Lecture 6: CV Pathophysiology IV Flashcards
What factors influence myocardial oxygen delivery?
- O2 carrying capacity of blood
- coronary blood flow
- coronary perfusion pressure
- coronary vascular resistance
- metabolic factors (adenosine, lactate, H+, CO2 - vasodilators)
- endothelial factors (NO and prostacyclin vasodilator, endothelin-1 constricts)
- neural factors (SNS leads to vasodilation because of increased O2 demand, PNS has no effect)
- atherosclerosis
What influences myocardial oxygen demand?
- HR
- cardiac contractility
- ventricular wall stress (enlarged ventricles need more O2; Law of Laplace)
What are the sex differences for CAD?
- leading cause of death for both
- more common in women
- estrogen has an anti-inflammatory effect but not if its synthetic
- men have more localized plaques –> easier to visualize and treat but more symptomatic
- women are more likely to have extensive plaques that minimize obstruction to blood flow
chest pain; too brief to cause cell death
angina pectoralis
irreversible necrosis of cardiac muscle cells
MI
What can be used to treat after an episode of angina?
- lifestyle changes
- vasodilators
- anti-coagulants
- beta-blockers
- statins
- PCI (angioplasty and stenting)
- coronary bypass surgery
insufficient blood flow (but not death)
ischemia
What is the difference in anterior and posterior wall MIs?
anterior - association with SNS; increased HR, contractility, and BP
posterior - association with vagus nerve; decreased HR an BP
What is angina typically preceded by?
increase in O2 demand (exercise, stress, sympathetic nerve activation)
What is stable angina?
when atherosclerotic coronary vessels reduce blood flow to critical levels
What is unstable angina?
when a clot causes ischemia but breaks down before necrosis occurs
How do you distinguish an MI from unstable angina?
enzymes tests that show enzymes released from dead myocardial cells
What events lead to coronary thrombosis?
- exposure of sub endothelial collagen (injury)
- turbulent flow contributes to clotting
- hemorrhage narrows vessel
- dysfunction of endothelium (low NO and prostacyclin levels)
Describe the symptoms of ischemia in men vs. women.
men - angina before and during MI
women - fatigue, sleep disturbances, and indigestion prior to an MI and SOB, weakness, fatigue, cold sweat, nausea during an MI
What changes occur on a molecular level during an MI?
- less ATP produced slows ion pumps leading the cell death
- lactic acid accumulates –> lower pH (results in functional changes in myocardium)
- rising K+ levels can cause arrhythmias
- rising Ca+ levels activate lipase that lead to cell death
- inflammation and myocardial edema
What changes occur on a molecular level after an MI?
-dead cells are cleared by macrophages and replaced by fibrotic scar tissue within 7 weeks
What changes occur on a functional level after an MI?
- decreased contractility/CO
- “stunned” or “hibernating” cells may region function
- ventricular remodeling (dilation of ventricle increases CO)
- ultimately will lead to heart failure though
What does a non-STEMI on an ECG indicate?
- partial occlusion or transient total occlusion of a vessel
- mild ischemia
- associated with high risk of MI but lower risk of death
What does a STEMI on an ECG indicate?
- total occlusion of a blood vessel
- greater risk of death
What are the serum markers for MI and what do they indicate?
creatine kinase - found in heart cells, indicative of damage
myoglobin - early indication of MI but less specific (found in other muscle)
troponin T and troponin I - cardiac specific
lactate dehydrogenase - peaks 3-5 days post MI
What can be used to treat an MI acutely?
- PCI (angioplasty and stenting)
- aspirin or heparin
- anti-ischemic therapy to decrease O2 demand including nitrates (veNOdilation), beta-blockers (decrease HR), calcium channel blockers (decrease HR and contractility)
What are potential causes of arrhythmia related to MI?
- damage to conduction pathway
- pH and ion permeability changes
- autonomic stimulation (PNS or SNS)
When does congestive heart failure occur and what are the consequences?
- develops when >40% of LV is damaged
- severely decreased CO and hypotension
- leads to further ischemic damage
- decreased SV leads to LV hypertrophy, which increased O2 demand
- mortality is >70%
What are some treatments for CHF?
- ionotropic agents (increase contractility and CO)
- arterial vasodilators (decrease afterload)
- intraaortic balloon pump (helps perfuse coronary and peripheral tissues
What are some long-term treatments for MI?
- daily aspirin
- beta-blockers
- ACE inhibitors
- statins/cholesterol-lowering drugs
- stop smoking
- exercise
What is SCD and what causes it?
sudden cardiac death; results from cardiac arrhythmia or dramatic bradycardia; often a result of CAD
Treatment for SCD?
defibrillation ASAP - brain dead can occur within 4-6 min after cardiac arrest
What are some triggers for cardiac events?
- anything that activates SNS (waking up, emotional stress, physical exertion, etc.)
- drugs
- exposure to air pollution
inability of the heart to pump blood at a sufficient rate to meet metabolic demands of the body (forward failure) or the ability to do so only under abnormally high cardiac filling pressures (backward failure)
congestive heart failure
What can cause CHF?
- MI
- pulmonary hypertension (increases after load of right heart)
What can cause pulmonary hypertension?
- atherosclerosis
- drug use
- congenital factors
- sleep apnea
What factors influence CO?
- HR
- SV
- preload
- afterload
- ventricular wall stress
- contractility
type of heart failure that results in an inability to pump blood out of the heart; typically due to impaired myocardial contractility or increased afterload
systolic dysfunction
type of heart failure with problems with filling; often due to an inability of the ventricle relax during diastole or ventricular stiffness
diastole dysfunction
How does the body compensate during heart failure?
- increase EDV by increasing blood volume or venous return
- increased thirst and fluid retention
- increase SNS activity and contractility
- cardiac hypertrophy (increases ability to pump)
How do the body’s compensatory mechanism for CHF become detrimental over time?
- increased blood volume leads to pulmonary congestion
- pulmonary edema leads to dyspnea or orthopnea and decreased O2 availability
- peripheral edema, especially in feet
- ascites, enlargement of liver, GI discomfort
How can you treat CHF?
- ACE inhibitors (most important)
- diuretics
- inotropic drugs (increase force of contraction)
- beta-blockers
- vasodilators
How is blood supply in the brain protected?
- anastomoses (interconnections between blood vessels, aka. circle of Willis)
- only 20% of people have a complete circle of Willis –> decrease chance of stroke
when a portion of the blood flow to the brain is blocked (85%)
ischemic (occlusive) stroke
when a blood vessel in the brain ruptures (15%); often results from congenital abnormalities
intracranial hemorrhagic stroke
area in which blood flow is at
ischemic core
area in which blood flow is at 20-50% and cells will remain viable for several hours; target of treatment
ischemic penumbra
Describe the mechanism of cell death.
- insufficient levels of glucose and O2 causes ATP depletion
- no ATP for ion pumps means that ion gradient can’t be maintained
- neuron undergoes anoxic depolarization where concentrations begin to equilibrate
- neurotransmitters released in massive quantities due to depolarization
- release of high levels of glutamate is toxic to adjacent neurons
- when blood flow is restored, oxygen reacts with accumulated substrates, creating free radicals which cause more oxidative injury (reperfusion injury)
What are some treatments for strokes?
ischemic - thrombolytic drugs (must be administered within 3 hours)
hemorrhagic - treated surgically or with blood-clot promoting and anti-hypertensive drugs
