Physiology Lectures 8 -11 Myocardial Performance Ch.5

Front 1

T-tubules

Back 1

invaginations of the sarcolemma that are intimately associated with the terminal cisternae of the sarcoplasmic reticulum.

Front 2

Describe molecular details of the resting state of muscle tissue.

Back 2

While the muscle is at rest, ATP is bound to the head of myosin. During the relaxed state the binding sites on actin are covered by the troponin complex, so that the head of myosin cannot bind to actin.

Front 3

Describe the molecular steps involved in muscle contraction.

Back 3

1) ATP binds to myosin head. Binding sites are covered by troponin complex.
2) muscle cell depolarized, triggers Ca2+ diffusion into cell. Ca2+ release channels in terminal cisternae of SR open
3) Ca2+ bind to troponin C at thin filaments, exposing binding sites on actin.
4) Cross-bridges form between actin on thin filaments and myosin on thick filaments.
5) ATP at the myosin head breaks down into ADP and Pi. The energy released causes neck of myosin molecule to flex, pulling thin filaments inward and causing sarcomere to contract.
6) Slow (L-type) Ca2+ channels in sarcolemma and calcium leak channels in the SR close
7) Ca2+ ions removed from troponin C and sequestered in the SR. Cross-bridges break and muscle rapidly relaxes.
8) If Ca2+ and ATP present, cycle repeats

Front 4

actomyosin: definition, function, mechanism

Back 4

The Actin-Myosin Complex. Possesses ATPase activity that catalyzes dissociation of ADP + Pi from actomyosin, with the energetic change used to induce flexion of the myosin head, shortening of the sarcomere.

Front 5

Excitation-Contraction coupling

Back 5

The role of calcium ions in mediating actin-myosin cross-bridge formation/muscle contraction

Front 6

Trigger-calcium: definition, function

Back 6

The small amount of Ca2+ that enters the sarcoplasm that binds ryanodine receptors on the cisternae of the SR, triggering the release of more Ca2+ via calcium release channels. It is this second wave of Ca2+ that is needed to reach the concentrations of Ca2+ needed for muscle contraction (10^-6)

Front 7

Positive inotropic action: definition, examples

Back 7

Increasing the contractility (slope of pressure/time curve).
E.g. of an agent with positive inotropic action = epinephrine.

Front 8

Mechanism of inotropic action of epinephrine.

Back 8

-Epi binds beta-1 receptors, causing increase in [cAMP]
- ^^[cAMP] increases cell metabolism (more ATP), and activates phosphorylase kinase which phosphorylates L-type Ca2+ channels in the sarcolemma, increasing their open-time --> more trigger calcium --> increased binding of ryanodine receptors on SR.
-increase Ca2+ in cytoplasm increases ATPase activity/cycling-rate of cross-bridges, increasing velocity of tension development. Ca2+ also binds troponin C and increases the number of cross bridges formed-- increasing peak contractile response.

Front 9

Negative inotropic action: definition, examples

Back 9

Decrease contractility by decreasing the cytoplasmic concentrations of Ca2+-- e.g. by blocking Ca2+ channels (verapamil) or beta-1 blockers (propranolol).

Front 10

Effects of verapamil

Back 10

Verapamil is a calcium channel blocker. When given intravenously, it slows the conduction of impulses through the AV node, and diminishes the influx of "trigger" calcium through L-type channels in the sarcolemma during phase 2. This decreases the trigger-calcium concentration, and thus the Ca2+-ryanodine receptor binding, and the release of Ca2+ from the SR. This causes less contractility and systolic force, and less blood is pumped into the aorta. Verapamil also blocks Ca2+ channels in smooth muscle of arteries so that they relax and increase arterial volume, lowering blood pressure.

Front 11

How does the muscle relax? How does epinephrine effect muscle relaxation? What effect is this?

Back 11

Muscles relax upon removal of Ca2+ from troponin C in the cytoplasm.
Epinephrine acting on beta-1 receptors increase [cAMP] which activates on phosphorylase kinase. Phosphorylase kinase phosphorylates 1) Ca2+ channels in sarcolemma (only effects contraction), 2) troponin I in thin filament, and 3) phospholamban, an inhibitor of a SRCa2+ pump. This is called the lusitropic effect of epinephrine.

Front 12

How is Ca2+ removed from the cytoplasm?

Back 12

1) Ca2+ pump (5%)
2) Ca2+/Na+ exchanger (10%)
the efficacy of this pump is determined by the sodium gradient, thus a Na+/K+ ATPase pump inhibitor will also inhibit this pump.
3) SRCa2+ pump (85%)

Front 13

Isotonic contraction

Back 13

Muscle contracts while the tension remains the same, and work is performed.

