Term
| What are the three general patterns of arteriosclerosis? |
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Definition
1. arteriosclerosis: affects small arteries and arterioles and may cause downstream ischemic injury. Anatomic variants hyaline and hyperplastic
2. Monckeberg medial sclerosis: characterized by calcific deposits in muscular arteries in persons typically older than 50. Deposits may undergo metaplastic change into bone. Lesions do not encroach on the vessel lumen and are usually not clinically significant
3. Atherosclerosis: "gruel" and "hardening" is the most frequent and clinically important pattern |
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Term
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Definition
Characterized by intimal lesions called atheromas that protrude into vessel lumens.
-atheromatous plaque consists of a raised lesion with a soft, yellow, grumous core of lipid (mainly cholesterol) covered by a white fibrous cap
-mechanically obstructs blood flow
-can rupture leading to catastrophic vessel thrombosis
-weaken underlying media and lead to aneurysm formation |
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Term
| Constitutional risk factors of IHD |
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Definition
AGE
-dominant influence
GENDER
-premenopausal women relatively protected
-after menopause the incidence increases and exceeds men
GENETICS
-family history is most significant independent risk factor |
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Term
| Modifiable risk factors in IHD |
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Definition
HYPERLIPIDEMIA
-more specifically hypercholesterolemia
-high LDL, low HDL
HYPERTENSION
-both systolic and diastolic are important
-most important cause of LVH
CIGARETTE SMOKING
DIABETES MELLITUS
-induces hypercholesterolemia |
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Term
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Definition
INFLAMMATION
-C-reactive protein is a circulating marker of inflammation
HYPERHOMOCYSTINEMIA
-caused by low folate and vitamin B12 intake
METABOLIC SYNDROME
-insulin resistance, glucose intolerance, hypertension and central obesity, abnormal adipose tissue signaling
LIPOPROTEIN A
FACTORS AFFECTING HEMOSTASIS
-Thrombin
Type A personality, lack of exercise, obesity |
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Term
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Definition
CRP
circulating marker of inflammation, simplest and most sensitive
-synthesized by the liver
-plays a role in the innate immune response by opsonizing bacteria and activating complement
-can activate local endothelial cells and induce a prothrombotic state
-increases adhesiveness of endothelium for leukocytes |
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Term
| response to injury hypothesis |
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Definition
views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury
-lesion progression occurs through the interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with the normal cellular constituents of the arterial wall |
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Term
| What are the pathological events in the response to injury hypothesis? |
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Definition
1.Endothelial injury
2.Accumulation of lipoproteins
3.Monocyte adhesion to the endothelium
-macrophages and foam cells
4. Platelet adhesion
5. Factor release
-induce smooth muscle cell recruitment
6. Smooth muscle cell proliferation and ECM production
7. Lipid accumulation |
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Term
| How does chronic hyperlipidemia contribute to atherogenesis? |
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Definition
1. increases local oxygen free radical production
-injures tissues, accelerates NO decay, reduces vasodilator activity
2. lipoproteins accumulate in intima and are oxidized (oxidized LDL)
-oxidized LDL is ingested by macrophages through a scavenger receptor producing foam cells
-stimulates release of GF, cytokines and chemokines
-cytotoxic to endothelial cells and smooth muscle cells and can induce endothelial cell dysfunction |
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Term
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Definition
-earliest lesions in atherosclerosis
-composed of foam cells
-not all are destined to become advanced lesions |
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Term
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Definition
-Key processes are intimal thickening and lipid accumulation
-Lesions appear eccentric on cross-section
-local flow disturbances leads to increased susceptibility of certain portions of a vessel wall to plaque formation
-abdominal aorta more involved than thoracic aorta |
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Term
| What are the 3 principal components of atherosclerotic plaques? |
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Definition
1. cells, including smooth muscle cells, macrophages, and T cells
2. ECM, including collagen, elastic fibers, proteoglycans
3. intracellular and extracellular lipid |
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Term
| What are the clinically important changes of atherosclerotic plaques? |
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Definition
1. Rupture, ulceration or erosion of intimal surface
-induces thrombosis
2. Hemorrhage into a plaque
-rupture of overlying fibrous cap or thin-walled vessels
-contained hematoma may expand the plaque or induce plaque rupture
3. Atheroembolism
-rupture can discharge atherosclerotic debris into the bloodstream producing microemboli
4. Aneurysm formation
-pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes weakness resulting in aneurysmal dilation and potential rupture |
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Term
| What arteries are the main targets of atherosclerosis? |
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Definition
Large Elastic Arteries
-aorta, carotid, and iliac arteries
Large and Medium Muscular Arteries
-coronary and popliteal |
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Term
| What are the major consequences of atherosclerosis? |
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Definition
MI, stroke, aortic aneurysms, peripheral vascular disease (gangrene of the legs)
Symptomatic atherosclerotic disease most often involves the arteries supplying the heart, brain, kidneys and lower extremities |
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Term
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Definition
Rubicon at which chronic occlusion significantly limits flow and demand begins exceeding supply
-in coronary and other circulations this typically occurs at approximately 70% fixed occlusion
-At this degree of stenosis patients classically develop angina on exertion (stable angina) |
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Term
| What are the 3 general categories that plaque changes fall into? |
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Definition
1. rupture/fissuring
-exposing highly thrombogenic plaque constituents
2. Erosion/ulceration
-exposing thrombogenic subendothelial basement membrane to blood
3. Hemorrhage into the atheroma
-expanding volume |
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Term
| What is the peak time of onset of acute MI? |
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Definition
between 6am and 12 noon
-adrenergic stimulation associated with waking and rising can cause blood pressure spikes followed by heightened platelet reactivity |
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Term
| What is vasoconstriction at the site of atheromas stimulated by? |
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Definition
1. circulating adrenergic agonists
2. locally released platelet contents
3. impaired secretion of endothelial cell relaxing factors (NO) relative to contracting factors (endothelin) as a result of endothelial cell dysfunction
4. mediators released from perivascular inflammatory cells |
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