Microvascular Complications Flashcards
(99 cards)
1
Q
What are the main sites of microvascular complications in DM?
A
- Retinal arteries
- Glomerular arterioles (kidney)
- Vasa nervorum (tiny blood vessels that supply nerves)
2
Q
What is the relationship between the severity of hyperglycaemia and microvascular disease?
A
- microvascular complications tend to develop according to the severity of hyperglycaemia
- the higher the sugar the higher the likelihood that your patient will develop them
3
Q
What is a normal HbA1c?
A
- below 6%
- anything above 6.5% is diabetes
- both micro and macrovascular disease increase with higher HbA1c
4
Q
What is the relationship between hypertension and microvascular disease?
A
- as BP increases, so does the risk of microvascular disease
5
Q
What factors influence microvascular disease?
A
- severity of hyperglycaemia
- hypertension
- genetics
- hyperglycaemic memory (someone who has recently been diagnosed with DM and control well right
6
Q
What is meant by hyperglycaemic control?
A
- Patitents have better outcomes if their blood glucose is well controlled from the start
- e.g. someone who was diagnosed 5 years ago and had good control from the start vs. someone who had poorly controlled diabetes for a number of years.
- problem: T2DM is more common but also less symptomatic in the beginning -> sometimes some of the damage has been done at the time of diagnosis
- screening is important especially in obese patients with FH od diabetes
- The risk of microvascular disease dramatically decreases if the sugar is controlled well.
7
Q
What are the mechanisms of glucose damage?
A
- hyperglycaemia and hyperlipidaemia cause
a) AGE RAGE
b) oxidative stress
c) hypoxia - this in turn causes inflammatory signalling cascade
- this causes local activation of pro-inflammatory cytokines
- this causes inflammation
- inflammation causes nephropathy, retinopathy and neuropathy
(the basic mechanism is increasing the amount of cytokines)
8
Q
What is diabetic nephropathy?
A
- Diabetic retinopathy is the main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
- very common in patients with diabetes
- diabetes causes retinal ischeamia which in turn causes vessel damage in the eye.
9
Q
What is the macula important for?
A
color vision
10
Q
Background diabetic retinopathy
A
- Hard exudates (cheese colour, lipid)
- Microaneurysms (“dots”)
- Blot haemorrhages
Protein goes out of vessles
Bulging out
Bleeding from vessles
11
Q
Pre-proliferative diabetic retinopathy
A
- Cotton wool spots also called soft exudates
- Represent retinal ischaemia
- vessels leaking out protein
if you don’t treat background retinopathy
12
Q
Proliferative diabetic retinopathy
A
- Visible new vessels
- On disk or elsewhere in retina
- the vessles are not oriented, they are going around.
13
Q
What is the main cause of blindness in people of work g age?
A
diabetic retinopathy
14
Q
When are cotton wool spots seen?
A
- In pre-proliferative diabetic retinopathy
- they are caused by:
15
Q
Maculopathy
A
- Hard exudates near the macula
- Same disease as background, but happens to be near macula
- This can threaten direct vision
16
Q
How do you manage (background) diabetic retinopathy?
A
- improve control of blood glucose
- warn patient that warning signs are present
- retinal scan 1x/year
- eye changes don’t happen immediately, they are slow changes
17
Q
How do you manage (pre-proliferative) diabetic retinopathy?
A
- Pre-proliferative (cotton wool spot)
- Suggests general ischaemia
- If left alone, new vessels WILL grow
- Needs: Pan retinal photocoagulation (Small laser beams fired at the back of the retina to prevent new vessles from forming)
18
Q
How do you manage proliferative diabetic retinopathy?
A
- Proliferative (visible new vessels)
- Also needs: Pan retinal photocoagulation (Small laser beams fired at the back of the retina to prevent new vessles from forming)
- the vessles will bleed if they are not treated
19
Q
How do you manage maculopathy?
A
- Only have problem around macula
- Needs only a GRID of photocoagulation
(NOT pan retinal photocoagulation)
20
Q
What is a GRID of photocoagulation? When is it used?
A
- used in maculopathy
- ???????????
21
Q
Which statement is correct regarding diabetic retinopathy?
a) Progression is unrelated to glycaemic control
b) Cotton wool spots are a feature of background retinopathy
c) Hard exudates are always treated with pan retinal photocoagulation
d) Maculopathy can threaten direct vision
e) Proliferative changes are best left untreated
A
d) is true
22
Q
Why is diabetic nephropathy important?
