wk1: AED - Cell Injury 2 Flashcards
What 4 things might hypoxia result from?
Reduced atm O2
Relatively less RBCs in blood stream (e.g. leukaemia)
Abnormal Hb (e.g. sickle cell disease)
Reduced blood supply (ischaemia)
How does reduced oxygenation affect the inside of mitochondria?
Severe vacuolisation
Describe the steps for ischaemia leading to cell swelling (7)
Ischaemia Reduces mito. oxygenation Reduce ATP Reduce Na+ pump activity Increase: intra Na & Ca and extra K+ Increase: H2O Cause acute cellular swelling
Describe the steps for ischaemia leading to lipid deposition (8)
Ischaemia Reduces mito. oxygenation Reduced ATP The assoc. change in Na, Ca, K and H2O Dilation of endoplasmic reticulum Detachment of ribosomes Reduce protein synthesis Lipid deposition
Describe the steps for ischaemia causing lysosomal enzyme release and autodigestion (6)
Mito. Oxygenation Reduce atp Increase glycolysis, decrease glycogen, increase lactate, decrease pH Nuclear chromatic clumping & swelling of lysosomes Release of lysosomal enzymes (hydrolases) Cellular digestion
Describe the steps for ischaemia causing increased Ca2+ in mitochondria (5ish)
Ischaemia Membrane damage Loss of phospholipids; altered cytoskeleton; increased free radicals; lipid breakdown Release of enzymes (CPK, LDH, etc); increased Ca2+ influx Increased Ca2+ in mito.
Identify the effects of Ischaemia (in green)
Identify the following effects of Ischaemia (in green)
Identify the following effects of Ischaemia (in green)
What 3 structures are most commonly affected by hypoxia in the eye?
Cornea
Retina
Optic Nerve
How much mitochondria is present in corneal endothelial cells? Why is this the case?
Corneal endothelial cells are rich in mitochondria. This is important in the control of corneal swelling, which involves ATP-dependent ion channels
What are the 2 most common causes of corneal hypoxia?
Lid closure during sleep (very mild)
CL wear
Name 2 consequences of restored oxygen supply in the eye (in tissues that can’t regenerate)
- Restoration of O2 to a tissue that contains dead or dying cells means the oxygen is initially used more vigorously by mito. - increased free radical generation - reduces efficiency of antioxidant = further damage 2. Necrotic cell death cause release of intracellular contents (eg lipases, proteases). During reperfusion - contents of dead cells may have secondary toxic/excitotoxic effects on recovering cells - leads to secondary apoptosis
Name 7 consequences of CL-related hypoxia
Reduced VA
Corneal oedema
Epithelial erosion (EPK)
Epithelial microcysts
Endothelial blebs
Stromal striae
Limbal neovascularisation
Compare the following images. Describe how CL wear has affected the corneal epithelium. (A = low dk/t lens-wearing eye; B = hyper dk/t lens-wearing eye; C = control eye)
CL hypoxia has reduced the proliferative capacity of basal epithelial cells. Note: how B is hyper dk/t (hyper oxygen transmissable) and thus suffers less from the effects of CL-induced hypoxia compared to A.
Compare the following 2 images of corneal epithelium (left = before, right = after 33 days CL wear). What has changed?
Corneal Hypoxia has taken place. The normal columnar basal epithelial cells have become shorter and fatter, note: how they appear more cuboidal in shape now. Also note: how the epithelium is now thinner
Compare these 2 images: How is contact lens wear affecting the corneal epithelium? (a = control; b = CL wear after 8 days. Images are of basement membrane. Arrows point to hemidesmosomes) [6]
As a result of CL-related hypoxia:
fewer tight junctions, desmosomes and hemidesmosomes, condensation of cell cytoskeleton & mitochondrial vacuolisation [labelled m]
Epithelial adhesion to basement membrane + neighbouring cells is altered (= reduced epithelial barrier efficiency)
How does CL-related hypoxia affect basal epithelial cell connection to the bowman’s membrane? What does this suggest?
Reduces the number of proteins that connect the basal epithelium cells to the bowman’s membrane. This suggests that the tight junctions and the desmosomes - interactions between the cell layers are starting to be impaired
Compare these 2 images. Image B represents changes in corneal epithelium with CL wear. What has changed here?
Loss of cells from epithelial surface a.k.a “desquamation” (due to hypoxia-induced cell death)
- results in SPK-NaFl pooling in these spots (the dark spots seen in image B)
[note: SPK = superficial punctate keratopathy, NaFl = i.e. fluoroscein pools]
In regards to the this retinal image, describe its features and name a condition that could be responsible for this appearance:
Overall palor of retina with a cherry red spot (circled). Cherry red spot represents choriocapilaris, which still receives blood supply so stands out during palor. Image indicates loss of blood supply, so it could be: ischaemia-related retinal hypoxia
On the left is a healthy retina, and on the right is a diseased retina. What has changed in the diseased retina? [8] And what condition might be responsible for this?
Late stage retinal ischaemia.
Changes include:
Oedema and pyknosis of ganglion cell nuclei
Necrosis of retinal tissue
Loss of photorceptor axons in outer plexiform
Loss of photoreceptor neurons in outer nuclear layer
Immune cells present (in GCL/NFL, look similar to pyknotic ganglion cells I think)
Thinner Inner Nuclear Layer
Inner half of retina (top half) becomes “homogenized” into a diffuse, relatively acellular zone (outer half relatively preserved)
Thick retinal blood vessels present (the big white ovals)
On the left is a healthy retina and on the right is a diseased retina. Looking at the histology, What has changed in the diseased retina? [3] What condition might be responsible for this?
Early-stage Retinal Ischaemia
Retinal architecture still intact
Oedema and pyknotic ganglion cell nuclei (ganglion cells are dying - apoptosis)
Immune cells moving in to “ng” (a.k.a ganglion cell and nerve fibre layer)
