Chapter 1.3 Cell Death

Question 1

What is the morphological hallmark of cell death?

Answer 1

Loss of nucleus

Question 2

How can morphological hallmark of cell death occur?

Answer 2

Loss of nucleus can occur by pyknosis (shrink down like ink dot), karyorrhexis (breaking up of nucleus into pieces), karyolysis (pieces broken down into basic building blocks)

Question 3

What is metaplasia? Give a classical example.

Answer 3

change in stress in organ leads to change in cell type, new cell type better suited to handle the stress. Commonly involves change in surface epithelium (squamous, columnar, urothelial)

occurs via reprogramming of stem cells.

Classic example: Barrett’s esophagus

Question 4

What two general things lead to acute inflammation?

Answer 4

infection

necrosis

Question 5

What is coagulative necrosis?

Answer 5

necrotic tissue that remains firm

cell shape and organ structure are preserved by coagulation of cellular proteins

nucleus disappears

characteristic of ischemic infarction of any organ except brain

Question 6

What does wedge-shaped and pale tissue indicate?

Answer 6

infarcted tissue
coagulative necrosis

(Wedge will point to area of occlusion, where dichotomous area was occurring)

Question 7

What 2 things does red infarction require? Give an example.

Answer 7

blood reenters tissue
loosely organized tissue

w testicle (blocking of venous supply when twist on cord, so blood can come in through artery which is thick walled, but vein collapses in twisting and blood cannot get out)

(tissue die because vein is blocked, blood re-enters bc artery somewhat open, blood piles, up, tissue of testicle relatively loose, creates Red Infarction)

Question 8

What is liquefactive necrosis? How does this occur?

Describe 3 clinical scenarios.

Answer 8

Necrotic issue becomes liquefied

enzymatic lysis of cells

• brain infarction
• abscess (walled off area of dead tissue, liquefied bc neutrophils contain hydrolytic enzymes that destroy the tissue)
• pancreatitis (activate enzymes of pancreas within pancreas itself… digest pancreas and liquefactive necrosis results, can be caused by hypercalcemia)

Question 9

If blood is cut to brain, is this liquefactive or coagulative necrosis? Why?

Answer 9

liquefactive

brain contains microglial cells (derivatives of monocytes, macrophages of brain) which contain hydrolytic enzymes that trash/destroy the tissue after it dies

Question 10

What two types of necrosis are associated with pancreatitis?

Answer 10

liquefactive necrosis of pancreatic parenchyma

fat necrosis of peri-pancreatic surrounding fat

Question 11

What is gangrenous necrosis?

Answer 11

resembles mummified tissue (dry)

characteristic of ischemia of lower limb and GI tract (diabetics- partial occlusion of popliteal artery)

if superimposed infection occurs, then liquefactive necrosis ensues (wet gangrene) wet=pus

Question 12

What is caseous necrosis?

Answer 12

soft friable necrotic tissue “cottage cheese-like” appearance

liquefactive necrosis with something else mixed in (coagulation)

-granulomatous inflammation due to TB or fungal infections

Question 13

What does fat necrosis look like? Describe mechanism.

Answer 13

chalky white (when fat dies, fatty acids are released and fatty acids can bind with Ca which is saponification)

when Ca deposits on dead fat, gives white, chalky appearance

Question 14

Where is fat necrosis seen?

Answer 14

Trauma!
trauma to fat (breast) …car accident and breast crushed against steering wheel. (release of fatty acids and then Ca binding those) so trauma can release those fatty acids

pancreatitis-mediated damage of peripancreatic fat

(Can appear as a mass,
“giant cells” “fat” “calcification”)

Question 15

What is saponification?

Answer 15

fatty acids released by trauma or lipase join with Ca

example of dystrophic calcification

Question 16

Give two examples of dystrophic calcification.

What are levels of serum Ca and P like?

Answer 16

dead or dying tissue which becomes an ignitius for Ca to deposit (saponification= dead fat which picks up Ca)

Samomma bodies - tumor cells outgrow blood supply, die, on top of those dying cells calcification can occur

Serum Ca normal, serum P normal

Question 17

What is metastatic calcification?

Answer 17

serum Ca high throughout blood so Ca can deposit throughout all tissues of body

NOT cancer.
Calcification that occurs in multiple tissues because of high Ca or high Phosphate

Question 18

What is fibrinoid necrosis?

What do you see upon staining?

Give 2 clinical examples.

Answer 18

necrotic damage to vessel wall

leaking of proteins into vessel wall (bright pink staining)

• malignant hypertension (high bp that presents with headache, renal failure… consequence is blood vessel wall can necrosis bc of high pressure)
• vasculitis

Question 19

In what circumstance would 30 year old woman present with fibrinoid necrosis?

Answer 19

pre-eclampsia (3rd trimester) elevated bp (protinuria)

fibrinoid necrosis of placenta (of placental blood vessels)

Question 20

Give 3 classical examples of apoptosis.

Answer 20

endometrial shedding during menstrual cycle

removal of cells during embryogenesis (space between fingers and toes)

CD8 T cell mediated killing of virally infected cells (MHC class I bc presenting endogenously made proteins by virus)

Question 21

Describe morphology of apoptosis.

Answer 21

Dying cell shrinks (becomes eosinophilic- bright pink)

nucleus condenses and fragments

apoptotic bodies fall from cell and are removed by macrophages; NOT followed by inflammation

Question 22

How is apoptosis mediated?

Answer 22

mediated by CASPASES which…

• activate proteases (to break down the cytoskeleton)
• activate endonucleases (break down DNA)

Question 23

How are caspases activated? What pathways?

Answer 23

• intrinsic mitochondrial pathway
• extrinsic receptor ligand pathway
• CD8 T cell pathway

Question 24

Describe the intrinsic mitochondrial pathway.

Answer 24

Bcl2’s role is to stabilize the mitochondrial membrane so cytochrome C cannot leak out

• (stimulus for apoptosis) :cellular injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2
• Cytochrome C leaks from inner mitochondrial matrix into cytoplasm and can activate caspases necessary to drive apoptosis further

Question 25

Describe extrinsic receptor ligand pathway mechanisms. Give examples.

Answer 25

something from outside world binds receptor on cell and activates apoptosis

FAS ligand binds FAS death receptor (CD95) on target cell

(T cells born in bone marrow, go to thymus to get educated, go through 2 layers of testing, positive selection they ask do you have ability to bind self antigen and MHC? If yes, it survives to negative selection. Do you have ability to bind self antigen too strongly? If so, then T cell destroyed during negative selection. Die by FAS ligand apoptotic pathway.)

TNF binds TNF receptor on target cell.

Question 26

Describe cytotoxic CD8 T cell pathway.

Answer 26

(CD8 recognize MHCI)

perforins create pores in membrane of target cell

granzyme enters pores and activates caspases

Question 27

What type of necrosis would be indicated by “giant cells” and “calcification”?

Answer 27

fat necrosis