Peripheral vascular disease Flashcards
Describe the histology of blood vessels
Broadly speaking, the layers of the vessel wall can be divided into three:
- tunica adventitia/connective tissue, supported by external elastic lamina*
- tunica media: comprised of smooth muscle cells
- tunica intima: endothelium and internal elastic lamina
Recall from Block 1 that there are three types of blood vessels:
- arteries
- capillaries
- veins
Arteries:
- has muscle and elastic layers in their walls
- wall is thick
- internal diameter of vessel or lumen is narrow
- no valves present
- usually contains oxygenated blood
- arteries can also dilate or constrict to control flow, in response to blood pressure changes
Capillaries:
- have walls 1 layer thick
- made of endothelial cells
- lumen as narrow as one RBC
- no valves present
- can either have oxygenated/deoxygenated blood- depends on state of exchange
Veins:
- wall contains muscle and elastic layers
- wall is very thin
- lumen is wide
- valves are present ^[unique feature]
- usually contains deoxygenated blood
Describe the histology of the aorta
The aorta is a large, elastic artery.
Three layers: tunica intima, media, adventitia
Notice that the tunica media makes the bulk of the wall of aorta.
An elastic stain (orcein stain) shows that tunica media is also rich in elastic fibres.
List artery diseases
- atherosclerosis
- arteriolosclerosis
- Monckeberg’s medial sclerosis
- Aneurysm
- Arterial dissection
List vein diseases
- DVT and thromboembolism
- Embolism (note arterial embolism is possible but rare)
- Varicose veins
and vasculitis ^[comes up again in phase 2]
Define arteriosclerosis and types
Arteriosclerosis
There are three types of arteriosclerosis, which is an umbrella term for the hardening of the arteries
- atherosclerosis = medium and large arteries (large vessel disease)
- arteriolosclerosis = small arteries and arterioles (i.e. small vessel disease)
- Monckberg’s medial sclerosis = muscular arteries ^[can cause structural problems with the vessel]
HI
Define and list types of atherosclerosis
Atherosclerosis
Atherosclerosis largely affects large elastic arteries e.g. aorta, and muscular arteries e.g. coronary arteries.
Types of atherosclerosis
Type I – Fatty dots - Foam cells
Type II – Fatty streak
Type III – Extracellular lipid pool
Type IV – Atheroma – Core of lipid
Type V – Fibroatheroma – Fibrotic layer
Type VI – Complicated – ulcer, calcium, haemorrhage, thrombus, embolism, aneurysm.
Describe the histology of atherosclerosis
The macroscopic image shows characteristic fatty streaks.
Foamy cells are an attempt by the body to engulf the accumulated lipid.
Increased thickness of intima due to atheroma
List risk factors for atherosclerosis
Risk factors
Risk factors can either be non-modifiable:
- genetics:
- male sex/post-menopausal female
- age
- inherited mendelian disorders e.g. dyslipidaemia especially familial hypercholesterolaemia, and hyperhomocysteinuria
- family history of cardiovascular disease (for females under 65, males under 55)
Or they can be modifiable:
*Diabetes Mellitus (types I+II)
*Hypertension
*Dyslipidaemia
*Smoking
*Severe obesity (BMI > 30)
*Dietary factors (high trans fats, high GI, red meat, low fiber, fruits/veg, moderate ETOH = protective)
*Sedentary lifestyle
*Miscellaneous
–End stage kidney disease
–Childhood Cancer Survivors with history of stem cell transplantation or chest XRT
–Structural heart disease (Aortic stenosis, aortic coarctation, cardiomyopathy, some congenital heart disease repairs)
–Previous Kawasaki disease
–Chronic inflammatory diseases e.g. Autoimmune, HIV
–Adolescent depression
HI
Describe the pathology of atherosclerosis
1)Factors (cholesterol/turbulence etc) → Endothelial dysfunction/injury allows
–Lipoproteins (LDL) begin accumulating in vessel wall intima
–Monocyte recruitment to vessel wall → macrophages (engulf lipid = foam cells)
–Platelet adhesion
2)Chronic Inflammation drives lesion progression
–Activated macrophages, platelets, endothelium release factors (chemokines, cytokines, growth factors) that cause
*T-cell recruitment and activation via inflammasome (IL-1) with further release of chemokines/cytokines (IFN-gamma)
*Smooth muscle recruitment and proliferation and ECM production (e.g. PDGF)
*Activated macrophages release reactive oxygen metabolites → LDL oxidation (inflammatory lipids)
3)Plaque Remodelling
–Plaques are dynamic and constantly changing
–Vulnerable plaques have thin fibrous caps and may not be the most occlusive (but are vulnerable to erosion/rupture/ulceration)
–Inflammatory states may encourage metalloproteinase/proteinase elaboration (mast cells and macrophages) → breakdown of connective tissue
–Eventually the intimal plaque begins to encroach on the media, with weakening of the vessel wall +/- aneurysm formation
Describe macroscopic findings in atherosclerosis
Macroscopic findings
UNCOMPLICATED
*Early lesions
–Fatty streaks (yellow fatty streaks elevate the endothelium)
–Limited luminal narrowing
*Established lesions
–Plaques progressively narrow the lumen
–Progressive calcification causes wall to become stiff and nonpliable–> leads to stasis - which is a further complicator
COMPLICATED
*Endothelial ulceration/plaque rupture with superimposed thrombus (may cause complete occlusion)
*Intraplaque haemorrhage (may cause complete occlusion)
*Other complications e.g. Aneurysm formation, rarely dissection
Note: complete occlusion –> downstream ischaemia
Note 2: recanalisation –> attempt to improve flow
Describe the complications of atherosclerosis seen in histology
- calcificaiton
- haemosiderin pigment suggestive of haemorrgae
- cholesterol clefts suggestive of old haemorrhage
- Lines of Zahn is characteristic
Define arteriolosclerosis
Arteriolosclerosis predominately affects small arteries and arterioles.
List arteriolosclerosis risk factors
- Genetics: increasing age (although not as severe as in patients with diabetes mellitus or hypertension)
- Acquired:
- hypertension
- diabetes
- some drugs e.g. calcineurin
Note:
Hypertension and diabetes are risk factors for atherosclerosis e.g. smoking also probably contributes to this disease as well
Briefly describe the pathology of arteriolosclerosis
Arteriolosclerosis has a complex pathogenesis.
It is caused by the deposition of hyaline proteinaceous material in the intima. This leads to two key things:
- plasma protein leakage across damaged endothelial cells
- stressed smooth muscles increase synthesis of protein matrix
Arteriolosclerosis is also characterised by loss of smooth muscle cells from media.
List and descrie the macroscopic and microscopic findings of arteriolosclerosis
Macroscopic findings of arteriolosclerosis
- there are no significant macroscopic findings – affected arterioles are too small
- any macroscopic findings reflect the complications of this disorder e.g. lacunar infarction in the deep grey matter, nephrosclerosis of kidneys reflecting chronic hypertensive damage
Microscopic findings of arteriolosclerosis
- mild to moderate (‘hyaline arteriosclerosis’)
- increasing thickness of intima, with deposition proteinaceous hyaline material
- lumen becomes progressively narrowed
- severe (‘hyperplastic arteriolosclerosis’)
- seen in cases of severe or malignant hypertension
- concentric initmal thickening
- concentric duplication of elastic lamina aka ‘onion skinning’
- in very severe cases, there is fibrinoid necrosis of the vessel wall aka ‘necrotising arteriolitis’
- microaneurysm can also form
This is commonly seen in the kidney: in diabetes both afferent and efferent arterioles are affected.
In hypertension, efferent arterioles is spared.
