Cell Death

Question 1

Hallmark of Cell Death

Answer 1

Loss of Nucleus

Question 2

3 Steps to Loss of Nucleus in Cell Death

Answer 2

Pyknosis (Shrinkage)
Karyorrhexis (Breaking into Pieces)
Karyolysis (PIeces → Building Blocks)

Question 3

2 Mechanisms of Cell Death

Answer 3

Necrosis (Murder)

Apoptosis (Suicide)

Question 4

Necrosis

Answer 4

Death of a LARGE group of cells
Followed by Acute Inflammation
Always Pathologic
6 Types

Question 5

6 Types of Necrosis

Answer 5

Coagulative
Liquefactive
Gangrenous
Caseous
Fat
Fibrinoid

Question 6

Coagulative Necrosis

Answer 6

Necrotic tissue that remains firm (due to coagulation of cellular proteins)
Tissue dies, but structure remains (except nuclei)

Question 7

Classic Example of Coagulative Necrosis

Answer 7

Ischemic Infarction (any organ EXCEPT brain)

Question 8

Path Findings of Coagulative Necrosis

Answer 8

Infarcted area wedge-shaped & pale
Wedge points to occlusion

If red infarction, that means blood re-entered a loosely-organized tissue

Question 9

Classic Example of Red Ischemic Infarction

Answer 9

Testicle w/ Hemorrhagic Infarction (torsion around vein → congestive infarct)

Question 10

Liquefactive Necrosis

Answer 10

Necrotic tissue becomes liquefied

Enzymatic lysis of cells & proteins

Question 11

3 Circumstances Leading to Liquefactive Necrosis

Answer 11

Brain Infarction (Microglia have liquefactive enzymes)
Abscess (PMNs have hydrolytic enzymes)
Pancreatitis (Hyperactive pancreas digests itself, also leads to Fat Necrosis)

Question 12

Gangrenous Necrosis

Answer 12

Coagulative Necrosis that resembles mummified tissue (Dry Gangrene)
Typically from ischemic insult to the lower limb, GI tract
Common in diabetics

Question 13

Gangrenous Necrosis + Superimposed Infection

Answer 13

Liquefactive Necrosis (Wet Gangrene)

Question 14

Caseous Necrosis

Answer 14

Soft, friable, cottage cheese appearance

Liquefactive + Coagulative

Question 15

Caseous Necrosis Classically Associated With

Answer 15

Granulomatous Inflammation due to TB or Fungal Infection

Mycobacterial or Fungal walls = Flour in the gravy

Question 16

Fat Necrosis

Answer 16

Fatty Acids released by trauma or lipase

Calcium deposits, forming Chalky-White appearance (saponification of Calcium)

Question 17

Fat Necrosis Classically Caused By

Answer 17

Trauma to fat (eg Breast) - Can present with a mass, due to giant cell reaction

OR

Peripancreatic fat in pancreatitis

Question 18

Saponification of Calcium Seen In

Answer 18

Fat Necrosis
vs.
Dystrophic Calcification
vs.
Metastatic Calcification

Question 19

Dystrophic Calcification

Answer 19

Dead or dying tissue = Nidus for calcium deposition

Ex. Psammoma Bodies, Saponification

Question 20

Metastatic Calficiation

Answer 20

Not always associated with metastatic CANCER

Elevated Ca or Ph (for whatever reason) in serum → Ca precipitates in tissues

Question 21

Fibrinoid Necrosis

Answer 21

Necrosis to blood vessel wall

Proteins leak into vessel wall → Bright pink staining

Question 22

Fibrinoid Necrosis Classically Seen In

Answer 22

Malignant Hypertension (Super high, headache, renal failure, papilledema) - Can be seen in pre-eclampsia
Vasculitis

Question 23

Significant Necrosis seen in Pre-Eclampsia

Answer 23

Fibrinoid Necrosis of Placental Vessels

Question 24

Apoptosis

Answer 24

Energy-Dependent, Genetically-Programmed Cell Death

Single cells or small groups of cells

Question 25

Examples of Apoptosis

Answer 25

Endometrial Shedding Embryogenesis CD8+ T-Cell mediated killing of virally-infected cells

Question 26

T Cell Lifespan

Answer 26

Born in Marrow Educated in Thymus Positive Selection (Can it bind self-Ag + MHC?) Negative Selection (Does it bind self-Ag too strongly?)

Question 27

Mechanism of T-Cell death during negative selection

Answer 27

Binds self-Ag too strongly → Apoptosis via FAS

Question 28

Apoptosis Morphology

Answer 28

``` Cell shrinks, becomes eosinophilic (from concentrated cytoplasm) Nucleus condenses & fragments Apoptotic bodies fall off cell Apoptotic bodies removed by macrophages No inflammation involved ```

Question 29

Apoptosis Mediators

Answer 29

Caspases activate: Proteases (Break down cytoskeleton) Endonucleases (Break down DNA)

Question 30

3 Caspase Pathways

Answer 30

Intrinsic Mitochondrial Pathway Extrinsic Receptor-Ligand Pathway Cytotoxic CD8+ T-Cell Pathway

Question 31

BCL2

Answer 31

Stabilizes mitochondrial membrane | Keeps Cytochrome C inside

Question 32

Intrinsic Mitochondrial Caspase Pathway

Answer 32

``` Cellular Injury OR DNA Damage OR Decreased Hormonal Stimulation (eg Estrogen) ↓ BCL2 Inactivation ↓ Cytochrome C moves from mitochondrial matrix into cytoplasm ↓ Caspases Activated ```

Question 33

Extrinsic Receptor-Ligand Caspase Pathway

Answer 33

``` FAS-L binds FAS Death Receptor (CD95) on target cell OR TNF binds TNF-R on target cell ↓ Caspases Activated ```

Question 34

Cytotoxic CD8+ T-Cell Caspase pathway

Answer 34

``` CD8+ T Cell recognizes MHCI Ag CD8+ T Cell binds and kills Perforin drill a hole Granzyme enters pores ↓ Caspases Activated ```