Atherosclerosis Pathology Flashcards
Types of blood vessels
Arteries: Large/elastic (aorta and major branches innominate, subclavian, common carotid iliac) and pulmonary artery (elastic arteries betweeen smooth muscle cells in media)
Medium sized or muscular (coronary renal arteries), (Muscular arteries mainly smooth muscle cells, elastic fibers limited to internal and external elastic lamina)
Small arteries and arterioles course within CT of organs (small arteries and arterioles, smallest branches of arteries). Media- essentially all smooth muscle cells. Arterioles thin internal elastic membrane, terminal arterioles no elastica (points of physiologic resistance), medial smooth muscle contraction adjusts BP and blood flow
Capillaries
Large cross sectional area with slow blood flow and thin walls, 7-8 microns in diameter, partially surrounded by smooth muscle like cells
Veins and venules
Venules- points where leukocytes emigrate in inflammation
Veins- large caliber, thin walled, contain 2/3 of blood volume
Lymphatics- drain interstitial fluid into blood, path for dissemination of disease
Endothelial cells response to injury
Stimulation: rapid, reversible responses, independent of new protein synthesis (contraction in response to histamine)
Activation: elaboration of gene products with biologic activity requires hours/days to develop
Vascular smooth muscle cells
Vasconstriction/dilation
Synthesis of collagen, elastin, proteoglycans
Elaboration of growth factors and cytokines
Migration to intima and prolife3ration in normal vasculat repair and pathologic processes (atherosclerosis)
Pro-GFs: PDGF, endothelin, thrombin, FGF, IFNy, IL1
Mechanism of intimal thickening
Endothelium, recruitment of smooth muscle cells or smooth muscle precursor cells to the intima, to smooth muscle cell mitosis, elaboration of extracellular matrix
Stereotyped response to vascular injury of any kind
Neointimal smooth muscels cant contract,
Arteriosclerosis
Arteriosclerosis (hardening of the arteries)
Atherosclerosis- elastic arteries and large medium muscle arteries contributes to 50% of all deaths in western world
Arteriolosclerosis- small arteries and arterioles, Monckeberg medial calcific sclerosis, fibromuscular intimal hyperplasia, smooth muscle thickening in transplants and after trauma
Monckeberg Arteriosclerosis
Calcific deposits in the internal elastic lamina of medim sized muscular arteries (typically radial and ulnar arteries)
> 50 years no obstruction to the blood flow, usually not clinically signifiacant
no obstruction
Atherosclerosis
Most prevalent and significant disease pattern
Progressive disease of elastic arteries and large to medium sized muscular arteries
2 basic types of damage:
Stenosis: by atheroma leading to ischemia, thrombosis, and or embolism
Aneurysm formation: leading to rupture and hemorrhage
Atherosclerosis
Elastic arteries- aorta (aneurysm with rupture), carotid arteries (occlusion causing stroke), iliac artereies (occlusion causing gangrene)
Large medium sized muscular arteries: coronary arteries (occlusion causing myocardial infarction), popliteal arteries (occlusion causing gangrene), renal artery (narrowing/occlusion causing secondary HTN), Mesenteric arteries (narrowing/occlusion causing bowel infarction)
Fatty streak morphology
Multiple yellow, flat dots to streaks, usually in aorta and later in coronaries
may be precursors of atheromas but not all fatty streaks develop into advanced lesions
Histology: lipid filled macrophages, extracellular lipid, few lymphocytes
lipid incorporation
LDL cholesterol is transported into the vessel wall
Endothelial cells and monocytes/Macrophages generate free radicals that oxidize LDL (oxLDL), resulting in lipid peroxidation
oxLDL is taken up by macrophages via SCAVENGER RECEPTORS
Uptake of oxLDL activates macrophages and releases proinflammatory cytokines
Fibrofatty plaque morphology
raised yellow white plaque in intima with soft yellow core and white fibrous cap
Fibrofatty plaque- often eccentric (only part of vessel circumference and patchy)
Advanced vulnerable plaques (at risk for rupture ulceration erosion and hemorrhage, lead to thrombosis embolism, progressive luminal narrowing to critical stenosis, atheroembolism, aneurysm formation- wall weakening leading to aneurysm and rupture
Stable plaques- thick fibrous caps, minimal inflammation, small lipid cores
Aneurysm formation
atrophy due to pressure and or ischemia of media, destruction of elastic fibers
leads to thinned weakened wall prone to rupture
Atherosclerosis pathogenesis
Chronic inflammatory response of arterial wall to endothelial injury , chronic endothelial injury/dysfunction –> increased permeability enhanced leukocyte adhesion (hemodynamic disturbances
Chronic hyper lipidemia candirectly impair endothelial cell function, lipoproteins accumulate in intima
Chronic endothelial injury–>endothelial ddysfunction–>smoothmuscle emigration from media to intima macrophage activation–>macrophages and smooth muscle cells engulf lipid –> smooth muscle proliferation
