wk1: AED - Cell Injury 1 Flashcards
Name 8 common causes of injury/stress to ocular tissues
Hypoxia
Chemicals and Drugs
Physical agents (e.g. FBs)
Microbial agents (e.g. corneal compromise in CL wearer)
Immunological agents (e.g. infective epithelial keratitis)
Genetic defects (e.g. photoreceptor degen in R.P)
Nutritional Imbalances
Ageing
Name and describe 5 types of cell adaptation
Atrophy - decrease size, loss of organelles
Hypertrophy - increase size
Hyperplasia - increase in number
Metaplasia - replacement of one cell type with another by differentiation/proliferation
Dysplasia - abnormal change in cell shape/size
Describe the features of a reversible injury of a cell [4]
organelles are swelling up
cell is adapting
nucleus begins to clump - distinct dark areas
lysosomes autophagy - cell eats at its own organelles to atrophy and/or reduce metabolic demand
Describe the features of a irreversible injury of a cell [4]
mitochondria swell
much greater defects in the cell membrane
cell membrane pores
cell nucleus darkens or fades
Describe the changes to corneal epithelium in a reversible injury [3]
Swelling of the stroma - stresses the epithelium (swelling of basal columnar epithelium and nuclear clumping of chromatin)
Loss of polarization of the epithelial tissue - shapes of the cells are less structured and organised
If stromal oedema removed - corneal epithelium returns to normal - as the cells can turn over (in regenerative tissue)
Name 2 indicators of a corneal injury becoming irreversible
Nuclear pyknosis and mitochondrial vacuolisation (which significantly reduces corneal thickness)
Describe the mediators of cell injury as a result of the following:
A) Hypoxia, Ischaemia
B) Multiple Injurous Stimuli
C) Mutations, cell stress, infection
D) Radiation, other insults
E) Infections, immunologic disorders
A: Reduced ATP
B: Increased ROS
C: Accumulation of misfolded proteins
D: Damage damage
E: Inflammation
What is the difference between apoptosis and necrosis
Apoptosis: active process, programmed process of autonomous cellular dismantling that avoids eliciting inflammation
Necrosis: passive, accidental cell death resulting from environmental pertubations with uncontrolled release of inflammatory cellular contents
Describe what happens to the cell when undergoing apoptosis [4]
Cell shrinkage
Chromatin condensation
Cell blebbing
Phagocytosis
Describe what happens to the cell when undergoing necrosis [3]
Compromised membrane; cell swelling
cell lysis: release of intracellular components
Name 3 situations that could result in necrosis of a cell
Physical trauma
Complement-mediated lysis
Lytic viral infection
Name 4 situations that could result in apoptosis of a cell
During development
Tissue homeostasis
Cell-mediated immunity
Hormone-mediated atrophy
How much inflammation and tissue disruption occurs in apoptosis?
No inflammation, little tissue degradation
Describe the following features of Apoptosis
A: Cell size
B: Nucleus
C: Plasma membrane
D: Cellular components
E: Adjacent inflammation
F: Physiologic or Pathologic role
A: Reduced (shrinkage)
B: Fragmentation into nucleosome-sized fragments
C: intact; altered structure, especially orientation of lipids
D: intact, may be released in apoptotic bodies
E: No
F: Often physiological means of eliminating unwanted cells; may be pathological after some forms of cell injury, especially DNA and protein damage
Describe the following features of Necrosis
A: Cell size
B: Nucleus
C: Plasma membrane
D: Cellular components
E: Adjacent inflammation
F: Physiologic or Pathologic role
A: Enlarged (swelling)
B: Pyknosis – Karyorrhexis – Karyolysis
C: Disrupted
D: Enzymatic digestion; may leak out of the cell
E: Frequent
F: Invariably pathologic (culmination of irreversible cell injury)
What is the tunica vasculosa lentis?
Is an extensive capillary network. spreading over the posterior and lateral surfaces of the lens of the eye. It disappears shortly after birth.
it wraps around the lens during development and regresses via apoptosis until vascularisation of the lens is reduced to nothing.
What happens if regression of tunica vasculosa lentis is incomplete?
Causes remnant or persistent hyaloid artery at vestigial, right at where the central retinal artery enters the optic disc
Name the 4 principle targets and biochemical mechanisms of cell injury
- Mitochondria and their ability to generate ATP and ROS under pathologic conditions
- Disturbance in calcium homeostasis
- Damage to cellular (plasma and lysosomal) membranes
- Damage to DNA and misfolding of proteins
Name the 2 major apoptotic pathways
- Mitochondrial (intrinsic) pathway
- Death receptor (extrinsic) pathway
Describe the process of the cell undergoing necrosis [7ish]
Acute depletion of ATP
Lead to Ca2+ accumulation within the cell – toxicity
Cell will try to counteract Ca2+ accumulation through ionic balancing via ion pumps that require ATP
Leads to further depletion of ATP
Leads to stress on mitochondria – cause dysfunction – result in developing ROS - damage cell - oxidative stress
Leads to protein misfolding and cell membrane compromised
Sets of inflammatory cascade at same time
How does Ca2+ accumulation affect endonucleases and DNA degradation?
Activates them
What is necrosis characterised as? [3]
Loss of ion channel function (overload of Na+ – activation of Na+/k+/ATPase – dissipation of ATP)
Ca+ dependent activation of endo-, proteo-, phospholip-, ases
Cell swelling, membrane blebbing, cytoskeleton breakdown
What do TUNEL assays do?
Detect DNA fragmentation by labeling the terminal end of nucleic acids
What is BrdU?
is an analogue of thymidine used in the BrdU assay to identify proliferating cells
Do visual field changes appear clinically in visual field tests before or after RGC apoptosis?
After. RGC apoptosis precedes clinically detectable changes in visual field tests
What is Annexin V used for?
Used in flow cytometry to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane
Between apoptosis and necrosis, which one involves denaturation of proteins leading to extensive amorphous coagulation of tissue during healing?
Necrosis
How much cellular residue is present in apoptosis?
very little cellular residue