A
- Associated morbidity and mortality (having kidney disease increases the risk of dying very much)
- Health care burden (financially)
- Treatment options present (good BP, good glucose, smoking cessation)
23
Q
What is an effect of DM and CKD?
A
- presence of DM and CKD increases the risk of cardiovascular events
- the highest prevelance of kidney disease is in the diabetes cohort
24
Q
In which cohort is the highest prevalence of kidney disease?
A
In the diabetes cohort
25
Histological features of kidney disease?
- glomerular
- vascular
- tubulointerstitial
26
Histological features of kidney disease - glomerular changes?
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis
27
Clinical features of diabetic nephropathy?
- Progressive proteinuria
- Increased BP
- Deranged renal function
28
What is the epidemiology of nephropathy in diabetics?
- Type 1 DM : 20-40% after 30-40 years
- Type 2 DM : Probably equivalent - BUT in T2DM they tend to be quite young at diagnosis and love with it for a long time. T2DM is diagnosed much later in life (around 40-50) so they ???????????rewatch that part of the lecture
29
Epidemiology of nephropathy in T2DM
- Age at development of disease
- Racial Factors
- Age at presentation
- Loss due to cardiovascular morbidity (they may die of a heart attack before they have problems with their eyes or kidneys)
30
Proteinuria ranges
- Normal Range <30mg/24hrs
- Microalbuminuric Range 30 - 300mg/24hrs
- Assymptomatic Range 300 - 3000mg/24hrs
- Nephrotic Range >3000mg/24hr
Sometimes very small protein cannot be detected on the dipstick which is why you measure microalbumin which if elevated is an early sign of kidney disease.
31
What are strategies for intervention in diabetic nephropathy?
- diabetes control - decrease blood glucose
- 37% decrease in risk of microvascular complications per 1% decrement in HbA1c
- BP control
- inhibition of the activity of the RAAS
- smoking cessation (something that kills patients with Kideny problems is cardiovascular disease)
It is very good to prevent the progression of kidney disease
32
What is a normal GFR? What GFR would require dialysis?
- normal is around 90
- around 30 would require dialysis
- ACE inhibitors are quite good for kidney function
33
Angiotensin 2
- Vasoactive effects
- 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
- Generation of ROS & NF-kB
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
34
Negative effects of Angiotensin 2
- Vasoactive effects -> detritus effects on the kidneys
- 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
- Generation of ROS & NF-kB
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
35
Which of these are features of diabetic nephropathy?
a) Affects all patients with diabetes over time
b) Associated with decreased blood pressure
c) Progressively increasing proteinuria
d) Unrelated to glycaemic control
e) Associated with a low risk of cardiovascular events
a) not the ones with good sugar and BP control that don't smoke
b) associated with high BP
c) true
d) dalse
e) false
36
Which of these are features of diabetic nephropathy?
a) Affects all patients with diabetes over time
b) Associated with decreased blood pressure
c) Progressively increasing proteinuria
d) Unrelated to glycaemic control
e) Associated with a low risk of cardiovascular events
a) not the ones with good sugar and BP control that don't smoke
b) associated with high BP
c) true
d) false
e) false
37
Diabetic neuropathy
- Diabetes is the most common cause of neuropathy and therefore lower limb amputation
- Small vessels supplying nerves are called vasa nervorum
- Neuropathy results when these get blocked
38
Neuropathy: disease initiation/progress
????????
39
Neuropathy: disease initiation/progress
INFLAMMATION
genetics, epigenetics, glycation
40
Peripheral neuropathy
- Longest nerves supply feet
- Loss of sensation
- More common in tall people
- Danger is that patients will not sense an injury to the foot (eg. Stepping on a nail)
- Loss of ankle jerks
- loss of vibration sense (using tuning fork)
- multiple fractures on foot X-ray (Charcot’s joint)
41
Which patients are more likely to have peripheral neuropathy?
- tall
| - poor glucose control
42
How do you examine neuropathy?
monofilament examination
43
Mononeuropathy
- Usually sudden motor loss
- wrist drop, foot drop
- Cranial nerve palsy: double vision due to 3rd nerve palsy
44
Pupil sparing 3rd nerve palsy
- Eye is usually “down and out”.
