Microvascular Complications of Diabetes Flashcards
As ….. ….. increases, the incidence of microvascular disease occurs
As blood pressure increases, the incidence of microvascular disease occurs
Where are the 3 sites of microvascular complications?
- Retinal arteries
- Glomerular arteries
- Vasa nervorum
How does HbA1C relate to the risk of microvascular complications?
The higher the HbA1C, the higher the risk of microvascular complications
List 4 risk factors for the development of microvascular complications
- Hyperglycaemia severity
- HTN
- Genetic
- Hyperglycaemia memory
Describe the concept of hyperglycaemic memory
- If someone had poor glycaemic control initially but then improved their glycaemic control, they will still have worse prognosis than someone who had a high level of control throughout
- Possibly due to irreversible alterations in proteins
Outline the step-wise mechanisms of glucose damage
- Hyperglycaemia and hyperlipidaemia
- AGE, oxidative stress and hypoxia lead to…
- Inflammatory signalling cascades
- Local activation of pro-inflammatory signalling cascades
- Inflammation
- Inflammation leads to diabetic retinopathy, nephropathy and neuropathy
Apart from the step-wise mechanism, what other pathways can increase the damage?
- AGE (advanced glycation end-product) pathways
- Polyol pathways
- Protein Kinase C
- Hexosamine
What are the 4 types of diabetic retinopathy?
- Background diabetic retinopathy
- Pre-proliferative diabetic retinopahty
- Proliferative diabetic retinopathy
- Maculopathy
What are the features that are visible in the fundoscopy image of the retina in background diabetic retinopathy?
- Hard exudates - proteins and lipids leakage
- Microaneurysms
- Blot haemorrhages
Label the features of the fundoscope on this diagram and thus determine what type of diabetic retinopathy this is
Background diabetic retinopathy
What are the visible features on fundoscopy that indicate pre-proliferative diabetic retinopathy?
- Pre-retinal haemorrhages
- ‘Cotton wool spots’ - soft exudates - representing local retinal ischaemia
Label the features of the fundoscope on this diagram and thus determine what type of diabetic retinopathy this is
- Pre-proliferative diabetic retinopathy
- Soft exudates ‘cotton wool spots’ and pre-retinal haemorrhage
What are the visible features on fundoscopy that indicate proliferative diabetic retinopathy?
- Visible new vessels
What type of diabetic retinopathy is indicated in the picture below and why did you come to your conclusion?
Proliferative diabetic retinopathy
What happens in maculpathy (a form of diabetic retinopathy)?
Hard exudates form at the macula, thereby impairing colour vision and, direct vision and visual acuity
How does diabetic retinopathy progess once started if left untreated?
- Start with background diabetic retinopathy
- Then pre-proliferative diabetic retinopathy - retinal ischaemia occurs here so this leads to…
- Proliferative diabetic retinopathy - as new vessel formation occurs in an attempt at compensation
- Maculopathy can occur after background diabetic retinopathy also due to hard exudate presence
How is diabetic retinopathy managed in background diabetic retinopathy?
- Warn the patient that the warning signs are present
- Ensure glycaemic control
How is diabetic retinopathy managed in pre-proliferative diabetic retinopathy?
- Pan-retinal photocaoagulation (laser) in the area of the retina undergoing changes to prevent bleeding prevent new vessel formation that will occur in proliferative diabetic retinopathy
How is diabetic retinopathy managed in pre-proliferative diabetic retinopathy?
- Same as in pre-proliferative diabetic retinopathy
- Pan-retinal photocoagulation (laser) the areas of the retina undergoing changes to prevent new vessel formation and prevent vessel bleeding
How is diabetic retinopathy managed in maculopathy?
- GRID photocoagulation (very localised laser treatment) to target only the hard exudates in teh macula which are causing the symptoms in maculopathy without burning the whole retina or large swathes as in pan-retinal photocoagulation
Give the features of diabetic nephropathy
- HTN
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
- Classical histological features
What are the 3 classical types of histological changes in diabetic nephropathy?
- Glomerular
- Vascular
- Tubulointerstitial
What kinds of glomerular changes can occur in diabetic nephropathy?
- Mesangial expansion
- Basement membrane expansion
- Glomerulosclerosis
What could be behind the histological changes that can be seen in diabetic nephropathy?
- Glomerulosclerosis itself can cause secondary effects on the tubulointerstitium
- High exposure to high [glucose] or glycated proteins can trigger histological changes
- High pressure within the glomerular capillaries can stimulate expansion of the matrix
- Angiotensin stimulates pathways that can result in matrix expansion
1) What is proteinuria?
2) What can proteinuria cause in nephrotic syndrome?
1)
- High protein in the urine - lots of protein lost in the urine - makes the urine look frothy
2)
- Hypalbuminaemia - low albumin in the blood
- Hypolabuminaemia → oedema because of osmosis
What are the stages of intervention in controlling diabetic nephropathy?
- Glycaemic control
- BP control
- Inhibition of RAAS
- Smoking cessation
What effects does ATII have at the kidneys?
- Vasoactive effects
- Mediation of glomerular filtration
- Increased tubular protein uptake
- Induction of pro-fibrotic cytokines
- Stimulates fibroblast production
- Stimulation of glomerular and tubular growth
- Podocyte effects
- Upregulation of adhesion molecules on endothelial cells
- Upregulation of lipoprotein receptors
- Induction of pro-inflammatory cytokines
- Generation of ROS and NF-kB
What are the vessels supplying nerves called?
Vasa nervorum
What is the basic pathophysiological basis of diabetic neuropathy?
- Hyperglycaemia causes blockage of the vasa nervorum due to glucose crystallisation therefore resulting
List the 6 types of diabetic neuropathy
- Peripheral polyneuropathy
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy
What is the main symptom of peripheral neuropathy?
Loss of sensation
What are associated risks / health issues associated with peripheral neuropathy
- At risk of joint problems
- Charcot’s joint - multiple fractures in feet visible on X-rays
- Ulcers
How can you test for / detect peripheral neuropathy?
- Monofilament examination to detect loss of sensation (a metal wire with set pressure placed at different points over the body)
- Loss of ankle jerks
- Loss of vibration sense - detectable using a tuning fork
What can you do to prevent patients getting ulcers in peripheral neuropathy?
- Advise they wear appropriate footwear
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
1) What is autonomic neuropathy?
2) What are the symptoms of autonomic neuropathy?
1)
- Loss of SNS and PNS nerves to GI tract, bladder and CVS system
2)
GI tract
- Dysphagia
- Delayed gastric emptying
- Constipation / nocturnal diarrhoea
Bladder dysfunction
Postural hypotension
Cardiac autonomic supply
- Possible cardiac sudden arrest too
What are 2 test you can do to test for autonomic neuropathy?
- Measure HR change in response to the Valsalva manouevre
- Look at R-R intervals on ECG
