AED - Cell Injury II - Week 1

Question 1

Define hypoxia.

Answer 1

Lack of sufficient oxygen to maintain normal cell function.

Question 2

Define anoxia.

Answer 2

Total lack of oxygen

Question 3

What is the most common cause of cell injury?

Answer 3

Hypoxia

Question 4

List 4 causes of hypoxia.

Answer 4

Reduced atmospheric oxygen (altitude)
Relatively less RBCs in the bloodstream (leukaemia)
Abnormal haemoglobin (sickle cell disease)
Reduced blood supply (ischaemia)p

Question 5

What is the most common cause of hypoxia?

Answer 5

Ischaemia

Question 6

List 4 cellular consequences of ischaemic hypoxia.

Answer 6

Severe vacuolisation of mitochondria
Membrane damage
Nuclear chromatin clumping
Release of lysosomal enzymes

Question 7

What are the three main ocular structures affected by hypoxia in the eye?

Answer 7

Cornea
Retina
Optic nerve

Question 8

What are retinal and optic nerve hypoxia usually related to?

Answer 8

Ischaemia or other blood disorders.

Question 9

Where does the cornea get its nutrients from?

Answer 9

Largely from the aqueous humour

Question 10

Where does the cornea get its oxygen from (2)?

Answer 10

Atmosphere and aqueous humour

Question 11

What are the two most common causes of corneal hypoxia?

Answer 11

Lid closure from sleep (very mild) and contact lens wear

Question 12

Is restoration of normal oxygen levels to hypoxic tissue generally good? Explain the consequences (2).

Answer 12

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

Question 13

List 7 symptoms of contact lens related hypoxia.

Answer 13

Reduced VA
Corneal oedema
Epithelial erosion (SPK)
Epithelial microcysts
Endothelial blebs
Stromal striae
Limbal neovascularisation

Question 14

What happens to the corneal epithelium with corneal hypoxia?

Answer 14

It shrinks, despite the cornea overall swelling

Question 15

What happens to cell-cell junctions of the corneal epithelium with hypoxia? What does this lead to?

Answer 15

They are reduced, leading to loss of cells from the surface - desquamation

Question 16

Describe SPK.

Answer 16

Desquamation leads to areas of cell loss, where fluorescein can pool.

Question 17

What happens to the proliferative capacity of basal epithelial cells with hypoxia?

Answer 17

Reduced

Question 18

What happens to squamous cell membrane permeability with hypoxia?

Answer 18

Increases

Question 19

Explain how the corneal epithelial layer thins ith hypoxia.

Answer 19

Hypoxia causes epithelial cell injury and death

Dead cells replaced less rapidly, thinning the epithelium

Question 20

What happens to proliferative activity in the corneal epithelial layer vs the limbus? What does this imply?

Answer 20

Decreased in the epithelium, increased at the limbus.

Implies that factors released from dying cells to stimulate rapid replacement by limbal stem cells.

Question 21

What are microcysts?

Answer 21

Large structures that contain cytoplasmic and cell membrane debris

Question 22

Where do microcysts release their contents?

Answer 22

Tear film

Question 23

hat does surface microcystic activity lead to?

Answer 23

Further punctate erosions of the corneal surface

Question 24

Describe what occurs with VEGF release (3) and why it is released.

Answer 24

Hypoxic corneal epithelial cells release VEGF
Stimulates limbal vascular dilation, then new vessel growth
New vessels form along the epithelial BM or stroma

Question 25

Can the drop in cell proliferation be reversed?

Answer 25

Yes, with restoration of sufficient oxygen

Question 26

Does reperfusion of hypoxic retinal tissue promote or stop continued cell death? Explain (3).

Answer 26

Promote, probably due to excess metabolism, free radical promotion and ongoing effects of by-products of necrotic cells

Question 27

Consider absolute retinal ischaemia. List the two layers it generally affects and two factors that indicate it is irreversible.

Answer 27

Ganglion cell layer and nerve fibre layer

Oedema and pyknotic nuclei indicate irreversible damage

Question 28

Where does the majority of apoptosis occur following reperfusion in retinal ischaemia? What does this result in?

Answer 28

Inner nuclear layer and ganglion cell layer

Retinal thinning

Question 29

List the two sources of injury with ischaemia and the process it is caused by.

Answer 29

Lack of oxygen - necrosis

Perfusion - apoptosis