Microvascular complications

Question 1

what are the sites of microvascular complications of diabetes?

Answer 1

1) retinal arteries
2) glomerular arteries i.e. kidneys
3) vasa nervorum i.e. vessels that supply the nerves

Question 2

how are microvasc complications exacerbated?

Answer 2

• 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.

Question 3

what are involved in the mechanisms of glucose damage?

Answer 3

o Polyol pathway.
o AGEs.
o Protein kinase C.
o Hexosamine.

Question 4

what is affected in diabetic retinopathy?

Answer 4

retina
can involve the macula (involved in colour vision and acuity)
located centrally

Question 5

what are the 4 types of retinopathy?

Answer 5

1) background DR
2) Pre-proliferative DR
3) proliferative DR
4) maculopathy

Question 6

what are the features of Background Diabetic Retinopathy?

Answer 6

o Hard exudates due to protein leakage (looks yellow)
o Microaneurysms – small blood vessels bulge/sprout
o Blot haemorrhages – blots of blood.

Question 7

pre-proliferative DR (diabetic retinopathy)

Answer 7

o Cotton wool spots (soft exudates)
– indicative of retinal ischaemia

looks faded yellow

Question 8

proliferative DR (diabetic retinopathy)

Answer 8

o Visible new vessels – on disc or elsewhere in retina (angiogenesis)

not well organised around the area of ischaemia i.e. not straight and grow in multiple direction s

Question 9

what is the feature of maculopathy?

Answer 9

similar to background retinopathy

o Hard exudates NEAR macula – threatens direct vision.

other:

• microaneurysm
• blot haemorrhages

Question 10

management of background DR

Answer 10

improve blood glucose control

warn patient of the early signs

Question 11

how is pre-proliferative DR managed?

Answer 11

suggests general ischaemia therefore stop it progressing to proliferative by pan-retinal photocoagulation (laser to retina)

Question 12

management of maculopathy

Answer 12

grid-retinal photocoagulation for just the macula

Question 13

what are the features of diabetic nephropathy?

Answer 13

hypertension
progressive increasing proteinuria
deteriorating kidney function
classic histological features.

Question 14

what risk is associated with CKD and diabetes?

Answer 14

risk of CV events increases

Question 15

what are the histological features of DN?

Answer 15

 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.
 Vascular.
 Tubulointestinal.

Question 16

how common is CKD in T1DM?

Answer 16

20-40% of T1DM patients have CKD after 30-40 years.

Question 17

how common is CKD in T2DM?

Answer 17

probably the same as T1DM (20-40%) but difficult to determine due to
– age of development of T2DM, racial factors, age at presentation, loss due to cardiovascular morbidity instead.

Question 18

what are the clinical features of Diabetic Nephropathy?

what is the hallmark feature?

Answer 18

1) Progressive proteinuria (hallmark for CKD) due to leaky glomerulus
o Normal range = <30mg/24hrs.
o Nephrotic range = >3000mg/24hrs.

2) Increased BP.
3) decreased renal function (GFR decrease)

Question 19

what are the interventions for DN?

Answer 19

• diabetic control (the lower the HbA1C, the lower the microvascular complications.)
• BP 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 growth and inflammatory pathways, thus inhibiting is good.
• stopping smoking

Question 20

example of ANGII receptor blocker (antagonist)

Answer 20

irbesartan

Question 21

what causes the production of renin in the juxta-glomerular cells?

Answer 21

• low perfusion pressure
• ## low tubular sodium

Question 22

where is ACE found?

Answer 22

in the lungs

Question 23

what can drugs target in RAS?

Answer 23

o Drugs blocking renin activity.
o ACE inhibitors.
o AT1 antagonists.

Question 24

what does diabetic neuropathy lead to in the later stages?

Answer 24

lower limb amputations due to blockage of blood supply to nerves

Question 25

types of DNeuro?

Answer 25

• peripheral neuropathy (affecting peripheral nerves-most common)
• mononeuropathy (affecting one nerve- blocked)
• mononeuritis multiplex (many nerves affected)
• radiculopathy (dermatomes affected, pain over spinal nerves)
• autonomic neuropathy
• diabetic amyotrophy (inflammation and loss of pain)

Question 26

peripheral neuropathy

Answer 26

• Affects the longest nerves that supply the feet and result in a loss of sensation.
• More common in tall people and people with poor glucose control.

Dangerous: people will not sense damage to the foot–> Charcot’s Foot

• investigated with monofilament examination – tracks loss of sensation.
• Characteristics – loss of ankle jerks, loss of vibration sense, multiple fractures on x-ray (Charcot’s joint).

Question 27

what is mononeuropathy?

two common signs?

Answer 27

motor loss of single nerve:
Usually sudden motor loss resulting in wrist and foot drop.

1) Cranial nerve palsy – double vision due to 3rd nerve palsy (“down and out”).

Question 28

what is affected in cranial nerve 3 palsy?

Answer 28

• Lateral rectus – abducent nerve – OUT.
• Superior oblique – trochlear nerve – DOWN.
• Pupil does respond to light.

Question 29

what 2 ways is the pupil affected in 3rd nerve palsy?

Answer 29

o Pupil-sparing:
PNS fibres on the outside thus they do not easily lose blood supply.
o Fixed dilated pupil:
An aneurysm can also case 3rd nerve palsy BUT the aneurysm will press on PNS fibres and cause a fixed dilated pupil.

Question 30

what makes up mononeuritis multiplex?

Answer 30

random combination of peripheral nerve lesions

Question 31

which dermatomes are usually affected in radiculopathy?

Answer 31

Radiculopathy: pain over spinal nerves therefore affects dermatomes

abdomen or chest wall
pain over spinal nerves

Question 32

what nerves are lost in autonomic neuropathy?

Answer 32

loss of SNS and PNS neves to GI tracts, bladder and CVS

Question 33

what is the effect of losing the nerves in autonomic neuropathy?

Answer 33

• Gi tract – dysphagia, delayed gastric emptying, constipation/nocturnal diarrhoea, bladder dysfunction (more SNS)
• Postural hypotension (vasodilation)
• Cardiac autonomic supply – can have sudden cardiac death (PNS dominance overcome)

Question 34

how can autonomic neuropathy be detected?

Answer 34

measure changed in HR in response to Valsalva manoeuvre

there should be a change in HR
look at ECG and compare R-R interval