Microvascular complications

Question 1

What are some of the sites of microvascular complications?

Answer 1

retinal arteries, glomerular arteries, vaso nervosum (vessels supplying nerves)

Question 2

What are microvascular complications?

Answer 2

occur in diabetes

• retinopathy
• neuropathy
• nephropathy

Question 3

What does the extent of damage depend on?

Answer 3

The severity of the hyperglycaemia

Question 4

How does high blood pressure affect the risk of microvascular complications?

Answer 4

the higher the blood pressure, the incidence of microvascular disease increases

Question 5

What is hyperglycaemia memory?

Is tissue damage from diabetes initially reversible?

Answer 5

• Describes the control of blood glucose over many years)

- There is tissue damage through originally reversible, and later irreversible alterations in proteins

Question 6

How does high blood glucose lead to damage, which pathways are involved?

Answer 6

High glucose levels cause many changes in the inflammatory cascades. This then leads to inflammation, causing problems in the eyes, kidneys and nerves.
There are pathways that make this damage worse:
- Polyol pathway
- AGEs
- Protein kinase C

• Hexosamine

Question 7

What is diabetic retinopathy?

Answer 7

The main cause of visual loss in people with diabetes and the main cause of blindness in people of working age.

Question 8

What is background retinopathy?

Answer 8

• It involves hard exudates (cheese colour, lipid), microaneurysms (“dots”) and blot haemorrhages
• Patients have leakage of protein through the vessels, resulting in hard exudates

Question 9

What happens if diabetes isn’t controlled (next stage of retinopathy)?

Answer 9

• Reaches the next stage: pre-proliferative diabetic retinopathy
• In this patients get ischaemia of the retina
• They get cotton wool spots (soft exudates)

Question 10

What happens if pre-proliferative retinopathy isn’t treated?

Answer 10

• Progresses to proliferative retinopathy
• New vessels form within the retina or optic disc
• Proliferative changes can affect vision and can bleed causing vision loss
• Vessels aren’t smooth and can hemorrhage

Question 11

What is maculopathy?

Answer 11

• A specific type of retinopathy, which affects colour vision (hard exudates near macula)
• Same disease as background diabetic retinopathy, but it occurs near the macular
• This can cause severe visual impairment, and threatens direct vision

Question 12

What is the macula?

Answer 12

A pigmented area surrounding the fovea near the centre of the retina in the eye, which is the region of keenest vision. Responsible for most of coloured vision/fine detail and has a high density of photoreceptors.

Question 13

How is diabetic retinopathy managed?

Answer 13

• Improve blood glucose control
• Patient must be told that the warning signs are present
• If background changes become pre-proliferative (cotton wool spots), this suggests general ischaemia. To prevent proliferative DR we can burn off parts of the retina: pan retinal photocoagulation
• If patients have proliferative DR (visible new vessels), they need urgent pan retinal photocoagulation
• Maculopathy only affects the macula (only affects colour vision) so
  instead of burning the whole retina, a grid of photocoagulation can be carried out, just on the macula

Question 14

What is pan retinal photocoagulation?

Answer 14

• Burning off parts of the retina
• Laser beams are targeted to parts of the retina undergoing changes
• This prevents vessel formation

Question 15

What are the features of diabetic nephropathy?

Answer 15

• hypertension
• progressively increasing proteinuria
• progressively deteriorating kidney function
• classical histological features

Diabetes is the commonest causes of kidney problems

Question 16

What are the histological features of diabetic nephropathy?

Answer 16

• glomerular changes
• vascular changes
• tubolointerstitial changes

Question 17

What are the glomerular changes the occur

Answer 17

• Mesangial cells expansion (VSMC of glomerular capillary)
• Basement membrane thickening
• Glomerulosclerosis (hardening of glomerulus)

Question 18

Why is it rare for nephrologists to do biopsies in patients with diabetic nephropathy?

Answer 18

By the time you have diabetic nephropathy, you should already have diabetic retinopathy. Biopsies are done when there haven’t been any changes in the eyes – this suggests that the cause of the kidney disease is not related to diabetes.

Question 19

Describe the epidemiology of diabetic nephropathy

Answer 19

Type 1 DM: 20-40% will have nephropathy after 30-40 years

Type 2 DM: Probably equivalent but difficult to determine because
age at development of disease, racial factors that predispose individuals to complications, age at presentation and loss due to cardiovascular morbidity

Question 20

What are the clinical features of diabetic nephropathy?

Answer 20

• Progressive proteinuria
• Increased BP
• Deranged renal function

Question 21

What are the different classification ranges of proteinuria?

Answer 21

Normal
<30mg/24hrs

Microalbuminuric
30 – 300mg/24hrs

Assymptomatic
300 – 3000mg/24hrs

Nephrotic
>3000mg/24hr

Question 22

Why do patients get oedema in diabetic nephropathy?

