3. Cell Injury II Flashcards
... is the lack of sufficient oxygen to maintain .... ... is the complete lack of oxygen. Hypoxia can result of from reduced atomosphereic O2, reduced ..., abnormal ... or reduced .... Hypoxia is the most common cause of ..., whereas ischemia is the most common cause of ....
Hypoxia is the lack of sufficient oxygen to maintain normal cellular function. Anoxia is the complete lack of oxygen. Hypoxia can result of from reduced atomosphereic O2, reduced RBCs numbers, abnormal haemoglobin or reduced blood supply (ischaemia). Hypoxia is the most common cause of cell injury, whereas ischemia is the most common cause of hypoxia.
How does the cornea obtain O2? How can corneal hypoxia occur?
The cornea is avascular, therefore it obtains O2 from the atmosphere. Hypoxia of the cornea can occur during sleep when lids are closed and during contact lens wear.
Restoration of ... after hypoxia is not always beneficial especially in tissues that cannot ..., such as the ... and ... tissues. This can cause surge in ... activity with increased ... usage, causing rapid accumulation of ... and thus reduced efficiency of the ..., the ... can cause further cell damage. Moreover, ... causes release of intracellular contents (e.g. ..., ...). During repercussion, the contents of dead cells may have ..., thus causing ....
Restoration of O2 after hypoxia is not always beneficial especially in tissues that cannot regenerate, such as the corneal endothelium and neural tissues. This can cause surge in mitochondrial activity with increased O2 usage, causing rapid accumulation of ROS and thus reduced efficiency of the antioxidant system, the free ROS can cause further cell damage. Moreover, necrotic cell death causes release of intracellular contents (e.g. lipases, proteases). During repercussion, the contents of dead cells may have secondary toxic/ excitotoxic effects, thus causing secondary apoptosis.
What are the consequences of CL-related hypoxia?
• Reduced VA
• Corneal oedema
• Epithelial erosion (SPK)
• Epithelial microcysts
• Endothelial blebs
• Stromal striae
• Limbal neovascularisation
Corneal hypoxia causes ..., where the epithelium ... while the corneal stroma .... Hypoxia causes fewer ..., ... and .... This affects epithelial ... to the basement membrane and to neighbouring cells, therefore reduces .... This allows easier .... Epithelial cells are lost (...), which can be observed as .... The proliferative capacity of ... are reduced with hypoxia, therefore there is an overall .... ... also forms, which are evidence of corneal epithelial cell death. These microcysts can move ... towards the ... and contribute to further ... of the corneal surface.
Hypoxic corneal epithelial cells also release ..., which stimulate ... and .... These vessels can invade the epithelial ... membrane or the .... If the growth crosses the visual axis, it can affect .... The reduction in epithelial cell proliferation is ... when sufficient O2 is replenished, this can return ....
Corneal hypoxia causes epithelial cell shrinkage, where the epithelium thins while the corneal stroma swells. Hypoxia causes fewer tight junctions, desmosomes and hemidesmosomes. This affects epithelial adhesion to the basement membrane and to neighbouring cells, therefore reduces epithelial barrier integrity. This allows easier invasion of bacteria/ viruses/ parasite. Epithelial cells are lost (desquamation), which can be observed as superficial punctuate keratopathy. The proliferative capacity of basal epithelial cells are reduced with hypoxia, therefore there is an overall thinning of the epithelium. Microcysts also forms, which are evidence of corneal epithelial cell death. These microcysts can move anteriorly towards the tear film and contribute to further punctuate erosions of the corneal surface.
Hypoxic corneal epithelial cells also release vasoactive factors (VEGF), which stimulate limbal vascular dilation and growth of new vessels. These vessels can invade the epithelial basement membrane or the stroma. If the growth crosses the visual axis, it can affect VA. The reduction in epithelial cell proliferation is reversible when sufficient O2 is replenished, this can return normal epithelial cell numbers.
What are the benefits of using silicon hydrogel contact lenses? What remains a caution with the use of these contact lenses?
Silicon hydrogels are a more oxygen permeable contact lens material and it thought to be less harmful due to less prone to cause corneal hypoxia. However, silicon hydrogel have not been proved to reduce the incidence of CL-related microbial keratitis.
What are the 5 causes of retinal ischaemic hypoxia?
• Retinal arteriolar occlusion (CRAO)
• Retinal venous occlusion (CRVO)
• Closure of retinal capillary networks (diabetes)
• Occlusion of choroidal vasculature
• Closure of ONH capillary networks
Just like corneal O2 reperfusion, reperfusion of retinal tissues after ... can promote .... This is theorised to be due to ..., ... formation and ongoing effects of .... Such that in ischaemia-related retinal hypoxia, there may be ... or ... depending on the extent of hypoxia. The retinal layers will become ... immediately, which appears as overall .... Retinal ... can occur later.
Just like corneal O2 reperfusion, reperfusion of retinal tissues after retinal/ optic nerve hypoxia can promote secondary apoptosis. This is theorised to be due to excess metabolism, free radical formation and ongoing effects of byproducts of necrotic cells. Such that in ischaemia-related retinal hypoxia, there may be asymptomatic or profound VA loss depending on the extent of hypoxia. The retinal layers will become swollen immediately, which appears as overall pallor with cherry red spot macula. Retinal necrosis or apoptosis can occur later.
Why is the outer retina largerly unaffected with retinal ischaemia?
There is a separate blood supply between the outer and inner retinal layers, therefore there will be different cell injury in presentation.
Retinal ischeamia occurs with ... with little ... production. The lack of ATP causes ... of INL, GCL, NFL. There will be some immediate ..., causing ... cell death.
Ischaemia prevents ..., thus causing increase in extracellular ... levels. There is little inflammation due to .... However, during reperfusion, there is a release of ... and causes ... and thus cell injury.
Retinal ischeamia occurs with acute stoppage of retinal blood supply with little ATP production. The lack of ATP causes oedema of INL, GCL, NFL. There will be some immediate pyknosis, causing necrotic cell death.
Ischaemia prevents glial resorption, thus causing increase in extracellular glutamate levels. There is little inflammation due to absolute ischaemia. However, during reperfusion, there is a release of inflammatory mediators and causes inflammatory cascades and thus cell injury.
Cell injury occurring in the ... phase may either be a consequence of ... that were already initiated during ischaemic phase. There is high levels of ...; high extracellular ..., leading to ... and thus ...; Ca2+ influx causes ... or activates ... pathways and ... responses. Cell injury can also be a result of inflammatory responses due to activation of the .... Overall cell injury will cause .... Retina is ..., unlike the cornea.
Cell injury occurring in the reperfusion phase may either be a consequence of cellular alterations that were already initiated during ischaemic phase. There is high levels of oxygen free radicals; high extracellular glutamate, leading to glutamate excitotoxicity and thus Ca2+ influx; Ca2+ influx causes necrosis or activates apoptotic pathways and inflammatory responses. Cell injury can also be a result of inflammatory responses due to activation of the complement cascade. Overall cell injury will cause retinal thinning. Retina is non-regenerative, unlike the cornea.
