Patho & Treatment - Peripheral Arterial Disease Flashcards
What type of arteries are atheromas more likely to form in?
Large, high flow arteries
What are the main preventable risk factors driving the development of peripheral artery disease?
Smoking
Diabetes
What are the various names given to peripheral arterial disease (PAD)?
Peripheral artery atherosclerosis
Peripheral artery occlusive disease (PAOD)
What is an atheroma?
A collection of lipids, cholesterol, fibroblasts and S.mm cells & collagen fibres – lying under the intima & projecting into the lumen within peripheral circulation
What occurs within the artery when an atheroma is there?
Endothelial dysfunction (NO) - limited vasodilation
Vessel stenosis & tissue ischaemia
Possible thrombus formation
What condition are you 40-60% more likely to have if you already have PAD?
Cerebral artery disease, atherosclerotic disease of the coronary and cerebral circulation
Name the risk factors for PAD
- Dyslipidaemia
- Sedentary lifestyle
- Hypertension
- Age (20% of >65 year olds)
- Gender - males have higher risk of PAD as in the UK more men smoke than women
- Diabetes - the main driving force behind PAD
- Smoking
How does smoking impact the integrity of the blood vessels?
Smoking activates the SNS i.e. nicotine activates nicotinic receptors on the adrenal medulla causing production and release of catecholamine
- This causes VC of arterioles - increases TPR - increasing blood pressure - increasing shearing forces and causing endothelial damage
Endothelial damage is the starting point of atheroma. The nicotine acts directly on the endothelial cells causing damage & it damages beta cells in islets of Langerhan in the pancreas
- If enough beta cells are damaged, hyperglycaemia occurs which then causes endothelial damage through glucose attachment to lipids and protein in the endothelial wall (i.e. glycosylation). This results in the formation of advanced glycolytic end products which precipitate an inflammatory response & causing more endothelial damage
What is the impact of smoking on the risk of getting PAD?
Smokers develop PAD 10 years earlier than non-smokers
Smokers are more likely to progress to amputation
Smoking is a greater risk factor for development of PAD than it is for developing CHD
How does sudden blood vessel occlusion occur?
A thrombus sitting on top of a pre-exisiting ruptured atheroma
This will result in an AMI
How is glycaemic control in diabetes measured longterm?
The % of glycosyated haemoglobin (Hb1Ac)
How does type 2 diabetes potentially cause PAD?
- Type 2 diabetes is associated with high levels of VAT
- VAT occurs due to poor diet & lack of exercise
- VAT secretes inflammatory cytokines which cause endothelial damage
- Hyperglycaemia caused when there is insulin resistance, hyperglycaemia is worsened by beta cell dysfunction. Hyperglycaemia causes endothelial cell damage by AGEs
- Both AGEs and cytokines cause a pro-inflammatory state
- Lipolysis of adipocytes occurs causing the release of FFAs as an end product. Resistin helps with uptake of FFAs to be taken up by liver & converted to LDLs which cause atheroma development
How does type 1 diabetes potentially cause PAD?
- Type 1 is driven by beta cell functioning - causing hyperglycaemia and endothelial damage
- A lack of insulin secondary to beta cell dysfunction causes breakdown of FFAs which are taken up (without the assistance of resistin) converted to LDLs by liver which causes atheroma formation
How is PAD classified in terms of disease progression?
Non-critical limb ischaemia
Critical limb ischaemia
What is the main symptom of non-critical limb ischaemia?
intermittent claudication (i.e. pain with activity)
What is the main symptom of critical limb ischaemia?
Intermittent claudication accompanied by one of the following symptoms;
- Rest pain
- Tissue loss or ulceration
- Tissue necrosis/gangrene
Describe the different levels in the Fontaine Classification of PAD
I. “Subclinical” – subtle changes e.g paraesthesia/anaesthesia – cold extremities – diminished pulses & restless leg syndrome
II. Characterised by intermittent claudication (treadmill test) (depending on how far they can walk)
IIa. Intermittent Claudication > 200m
IIb. Intermittent Claudication < 200m
III. Rest pain (initially at night)
IV. Ischaemic ulcers or gangrene
Describe thermal imaging used to diagnose PAD?
identifies warm and cold areas of the leg. Warm = i.e. red areas where the blood can perfuse. Cold = purple, dark green, yellow - blood is not perfusing here and there may be an atheroma in that artery
Describe the ankle-brachial pressure index (ABPi)
Its used to diagnose PAD
Systolic pressure is taken at brachial artery and compared to systolic pressure taken at posterior tibial or the dorsalis pedis artery
Name all the ways PAD can be measured
Fontaine classifcation Thermal imaging Ankle brachial pressure index (ABPi) Doppler & pulse volume recordings Angiogram
Name the ABPi score for each clinical status
Symptom free: 1
Intermittent claudication: 0.95 - 0.5
Rest pain: 0.5 - 0.3
Gangrene and ulceration: <0.2
Name the symptoms of lower limb ischaemia
- Intermittent claudication - excruciating muscle pain causing a mismatch between O2 demand and actual blood flow. Is evident when patient undertakes physical activity
- Diminished /absent pulse - atheroma has ruptured, blood flow has been interrupted and a thrombus has formed
- Atrophic skin changes - poor nutrition to skin as there is inadequate arterial blood supply. Dry, flaky, shiny skin
- Skin colouration
- Elevation pallor & dependent rubor (redness) - pallor when foot is horizontal and gets worse when foot is raised.
- Sensory disturbances - becomes worse as the disease progresses
- Cold extremities
- Sarcopenia
What is the arch of pain in intermittent claudication?
Where is pain located typically in intermittent claudication?
Pain subsides after physical activity has ceased. When the atheroma gets larger the ischaemic threshold is reduced
Femero-popliteal (calves) is the most common artery
What is the outcome of intermittent claudication?
40% improve over 2 years
40% remain unchanged
20% will deteriorate & develop critical limb ischaemia
2-8% need amputation
How does sarcopenia occur in PAD?
Occurs due to sedentary behaviour causing disuse atrophy (due to the pain associated with intermittent claudication will cause the patient to reduce their levels of physical activity)
Loss of muscle fibres driven by age & death of anterior horn cells
Inflammatory processes (reactive oxygen species and inflammatory cytokines) drive muscle atrophy and sarcopenia