What is the morphological hallmark of cell death?
Loss of the nucleus
What is pyknosis?
Shrinkage of the nucleus
What is Karyorrhexis?
Breakdown of the nucleus into pieces
What is karyolysis?
The complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases
What are the three major stages of cell death?
- Pyknosis
- Karyorrhexis
- Karyolysis
True or false: necrosis is alway pathologic
True
What is the major difference between necrosis and apoptosis?
Necrosis is followed by inflammation
What, generally, is coagulative necrosis?
Necrotic tissue that retains its shape and firmness d/t preservation of the organ structure and coagulation of cellular proteins
What happens to the nucleus with coagulative necrosis?
Disappears
Coagulative necrosis can be characteristic of necrosis in any organ, except for which?
Brain
What process produces coagulative necrosis?
Ischemic infarction
What is the general shape of areas of infarcts?
Wedge shaped
What causes a red infarction?
If blood reenters an area of loosely organized tissue that underwent necrosis
Why is it essential that CT is loose if a red infarct is to occur?
Needs to be able to hold the blood
What occurs with liquefactive necrosis?
Enzymatic lysis of cells and proteins resulting in liquefaction
What are the three classic circumstances in which liquefactive necrosis occurs?
- Brain infarction
- Abscesses
- Pancreatitis
Why is it that the brain in particular undergoes liquefactive necrosis?
Microglial cells release oxygen radicals and crush the brain tissue like Stalin
Why is different about the cells that mediate liquefactive necrosis in abscesses as compared to the brain?
PMNs do it in abscesses
Microglial cells do it in the brain
What causes the liquefactive necrosis of the pancreas?
Enzymes of the pancreas digest pancreas
What is gangrenous necrosis?
Coagulative necrosis that resembles mummified tissue
Where in the body does gangrenous necrosis classically occur (but not the only place)?
Lower limb and GI tract
What makes gangrene “wet”?
Superimposed infection on the gangrenous necrosis
What is caseous necrosis? What classically causes this type of necrosis?
Combination of coagulative and liquefactive necrosis
Granulomatous inflammation d/t TB or fungal infx
What is the gross appearance of caseous necrosis?
Cottage cheese
What is the classic gross appearance of fat necrosis? What causes this?
Chalky white appearance d/t Ca deposition
What is saponification?
the alkaline hydrolysis of the fatty acid ester–FAs released by trauma or lipase join with Ca
What type of necrosis does the pancreas undergo?
Pancreas itself = liquefactive
Fat necrosis of the peripancreatic fat
What are the two classic regions of the body that undergo fat necrosis?
Peripancreatic fat
Breast trauma
What type of cell might be seen with fat necrosis?
Giant cells
What are the two general processes of Ca deposition in the body?
- Necrotic tissue become a nidus for Ca deposition
- psammoma bodies
What happens to serum Ca levels with dystrophic calcification? Serum phosphate?
Both normal
What is metastatic calcification? What are the relative serum Ca and phosphate levels with this?
Increased concentration of Ca and phosphate in the serum pathologically deposit Ca into tissues
True or false: metastatic calcification always occurs d/t a cancer somewhere?
False–just means that Ca levels are high. Cancers can however, cause this, but it is not required.
What is fibrinoid necrosis?
Necrotic damage to the blood vessel wall from the leakage of proteins from serum
What causes the bright pink staining characteristics of fibrinoid necrosis?
Leakage of proteins into vessel wall
What are the two major (general) causes of fibrinoid necrosis?
Malignant HTN or vasculitis
What causes fibrinoid necrosis of the placenta?
Preeclampsia
True or false: apoptosis requires energy
True
Does apoptosis involve a single cell, or groups of cells
Either
What is the process that causes separation of the fingers during embryogenesis?
Apoptosis
What causes the endometrial lining to be shed during menses?
Apoptosis of the endometrial lining
Does CD8+ T cell killing cause necrosis or apoptosis?
Apoptosis
What are the general morphological changes that occur with apoptosis?
Shrinkage of the cell with intense eosinophilia, and budding off of cell contents
What happens to the nucleus with apoptosis?
Nucleus condenses and fragments
What happens to the apoptotic bodies that fall off of the cell?
Macrophages eat ‘em up
What enzymes are the key mediators of apoptosis?
Caspases
What is the role of the proteases that caspases activate?
Break down the cell cytoskeleton
What is the function of the endonucleases that caspases activate?
Break down DNA
What is the key sign of irreversible damage?
membrane damage
What is the intrinsic mitochondrial pathway that leads to apoptosis?
Damage of some sort deactivates Bcl2
What is the role of Bcl2?
Stabilizes the mitochondrial membrane, to prevent cytochrome C from leaking out and killing the cell
What is the receptor that activates the extrinsic receptor-ligand pathway of apoptosis?
Fas ligand binds to Fas death receptor (CD95)
How are maturing T cells killed in the thymus if they do not pass positive or negative selection?
Fas-L and receptor
What are the three major pathways of apoptosis activation?
- Intrinsic mito pathway
- Fas-Fas-L interaction
- Cytotoxic CD8 T cell
How do CD8+ T cells cause apoptosis? (2 enzymes)
Perforins create pores in membrane or target cell, and granzyme enters pore and activates caspases