What happens to recurrent and persistent hyperglycaemia
- Glucose becomes irreversibly bound to RBC, blood vessel walls and interstitial tissue
- One byproduct of this irreversible binding is advanced glycosylation end products (AGE) that leads to 4 main problems
What are the 4 main problems that AGE cause due to recurrent/persistent hyperglycaemia
- AGE binds to cells and increases release of inflammatory cells - increase permeability = monocytes and LDL move into endothelial layer and become macrophages to engulf LDL= foam cells which narrow BV, rupture and plaque formation
- Decreased nitric oxide - loss the ability to vasodilate BV = vasoconstriction
- Coagulant changes - promotes platelet aggregation - increases clotting = increases risk of thrombosis
- Increases oxidative stress/damage - imbalance between the production of free radicals (that damage cells) and our bodys ability to fight the, off - fibrosis of tissue (thickened and inflexible)
What are 3 complications that AGE
- Atherosclerosis - plaque build up
- Arteriosclerosis - artery wall stiffens
- Inflammation
What are micro vascular complications of poorly unmanaged diabetes
Retinopathy: accumulation of AGE = chromic inflammation = oxidative damage / sclerosis and thickening of capillaries = RBC aggregate + macular thickness = poorly managed hypertension will reduce NO causing increased BP = increase pressure on eye = haemorrhage and micro aneurysm = decreased perfusion = ischemia
Nephropathy: hyperglycaemia = hyperfiltration in glumeruli = glomeruli are injured = microalbuminuria which allows certain products to move through that shouldn’t (albumin) = increase affecting Arteriolosclerosis dilation due to dysfunction in vasoconstriction= increases glomeruli pressure = reduce surface area and filtration - renal failure
Neuropathy: AGE = reduced NO = vasoconstriction = reduced blood to neves = ischemia = impaired axonal transport = demyelination - nerves loose myelin sheath = nerves slow down and damage nerve endings, = ALOC, pain, numbness, risk of infection
What are macro vascular complications of persistent hyperglycaemia
Atherosclerosis:
- AGE = reduced NO = vasoconstriction = HT.
- Vascular changes to wall and thickening of vessel ‘ damage to artery wall
- Overtime substances (cholesterol,fats,waste) travelling in blood accumulate inside damage area
- Chemical reactions causes cholesterol to oxides
- Initiate inflammatory response
- Monocytes from blood stream travel to site, turn into macrophages and eat cholesterol
- Macrophages then turn into foam cells which accumulate to form plaque
- As plaque increases in size, arterial wall hardens.
- Smooth muscles cells within arterial wall begin to multiply and move onto surface of plaque to form fibrous cap
- Overtime cap may erode/be, to form a clot that reduces or blocks blood flow
- Results in coronary artery disease, cerebral vascular disease, peripheral vascular disease,
How is increased risk of infection associated with persistent hyperglycaemia
Under normal conditions
- bacterial infection results in release of chemokines that attract circulating neutrophils to endothelium (process of chemotaxis)
- Molecules on the endothelial cell surface allow the neutrophil to be captured then roll along and adhere migrate into tissue to reach infection.
- Neutrophil engulf bacteria and eliminate them via phagosomes (process of phagocytosis)
In hyperglycaemia
- Chemotaxis is reduced, and adherence is reduced. Therefore results in reduced activation of macrophages - reduced phagocytosis
- Also effects complement cascade. Reduces MAC (membrane attack complex) which role was to make bacteria porous to influx fluid for cell death - reduces immune system
- Skin damage: reduced perfusion - reduced fighting off organism
- Neuropathy: reduced pain sensation - reduced early warning signs.
