What is a cell adaptation?
Reversible change
Sign of stress/sub-lethal (not killing cell)
What is a accumulation/degeneration?
Irreversible change (usually)
Sign of cell injury/sub-lethal
How are Reactive Oxygen Species (ROS) formed?
Side reaction of oxidative phosphorylation
Incomplete reduction of O2 to H2O by Complex IV
Give examples of ROS
1.) Superoxide: O2-
2.) H2O2 (hydrogen peroxide)
3.) OH- (hydroxyl free radical)
What are the three damages caused by ROS?
1.) Peroxidizes lipids
-chemically changes phospholipids
2.) Breaks DNA backbone
3.) Deforms proteins
-affecting AA of proteins + denatures then so no function
Name the ROS from other sources (non-mitochondrial)
1.) Radiation
2.) Inflammation
3.) O2 Toxicity
4.) Reperfusion injury
Explain the reperfusion mechanism
A.) Ischemia occurs via an occluded BV
b.) Hydropic change + reactive vasodilation occurs to release clot
c.) Reperfusion = blood now flowing through vessel
-vessel unoccluded, but increased blood flow causes a very high O2 delivery which increases ROS
What antioxidants are endogenous?
Within body
Superoxide dismutase
Catalase
Glutathione
What antioxidants are exogenous?
Outside the body
Vitamin C/ascorbate
Vitamin E/tocopherol
Vitamin A or Beta-carotene
What is the definition of apoptosis?
Active process of programmed cell death
What are the 2 apoptosis pathways?
1.) Intrinsic Pathway = signal within mitochondria
2.) Extrinsic Pathway = signal non-mitochondrial
What are the different intrinsic apoptosis pathway signals?
A.) Free radicals
B.) DNA damage
C.) Loss of trophic factors
Describe the intrinsic pathway of apoptosis via free radicals
1.) ROS cause peroxidation of mitochondrial outer membrane
2.) Pore created in membrane �> cytochrome C escapes through damaged membrane into cytoplasm
3.) Cytochrome C activates cascade cascade pathway
4.) Causes apoptosis �> cell dies
What is Cytochrome C
Part of ETC
Mobile within compartment of mitochondria
How does Cytochrome C leak?
Damaged mitochondrial outer membrane
Activation of Bax/Bak via p53
What are the different forms of adaptation?
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
What is atrophy?
Same number of cells but they are getting smaller
What is the etiology of atrophy?
Lack of nutrition (Lack of O2, decreased glucose)
Loss of trophic factors � hormones, neurotransmitters
Describe the loss of trophic factors - neurotransmitters
NTs bind receptors on the surface of cells
Activates signal transduction pathways in cell
If not being used, these cells will shrink
Describe the atrophy of glaucoma/amblyopia
This is an example of the organ shrinking from underuse
Decreased NT to the retinal ganglion cells �> cells die so optic disc shrinks
What is the definition of hypertrophy?
Same number of cells, just bigger
What is the etiology of hypertrophy?
Increase in nutrition (O2, glucose)
Increase in trophic factors � hormones, NTs
What is the pathogenesis of hypertrophy?
Increased protein and membrane production
Is hypertrophy the only thing that occurs? Can it occur with other adaptations?
Occurs alone
Can occur with hyperplasia
Examples of hypertrophy
If many cells become hypertrophic, the entire organ gets larger
Congenital Hypertrophy of the RPE (CHRPE)
Describe the relationship between CHRPE, hypertrophy, and FAP
CHRPE = when the retinal pigment epithelium becomes hypertrophic
FAP �> cancer that people can get with CHRPE
What is the definition of hyperplasia?
Increase in number of cells
Can occur with hypertrophy
What are two ocular diseases due to hyperplasia?
Pinguecula
Pterygium
What is a pinguecula?
Triangular-shaped yellowing of the conjunctiva
What causes the yellowing of this certain part of the eye in a pinguecula?
Hyaline degeneration �> collagen accumulation
What causes a pinguecula?
Wind
Dryness
Sun
What is a pterygium?
White of eye growing on top of the cornea
What are the causes of a pterygium?
Wind
Dryness
UV radiation
So why do some people get a pinguecula and some a pterygium?
Don't know the reason that some people develop one and some the other
What is the definition of metaplasia?
One differentiated cell-type is replaced by another
Often reversible
What are two examples of metaplasia?
1.) Squamous metaplasia
2.) Columnar metaplasia
Where does/can squamous metaplasia occur?
Trachea
Conjunctiva
What is squamous metaplasia?
Columnar cells die and are replaced by squamous cells
Named by the cell it becomes
In the trachea: smokers damage columnar cells + replaced
-cough/bronchitis b/c of this
Describe squamous metaplasia in the conjunctiva
Columnar cells �> squamous cells
Lack of Vitamin A
Can develop dry eye from this
What is a disease that is an example of columnar metaplasia?
GERD: gastroesophogeal reflux disease
What happens in GERD to the cells?
Acid reflux from the stomach goes to the esophagus �> esophageal cells change
Contrast ischemia with Reperfusion injury and their respective types of cell death
Ischemia = occluded BV causes blood to be unable to flow through
-Cells become hypoxic because no O2 flow
-Causes hydropic change of the cell
-Necrosis
Reperfusion:
a.) ischemia due to occluded BV
b.) Hydropic change + reactive vasodilation
-to release clot
c.) vessel i occludes = increased blood flow rapidly = lots of O2 delivery = increased ROS
-Can cause damage to cells
-Apoptosis more likely to occur