Front 14

Mitral valve prolapse

Back 14

When the chordae tendinare, papillary muscles, or leaflets of the mitral valve get stretched or damaged, blood can rush back into the left atrium during the end of systole creating a clicking noise followed by an end-systolic murmur.

Front 15

Relationship between Velocity of muscle shortening and Load. Describe the graph. Describe the effects of stretching or NE on the graph.

Back 15

Velocity highest when Load is 0. Velocity slowest when Load is at Maximum. Graph would be asymptotic (V = 1/L.

Stretching would increase the number of cross bridges that form (because overlapping filaments prevent some cross bridges from forming)-- thus increasing the velocity at any given load.
Norepinephrine increases the rate of cross-bridge cycling, increasing the velocity at any given load.

Front 16

LaPlace equation

Back 16

T = P x R/2

Tension is equal to the product of the pressure and the radius/2. Thus the larger the volume of the heart, the greater the tension in the tissue.

Front 17

Discuss the LaPlace equation in relation to heart failure.

Back 17

In a patient with heart failure and a dilated ventricle, the same end-diastolic pressure will generate a much higher tension than a normal heart because of the increased radius. Thus, the dilated ventricle needs to generate a greater force to overcome the greater tension, increasing its energy needs (ATP, O2, blood flow) greatly. Pt may develop angina pectoris if energy needs not met (e.g. during exertion).

Front 18

Discuss the LaPlace equation in relation to why hypertension causes ventricular hypertrophy?

Back 18

In HTN, the ventricle needs to generate a greater tension. This can be spread over more myofibrils by hypertrophy-- in fact, the thickness of the ventricle wall (H) is inversely related to the tension in the wall by: T = PR/2H

Front 19

How does nitroglycerine work in treating angina pectoris?

Back 19

NGN, a venodilator, dilates veins so that they hold more blood and reduce venous return. With a lower pre-load, the ventricles aren't stretched as much, and the tension is reduced, along with the increased energy/blood demands

Front 20

Define ventricular compliance

Back 20

∂V/∂P

The change in volume per change in diastolic filling pressure. The inverse of elasticity.

Front 21

Define preload

Back 21

The load on the myocardial fibers just before they contract in systole.

Front 22

Define afterload

Back 22

The impedance that prevents blood from the heart from being pumped into the aorta. Initially caused by the closed aortic valve, and then by resistance to blood flow in the peripheral direction.

Front 23

Describe a PAWP vs End-diastolic volume curve. What information can it tell you?

Back 23

PAWP = pressure
EDV = volume

It's a pressure vs. volume curve. You can use it to calculate compliance C = ∂V/∂P. The graph shows that PAWP increases exponentially as EDV increases. Hypertrophy would cause it to rise faster (PAWP increased at all volumes), and a lower compliance (C =∂V/∂P, ∂P >> ∂V)

Front 24

What is end-diastolic volume?

Back 24

The measure of blood in the ventricle after filling.

Front 25

Describe the pressures generated by isovolumic ventricular contraction at various pre-load end-diastolic volumes.

Back 25

The larger the EDV (and thus stretching of the ventricular muscle fibers), the greater the intraventricular systolic pressure (Frank-Starling Law). This effect is increased by stretching, or sympathetic stimulation.

Front 26

Ejection fraction: definition, use, and normal values

Back 26

The ejection volume is equal to the Stroke Volume divided by the End Diastolic Volume:
EF = SV / EDV

Ejection fraction is a useful clinical measure of contractility-- instead of measure pressure/time changes with a catheter. A normal heart will eject 2/3 of its EDV,

Front 27

Describe the pressure-volume loop of the cardiac cycle.

Back 27

A PV Graph (Ventricular Pressure vs Left Ventricular Volume) will show the heart functioning between two curves: an upper Maximum intraventricular pressure curve, and a lower Ventricular Compliance Curve.

1) At the end of systole, the LV has about 42ml of blood in it. Diastole begins. When LV pressure drops below LA pressure (10mmHg), the Mitral valve opens. LA forces about 80ml into LV, until it reaches its end diastolic volume of 120ml.

Front 28

End systolic volume

Back 28

Volume of blood in the ventricle at the end of systole. This is usually 1/3 of the stroke volume, or about 40ml.
2) As LV contracts, its pressure increases above LA pressure and Mitral Valve Closes. Heart contracts, increasing pressure without increasing volume: this is isovolumic contraction.
3) As intraventricular pressure exceeds the diastolic pressure exceeds the diastolic blood pressure in the aorta (about 80mmHg) the Aortic Valve opens, blood begins to eject from the ventricle into the aorta.
4) The intraventricular blood pressure peaks at slightly above aortic pressure (about 120mmHg) during systole before beginning to fall.
5) As volume is now decreasing in the left ventricle, its capacity to generate pressure decreases as well. As the ventricle relaxes, IV pressure falls below aortic pressure and Aortic valve closes. Pressure then drops isovolumically.

