Pathophysiology of diabetes Flashcards
What is diabetes?
heterogenous group of disorders. Characterised by an absolute or relative deficiency of insulin and/or insulin resistance
What is type I diabetes?
10% of people have this type and it is an autoimmune destruction of b cells
What is type II diabetes?
90% of people have this type and it is due to insulin resistance
What are the initial symptoms of diabetes?
polydipsia, polyuria, polyphagia
What are extreme systemic complications of diabetes?
ketoacidosis leading to coma and death. general cardiovascular disease. peripheral microvascular anomalies. peripheral neuropathy. renal dysfunction
Why does polydipsia and polyuria occur?
due to the kidneys wanting to remove unwanted metabolites and waste from the blood. whatever is left over is urine and the body wants to flush everything out hence making you thirsty
How does hyperglycaemia lead to diabetic complications?
increased polyol pathway flux
increased advanced glycation end product
activation of protein kinase C
increased hexosamine pathway flux
What does aldose reductase and the polyol pathway cause?
Causes excess sorbitol
What does excess sorbitol cause?
changed osmotic gradient
sorbitol oxidation
NADPH imbalance
reduction in gluthione?
What results from reduced gluthione?
Glutathione deficiency leads to increased oxidative stress greatly reduced ability to detoxify
What happens when there is increased AGE formation due to intracellular hyperglycaemia?
Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function.
What happens when there is increased activation of protein kinase C due to hyperglycaemia?
hyperglycaemia increases diacylglycerol (DAG) which activates protein kinase C and leads to a range of mainly vascular changes such as blood flow abnormalities, capillary occlusion, vascular occlusion, vascular permeability angiogenesis
What happens when there is increased hexosamine flux due to hyperglycaemia?
results in increased gene expression of plasminogen activator inhibitor-1 and TGB-b1 and these can cause vascular and capillary occlusion
What are the ocular complications of diabetes due to DR?
retinal detachment,08 cataract, rubeosis iridis, cataract, optic neuropathy, glaucoma, retinal vein occlusion, optic disc swelling
What causes diabetic keratopathy?
structural & functional abnormalities and enzymatic dysregulation
