Pathophys.ppt

PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE (CVD)

leading cause of death in the U.S. for men and women

42% of all deaths (1 out every 2.4 deaths)

an average of one death every 33 seconds

CARDIOVASCULAR DISEASE

claims as many lives as the other top 8 causes of death combined

1/6th are under age 65 From 1984 -1994 CVD deaths declined

22% (although the actual number of deaths dropped only 3%)


includes: coronary artery disease stroke hypertension congenital heart disease valvular heart disease rheumatic heart disease arrhythmias


Coronary Artery Disease (CAD) or Coronary Heart disease (CHD) single leading cause of death in the U.S.

(20% of all deaths) May result in:

angina pectoris myocardial infarction sudden cardiac death congestive heart failure

KEY TERMS: Pg 412 Resource Manual

Myocardial Infarction

1.5 million myocardial infarctions (MI’s) per year 500,000 fatal 250,000 die within an hour of onset

(sudden MI)


13.5 million alive today with history of MI 5% of MI in people under 40 years old 45% under 65 years old In 48% of men and 63% of women who

died suddenly of MI, there were no previous symptoms

Coronary Heart Disease

atherosclerosis progressive build-up of plaque on the

inside of the artery wall large arteries

arteriosclerosis “hardening” of the arteries thickening of arterial wall loss of elastic tissue


Causes of Atherosclerosis Risk factors - increase the probability

of developing the disease Primary or major risk factors (pg 415): hypertension dyslipidemia cigarette smoking physical inactivity obesity


Secondary risk factors diabetes personality type / stress family history of CHD age gender race


Risk factors Key Terms – pg 96 Resource Manual Other classification scheme – Box 5-1 pg 97 Lipid classification:

Box 5-2 pg 98-100 Blood pressure pg 103 Obesity pg 104 Emerging risk factors Framingham Risk Assessment

Coronary Arteries

Normal coronary arteries left main left anterior descending (LAD) circumflex right coronary artery posterior descending artery (PDA)

Process of Atherosclerosis

Atherosclerosis - lesions of the large and medium-sized arteries with deposits in the intima of yellowish plaques containing cholesterol, lipoid material , and lipophages

3 stages of development Intimal thickening- reversible Fatty streaks - reversible Fibrous plaques - irreversible (at least

for the most part)


Endothelium or endothelial layer (figure 29-1 pg 412):

lines inside of arterial walls in direct contact with blood controls passage of substances from

blood into arterial wall Anti-thrombotic = inhibit blood clots


Endothelial Cells: Produce several vasoactive substances

Prostacyclin - vasodilator; antithrombotic

Endothelial derived relaxing factor (EDRF) or nitric oxide - inactivates platelets; inhibits smooth muscle cell migration and proliferation


Endothelial Cells under normal conditions - protect against

the development of atherosclerosis when damaged - play a major role in its

development Box 29-1 pg 413 - causes of endothelial

injury


layers of the artery intima media adventitia - contain collagen, elastin, and

fibroblasts; contain the vasa vasorum= small blood vessels


Smooth muscle cells located primarily in the medial layer contractile synthetic

sensitive to growth promoting factors(prolifitive) and migrating factors


Platelets tiny cells in the blood stream that repair

“holes” in the arterial wall (intima) “platelet plug” prevents blood loss prothrombotic - clot forming

Monocytes and Macrophages cells of the immune system activated at sites of arterial injury


Fibroblasts type of connective tissue in response to growth factors, migrate

from the media to intima and synthesize fibrous tissue (along with smooth muscles)

Foam Cells cells formed from other cells such as

macrophages which release cholesterol into the extracellular space giving rise to fatty streaks

Process of Coronary Artery Disease

Injury hypothesis of CAD endothelial disruption is the first step in a

series of events risk factors may be involved in causing the

initial injury Box 29-1 pg 413 Resource Manual - list of

factors that may result in endothelial injury

“Inflammatory response”: Box 29-2 pg 413


Following endothelial injury, a number of pathologic events occur which often lead to narrowing of the arterial lumen diameter

Endothelial disruption can lead to: mitogenic effects - growth of tissues

/cells chemotactic effects - migration of cells

Injury hypothesis of CAD figure 29.2 Resource Manual


Relationship of cardiovascular disease risk factors to the “Injury hypothesis” tobacco use - Box 29-3 pg 415 diabetes - Box 29-4 pg 415 hypertension dyslipidemia


progression of atherosclerosis is non-linear some lesions are stable over many years some progress rapidly within months

Rupture of Fissuring of plaques from turbulent flow or chemical factors may lead to mural thrombi (platelet

aggregation) of varying sizes at these sites Thrombi may be incorporated into the

plaque during this process


Coronary atherosclerosis can occur diffusely (long length of artery) with occasional discrete, localized areas of more pronounced narrowing of the vessel lumen that may produce obstruction of blood flow.

