17. Microvascular complications Flashcards
What are the sites of microvascular complications?
- Retinal arteries
- Glomerular arterioles (kidney)
- Vasa nervorum (supply nerves)
Why does high glucose lead to microvascular damage?
- Oxidative stress, hypoxia etc.
- Changes in the inflammatory cascades
- Local activation of pro-inflammatory cytokines
- Retinopathy, nephropathy, neuropathy
(genetic predisposition also has an affect)
Describe diabetic retinopathy and its progression
• Main cause of visual loss in people with diabetes, and blindness in people of working age
• Involves hard exudates, microaneurysms and blot haemorrhages
• Reaches ‘pre-proliferative diabetic retinopathy’ if diabetes is not controlled
- get cotton wool spots (soft exudates) - represents retinal ischaemia
• If not treated, reaches ‘proliferative retinopathy’
- visible, new vessels form within the retina
- not smooth and can haemorrhage
What is maculopathy?
- Type of retinopathy that affects colour vision
- Same disease, but hard exudates are near macula
- Only affects the macula
- Causes severe visual impairment and threatens direct vision
How can you prevent the progression of retinopathy?
- Pan-retinal photocoagulation
- Laser beams target parts of the retina and burn them off
- This prevents vessel formation
- Urgent procedure if patients have proliferative DR
How can you prevent the progression of maculopathy?
- Grid of photocoagulation
* Just carried out on the macula
What are the signs of diabetic nephropathy?
- Hypertension
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
- Classic histological features
What is the most common cause of kidney problems?
Diabetes
What are the histological features of diabetic nephropathy?
• Glomerular changes - mesangial expansion - BM thickening - glomerulosclerosis • Vascular changes • Tubulointerstitial changes
When are biopsies done on patients with diabetic nephropathy?
- Rarely done
- By the time you have diabetic nephropathy, you should already have diabetic retinopathy
- Biopsies done when there haven’t been any changes in the eyes - suggest kidney disease is not related to diabetes
How does the epidemiology of diabetic nephropathy compare in T1D and T2D?
• T1D - 20-40% have nephropathy after 30-40 years
• T2D
- probably equivalent
- complications probably occur between 60-70
- racial factors predispose to complications
- loss due to cardiovascular morbidity
What is the normal and nephrotic range of proteinuria?
- Normal <30mg/24hr
* Nephrotic >3000mg/24hr
What is hypoalbuminaemia and how is this related to diabetes?
- Low albumin (protein) in the blood
- Causes patients to become oedematous (fluid in legs and feet)
- Part of nephrotic syndrome
What are the (4) stages of intervention in diabetic nephropathy?
- Diabetes control
- Blood pressure control
- Inhibition of activity of the RAS
- Stopping smoking
What are the effects of Angiotensin II?
- Vasoconstriction
- Mediation of glomerular hyperfiltration
- Increased tubular uptake of proteins
- Induction of pro-fibrotic and pro-inflammatory cytokines
- Stimulation of glomerular and tubular growth
- Podocyte effects
- Upregulation of adhesion molecules on endothelial cells
- Upregulation of lipoprotein receptors
- Stimulates fibroblast proliferation
How do ACE inhibitors affect renal function?
- Reduce worsening
* Improve function in patients with diabetic nephropathy
What is the most common cause of neuropathy?
Diabetes
When do you get neuropathy?
Vasa nervorum vessels get blocked
What are the changes seen in diabetic neuropathy?
- Peripheral polyneuropathy
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy - muscle affected
What is peripheral neuropathy?
- Longest nerves are affected in the body e.g. those supplying the feet
- Loss of sensation
- More common in tall people
How can you test sensation in the feet in the clinic?
- Monofilament - metal wire with a set pressure
* Placed at different positions on the bottom of the foot
What are the risks with having peripheral neuropathy?
• Danger of not sensing injury to the foot
• Risk of joint problems
- don’t know how much pressure to put on your foot
• Results in loss of ankle jerks and loss of vibration sense
• Cause multiple fractures
What is mononeuropathy and how does it present?
• One part of the nerve doesn’t work (commonly affect the muscles)
• Usually sudden motor loss (wrist drop, foot drop)
• Patient may get cranial nerve palsies
- most common is a 3rd nerve palsy - double vision
What is pupil sparing third nerve palsy?
• Oculomotor nerve has various parasympathetic fibres on the outside
- these don’t easily lose blood supply in diabetes - continue to work
- pupil is therefore spared and responds to light
• Eye is usually ‘down and out’
- trochlear nerve pulls it down, abducens nerve pulls it out
•
When is third nerve palsy non-pupil sparing?
- If someone has an aneurysm that causes third nerve palsy
- Parasympathetic fibres are compressed
- Causes fixed dilated pupil
What is mononeuritis multiplex?
A random combination of peripheral nerve lesions
What is radiculopathy?
- Pain over spinal nerves
* Usually affecting a dermatome on the abdomen or chest wall
What is autonomic neuropathy?
- Loss of sympathetic and parasympathetic nerves to GIT, bladder and CVS
- GIT - dysphagia, delayed gastric emptying, constipation/nocturnal diarrhoea, bladder dysfunction
- Postural hypotension
- Cardiac autonomic supply - case reports of sudden cardiac death
When do you measure changes in the HR with an autonomic neuropathy?
- Measure HR in response to Valsalva manoevre
- Normally a change in heart rate
- Look at ECG and compare R-R intervals
