Microvascular Complications Flashcards
What are the sites of microvascular complications?
Retinal arteries
Glomerular arteries – kidneys
Vasa nervorum – blood vessels that supply the nerves
What can exacerbate microvascular complications?
Severity of hyperglycaemia – the worse the hyperglycaemia, the worse the damage.
- The higher the HbA1C, the worse the microvascular complications
Hypertension
Genetic
Hyperglycaemic memory – poor diabetes control, even for a brief period, will give an increased risk of microvascular complications compared to someone that has had good control throughout
Tissue damage through originally reversible and later irreversible alterations in proteins
What are the mechanisms of glucose damage?
Polyol pathway
AGEs
Protein kinase C
Hexosamine
What are the different types of diabetic retinopathy?
** The macula is involved in colour vision and acuity and is located centrally.
- Background diabetic retinopathy:
- Hard exudates
- Microaneurysms – small blood vessels bulge
- Blot haemorrhages – blots of blood - Pre-proliferative diabetic retinopathy:
- Cotton wool spots (soft exudates) – retinal ischaemia - Proliferative retinopathy:
- Visible new vessels – on disc or elsewhere in retina
4, Maculopathy (same as background but near macula):
- Hard exudates near macula – threaten direct vision
How is each retinopathy managed?
Background – improve blood glucose control and warn the patient
Pre-proliferative – suggests general ischaemia so to stop it progressing to proliferative, need: Pan-retinal photocoagulation – laser to retina
Proliferative – pan-retinal photocoagulation
Maculopathy – grid-retinal photocoagulation (just at macula)
What are the features of nephropathy?
hypertension
progressive increasing proteinuria
deteriorating kidney function
classic histological features.
What are the histological features nephropathy?
Glomerular:
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis – hardening of capillaries
- If there is no retinopathy, any CKD cannot be due to diabetes – these come together
What are the clinical features of diabetic nephropathy?
Progressive proteinuria – hallmark for CKD
- Normal range = <30mg/24hrs
- *Nephrotic range = >3000mg/24hrs
Increased BP
Deranged renal function – GFR decrease
What is the intervention for diabetic nephropathy?
Diabetic control – the lower the HbA1C, the lower the microvascular
Blood pressure control – control of blood pressure will slow down the deterioration of kidney function
Inhibition of RAS – ACE inhibitors reduce rate of decline of creatinine and thus kidney function.
- AngII is involved in many growth and inflammatory pathways, thus inhibiting is good
Stopping smoking
What are the negative effects of angiotensin 2 on diabetic nephropathy?
- vasocative effects
- mediation of glomerular hyperfiltration
- increased tubular uptake of proteins
- induction of pro fibrotic cytokines
- stimulation of glomerular and tubular growth
- podocyte effects
- induction of pro inflammatory cytokines
- generation of ROS and NF-kB
- stimulates fibroblast proliferation
- upregulation of adhesion molecules on endothelial cells
- upregulation of lipoprotein receptors
Which parts of the RAS system do drugs target?
- Low perfusion means renin will be produced by the juxta-glomerular cells.
ACE is found in the lungs.
Drugs can target:
- Drugs blocking renin activity.
- ACE inhibitors.
- AT1 antagonists.
- Irbesartan is a AngII-R antagonist
What is diabetic neuropathy?
Neuropathy results when the small vessels supplying the vasa nervorum get blocked
- Diabetes is the most common cause of neuropathy and therefore lower limb amputation
What are the different types of diabetic neuropathy?
peripheral polyneuropathy
mononeuropathy
mononeuritis multiplex
reticulopathy
autonomic neuropathy
diabetic amyotrophy
What are the features of peripheral neuropathy?
Affects the longest nerves that supply the feet and result in a loss of sensation - affects peripheral nerves
More common in tall people and people with poor glucose control
Danger is people will not sense damage to the foot
Can be investigated by doing a – monofilament examination – tracks loss of sensation
Characteristics – loss of ankle jerks, loss of vibration sense, multiple fractures on x-ray (Charcot’s joint)
What are the features of mononeuropathy?
only one nerve blocked
Usually sudden motor loss resulting in wrist and foot drop
Cranial nerve palsy – double vision due to 3rd nerve palsy (“down and out”).
- Lateral rectus – abducent nerve – OUT
- Superior oblique – trochlear nerve – DOWN
- Pupil does respond to light
> Pupil-sparing as PNS fibres on the outside thus they do not easily lose blood supply
> An Aneurysm can also case 3rd nerve palsy BUT the aneurysm will press on PNS fibres and cause a fixed dilated pupil
