1F Foundations 6 - Cellular Suffering & Death Flashcards
Physiologic situations of apoptosis?
- Embryogenesis
- Cell breakdown (during menstruation)
- Proliferation of cell populations (to keep cell populations constant)
Pathologic situations of apoptosis?
- DNA damage (e.g. radiation, hypoxia)
- Misfolded proteins (e.g. gene mutations, exposure to free radicals)
- Infections (e.g. HIV)
Descriptive histological characteristics of apoptosis?
- Shrinkage
- Pyknosis (condensation of nuclear chromatin –> shrinkage of the nucleus. Makes the nucleus look more basophilic (darker))
- Membrane blebbing
- Karyorrhexis (Nuclear fragmentation
- Apoptotic bodies
- No inflammation
- Phagocytosis
Ultimate initiators of apoptosis?
Caspases
- Exist in inactive form
- Active when cleaved
What is the function of the Bcl-2 protein family?
- Closely regulate the permeability of the mitochondrial membrane
- “Anti-apoptotic”
What is the function of Bax?
- To go into the mitochondrial membrane and create channels to allow contents of the mitochondria to flow out
- “Pro-apoptotic”
What is let out of the mitochondria during the apoptotic process to start cellular breakdown?
Cytochrome c
Cytochrome c activates what to start apoptosis?
Cytosolic caspases
Receptors in the extrinsic apoptotic pathway?
- Fas-R (CD95)
- TNF
Ligands that activate receptors in the extrinsic apoptotic pathway?
- Fas - Ligand
- TNF - alpha
Mechanism of Killer T cell extrinsic pathway?
Cytotoxic (killer) T cells release Perforin (punctures wholes in the cell) and Granzyme B (enters cell and activate caspases directly)
Where does p53 arrest the cell in the cell cycle?
Between G1 and S
tumour suppressor protein p53 prompts what to DNA in G1?
Repair by enzymes or destruction if damage is irreparable
Where and what? Coagulative necrosis
- Heart
- Liver
- Kidney
- Gelatinous substance in dead tissue
- Occurs in low oxygen environments (e.g. infarction)
Where and what? Liquefactive necrosis
- Brain
- Bacterial abscesses
- Pleural effusions
- Viscous liquid mass
- Major inflammatory response
Where and what? Caseous necrosis
- TB
- Systemic fungal infections
- Coagulative + liquefactive
- “Clumpy cheese”
Where and what? Fatty necrosis
- Peripancreatic fat (saponification via lipase)
- Activation of lipases
Where and what? Fibrinoid necrosis
- Blood vessels
- Immune-mediated vascular damage
Where and what? Gangrenous wet necrosis
- Extremities
- GI tract
-Bacterial infections
Where and what? Gangrenous dry necrosis
- Toes and feet
- Ischemic coagulative
What cellular by-products can you detect in serum when following is injured? Cardiac myocytes
- Myoglobin
- CPK
- CKMB
- Troponin I
What cellular by-products can you detect in serum when following is injured? Skeletal myocytes
- CPK
- Aldolase
- Myoglobin
What cellular by-products can you detect in serum when following is injured? Hepatocytes
- AST
- ALT
- Alkaline phosphatase
- GGT
What cellular by-products can you detect in serum when following is injured? Salivary gland cells
-Amylase