Heart disease Flashcards
define : atherosclerosis
chronic, progressive inflammatory process of multifactorial etiology -> fibro fatty plaques which narrow vascular lumen and degenerative changes of vascular media
distribution of atherosclerosis
nonrandom-> ostia and branch points . abdominal aorta, coronary art, popliteal, internal carotid, circle of willis
fatty streaks
foam cells, t lymphocytes and small amounts of extracellular lipids
- found in aorta of all children > 10 yrs
- not all become plaques
plaques
smooth muscle cells , Macrophages, lymphocytes, ECM and a lipid core
location: elastic arteries -> aorta, carotid and iliac
lg and medium muscular arteries-> coronary and popliteal
advanced atheromatous plaques
progressive enlargement via denergeration, synthesis and remodeling
- neovascularization
- calcification
cellular constituents of a plaque (4)
endothelial cells - injury -> primary process in plaque formation -> upregulation of endothelial adhesion molecules and facilitate inflammatory cell egress into intima of vessels
-> endothelial become leaky allowing insudation of plasma proteins ( albumin and fibrinogen) and lipids into vessel walls
lymphocytes ( primary T cells) important mediators of chronic inflammatory cascade -> activated T cell release interferon gamma that activates macrophages
macrophages ( from circulating monocytes)
-attracted to areas of injury by adhesion molecules ( VCAM-1, ICAM-1 P-selectin)
-pro-inflammatory -> IL-1 and TNF -> increase adhesion of leukocytes
-O2 species produced -> oxidize the LDL with in the atheroma
oxidized LDL is toxic to endothelial and vascular smooth muscle cells
vascular smooth muscle cells -> migrate from vascular media -> proliferate and secrete ECM proteins ( collagen, elastin and glycoproteins)
complicated atherosclerotic lesion
erosion, ulceration or rupture, hemorrhage , thrombosis , aneurysm
thrombosis formation-> increase stenosis leading to local ischemia - plaque rupture/ fragmentation > embolization -> distal ischemia
pathogenesis of plaque formation
response to injury -
endothelial injury -> inflammation -> accumulation of lipoproteins -> oxidation of lipoproteins -> adhesion of monocytes and platelets -> migration and proliferatiion of smooth muscle cells
endothelial injury leads to what
leads to increase in endothelial permeability and leukocyte adhesion
- etiology : unknown. multifactorial , homocysteine, circulating derivatives of cigarette smoke, viruses
- important factors - turbulent blood flow ( plaque disruption), hypercholesterolemia
- endothelial cells release : growth factor, chemokines, cytokines, pro-coagulant proteins, adhesion molecules, vasoactive mediators
hypoxemia vs ischemia
hypoxemia - failure to deliver adequate oxygenated blood to tissues
ischemia- hypoxemia along with the inadequate removal of metabolites
clinical manifestations of IHD
angina pectoris -1. stable angina -> pain with exercise
2. unstable angina- > pain at rest of increased frequency
MI - necrosis of myocardium due to ischemia
chronic IHD with heart failure
sudden cardiac death
pathophys for most angina , mi and scd
- coronary atheroslcetoric plaque disruption
2. thrombus formation 3. myocardial ischemia
transmural MI
necrosis of the full thickness of the ventricular wall
- distribution of a single coronary artery
- thrombus superimposed on paque - complete occlusion
subendocardial MI
- limited to the inner 1/3 to 1/2 of the ventricular wall
- may extend laterally beyond the distribution of the involved coronary artery
- incomplete occlusion +/- vasospasm
- subendocardium is the least well perfused area of heart muscle - relies on diffusion of oxygenated blood from ventricular space
- thrombus is lysed before necrosis extends across the full thickness of the wall > severe drop in systemic BP
sequence of events in MI
- sudden change/ disruption of a plaque
- release of collagen and plaque contents
- stim of platelet adhesion, aggregation and activation
- release of platelet aggregation ( thromboxane A2- potent vasoconstrictor)
- vasospasm and activation of extrinsic pathway-> adding to thrombus mass
- occlusion
