Week 2

Question 1

What happens to recurrent and persistent hyperglycaemia

Answer 1

1. Glucose becomes irreversibly bound to RBC, blood vessel walls and interstitial tissue
2. One byproduct of this irreversible binding is advanced glycosylation end products (AGE) that leads to 4 main problems

Question 2

What are the 4 main problems that AGE cause due to recurrent/persistent hyperglycaemia

Answer 2

1. 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
2. Decreased nitric oxide - loss the ability to vasodilate BV = vasoconstriction
3. Coagulant changes - promotes platelet aggregation - increases clotting = increases risk of thrombosis
4. 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)

Question 3

What are 3 complications that AGE

Answer 3

1. Atherosclerosis - plaque build up
2. Arteriosclerosis - artery wall stiffens
3. Inflammation

Question 4

What are micro vascular complications of poorly unmanaged diabetes

Answer 4

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

Question 5

What are macro vascular complications of persistent hyperglycaemia

Answer 5

Atherosclerosis:

1. AGE = reduced NO = vasoconstriction = HT.
2. Vascular changes to wall and thickening of vessel ‘ damage to artery wall
3. Overtime substances (cholesterol,fats,waste) travelling in blood accumulate inside damage area
4. Chemical reactions causes cholesterol to oxides
5. Initiate inflammatory response
6. Monocytes from blood stream travel to site, turn into macrophages and eat cholesterol
7. Macrophages then turn into foam cells which accumulate to form plaque
8. As plaque increases in size, arterial wall hardens.
9. Smooth muscles cells within arterial wall begin to multiply and move onto surface of plaque to form fibrous cap
10. Overtime cap may erode/be, to form a clot that reduces or blocks blood flow
11. Results in coronary artery disease, cerebral vascular disease, peripheral vascular disease,

Question 6

How is increased risk of infection associated with persistent hyperglycaemia

Answer 6

Under normal conditions

1. bacterial infection results in release of chemokines that attract circulating neutrophils to endothelium (process of chemotaxis)
2. Molecules on the endothelial cell surface allow the neutrophil to be captured then roll along and adhere migrate into tissue to reach infection.
3. Neutrophil engulf bacteria and eliminate them via phagosomes (process of phagocytosis)

In hyperglycaemia

1. Chemotaxis is reduced, and adherence is reduced. Therefore results in reduced activation of macrophages - reduced phagocytosis
2. 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
3. Skin damage: reduced perfusion - reduced fighting off organism
4. Neuropathy: reduced pain sensation - reduced early warning signs.