AED - Cell Injury II - Week 1 Flashcards
Define hypoxia.
Lack of sufficient oxygen to maintain normal cell function.
Define anoxia.
Total lack of oxygen
What is the most common cause of cell injury?
Hypoxia
List 4 causes of hypoxia.
Reduced atmospheric oxygen (altitude)
Relatively less RBCs in the bloodstream (leukaemia)
Abnormal haemoglobin (sickle cell disease)
Reduced blood supply (ischaemia)p
What is the most common cause of hypoxia?
Ischaemia
List 4 cellular consequences of ischaemic hypoxia.
Severe vacuolisation of mitochondria
Membrane damage
Nuclear chromatin clumping
Release of lysosomal enzymes
What are the three main ocular structures affected by hypoxia in the eye?
Cornea
Retina
Optic nerve
What are retinal and optic nerve hypoxia usually related to?
Ischaemia or other blood disorders.
Where does the cornea get its nutrients from?
Largely from the aqueous humour
Where does the cornea get its oxygen from (2)?
Atmosphere and aqueous humour
What are the two most common causes of corneal hypoxia?
Lid closure from sleep (very mild) and contact lens wear
Is restoration of normal oxygen levels to hypoxic tissue generally good? Explain the consequences (2).
Generally is good but:
-Restoration of oxygen to a tissue that contains dead or dying cells means that oxygen is initially used more vigorously by mitochondria
–Increases generation of free radicals and reduces antioxidant efficiency
-Contents of dead cells may have secondary toxic/excitotoxic effects on recovering cells leading to secondary apoptosis
List 7 symptoms of contact lens related hypoxia.
Reduced VA
Corneal oedema
Epithelial erosion (SPK)
Epithelial microcysts
Endothelial blebs
Stromal striae
Limbal neovascularisation
What happens to the corneal epithelium with corneal hypoxia?
It shrinks, despite the cornea overall swelling
What happens to cell-cell junctions of the corneal epithelium with hypoxia? What does this lead to?
They are reduced, leading to loss of cells from the surface - desquamation
Describe SPK.
Desquamation leads to areas of cell loss, where fluorescein can pool.
What happens to the proliferative capacity of basal epithelial cells with hypoxia?
Reduced
What happens to squamous cell membrane permeability with hypoxia?
Increases
Explain how the corneal epithelial layer thins ith hypoxia.
Hypoxia causes epithelial cell injury and death
Dead cells replaced less rapidly, thinning the epithelium
What happens to proliferative activity in the corneal epithelial layer vs the limbus? What does this imply?
Decreased in the epithelium, increased at the limbus.
Implies that factors released from dying cells to stimulate rapid replacement by limbal stem cells.
What are microcysts?
Large structures that contain cytoplasmic and cell membrane debris
Where do microcysts release their contents?
Tear film
hat does surface microcystic activity lead to?
Further punctate erosions of the corneal surface
Describe what occurs with VEGF release (3) and why it is released.
Hypoxic corneal epithelial cells release VEGF
Stimulates limbal vascular dilation, then new vessel growth
New vessels form along the epithelial BM or stroma
Can the drop in cell proliferation be reversed?
Yes, with restoration of sufficient oxygen
Does reperfusion of hypoxic retinal tissue promote or stop continued cell death? Explain (3).
Promote, probably due to excess metabolism, free radical promotion and ongoing effects of by-products of necrotic cells
Consider absolute retinal ischaemia. List the two layers it generally affects and two factors that indicate it is irreversible.
Ganglion cell layer and nerve fibre layer
Oedema and pyknotic nuclei indicate irreversible damage
Where does the majority of apoptosis occur following reperfusion in retinal ischaemia? What does this result in?
Inner nuclear layer and ganglion cell layer
Retinal thinning
List the two sources of injury with ischaemia and the process it is caused by.
Lack of oxygen - necrosis
Perfusion - apoptosis