Answer 22

With protein loss in the urine, patients have reduced protein in the blood. Patients get hypoalbuminaemia, and with that, they become odematous (lots of fluid in the legs and feet).

Question 23

What are the different stages of intervention in diabetes?

Answer 23

• Diabetes control
• Blood pressure control
• Inhibits the renin-angiotension system
• Stop smoking

Question 24

What are the effects of angiotensin 2?

Answer 24

• Vasoactive effects
• Mediation of glomerular hyperfiltration
• Increased tubular uptake of proteins
• Induction of pro fibrotic cytokines
• 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 & NF-kB
• Stimulates fibroblast proliferation

Question 25

Give an example of an AG2 receptor blocker

Answer 25

irbesartan

Question 26

What happens in diabetic neuropathy?

Answer 26

Diabetes is the most common cause of neuropathy and therefore lower limb amputation. - Small vessels supplying nerves are called vasa nervorum - These small vessels can be affected by hyperglycaemia - Neuropathy results when these vessels get blocked

Question 27

What are some of the changes seen in diabetic neuropathy?

Answer 27

- Peripheral polyneuropathy - Mononeuropathy – one nerve affected - Mononeuritis multiplex - Radiculopathy – dermatomes affected - Autonomic neuropathy - Diabetic amyotrophy – muscle affected

Question 28

What are the types of drugs that can target the renin angiotensin system?

Answer 28

- renin activity blocking drugs - ace inhibitors - AT2 blocker

Question 29

Which factors lead to diabetic neuropathy?

Answer 29

Hyperglycaemia, along with genetic predisposition, causes inflammation, which then leads to diabetic neuropathy.

Question 30

What is peripheral neuropathy?

Answer 30

- The longest nerves are affected in the body (e.g. those supplying feet) - This results in loss of sensation - This is more common in tall people - The danger is that patients will not sense an injury to the foot - In patients with poor glucose control, we should monitor their peripheral sensation on a regular basis. We should encourage these patients to wear proper footwear

Question 31

What is monofilament examination?

Answer 31

- In clinic, the patient’s feet are exposed - The sensation is tested using a monofilament (a metal wire, with a set pressure) - The monofilament is placed on to the bottom of the foot, at different positions. We then ask the patient to tell us if they feel sensation - If they don't, we need to think about education, to prevent ulcers from occurring

Question 32

Why may patients with loss of sensation in their feet get joint problems?

Answer 32

- If you can’t feel your foot, you may not know how to put pressure on your foot in a certain place - This results in loss of ankle jerks and loss of vibration sense - This causes multiple fractures, seen on a foot x-ray (Charcot’s joint) - Ensuring that patients have correct footwear can prevent this

Question 33

What is mononeuropathy?

Answer 33

- When one part of the nerve doesn’t work (these nerves commonly affect the muscles of the body) - There is usually sudden motor loss (wrist drop, foot drop) - Patients may get cranial nerve palsies (most common is a 3rd nerve palsy -> double vision)

Question 34

What is pupil sparing third eye palsy?

Answer 34

- In this condition, the eye is usually down and out, the 6th nerve pulls eye out and the 4th nerve pulls it down. And the pupil responds to light - In diabetes, the pupil is spared. If a 3rd nerve lesion is pupil sparing, it is probably related to diabetes or a vascular disease. If the pupil is not spared, it is probably related to a compressive lesion. - The 3rd cranial nerve has various parasympathetic fibres on the outside of the nerve - In diabetes, these parasymapthetic fibres don’t easily lose blood supply – so they continue to work - The pupil will therefore be spared - If someone has an aneurysm that causes third nerve palsy, the parasympathetic fibres are compressed - This causes a fixed dilated pupil (non-pupil sparing)

Question 35

What is mononeuritis complex?

Answer 35

A random combination of peripheral nerve lesions.

Question 36

What is radiculopathy?

Answer 36

Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall.

Question 37

What is autonomic neuropathy?

Answer 37

- Loss of sympathetic and parasympathetic nerves to GI tract, bladder and cardiovascular system. - GI tract Dysphagia, delayed gastric emptying, constipation/nocturnal diarrhoea, bladder dysfunction - Postural hypotension Can be disabling: collapsing on standing - Cardiac autonomic supply Case reports of sudden cardiac death

Question 38

How should autonomic neuropathy be measured?

Answer 38

With an autonomic neuropathy, measure changes in heart rate in response to Valsalva manoevre. Normally there is a change in heart rate. Look at the ECG and compare R-R intervals

Question 39

What is diabetic amyotrophy?

Answer 39

- Inflammation | - Weakness followed by wasting of muscle