Non-atherosclerotic coronary obstructions Coronary vasospasm Intracoronary thrombus

Atherosclerotic Plaques

Described as “percent occlusion” or “percent stenosis” Example 90% stenosis of the LAD

Obstructive coronary atherosclerosis is used to describe CAD that is severe enough to reduce blood flow

Severity of coronary atherosclerosis is detected using coronary angiography coronary angiogram

Atherosclerotic Plaques

Regression of CAD using non-invasive interventions Diet Exercise Medications

Treatment Options for CAD

“Revascularization” Procedures Percutaneous Transluminal

Coronary Angioplasty (PTCA) Coronary Artery Bypass Surgery

(CABS) or Coronary Artery Bypass Graft (CABG) surgery

Coronary Atherectomy and Rotablator

Laser Angioplasty

Percutaneous Transluminal Coronary Angioplasty (PTCA)

Coronary Obstructions After Cardiac Interventions

Restenosis - reocclussion of obstructive lesion

Tend not to be as lipid rich as original plaque and are highly related to thrombosis

Approximately 35% at 5 years from original CABS

Approximately 45% at 6 months for PTCA Restenosis rate reduced using coronary

stents after PTCA

Progression of Atherosclerosis

Rate of progression is highly related to number and severity of risk factors Native vessels Saphenous vein grafts Internal mammary grafts After PTCA and other interventions

Exercise and Atherosclerosis

Independently reduces risk of CAD Slows rate of progression by acting on

other risk factors Increases fibrinolytic activity May stimulate the formation of collateral

vessels when one or more obstructive lesions are present

Manifestations of Coronary Atherosclerosis: Coronary Blood Flow

heart - completely aerobic organ coronary blood flow = “myocardial oxygen

“supply” oxygen requirements of the myocardium =

myocardial oxygen “demand” at rest, myocardium extracts 85% or more

of oxygen from blood exercise: 5-6 fold increase in coronary

blood flow

Coronary Blood Flow

Normal conditions: coronary supply is closely regulated to myocardial O2 demand

auto regulation factors of myocardial oxygen demand:

heart rate stroke volume cardiac output systolic blood pressure total peripheral resistance

Coronary Blood Flow

Determined by arterial pressure and vascular resistance

intramyocardial pressure also affects coronary flow systole vs. diastole (figure 29.5 pg 417

Resource Manual) reduction of luminal diameter reduces flow

luminal area obstruction of >75% causes blood flow reduction at rest

“hemodynamically significant lesion”

Coronary Blood Flow

Atherosclerotic arteries have limited ability to vasodilate

Atherosclerotic arteries are deficient in EDRF (nitric oxide) which increase likelihood of a mural thrombus

Myocardial Ischemia

coronary blood flow does not adequately meet myocardial oxygen demand

results in progressive abnormalities in cardiac function = ischemic cascade stiffening of the left ventricle results in decreased diastolic filling

(diastolic dysfunction) impaired systolic emptying

hypokinesis, akinesis, dyskinesis

Myocardial Ischemia

Systolic impairment demonstrated by segmental wall motion abnormalities reduction in left ventricular ejection

fraction reduced stroke volume

echocardiogram “stress echo”

Myocardial Ischemia

EKG changes ST segment depression ST segment elevation T wave inversion ventricular arrhythmias

Myocardial Ischemia

reversible no permanent cardiac damage prolonged ischemia

irreversible damage may occur = necrosis of myocardial tissue (myocardial infarction)

Angina Pectoris

heart pain due to myocardial ischemia characteristics of “typical” or “classic”

pressure, tightness, squeezing, heaviness, or choking

radiates down left arm, back, and/or jaw occurs with physical activity, emotional

stress, cold weather, heavy meals last few minutes or until activity ceases

Myocardial Ischemia

angina pectoris relieved with rest nitroglycerin

stable angina atypical angina unstable angina Prinzmetal’s angina

STABLE CAD

Presence of hemodynamicaly significant lesion(s)

anatomically stable lesions that result in: predictable, reproducible ischemia

and/or angina


Result of severe, prolonged (>60 min) ischemia in the presence or absence of angina

irreversible heart muscle damage - necrosis MI can occur in lesions with less than 50%

stenosis rupture prone plaques explains why many persons who

experience MI do not report a history of angina before infarction

Acute MI

Thickness of walls affected: transmural infarction - Q wave subendocardial infarction - non Q wave

Location of wall anterior,posterior, lateral, anterolateral,

inferior, septal Location by ECG (Table 29.1 pg 420)

Acute Myocardial Infarction

Location of obstructive lesion determines wall(s) affected proximal vs. distal occlusion

Diagnosis of Acute MI

Symptoms ECG

figure 27.4 Resource Manual evaluation of cardiac enzymes

page 235 Resource Manual lactate dehydrogenase (LDH) Creatinine phosphokinase (CK)

CK-MB elevated in first 24 hrs

Treatment of MI

Early reperfusion streptokinase or tissue plasminogen

activator (tpa) “rescue” angioplasty emergent CABS

nitroglycerine beta blockers

Post-Myocardial Infarction

Necrosis, scarring during first 6-12 weeks Infarct dilation and remolding - thinning

of ventricular wall and enlargement of cardiac chambers

may develop congestive heart failure


Characteristics associated with higher risk of reinfarction and death EF<40% ischemia during low intensity exercise poor exercise capacity (<4 METS) complex ventricular arrhythmias

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