Cell Death Flashcards
Hallmark of Cell Death
Loss of Nucleus
3 Steps to Loss of Nucleus in Cell Death
Pyknosis (Shrinkage)
Karyorrhexis (Breaking into Pieces)
Karyolysis (PIeces → Building Blocks)
2 Mechanisms of Cell Death
Necrosis (Murder)
Apoptosis (Suicide)
Necrosis
Death of a LARGE group of cells
Followed by Acute Inflammation
Always Pathologic
6 Types
6 Types of Necrosis
Coagulative Liquefactive Gangrenous Caseous Fat Fibrinoid
Coagulative Necrosis
Necrotic tissue that remains firm (due to coagulation of cellular proteins)
Tissue dies, but structure remains (except nuclei)
Classic Example of Coagulative Necrosis
Ischemic Infarction (any organ EXCEPT brain)
Path Findings of Coagulative Necrosis
Infarcted area wedge-shaped & pale
Wedge points to occlusion
If red infarction, that means blood re-entered a loosely-organized tissue
Classic Example of Red Ischemic Infarction
Testicle w/ Hemorrhagic Infarction (torsion around vein → congestive infarct)
Liquefactive Necrosis
Necrotic tissue becomes liquefied
Enzymatic lysis of cells & proteins
3 Circumstances Leading to Liquefactive Necrosis
Brain Infarction (Microglia have liquefactive enzymes)
Abscess (PMNs have hydrolytic enzymes)
Pancreatitis (Hyperactive pancreas digests itself, also leads to Fat Necrosis)
Gangrenous Necrosis
Coagulative Necrosis that resembles mummified tissue (Dry Gangrene)
Typically from ischemic insult to the lower limb, GI tract
Common in diabetics
Gangrenous Necrosis + Superimposed Infection
Liquefactive Necrosis (Wet Gangrene)
Caseous Necrosis
Soft, friable, cottage cheese appearance
Liquefactive + Coagulative
Caseous Necrosis Classically Associated With
Granulomatous Inflammation due to TB or Fungal Infection
Mycobacterial or Fungal walls = Flour in the gravy
Fat Necrosis
Fatty Acids released by trauma or lipase
Calcium deposits, forming Chalky-White appearance (saponification of Calcium)
Fat Necrosis Classically Caused By
Trauma to fat (eg Breast) - Can present with a mass, due to giant cell reaction
OR
Peripancreatic fat in pancreatitis
Saponification of Calcium Seen In
Fat Necrosis vs. Dystrophic Calcification vs. Metastatic Calcification
Dystrophic Calcification
Dead or dying tissue = Nidus for calcium deposition
Ex. Psammoma Bodies, Saponification
Metastatic Calficiation
Not always associated with metastatic CANCER
Elevated Ca or Ph (for whatever reason) in serum → Ca precipitates in tissues
Fibrinoid Necrosis
Necrosis to blood vessel wall
Proteins leak into vessel wall → Bright pink staining
Fibrinoid Necrosis Classically Seen In
Malignant Hypertension (Super high, headache, renal failure, papilledema) - Can be seen in pre-eclampsia Vasculitis
Significant Necrosis seen in Pre-Eclampsia
Fibrinoid Necrosis of Placental Vessels
Apoptosis
Energy-Dependent, Genetically-Programmed Cell Death
Single cells or small groups of cells
Examples of Apoptosis
Endometrial Shedding
Embryogenesis
CD8+ T-Cell mediated killing of virally-infected cells
T Cell Lifespan
Born in Marrow
Educated in Thymus
Positive Selection (Can it bind self-Ag + MHC?)
Negative Selection (Does it bind self-Ag too strongly?)
Mechanism of T-Cell death during negative selection
Binds self-Ag too strongly → Apoptosis via FAS
Apoptosis Morphology
Cell shrinks, becomes eosinophilic (from concentrated cytoplasm) Nucleus condenses & fragments Apoptotic bodies fall off cell Apoptotic bodies removed by macrophages No inflammation involved
Apoptosis Mediators
Caspases activate:
Proteases (Break down cytoskeleton)
Endonucleases (Break down DNA)
3 Caspase Pathways
Intrinsic Mitochondrial Pathway
Extrinsic Receptor-Ligand Pathway
Cytotoxic CD8+ T-Cell Pathway
BCL2
Stabilizes mitochondrial membrane
Keeps Cytochrome C inside
Intrinsic Mitochondrial Caspase Pathway
Cellular Injury OR DNA Damage OR Decreased Hormonal Stimulation (eg Estrogen) ↓ BCL2 Inactivation ↓ Cytochrome C moves from mitochondrial matrix into cytoplasm ↓ Caspases Activated
Extrinsic Receptor-Ligand Caspase Pathway
FAS-L binds FAS Death Receptor (CD95) on target cell OR TNF binds TNF-R on target cell ↓ Caspases Activated
Cytotoxic CD8+ T-Cell Caspase pathway
CD8+ T Cell recognizes MHCI Ag CD8+ T Cell binds and kills Perforin drill a hole Granzyme enters pores ↓ Caspases Activated
