Lilly Ch 5-7 Atherosclerosis, Ischemic Heart Disease, ACS Flashcards
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
***** Coronary flow
directly proportional to Pressure and Resistance relationship Q =P/R
***Coronary Perfusion Pressure predominace of
coronary perfusion takes place during diastole (unlike systemic arteries in systole)
Systolic coronary flow in smallr branches IMPAIRED BY COMPRESSION of CONTRACTING MYOCARDIUM
**Perfusion pressure approximated by
Aoric Diastolic Pressure
**Conditions that Decrease aortic diastolic pressur e
decrease coronary perfusion and O2 supply.
**CORONARY VASCULAR RESISTANCE influenced by 2 factors
EXTERNAL COMPRESSION
INTRINSIC CORONARY VASCULAR TONE
***CVR influncer: external compresion
Myocardial contraction ↑intraventricular pressure
– Subendocardium adjacent to ↑intraventricular
pressure has ↓perfusion
– Subendocardium most vulnerable to ischemic change
***CVR influencer: Intrinsic Coronary Vascular Tone
– Heart cannot ↑ O2 extraction : ↑demand must be met
by ↑flow ( controlled by coronary vascular Tone)
**Intrinsic Coronary Vascular Tone (MEN)
Influenced by 3 items:
A) METABOLITES During hypoxia, ADP & AMP accumulate, degrade into Adenosine = vasodilation =↑flow B) ENDOTHELIAL FACTORS – Prostacyclin & NO = vasodilators – Endothelin 1 = vasoconstrictor C) NEURAL INNERVATION – Sympathetic effects on receptors in coronary vessels α1 = vasoconstrict β2 = vasodilate
**3 Determinents of Oxygen demand (HCV)
Ventricular Wall stress
HR
Contractility
*Ventricular Wall Stress caused by
Related to :
Formula is ?
1) Stretching force on myocardial fibers pulling them apart 2) and the energy expended in opposing that force.
• Wall stress related to: – Intraventricular pressure (P) – Radius of the ventricle (r) – Wall thickness (h)
= Px R/ 2h
**Pathophysiology of Ischemia from
atherosclerosis
• The 2 most important factors:
1) FIXED VESSEL NARROWING
– Radius has biggest effect on flow in Poiseuille’s Law:
Q= Change in P x Pi X r ^4 / 8 nL
2)ABNORMAL VASCULAR TONE
– Dysfunctional endothelial cells in atherosclerosis fail to
release vasodilators
– vasoconstriction occurs instead = ischemia
– Also loss of antithrombotic effect = ↑risk of ischemia
**4 consequences of ISCHEMIA (SACC)
Consequences of Ischemia
- SOB
- Chest pain
- Arrhythmias
- Cardiogenic Shock
***SOB with ISCHEMIA how? (TICC)
SOB
– Ischemia results in ↓ contraction & relaxation
– Causes elevated LV diastolic pressure
– Transmitted back to pulmonary capillaries
– Causes pulmonary congestion & SOB
***Chest Pain with ISCHEMIA how ?
– Accumulated metabolic products activate pain receptors
**Arrhythmias with ISCHEMIA how?
– Damaged myocytes undergo altered ion transport
***Cardiogenic Shock with ISCHEMIA how?
– Impaired myocardial function =↓ C.O.
***3 forms of Angina (SUV)
Three forms: – Stable – Variant – Unstable
**Stable angina
- Transient
- Precipitated by physical activity / emotional stress
- Relieved by rest (within a few minutes)
- EKG: temporary ST Depression
** VARIANT ANGINA
Pain at rest
• Caused by spasm, not ↑O2 demand
• EKG: ST elevation
• a.k.a. “Prinzmetal Angina
**UNSTABLE ANGINA
Increased frequency & duration of Pain at Rest
• EKG: ST depression
• High risk of progression to MI if untreated
***Non-ST segment elevation MI
• Partial occlusion of main coronary artery, or total
occlusion of small branch
• Partial thickness wall damage
• ST seg depression and/or T wave inversion
**What are the 3 markers of NSTEMI and STEMI?
Markers: – Troponin I – CKMB – troponin T – (also ↑wbc, ESR, CRP)
*****ST elevation MI
Comment on thickness
Complete acute thrombus occlusion of main
coronary vessel
• Full thickness wall damage
***** EKG changes of STEMI
- ST elevation - indicates full thickness wall injury
- Pathologic Q - indicates muscle necrosis
- T wave inversion - indicates muscle ischemia
****ACS summary Partially occlusive thrombus EKG changes :\_\_\_\_\_\_and/or\_\_\_\_\_ If biomarkers POSITIVE \_\_\_\_\_ If biomarkers NEGATIVE \_\_\_\_\_\_\_
ST segment depression and/or T- wave inversion
NSTEMI
Unstable angina
**ACS summary
Occlusive thrombus
EKG changes :______and___ (later
biomarkers POSITIVE _____
ST elevation and Q waves later
STEMI
