Left Atrioventricular Valve (aka bicuspid valve)

- when open, blood flows from left atrium to left ventricle

- when closed, causes S1 (the first heart sound - "lub") at end diastole (to prevent backflow from left ventricle to left atrium)

- Mitral valve is adjoined to papillar muscle and chordae tendinae that help valve to close when pressure in ventricle is higher than pressure in atrium

- defect causes 3 types of murmers

1. Mitral regurgitation

2. Mitral valve prolapse

3. Mitral stenosis

Tricuspid valve that shunts blood from left ventricle to aorta and systemic circulation

- when closed, causes S2 (the second heart sound - "dub") at end of systole

- defects causes 2 types of murmers

1. Aortic stenosis

2. Aortic regurgitation

Semilunar valve that shunts blood from right ventricle to pulmonary artery into pulmonary circulation.

- Pulmonic stenosis may cause systolic ejection murmer

Shunts blood from right atrium to right ventricle

- Tricuspid regurgitation causes holosystolic (aka pansystolic) heart murmer

= LV "Wall Stress" at end diastole (or BEFORE contraction)

= EDV (end-diastolic volume)

= length of sarcomere BEFORE contraction

Explanation:

EDV is the volume of blood in the LV BEFORE contraction or at the END of diastole where LV is completely relaxed and is filled with blood. The greater the EDV, the greater the preload because the more blood you have in the LV the more pressure or stress it will put on the LV wall (aka "Wall Stress"). Increased preload or wall stress will then stretch out the sarcomere unit increasing its length. The longer the sarcomere is BEFORE contraction, it will generate more force for contraction which results in greater stroke volume. This is known as Frank-Starling Mechanism. Mwahaha!

Increasing preload (aka EDV or "Wall Stress") increases the amount of tension muscle fibers experience. Remember, preload is also a measure of the length of the sarcomere, thus, increasing preload increases the LENGTH of the sarcomere which increases the TENSION. The length-tension curve depends on CONTRACTILITY (aka ionotropy). So now, if you increase ionotropy by giving pt NE (norepinephrine) you will increase the tension and thus force of contraction and thus stroke volume for a given preload (sarcomere length).

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Contractility:

What increases it?

aka Ionotropy is the intrinsic ability of cardiac muscle to develop a force (to contract) at a given length

What increases ionotropy?

1. Increased HR: an increased HR means that you've increased the number of APs (action potentials) per minute  which increases Ca2+ influx and thus tension

a. Positive/ascending staircase

b. Postextrasystolic Potentiation: the extrasystolic beat causes more Ca2+ to enter myocardial fiber and so the beat immediately after the extra beat hasd more contraction

2. Catecholamines (bind B1 receptors)/Sympathetic activation does two things...

a. increases Ca2+ influx

b. inactivates phospholamban via phosphorylation and thus activates SERCA allowing more Ca2+ to be resequestered into SR allowing for faster relaxation and more contraction (simply because there is now more Ca2+ that can be released from SR)

3. Digitalis (cardiac glycoside): inhibits Na-K pump, thus Na enters the cell and ruins gradient, in turn, the Na-Ca pump that depends on the Na gradient is diminished which causes an influx of Ca2+

Contractility:

What decreases it?

The F-S Mechanism is based off of the lenth-tension relationship. Most importantly, it is the heart's intrinsic way of synchronizing CO with increased venous return. The greater the venous return, the greater the CO. Increasing contractility shifts the curve up and increases CO for any particular EDV/preload, vice versa.

*NOTE: SV is another way of saying CO (it's just the amount of blood ejected during systole, which ultimately depends on 3 things...TBA)

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Stroke Volume

vs.

Cardiac Output

Stroke Volume (SV): volume of blood ejected from LV during systole per heart beat

Cardiac Output (CO): volume of blood ejected from LV during systole per minute

CO = SV × HR

Three variable determine CO (or SV):

1. Contractility: anything that increases ionotropy increases SV

2. Preload: anything that increases preload increases SV

3. Afterload: anything that increases afterload DECREASES SV

Very similar to preload = LV "Wall Stress" DURING ejection

Key difference between preload and afterload is that afterload curve has many different time points (in other words the afterload is constantly changing) whereas the preload is constant (EDV/ LV "wall stress" BEFORE contraction).

Furthermore, the LV "Wall Stress" is technically only one variable that determines afterload. Afterload also includes...