Front 29

End diastolic volume

Back 29

Volume of blood in the ventricle right before systole, after it has just been filled. This is usually about 120ml.

Front 30

Stroke volume on the PV-loop graph

Back 30

Stroke Volume is equal to the difference between points 1) and 2) on the PV-loop graph. This is the difference between the end-systolic volume and the end-diastolic volume.

Front 31

Frequent causes of decreased myocardial contractility

Back 31

Side effects of negative inotropic drugs (calcium channel blockers, beta-adrenergic blockers), hypoxemia, acidosis.

Front 32

Heterometric autoregulation

Back 32

A term used to describe the Frank-Starling effect: heterometric because a change in the length of ventricular fibers creates the autoregulation of stroke volume.

Front 33

Most reliable index of myocardial contractility.

Back 33

Maximum rate of increase in ventricular pressure : ΔP/ΔTmax measured during the isovolume phase of systole with a catheter inserted into the LV.

Front 34

Effect of inspiration, expiration on ventricular preloads

Back 34

Inspiration --> relative vacuum in thoracic cavity --> more blood drawn into right atria, right ventricle --> stroke volume of RV automatically increased.

Inspiration --> lung vessels distend, hold more blood --> LA, LV preload diminishes --> Left Ventricle stroke volume decreased.

On expiration, the opposite happens.

Front 35

What do changes in contractility look like on the PV-loop graph, and what causes each.

Back 35

Increased contractility (e.g. SNS stimulation) results in a steeper slope of the ESVPC curve.

Decreased contractility (e.g. ventricular failure) results in a less steep ESVPC curve.

Front 36

Describe the heart's compensations for hypertension, and the changes one would see in the PV-loop graph.

Back 36

1) Increased diastolic BP (afterload) increases the pressure required to open the aortic valve (elevation in point 3). This results in a decrease in the stroke volume and ejection fraction (point 5).
2) This increased afterload is compensated for via Frank-Starling from increase end-systolic volume (more volume--> greater pressure generated) due to decreased stroke volume/ejection fraction (Points 2,3 move right)
3) Sympathetic stimulation increases the slope of the ESVP curve/myocardial contractility, increasing the ejection fraction without the increased preload needed for Frank-Starling.
4) The increased tension eventually hypertrophies the ventricle, decreasing its compliance (increasing the DVP Curve). This rotated curve required a higher filling pressure (PAWP) and may cause pulmonary edema.

Front 37

Why do two different PV-loops with the same area (work) have different energy requirement?

Back 37

Because the isovolumic phase requires more ATP than the rapid ejection phase (energy needs of pressure work > energy needs of volume work).

Front 38

Pressure-rate product

Back 38

The product of the systolic blood pressure and the heart rate: this gives a simple and practical indicator of ATP and O2 utilization.

Front 39

Cardiac Output

Back 39

Cardiac Output = Stroke volume x Heart Rate

CO = SV x HR

Front 40

Fick's Principle

Back 40

CO = VO2total/(Ca)2 - CvO2)
the cardiac output is equal to the oxygen consumption of the whole body (VO2) over the difference in the arterial oxygen content (CaO2) and the mixed venous oxygen content (CvO2).

Front 41

Cardiac Index

Back 41

CI = CO/surface area of pt

CI is a measure of cardiac output that is normalized for body size/surface area.

Front 42

The path of Swan-Ganz catheter, what is measured, and what pressure patterns to expect in each compartment.

Back 42

1) SVC right before the atrium: this will measure the Central Venous Pressure (CVP). The pressure will fate with respiration between 5 and 10 mmHg.
2) Right Atrium: Right Atrial Pressure is measured, and should appear as an A-wave, C-wave, and V-wave. A-wave presents atrial contraction, and follows the P-wave on the EKG. The C-wave represents the tricuspid valve bulging into the atrium during systole, and comes right after the QRS complex. V wave is due to atrial filling near the end of systole.
3) Now in the right ventricle, the pressure oscillates regularly between 0 and 25mmHg
4) Once in the pulmonary artery, there is a step-up in diastolic pressure so that the pressure fluctuates between 15 and 25mmHg
5) Once the catheter has been wedged into a lower lobe of the lung, thermodilution can be used to measure Cardiac Output. Additionally, sBP, dBP, PP, and MAP (dBP + 1/3 sBP) can be calculated

Front 43

Mean Systemic Arterial Pressure: definition, and how to obtain.

Back 43

MSAP = dBP + 1/3sBP
Obtained through a radial artery cannula.

Front 44

How does ischemic, injured, or infarcted tissue cause dyspnea?

Back 44

Compliance of the ventricle decreases -> pressure required to fill ventricle increases -> pressure required to fill atrium increases -> pressure increases in pulmonary veins and capillaries -> pulmonary filtration into alveoli and interstitium -> fluid reduces compliance of alveoli -> difficulty inspiring: dyspnea

Front 45

Why does someone whose stroke volume decreases develop a rapid heart rate?

