Atherosclerosis Flashcards
Describe the normal structure of blood vessels
3 main layers:
Tunica Intima, 3 layers:
- Endothelium: single layer of squamous epithelial cells
- Basal lamina: thin extracellular layer comprised mostly of collagen proteoglycans and glycoproteins
-
Sub-endothelial layer: Consists of loose connective tissue
- In arteries and arterioles contains a sheet (lamella) of elastic fenestrated material called the internal elastic membrane
Tunica Media
- Consists mainly of circumferentially arranged layers of smooth muscle
- Also contains elastin, reticular fibres and proteoglycans between smooth muscle cells.
- This layer is thick in arteries, extends from internal → external elastic membrane.
Tunica Adventitia
- Separated from tunica media by external elastic lamina
- Outermost connective tissue layer composed of longitudinally arranged collagenous tissue and elastic fibres.
What separates the tunica media from the tunica adventitia?
External elastic lamina
What is the difference in tunica media between veins and arteries?
Arteries have much thicker tunica media composed of more smooth muscle to accommodate higher blood pressure and pulsatile flow.
Veins have a thinner tunica media to allow for distensibility and capacitance.
What happens to the ratio of vessel wall thickness to lumen diameter as arteries branch into arterioles?
Why does this occur?
The ratio increases to allow for precise regulation of intravascular pressure
In which type of artery does atherosclerosis most commonly occur?
Where does arteriolosclerosis normally occur?
Atherosclerosis mostly occurs mainly in large elastic arteries (e.g. aorta, common carotid and common iliac) and the large and medium sized muscular arteries (e.g. renal, coronary, popliteal). E.g:
- Cerebral infarction (stroke)
- Reno-vascular disease
- Myocardial infarction
- Aortic aneurysms
Arteriolosclerosis normally occurs in arterioles due to hypertension.
What are the 3 main artery types?
Large (elastic) arteries:
- Convey blood from heart to pulmonary or systemic circulation
- E.g. aorta and pulmonary arteries as well as their main branches: brachiocephalic, common carotid, subclavian and common iliac arteries.
Medium (muscular) arteries:
- Most of the named arteries of the body
Small arteries and arterioles:
- Small arteries: often up to 8 layers of smooth muscle
- Arterioles: often only 2 layers of smooth muscle
What is the endothelium?
What are its functions?
Continuous sheet of epithelial cells lining the entirety of the vascular tree.
Endothelial activation is the process of endothelial change in response to various stimuli.
Functions include:
- Maintenance of a selective permeability barrier allowing the selective movement of small molecules between the blood and tissues.
-
Maintenance of non-thrombogenic barrier- normal endothelium does not support adherence of platelets or formation of thrombi on its surface.
- Damaged endothelium releases pro-thrombogenic agents (vWF, tissue factor)
- Modulation of blood flow and vascular resistance by the secretion of vasoconstrictors (endothelin, prostaglandins H2 and thromboxane A2) and vasodilators (NO, prostacyclin)
- Regulation and modulation of immune responses by controlling the interaction of lymphocytes with endothelial surface through the expression of adhesion molecules and their receptors.
- Modification of lipoproteins by oxidation by free radicals released by endothelial cells.
What is the role of vascular smooth muscle cells?
Mediate vasoconstriction or vasodilation in response to physiological or pharmacological stimuli
Upregulate collagen, elastin and proteoglycan production
Elaborate growth factors and cytokines
Which is the most common acquired abnormality of the blood vessels?
Atherosclerosis
What is arteriosclerosis?
What are the 3 main types?
Arteriosclerosis is a generic term referring to the hardening of the arterial walls and loss of elasticity.
3 types:
- Arteriolosclerosis: affects arterioles
- Atherosclerosis: affects larger and medium sized arteries
- Mockenburg medial sclerosis: calcific deposits in muscular arteries.
Where do atherosclerotic lesions most commonly begin?
In the tunica intima of large elastic arteries following endothelial injury which leads to endothelial dysfunction.
Which factors pre-dispose endothelial injury?
LDL cholesterol lipidaemia
Hyperglycaemia
Hypertension
Increased toxin levels (e.g. from smoking)
Viral and bacterial infections
Describe the pathogenesis of atheroma
- Endothelial injury leads to endothelial dysfunction
- Endothelial dysfunction causes increased permeability to LDL cholesterol and increased adherence of white blood cells to the endothelium.
- Endothelial injury also causes increases the production of reactice oxygen species which oxidise LDL in the tunica intima.
- In response to this injury, monocytes from the blood stream enter the site and differentiate into macrophages
- Macrophages phagocytose oxidised LDL, transforming themselves into foam cells loaded with lipid containing vesicles.
- Foam cells and infiltrated T-cells form initial atherosclerotic lesion (fatty streak)
- Lesion remodels and grows into fibrofatty plaque as smooth muscle cells migrate from the tunica media and fibroblasts form protective connective tissue capsule.
- This lesion is known as atheromatous plaque
Define atheromatous plaque
A thick layer of fibrous connective tissue containing scattered smooth muscle cells, macrophages, foam cells, T-lymphocytes, cholesterol crystals and cell debris.
What are the microscopic and macroscopic features of fatty streaks?
Microscopic: Lipid filled foam cells (macrophages) but are only minimally raised and do not cause flow disturbance.
Macroscopic: Begin as minute yellow, flat macules that coalesce into elongated lesions >1cm in length.
Label the features of the histological image
L = Lumen
F = Fibrous Cap
C = Central nectorotic (mostly lipid) core
What do the principal pathophysiological outcomes of atherosclerosis depend on?
- Size of the affected vessel:
- Smaller vessel occlusion compromises tissue perfusion
- Size and stability of the plaques:
- Plaque rupture can expose atherosclerotic plaque contents leading to thrombosis and/or distal embolism
- Degree of disruption to vessel wall:
- Aneurysm formation can lead to secondary rupture and/or thrombosis.