1. Aortic valve resistance

2. Systemic vascular resistance

3. Arterial blood pressure

4. LV Wall Stress

5. Stenotic valve

These are ALL FORCES the LV must pump against to push blood from LV into aorta = AFTERLOAD. 

Afterload (which is again, all the forces LV must pump against during ejection) will thus DECREASE the velocity of contraction which will also DECREASE the blood volume ejected (SV).

Preload INCREASES the velocity of contraction because the longer the sarcomere is before contraction, the more tension and force of contraction, and the faster the contraction will be.

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a - Ventricular Filling: in order for the LV to fill, the pressure in the LV must be LOWER than pressure in LA so that blood can flow from HIGH to LOW pressure. When this pressure gradient is formed, the mitral valve opens allowing blood to flow from LA to LV. LV volume increases to 140 ml which is the end-diastolic volume - point 1 (total blood volume in LV after filling - corresponds to preload!!!)

b - Isovolumetric Contraction: LV begins to contract AFTER the mitral valve closes (S1). This contraction however is NOT accompanied by a change in volume and thus although LV is contracting, the volume in the LV does NOT decrease because the aortic valve has not opened yet.

c - Ventricular Ejection: LV contraction causes an increase in pressure in the LV and once LV pressure exceed aortic pressure the aortic valve will open (remember, blood flows from HIGH to LOW). Moving from point 2 to 3, there is a decrease in LV volume for blood is being ejected - how much blood? - STROKE VOLUME!!! (SV corresponds to the width of the P-V loop). The volume of blood remaining within LV is the end-systolic volume (point 3).

d - Isovolumetric Relaxation: LV begins to relax and eventually when aortic pressure exceeds LV pressure, the aortic valve closes (S2). Since at this point all valves are closed, even though LV is still "relaxing" there is no change in volume.

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1. Increasing Preload: increasing length of sarcomere or LV wall stress BEFORE contraction results in greater force of contraction resulting in greater SV. Thus, the end-diastolic volume increases and the width of the P-V loop which again corresponds to an increase in SV.

2. Increasing Afterload: increasing afterload in LV means that you've increased aortic pressure (remember, afterload refers to all types of stress LV experiences during ejection including high aortic pressure). Due to this increased afterload (aka high aortic pressure), LV has to pump harder against that pressure and so the volume of blood the LV is able to eject decreases (SV decreases), which essentially means that the amount of blood remaining in the LV after contraction increases (end-systolic volume increases).

3. Increasing Contractility: increasing ability of LV to contract increases tension and thus increases SV. Thus, increasing the volume of blood ejected from LV means decreasing volume of blood that remains in LV after ejection (decreased end-systolic volume).

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Understand both curves (explain why they increase/decrease with right atrial pressure)

1. Intersection of curves: operatin point of heart (CO = venous return)

2. X-intercept: At this point, CO and venous return are zero meaning that there is NO FLOW within CV system. At this point, you can measure the Mean Systemic Pressure which is the pressure of the whole CV system which equals the right atrial pressure (again, when heart is literally stopped).

1. Shift to the right:

Increase in Mean Systemic Pressure due to

a. increase in blood volume

b. decrease in venous compliance (which shifts blood to arteries, increasing pressure)

2. Shift to the left:

Decrease in Mean Systemic Pressure due to

a. decrease in blood volume

b. increase in venous compliance

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Venous return curve changes slope when TPR (total peripheral resistance changes)

1. Clockwise Shift: a decrease in TPR (aka vasodilation) causes an increase in venous return (more blood flow from arteries to veins and back to heart)

2. Counterclockwise Shift: an increase in TPR (aka vasoconstriction) causes a decrease invenous return (decrease in blood flow from arteries to veins and back to heart)

***It is important to note that changing TPR will cause a shift both in venous return curve as well as CO curve. Thus....

1. Increasing TPR: decreases both venous return and CO (due to increased aortic pressure) - new set point with decreased CO and venous return BUT right atrial pressure is the same

2. Decreasing TPR: increases both venous return and CO (again, set point is higher but right atrial pressure remains the same)

***Please go to flashcard "Cardiac & Vascular Function Curve Overview" to view big picture

Iontropic Agents change CO curve.

1. Positive Ionotropic Agents (e.g. digitalis): increases contractility and thus increases CO. CO curve shifts upward, thus intersection of both curves where CO = venous return occurs at a LOWER atrial pressure 

2. Negative Ionotropic Agents: decrease contractility and decrease CO, thus CO curve shifts downward

Interval from beginning of P to beginning of Q wave (which is inital depolarization of the LV).

