Pathophysiology of Diabetes: Ocular Flashcards
What is Diabetes Mellitus?
This is a heterogenous group of diabetes.
How is Diabetes characterised?
- Characterised by an absolute or relative deficiency of insulin and/or insulin resistance
- Results in various mechanisms of abnormal metabolism of carbohydrates, fats and proteins
What are initial symptoms of DM?
- Polydipsia (excessive thirst)
- Polyuria (excessive urine production)
- Polyphagia (excessive food intake)
Why does polyuria and polydipsia occur?
The kidneys filter blood to remove any unwanted metabolites and wastes.
Glucose gets reabsorbed by the renal tubules
In diabetes glucose concentration in blood exceeds the capacity of the tubules, so glucose spills to the urine
Why the polyphagia?
Glucose is taken up by cells under action of GLUT receptors
- GLUT 1 maintains basal glucose uptake and GLUT 2 is found in the Liver & Pancreas
Has low glucose affinity but is used for glucose sensing
- GLUT 3 highly enriched brain and GLUT 4 is found in muscle and is insulin sensitive
What is the Polyol Pathway Flux?
Increased glucose is reduced to sorbitol which then converts to fructose.
Inhibition of aldose reductase NADPH —-> NADP+
Inhibition of sorbitol dehydrase
NAD+ —-> NADH
What is advanced glycation end-product (AGE) formation?
- Intracellular proteins modified by AGEs
- ECM components modified by AGE precursors interact abnormally with other matrix components and bind integrins
- Plasma proteins modified by AGE precursors bind AGE receptors, producing ROS
What is the Hexosamine Flux?
Increased flux through the hexosamine pathway results in increased gene expression of plasminogen activator inhibitor-1 [PAL-1] and [TGF-B1]
What is diabetic keratopathy?
- Basement membrane thickened
- Reduction in corneal basal epithelial cells
- Decreased penetration of anchoring hemidesmosomes (increased epithelial erosions)
- Endothelial cell dropout
- Stromal oedema
What type of neovascularisation occurs on the iris?
Rubeosis iridis - secondary to proliferative retinopathy
induce new (abnormal) blood vessel growth from the iris vessel
New vessels may haemorrhage
How is ciliary body affected by diabetes?
It thickens the ciliary body basement membrane, this can be measured by an OCT
Vitrectomy effectively manages thickening
How is the lens affected by diabetes?
lens appearance changes early and gives a ‘snowstorm’ appearance in cortex
Typical presentation is a cortical spoke cataract, accelerated posterior subcapsular cataract
What is capillary and arteriolar occlusion?
- Results in the formation of microaneurysms, intraretinal hemorrhages, hard and soft exudates and infarcts of the nerve fibre layer (cotton wool spots)
What is capillary and arteriolar leakage?
- Results in macular oedema and hard exudates
What is neovascularisation?
- Results in vitreous hemorrhage, fibrosis and retinal detachment
