Endocrinology 18 - Microvascular Complications Flashcards
List the sites of microvascular complications
- Retinal arteries
- Glomerular arterioles
- Vasa nervorum (tiny blood vessels that supply nerves)
List the causes of microvascular complications
- Severity of hyperglycaemia
- Hypertension
- Hyperglycaemic memory (better control longer term results in reduced risk of microvascular disease)
- Tissue damage through originally reversible and later irreversible alterations n proteins
Describe the mechanism of glucose microvascular damage
- High glucose results in high cytokines, inflammation, and nerve damage in the feet eyes and kidneys
- Polyol pathway
- AGEs
- Protein kinase C
- Hexosamine
What is diabetic retinopathy the cause of?
- Main cause of visual loss in people with diabetes
- Main cause of blindness in people of working age
Describe background diabetic retinopathy
- Hard exudates (cheese colour lipid - protein goes out of the vessels)
- Microaneurysms (bulging vessles)
- Blot haemorrhages (bleeding from these vessels)
Describe pre-proliferative diabetic retinopathy
- If you don’t treat background diabetic retinopathy
- Cotton wool spots also called soft exudates
- Represent retinal ischaemia
Describe proliferative retinopathy
- Visible new vessles
- On disk of elsewhere in retina
Describe maculopathy
- Hard exudates near the macula
- Same disease as background, but near the macula
- Can threaten direct vision
How is background diabetic neuropathy treated?
- Improve blood glucose control
- Warn patient that warning signs are present (screen once a year)
How is pre-proliferative diabetic retinopathy managed?
- Suggests general ischaemia, if left new vessels will grow
- Pan retinal photocoagulation (small laser beams fired into the back of the retina to prevent new vessels forming and bleeding)
What is needed in management of proliferative diabetic retinopathy?
Pan retinal photocoagulation
How is maculopathy managed?
- Only problem around the macula
- Needs a grid of photocoagulation (targeted to the macula)
List the glomerular changes in nephropathy
- Mesangial cell expansion
- Basement membrane thickening (important)
- Glomerulosclerosis
Describe the epidemiology in nephropathy
- T1DM 20-40% after 30-40 years (lower risk of cardiovascular disease as usually younger)
- T2DM - probably equivalent, but depends on age of development, race, age at presentation, and loss due to cardiovascular morbidity
List the clinical features of diabetic nephropathy
- Progressive proteinuria (urine dipstick or microalbumin)
- Increased BP
- Deranged renal function
(- Increased risk of heart disease)
List the strategies for intervention in diabetic nephropathy
- Diabetic control
- Blood pressure control (ACE inhibitors)
- Inhibition of activity of the RAS system
- Stopping smoking
How does inhibition of RAS system stop diabetic nephropathy?
Angiotensin II has negative effects on the kidney
- 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
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
What is diabetic neuropathy?
When small vessels supplying nerves (vasa nervorum) are blocked
List the types of diabetic neuropathy
- Peripheral polyneuropathy (most common - glove and stocking distribution)
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy
What is peripheral neuropathy?
- Most common is loss of sensation in nerves supplying feet
- More common in taller people
- Danger is that patients will not sense injury
- Patients with poor glucose control
How is peripheral neuropathy characterised?
- Loss of ankle jerks
- Loss of vibration sense (using tuning fork)
- Multiple fractures on x ray (Charcots joint)
What is mononeuropathy?
- Sudden motor loss (usually)
- Wrist drop/ foot drop
- Cranial nerve palsy
- Double vision due to third nerve palsy
What is pupil sparing third nerve palsy?
- Eye is down and out
- Pupil responds to light
- Probably caused by diabetes
What are the signs of a space occupying lesion that causes a third nerve palsy?
Will press on parasympathetic fibres first, causing a 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 GI tract, bladder, cardiovascular system.
List the symptoms of autonomic neuropathy
GI
- Difficulty swallowing
- Delayed gastric emptying
- Constipation/ nocturnal diarrhoea
- Bladder dysfunction
Postural hypotension
Cardiac autonomic supply
- Reports of sudden cardiac death
How is autonomic neuropathy monitored?
- Measure changes in heart rate in response to Valsalva manoevre (forceful attempted exhalation against a closed airway, usually done by closing one’s mouth, pinching one’s nose shut then exhaling)
- Normally there is a change in heart rate
- Look at ECG and compare R-R intervals
What is used to test peripheral neuropathy?
Monofilament examination - nylon wire bends applying specific amount of force
List the predisposing factors for foot disease in diabetes
- Neuropathy (motor, sensory, autonomic)
- Peripheral vascular disease
Describe the epidemiology of diabetic food disease
- 2-3% diabetics in England and Wales
- Past or current foot disease 5-7%
- Risk of amputation 60 times higher (poor prognosis in diabetics)
- 10% bed occupancy due to diabetes related problems (half of this diabetic foot disease)
What is the pathway to foot ulceration?
- Sensory neuropathy (step on nails/ burns)
- Motor neuropathy (imbalance between flexors and extensors causes shape of the foot to be lost, clawing of toes causes pressure disturbance)
- Glycosylated tendons and limited joint mobility (collagen flexibility is lost)
- Autonomic neuropathy (loss of control of sweat glands causes dry skin)
- Atherosclerosis (peripheral vascular disease - reduced blood supply)
- Trauma, reduced resistance to infection, and retinopathy (cant see obstacles in the way)
What are the main types of foot disease?
- Neuropathic (numb, warm, dry, palpable pulses and ulcers at points of high pressure loading)
- Ischaemic foot (cold, pulseless, ulcers at foot margins)
- Neuroischaemic (both - numb, cold, dry, pulseless, ulcers at points of high pressure loading + at foot margins)
How is the foot of a diabetic patient assessed?
- Appearance (deformity)
- Feel (hot/ dry)
- Foot pulses (dorsalis pedis and posterior tibial pulse)
- Neuropathy (vibration, temperature, reflex, fine touch)
How is diabetic foot disease prevented?
- Control sugar
- Dyslipidaemia treated
- Diet and exercise (weight loss)
- Inspect feet
- Stop smoking
- Hypertension
- Education
How is foot ulceration managed?
Relief of pressure
- Bed rest (risk of DVT, heel ulceration)
- Redistribution of pressure/total contact cast
- Antibiotics, possibly long term
- Debridement (surgery - removal of dead tissue/calluses)
Revascularization
- Angioplasty
- Arterial bypass surgery
Eventual amputation of the foot
Where do ulcers commonly occur in foot disease?
Ball of the great toe