Back 45

To maintain Cardiac Output:
CO = SV x HR

Front 46

Physiologic Splitting of S2

Back 46

Occurs upon inspiration due to delayed closing of pulmonic valve when venous return to the right ventricle increases during inspiration-- so right ventricular ejection takes slightly longer.

Front 47

Fixed Splitting of S2

Back 47

Pathological fixed (or wide) splitting of S2. This could be for several reasons, such as when impulse conduction is delayed to the right ventricle by right bundle branch block, when ejection is slowed by an increased afterload due to a stenotic pulmonary valve, or when the preload of the RV is increased by reflux of blood from the left atrium into the right through an atrial septal defect.

Front 48

Paradoxical Splitting of S2

Back 48

Caused by pathological conditions that slow the emptying of the left ventricle, causing an abnormal delay in closure of the aortic valve so that A2 occurs after P2. Could be caused by left bundle branch block, increased afterload due to stenotic aortic valve, or when LV contractility is substantially reduced-- e.g., after an MI.

Front 49

Summation Gallop

Back 49

When the period of diastole is shortened at fast heart rates

Front 50

Mitral Stenosis: describe changes in the atrial pressure curve, what sounds to hear upon auscultation, and why you hear these sounds.

Back 50

Because of the stenosed mitral valve, much higher pressures need to be achieved to open the mitral valve, so that the pressure gradient between the increased A-wave and the ventricular pressure is large. The y-descent is shallow because blood flows more slowly into the ventricle during the period of rapid filling.
Sounds to expect: two diastolic murmurs. The first is a low-rumbling murmur preceded by an opening snap of the stiff leaftlets being opened. This occurs early in diastole during rapid filling.

The second murmur occurs at the end of diastole when the hypertrophied left atrium forces blood into the left ventricle. This murmur ends with S1.

Front 51

What does R/S > 1 in V1 indicate?

Back 51

Right ventricular hypertrophy

Front 52

What to expect in the EKG of mitral stenosis?

Back 52

The ECshould show left atrial hypertropy (a biphasic P wave in lead V1 with an accentuated second (downward) component (P-mitrale). With time, pulmonary HTN develops, increasing RV afterload, and RV hypertrophy so that the R-wave in V1 is greated than the S-wave. May also present with Right Axis Deviation.

Front 53

Mitral insufficiency/regurgitation: describe pressure changes in the left atrium, and what to expect to hear upon auscultation.

Back 53

Mitral insufficiency is characterized by a soft S1 fused with a holosystolic (pansystolic) murmur which ends with S2. S3 is also present.
Because blood leaks back into the atrium during systole, a large V-wave is produced in the left atrial pressure tracing. When mitral valve opens again, blood rushes into LV (seen as sharp Y-descent) generating an S3.

Front 54

What do you expect to hear upon auscultation of a patient with rheumatic heart disease?

Back 54

In rheaumatic heartdisease the leaflets of the mitral valve are stiff and the chordae tendinae short, allowing blood to leak back into the left atrium as the left ventricle contracts during systole (mitral insufficiency). This results in a large v-wave in the left atrial pressure tracing. When the mitral valve opens, blood rushes into the LV, creating a third heart sound S3.

Front 55

Aortic Stenosis: describe pressure changes in the left ventricle and aorta, and what to expect to hear upon auscultation, and the EKG.

Back 55

Increase pressure gradient across aortic valve, with LV pressure reaching over 200mmHg, whereas aortic/brachial pressure initially normal but later decreases as aortic stenosis progresses.

Expect to hear an S4 heart sound, as well as a systolic ejection murmur: a diamond shaped/crescendo-decrescendo mumur over the aortic listening area, and over the carotid arteries.

EKG should show S(V1) + R (V5) > 35mm

Front 56

Aortic insufficiency/regurgitation: describe pressure changes in the left ventricle and aorta, and what to expect to hear upon auscultation, and the EKG.

Back 56

Due to a faulty valve, some of the stroke volume leaks from the aorta back into the LV during diastole, resulting in a large stroke volume. This back-flux is initially compensated for by Frank-Starling, and later by LV Hypertrophy. Low aortic BP eventually leads to coronary insufficiency, ischemia, and LV failure.

Upon auscultation one would expect to hear two diastolic murmurs: 1) an early diastolic decrescendo murmur which starts with S2, and 2) an Austin-Flint presystolic murmur. The Austin-Flint murmur is caused by a jet of blood from the leaking aortic valve hitting the anterior leaflet of the mitral valve so that it does not open completely.

EKG would show EKG should show S(V1) + R (V5) > 35mm

There is a rapid fall in aortic pressure during diastole,