*Changes with AV node conduction (e.g. heart block decreases AV node conduction which increases PR interval), Why? because PR interval is a measure of the conduction delay through the AV node (normally < 120 msec)...so the time it takes from the electric conduction to go through the AV node and actually stimulate depolarization and contraction of ventricles. Why is their a delay - why does AV node conduction velocity the slowest? To allow time for ventricular filling.

1. Sympathetics increase AV node conduction velocity which DECREASES PR interval (may compromise ventricular filling!!!)

2. Parasympathetics decrease AV node conduction velocity which INCREASES PR interval

depolarization of ventricles

(normally <120 msec)

T wave

SA node

↓

Atria

↓

 AV node

↓

common bundle

↓

L & R bundle branches

↓

Purkinje fibers

↓

Ventricles

VAP (Ventricular Action Potential)

Phase 4

Resting Membrane Potential

Membrane is highly permeable to K+ - influx and efflux of K+ reaches equilibrium - cell membrane reaches resting potential of -90 mV which is close to the K+ equilibrium potential

VAP

Phase 0

Upstroke

Very rapid and transient increase in Na+ conductance - Na+ flows into cell causing membrane depolarization. At peak of VAP, membrane potential reaches Na+ equilibrium potential (+20 mV)

VAP

Phase 1

Initial Repolarization

Na+ voltage gated channels are inactivated as quickly as they opened and some K+ voltage-gated channels open causing an initial efflux of K+ and thus an initial decrease in membrane potential

VAP

Phase 2

Plateau

Ca2+ voltage-gated channels open causing an transient INFLUX of Ca2+. K+ voltage-gated channels are still open and so there is still an EFFLUX of K+. Both ions end up balancing each other out thus membrane potential does not change and is stable

VAP

Phase 3

Repolarization

Ca2+ voltage-gated channels close and K+ efflux predominates - large K+ efflux allows for hyperolarization in which membrane potential reaches resting state (close to K+ equilibrium potential)

Pacemaker Action Potential (PAP)

vs.

Ventricular Action Potential (VAP)

PAP...

1. Do NOT have a resting potential (they are never at rest - always either depolarizing or hyperpolarizing)

2. Automaticity - they do NOT need gap junctions to communicate with other cells  - to stimulate their own APs - they can stimulate their own APs

3. "slow" APs - the depolarizing phase (Phase 4 and 0) are slower compared to VAPs

Slow Depolarization

*accounts for automatic/pacemaker activity of SA node

slow Na+ influx

PAP

Phase 0

Upstroke

Ca2+ Influx (Na+ influx doesn't stop) but in addition to Na+, Ca2+ voltage-gated channels open causing membrane potential to go close to Ca2+ equilibrium potential

PAP

Phase 3

Repolarization

Efflux of K+ BUT membrane potential although goes more negative does NOT reach K+ equilibrium potential and definitely doesn't stay low for long - causes almost an immediate slow depolarization (Phase 4) after it reaches about -60 mV

Slope of Phase 4 (slow depolarization - Na+ influx) for pacemaker cell corresponds ot HR!!! Thus, changing the slope will change HR.

1. Sympathetic stimulation increase probability for If Na+ channels to be open, thus increases HR.

2. Catecholamines increase depolarization (Na+ influx) and thus increase HR.

3. Parasympathetics (ACh) and adenosine  decrease rate of diastolic depolarization and thus decrease HR.

Increases firing rate of SA node thus increases HR

How?

***Activation of Sympathetics and release of NE that bind to B1 receptors.

1. Increase rate of phase 4 depolarization in PAP (SA node).

2. Reaches threshold faster thus more APs occur in unit time.

3. Increased If - Na+ influx - during phase 4.

4. Increase SA node firing rate.

5. Increase HR.

Decreases firing rate of SA node thus decreases HR

How?

***Activation of parasympathetics (ACh binds to muscarinic receptors ONLY in SA node, AV node, and atria - NO PS in ventricles)

1. Decrease rate of slow depolarization in Phase 4 of PAP in SA node cell (decrease If - Na+ influx)

2. Decreases APs per unit time since more difficult to reach threshold potential

3. Decreases overall SA node firing rate

4. Decreases HR

Decreases AV node conduction velocity thus increases PR interval (this occurs by decreasing Ca2+ influx and increasing K+ efflux)

***Activation of parasympathetics (ACh binds to muscarinic receptors ONLY in SA node, AV node, and atria - NO PS in ventricles)