Atherosclerosis Flashcards
definition: Arteriosclerosis
“Hardening of the arteries” – a group of disorders that have in common thickening and loss of elasticity of arterial walls. Three distinctive
morphological variants are recognised
Atherosclerosis
progressive disease affecting the intima of elastic and
muscular arteries characterised by focal atheromas (fibrofatty plaques) consisting
of a lipid core covered by a fibrous cap. Atherosclerosis overwhelmingly accounts
for more death and serious morbidity in the Western world than any other
disorder.
Monckeberg’s medial sclerosis
characterised by calcification of the media of
muscular arteries.
Arteriolosclerosis
Characterised by the proliferative or hyaline thickening of the walls of small arteries and arterioles
Major predisposing factors for atherosclerosis
Diet and hyperlipidaemias (hypercholesterolaemia, hypertriglyceridaemia)
Hypertension – both systolic and diastolic hypertension
Cigarette smoking – esp. responsible for increasing heart disease in women
Diabetes mellitus – 2x risk of myocardial infarct, 8x-150x risk of gangrene of the extremities
Minor predisposing factors for atherosclerosis
Obesity Physical inactivity Male gender Increasing age Family history Stress (“type A” personality – competitive, stressful lifestyle) - controversial Oral contraceptives - controversial High carbohydrate intake - controversial
AHA stages of atherosclerosis
Type I – Lipid is present in macrophages in the intima
Type II – Lipid is present in both macrophages and smooth muscle cells
Type III – Fibrous plaque
Type IV – Complex plaque (fibrous cap overlying a lipid core)
Pathogenesis of atherosclerosis
The lesions of atherosclerosis are initiated as a response to some form of injury to arterial endothelium.
There are roles for endothelial injury, macrophages
and other inflammatory and immunological mechanisms, smooth muscle cell proliferation, hyperlipidaemia and thrombosis.
Endothelial injury: role
Endothelial damage is a major risk factor in atherogenesis (well shown in experimental animals) but early lesions in humans develop at sites of intact
endothelium.
Endothelial damage is a major risk factor in atherogenesis (well
shown in experimental animals) but early lesions in humans develop at sites of intact
endothelium.
Monocytes migrate into the intima and then accumulate low-density lipoprotein (LDL) to produce foam cells.
Monocytes/macrophages express the LDL receptor and a specific receptor
(scavenger receptor) for oxidised LDL (oxidised by EC, platelet or white blood cell enzymes).
T cells (CD4+ and CD8+) are found in plaques – role uncertain.
Smooth muscle proliferation
With lipid accumulation, smooth muscle cell
proliferation and extracellular matrix deposition in the intima are the major processes
for the progressive growth of plaques.
Hyperlipidemia
Hyperlipoproteinaemia is the abnormality common to most syndromes of premature atherosclerosis.
Can be primary (due to a genetic defect) or
secondary to some other disorder (e.g. nephrotic syndrome, alcoholism, hypothyroidism, and diabetes mellitus). Increases in the plasma level of LDL may
increase the level of lipid penetration in the arterial wall.
Hyperlipoproteinaemia may also directly alter EC function.
Infaction definition
An infarct is an area of ischaemic necrosis within a tissue or organ,
produced by occlusion of either its arterial supply or its venous drainage.
Infarcts usually result from acute arterial occlusion
White infarcts occur
(1) with arterial occlusion and (2) in solid tissues e.g. heart,
spleen, kidneys.
Red infarcts occur
(1) with venous occlusions, (2) in loose tissues e.g. lung, (3) in
tissues with a double circulation e.g. liver and (4) in tissues that are previously
congested.
Transmural infarct (MI)
(commonest) – the ischaemic necrosis involves the full or
nearly full thickness of the ventricular wall in the distribution of a single coronary
artery. Usually associated with coronary atherosclerosis, plaque rupture and superimposed
thrombosis.
Subendocardial Myocardial infarct
(= Acute coronary syndrome) – this constitutes an area of ischaemic necrosis limited to the inner one-third, or at most one-half, of the
ventricular wall. There is diffuse stenosing coronary atherosclerosis and global
reduction of coronary flow (e.g. due to shock) but no plaque rupture and no
thrombosis.
