoxic t lymphocytes release perforin (perforates cell mem) and granzyme (granule storage molecule that activates caspases) which kill virus-infected cells

Front 16

What are the 3 mechanisms of caspase activation?

Back 16

1.) extrinsic pathway (receptor-ligand interactions via the "death domain" lead to caspase activation within the cell
2.) intrinsic/mitochondrial pathway (the balance between pro- and anti-apoptotic members of the Bcl family swings toward pro-apoptotic --> pro-apoptotic Bcl makes cell membrane more leaky --> cyt c, etc (caspase activators) escape
3.) cytotoxic Tcells release perforin and granzyme

Front 17

what does alpha-1 antitrypsin do?

Back 17

tempers the activity of proteases

where is it produced? what family of proteins is it in?

Hint 17

liver

serpins (serine protease inhibitors). its a protease!

Front 18

What is the mechanism of acetaminophen overdose --> necrotic cell death?

Back 18

5% of acetaminophen is converted to a reactive intermediate that can usually be neutralized by antioxidant mechanisms (i.e. red. glutathione), but if these mechanisms are overwhelmed than the reactive intermediate goes wild and brings about hepatic necrosis

Front 19

What type of receptors to chemotactic agents generally bind to?

Back 19

G protein coupled receptors

What are the effector agents that the activated G proteins activate?

Hint 19

phospholipase C
phosphoinositol 3 kinase
protein tyrosine kinase