Cell injury and death Flashcards
What is apoptosis?
Programmed cell death/ cell suicide
Ordered, regulated process
What is necrosis?
Uncontrolled cell death
Inflammatory
What is the difference in earliest changes?
A: Cell shrinking
N: Cell swelling
What is the difference in membrane?
A: Remains intact/ blebbing
N: loss of integrity
What is the difference in Chromatin?
A: Aggregation at nuclear membrane
N: n/a
What is the difference in vesicles?
A: Formation of membrane enclosed vesicles (apoptotic bodies)
N: No vesicle formation; lysis
What is the difference in termination?
A: Continued fragmentation into smaller bodies
N: Complete lysis
What is the difference in regulation?
A: Tightly controlled
N: Loss of homeostatic regulation
What is the difference in energy requirement?
A: Energy dependent
N: Passive, no energy requirement
What is the difference in DNA?
A: Non-random fragmentation prior to apoptotic body formation- every histone ahs 2.5 turns of DNA, distinct cleavage
N: Random fragmentation after cell lysis
What is the difference in effector mechanisms?
A: Caspase cascade
N: n/a
What is the difference in extent?
A: Localised, individual cells
N: Groups of cells, indiscriminate
What is the difference in cause?
A: Triggered- withdrawal of survival factor or pro-apoptotic stimulus
N: Evoked by significant non-physiological disturbance
What is the difference in elicited responses?
A: No inflammatory response and bystander damage
N: Significant inflammatory response and bystander damage
What causes cell injury?
Lack of oxygen (hypoxia), physical agents (temp, pressure, electricity, radiation), chemicals and drugs, (wrong concentration) infectious agents, immune reactions, genetic defects (lack enzyme leads to build up or no product), nutrition deficiency or imbalance
Describe a reversible cell injury
Rapid changes, swelling due to loss of ion/ fluid homeostasis, Fat accumulation (steatosis), irreversible if persistent injury, point of no return not defined, membrane intact
What are the different apoptosis mechanisms?
Extrinsic- receptor-ligand interaction (FAS) activates Caspase 8 enzymes
Intrinsic- Withdrawal of growth factor/hormone, imbalance between BCL2 regulators and pro-apoptotic proteins causes leaking from mitochondria, activates Caspase 9
How do Caspases work?
Inactive when pro-domain attached, inhibit activity
Inactive monomer undergoes dimerization and interchain cleavage to activate enzyme
What is an example of physiological apoptosis?
Gut epithelium of large intestine- constant proliferation of bottom, constant apoptosis at top= conveyor belt
Failure= benign tumour growth as cells still proliferate
BCL2 protein stops apoptosis (mutation)
What are the types of necrosis?
Coagulative Liquefactive Caseous Gangrenous (dry) Fat
What is coagulative necrosis?
Cell proteins denature, glue together, form ghost outlines
Nuclei degraded, cells stains more deeply
Hypoxia to heart muscle secondary to reduced blood supply (ischaemia)- only if patients stays alive
Scarring/ evidence of prior events
What is liquefactive necrosis?
Cell protein digested, loss of tissue architecture
Infiltration by inflammatory cells (neutrophils)- pus
Secondary infection by bacteria- wet gangrene
Lipid rich tissue- cerebral infarction/ brain
What is caseous necrosis?
End result of granulomatous inflammation
Granulomas- large aggregates of macrophages, epithelioid and giant cells
Mycobacterial infection- TB, tissue in middle dies
What is dry gangrene?
Coagulative necrosis of extremity due to slowly developing vascular occlusion (diabetic)
Reduced blood supply to periphery
Not bacterial so not wet
What is fat necrosis?
Degradation of fatty tissue by lipases, forming chalky deposits
In acute pancreatitis, trauma to fatty tissues
