Lilly Ch 5-7 Atherosclerosis, Ischemic Heart Disease, ACS Flashcards
(50 cards)
Leading cause of mortality/morbidity in the
developed world______
Atherosclerosis
**Atherosclerosis is a _______
Chronic inflammatory condition involving endothelial cells, smooth muscle cells, lipids, macrophages and thrombosis
3 layers of the Normal Arterial Wall (MIA)
3 layers:
Intima (interna)
Media
Adventia (externa)
**What are the different parts of the Intima Layer **
Endothelial cells
– Basement membrane
– Internal elastic lamin
What are the different parts of the Media layer
– Smooth muscle cells
– External elastic lamina
Endothelial cells of the intima in contact with
the blood.
_________overlies smooth muscle of the media.
Internal elastic lamina
separates media from adventitia
External elastic lamina
The endothelial cells Some Vasodilators (2) Some Vasoconstrictors (1)
Produce substances that modulate smooth muscle - Vasodilators - Prostacyclin - nitric oxide (NO) Vasoconstrictors: • endothelin
In addition, Endothelial cells
oppose local inflammation
Resist leukocyte adhesion
***Do smooth muscle cells play a role in inflammation. Explain
– They produce Vasoconstriction/dilation – Produce extra cellular matrix – Synthesize vasoactive inflammatory mediators: • IL-6 • TNF- α Promote leukocyte proliferation Induce endothelial expression of LAM (leukocyte adhesion molecules)
*****2 vasoactive inflammatory MEDIATORS
Il-6
TNF-α
***Explain the 6 steps of Plaque evolution
Evolution of Plaque
- 1. Various stressors cause endothelial dysfunction
allows entry of lipids into subendothelial space
2 and 3 - Oxidized lipids cause cytokine release from
endothelium = chemoattractant for monocytes
4 - Monocytes take in lipids, become foam cells
5 - Impaired foam cells produce superoxide anion O2-
and MMP (Matrix Metalloproteinases)
6- Smooth muscle cells migrate into intima
7 - Muscle cells divide and produce matrix, enlarging
plaque
8-Some muscle cells undergo apoptosis, fibrofatty
lesion forms, lipid core with fibrous cap
**Endothelial Stressors
• Endothelial dysfunction from cell injury secondary to various
•* Laminar flow favors production of NO which is a
–
–
–
****Turbulent flow impairs ____________ functions
****Places where turbulent flow occurs? ***
Endothelial Stressors • Endothelial dysfunction from cell injury secondary to various agents, chemical irritants, physical forces, hydrodynamic stress • Laminar flow favors production of NO – Vasodilator – Inhibits platelet aggregation – Has anti-inflammatory effects Turbulent flow impairs atheroprotective functions – Occurs at bifurcations • ***Common carotid • ***Left coronary artery
Stages of Plaque Development
- Fatty streak forms
- Plaque forms
- Plaque rupture with Thrombus
Describe how inflammation alters plaque stability
Inflammatory cytokines stimulate foam cells to
secrete ***MMP – Breaks down collagen & elastin – Weakens fibrous cap predisposing it to rupture
(Thin fibrous cap & large lipid core predispose
to rupture and thrombus formation)
Stable plaque
Vulnerable Plaque
thick
thin
**Biomarkers of Risk: Homocysteine
- Elevated levels found in coronary, cerebral & PAD
– Promotes oxidative stress, vascular inflammation & platelet aggregation
**Biomarkers of Risk: Lipoprotein
– Variant of LDL
– Competes with normal plasminogen activity
– Encourages inflammation & thrombosis
**Biomarkers of Risk: CRP
– Elevated in systemic inflammation with atherosclerosis
– High sensitivity predictor for MI, CVA, PAD & sudden cardiac
death
**Ischemic Heart Disease **
Arises from an imbalance between myocardial
oxygen supply & demand
***Determinants of O2 SUPPLY
Coronary blood flow Coronary Perfusion Pressure Coronary vascular resistance External compression Intrinsic Regulation/tone Local Metabolites Endothelial factors Neural innervation
**Myocardial Oxygen Supply
• Depends on 2 things
coronary flow And O2 content of the blood
directly proportional to Pressure &
inversely proportional to Resistance
**O2 content determined by
Hb & degree of systemic oxygenation
