atheroma
the accumulation of intracellular and extracellular lipid in the intima of large and medium sized arteries
atherosclerosis
the thickening and hardening of arterial walls as a consequence of atheroma in large and medium sized arteries
where does atherosclerosis occur
- aorta - especially abdominal
- coronary arteries
- carotid arteries
- cerebral arteries
- leg arteries
structure of normal artery
- intima
- media
- adventitia
medial layer of artery
contributes to most of the mechanical strength of an artery
atheroma macroscopic features
- fatty streak
- simple (fibrous) plaque
- complicated plaque
fatty streak
comprises a slightly elevated zone on the arterial wall caused by accumulation of a small number of lipid laden cells
simple (fibrous) plaque
lipid accumulates both free and in cells, smooth muscle cells also migrate from the media, fibrosis develops around the lipid and forms a cap over the lesion
complicated plaque
ulcers and fissures of the fibrous cap expose plaque contents resulting in thrombosis
cause of atherosclerosis
- process not fully understood
- current hypothesis: response t injury
- initiated by endothelial dysfunction
daily dietary cholesterol intake
300mg
cholesterol
carried in the blood attached to proteins called lipoproteins
two main forms:
- LDL (low density lipoproteins)
- HDL (high density lipoprotein)
LDL
is removed from the circulation by either LDL receptors or by scavengers cells such as monocytes or macrophages
how does oxidised LDL form
occurs when the LDL particles react with free radicals
risk factors that increase the levels of oxidised LDL
- consuming a diet that is high in trans fats
- smoking
- poorly controlled diabetes
- metabolic syndrome, which is often a precursor of diabetes
- exposure to toxins through pollution and preservatives
- stress
hyperlipidemia
blood has too many lipids (or fats) such as cholesterol and triglycerides
when LDL becomes oxidized
it goes directly into the endothelium and may alter the endothelial permeability
atheroma prevention
- no smoking
- diet ~ reduce fat intake
- not too much alcohol
- regular exercise
antiplatelet function in normal endothelium
- adenosine diphosphate ~ degrades ADP from platelets
- prostacyclin ~ produced by the enzyme cycloxygenase
- nitric oxide
anticoagulant function in normal endothelium
- heparin-like-molecules ~ activate antithrombin III
- thrombomodulin (activates protein C)
- protein S
antithrombotic function in normal endothelium
- fibrinolytic ~ prevents blood clots from growing
- t-PA
procoagulant functions in damaged endothelium
- production of vWF (von Willebrand Factor~ protein that helps blood to clot)
- production of tissue factor
- binding of factors IXa and Xa