- (6th nerve pulls eye out and 4th nerve pulls it down).
- 3rd nerve plasy with pupil spared: think of diabetes
- 3rd nerve palsy and pupil does not respond to light: think of place occupying lesions
- parasympathetic fibres on outside.
- Thus they do not easily lose blood supply in diabetes
45
What are the signs of a space occupying lesion that causes a third nerve palsy ?
- e.g. aneurysm
| - Will press on parasympathetic fibres first causing fixed dilated pupil
46
Mononeuritis multiplex
A random combination of peripheral nerve lesions
47
Radiculopathy
Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall.
48
Radiculopathy
- Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall (so in a way similar to shingles)
- very rare
49
Autonomic neuropathy
- Loss of S and PS nerves to GI tract, bladder, cardiovascular system.
- Occur when diabetes has been going on for a long time.
- Some patients may be incontinent, some may develop arrhythmias
50
How do you examine autonomic neuropathy?
- Measure changes in heart rate in response to Valsalva manoevre
- Normally there is a change in heart rate
- Look at ECG and compare R-R intervals
51
Valsalva manouvre
blow onto a syringe and measure HR, measure if respiraton changes occur as well
52
Valsalva manouvre
blow onto a syringe and measure HR, measure if respiraton changes occur as well
53
What is the main cause of blindness in people of work g age?
diabetic retinopathy
54
Hard exudates
normally hard exudates are background changes UNLESS they occur at the macula where they can cause vision loss -> Maculopathy
55
What kind of changes are cotton wool spots?
Pre proliferative
56
When do hard exudates not have to be treated?
If they occur in the periphery of the retina
57
Are kidney biopsies often done in clinical practice?
No, mostly you look at the clinical aspects, glucose, hypertension
-> only do them if you are unsure (e.g. If not due to sugar or BP and the other kidney markers are normal and don't reveal the cause
58
What is the first sign of any renal disease?
A small rise in micro albumin
59
How do you manage maculopathy?
- Only have problem around macula
- Needs only a GRID of photocoagulation
(NOT pan retinal photocoagulation)
60
What is a GRID of photocoagulation? When is it used?
- used in maculopathy
| - ???????????
61
What are the features of diabetic nephropathy?
- Hypertension
- Progressively increasing proteinuria
- Progressively deteriorating kidney function
- Classic histological features
62
Why is diabetic nephropathy important?
- Associated morbidity and mortality (having kidney disease increases the risk of dying very much)
- Health care burden (financially)
- Treatment options present (good BP, good glucose, smoking cessation)
63
What is an effect of DM and CKD?
- presence of DM and CKD increases the risk of cardiovascular events
- the highest prevelance of kidney disease is in the diabetes cohort
64
In which cohort is the highest prevalence of kidney disease?
In the diabetes cohort
65
Histological features of kidney disease?
- glomerular
- vascular
- tubulointerstitial
66
Histological features of kidney disease - glomerular changes?
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis
67
Clinical features of diabetic nephropathy?
- Progressive proteinuria
- Increased BP
- Deranged renal function
68
What is the epidemiology of nephropathy in diabetics?
- Type 1 DM : 20-40% after 30-40 years
- Type 2 DM : Probably equivalent - BUT in T2DM they tend to be quite young at diagnosis and love with it for a long time. T2DM is diagnosed much later in life (around 40-50) so they ???????????rewatch that part of the lecture
69
Epidemiology of nephropathy in T2DM
- Age at development of disease
- Racial Factors
- Age at presentation
- Loss due to cardiovascular morbidity (they may die of a heart attack before they have problems with their eyes or kidneys)
70
Proteinuria ranges
- Normal Range <30mg/24hrs
- Microalbuminuric Range 30 - 300mg/24hrs
- Assymptomatic Range 300 - 3000mg/24hrs
- Nephrotic Range >3000mg/24hr
Sometimes very small protein cannot be detected on the dipstick which is why you measure microalbumin which if elevated is an early sign of kidney disease.
71
What are strategies for intervention in diabetic nephropathy?
- diabetes control - decrease blood glucose
- 37% decrease in risk of microvascular complications per 1% decrement in HbA1c
- BP control
- inhibition of the activity of the RAAS
- smoking cessation (something that kills patients with Kideny problems is cardiovascular disease)
It is very good to prevent the progression of kidney disease
72
What is a normal GFR? What GFR would require dialysis?
