Chapter 1.3 Cell Death Flashcards
What is the morphological hallmark of cell death?
Loss of nucleus
How can morphological hallmark of cell death occur?
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)
What is metaplasia? Give a classical example.
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
What two general things lead to acute inflammation?
infection
necrosis
What is coagulative necrosis?
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
What does wedge-shaped and pale tissue indicate?
infarcted tissue
coagulative necrosis
(Wedge will point to area of occlusion, where dichotomous area was occurring)
What 2 things does red infarction require? Give an example.
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)
What is liquefactive necrosis? How does this occur?
Describe 3 clinical scenarios.
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)
If blood is cut to brain, is this liquefactive or coagulative necrosis? Why?
liquefactive
brain contains microglial cells (derivatives of monocytes, macrophages of brain) which contain hydrolytic enzymes that trash/destroy the tissue after it dies
What two types of necrosis are associated with pancreatitis?
liquefactive necrosis of pancreatic parenchyma
fat necrosis of peri-pancreatic surrounding fat
What is gangrenous necrosis?
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
What is caseous necrosis?
soft friable necrotic tissue “cottage cheese-like” appearance
liquefactive necrosis with something else mixed in (coagulation)
-granulomatous inflammation due to TB or fungal infections
What does fat necrosis look like? Describe mechanism.
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
Where is fat necrosis seen?
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”)
What is saponification?
fatty acids released by trauma or lipase join with Ca
example of dystrophic calcification
Give two examples of dystrophic calcification.
What are levels of serum Ca and P like?
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
What is metastatic calcification?
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
What is fibrinoid necrosis?
What do you see upon staining?
Give 2 clinical examples.
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
In what circumstance would 30 year old woman present with fibrinoid necrosis?
pre-eclampsia (3rd trimester) elevated bp (protinuria)
fibrinoid necrosis of placenta (of placental blood vessels)
Give 3 classical examples of apoptosis.
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)
Describe morphology of apoptosis.
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
How is apoptosis mediated?
mediated by CASPASES which…
- activate proteases (to break down the cytoskeleton)
- activate endonucleases (break down DNA)
How are caspases activated? What pathways?
- intrinsic mitochondrial pathway
- extrinsic receptor ligand pathway
- CD8 T cell pathway
Describe the intrinsic mitochondrial pathway.
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