- normal is around 90
- around 30 would require dialysis
- ACE inhibitors are quite good for kidney function
73
Angiotensin 2
- Vasoactive effects
- 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
- Generation of ROS & NF-kB
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
74
What effects does ACE have?
1. AT1 -> AT2
| 2. Bradykinin -> inactive peptide
75
Which of these are features of diabetic nephropathy?
a) Affects all patients with diabetes over time
b) Associated with decreased blood pressure
c) Progressively increasing proteinuria
d) Unrelated to glycaemic control
e) Associated with a low risk of cardiovascular events
a) not the ones with good sugar and BP control that don't smoke
b) associated with high BP
c) true
d) dalse
e) false
76
What is the most common cause of lower limb amputation?
Diabetes -> neuropathy
77
Diabetic neuropathy
- Diabetes is the most common cause of neuropathy and therefore lower limb amputation
- Small vessels supplying nerves are called vasa nervorum
- Neuropathy results when these get blocked
78
Neuropathy: disease initiation/progress
????????
79
Types of diabetic neuropathy
- Peripheral polyneuropathy
- Mononeuropathy
- Mononeuritis multiplex
- Radiculopathy
- Autonomic neuropathy
- Diabetic amyotrophy
80
Peripheral neuropathy
- Longest nerves supply feet
- Loss of sensation
- More common in tall people
- Danger is that patients will not sense an injury to the foot (eg. Stepping on a nail)
- Loss of ankle jerks
- loss of vibration sense (using tuning fork)
- multiple fractures on foot X-ray (Charcot’s joint)
81
Which patients are more likely to have peripheral neuropathy?
- tall
| - poor glucose control
82
How do you examine neuropathy?
monofilament examination
83
Mononeuropathy
- Usually sudden motor loss
- wrist drop, foot drop
- Cranial nerve palsy: double vision due to 3rd nerve palsy
84
Pupil sparing 3rd nerve palsy
- Eye is usually “down and out”.
- (6th nerve pulls eye out and 4th nerve pulls it down).
- 3rd nerve plasy with pupil spared: think of diabetes
- 3rd nerve palsy and pupil does not respond to light: think of place occupying lesions
- parasympathetic fibres on outside.
- Thus they do not easily lose blood supply in diabetes
85
What are the signs of a space occupying lesion that causes a third nerve palsy ?
- e.g. aneurysm
| - Will press on parasympathetic fibres first causing fixed dilated pupil
86
Mononeuritis multiplex
A random combination of peripheral nerve lesions
87
Radiculopathy
Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall.
88
Autonomic neuropathy
- Loss of S and PS nerves to GI tract, bladder, cardiovascular system.
- Occur when diabetes has been going on for a long time.
- Some patients may be incontinent, some may develop arrhythmias
89
What are the effects of autonomic neuropathy?
GI tract:
- difficulty swallowing
- 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
=> from a patient perspective this is very debilitating
90
How do you examine autonomic neuropathy?
- Measure changes in heart rate in response to Valsalva manoevre
- Normally there is a change in heart rate
- Look at ECG and compare R-R intervals
91
Valsalva manouvre
blow onto a syringe and measure HR, measure if respiraton changes occur as well
92
What do cotton wool spots represent?
Retinal Ischaemia
93
Hard exudates
normally hard exudates are background changes UNLESS they occur at the macula where they can cause vision loss -> Maculopathy
94
What kind of changes are cotton wool spots?
Pre proliferative
95
When do hard exudates not have to be treated?
If they occur in the periphery of the retina
96
Are kidney biopsies often done in clinical practice?
No, mostly you look at the clinical aspects, glucose, hypertension
-> only do them if you are unsure (e.g. If not due to sugar or BP and the other kidney markers are normal and don't reveal the cause
97
What is the first sign of any renal disease?
A small rise in micro albumin
98
What is the difference between 3rd nerve palsy from diabetes and another cause?
The pupil still responds to light in diabetes, there is dual blood supply (PS fibres outside, can be damaged Ibn compressive lesion but preserved in diabetes)
99
Summary
- Glycaemic control central to microvascular complications
- Other factors may accelerate
- Major cause of morbidity for patients with diabetes
