Cardiovascular physiology plus

Question 1

Changes of blood flow after birth (3)

Answer 1

1) All bypasses (ductus arteriosus, ductus venosus, and foramen ovale) close
2) Umbilical vein/ artery obliterates
3) Removal of placenta

Question 2

What feature of cardiac muscle allows automaticity of action potential to be rapidly transmitted, allowing contraction of the myocytes simultaneously?

Answer 2

Intercalated discs, which connected the myocytes, have gap junctions that allow spread of depolarization from one cell to all of the cells, allowing a unified contraction.

Question 3

Phases of myocardial/ ventricular action potential

Answer 3

Phase 4: until stimulated, resting potential (transmembrane potential) stable at approximately -90 mV due to high permeability through residual, leaky K+ channels.

Phase 0: Rapid upstroke; VG Na+ channels open → influx of Na+

Phase 1: Initial repolarization- transient inactivation of VG Na+ channels. VG K+ begins to open, resulting in some K+ efflux.

Phase 2: Plateau phase; K+ efflux is balanced by Ca2+ influx via VG Ca2+ channels. Ca2+ influx triggers additional Ca2+ release from SR → myocyte contraction.

Phase 3: Rapid repolarization; massive K+ efflux via opening of VG slow K+ channels and closure of VG Ca2+ channels; return back to -90 mV.

Phase 4

Question 4

Excitation contraction coupling in cardiac muscle (8)

Answer 4

1) Current spreads via gap junctions
2) AP travel along plasma membrane + T tubules
3) Ca2+ channels open in plasma membrane + SR
4) Ca2+ in cytoplasm induces Ca2+ release from SR
5) Ca2+ binds troponing → exposes myosin binding sites
6) Cross-bridge cycling (contraction)
7) Ca2+ is actively transported back into SR and ECF (via Ca2+ and Na+ transporter)
8) Tropomyosin blocks myosin-binding sites (muscle relaxation)

Question 5

What is meant by Ca2+ mediated Ca2+ release?

Answer 5

During myocyte AP, additional calcium that comes into cell during plateau phase prolongs cross-bridge cycling time and stimulates release of more calcium in SR.

Question 6

Preload

Answer 6

The ventricular wall tension at the end of diastole. In clinical terms, the stretch on the ventricular fiers just before contraction, often approximated by the end-diastolic pressure or volume.

Question 7

Cardiac ouput formula

Answer 7

CO = SV x HR (mL or L/min)

Question 8

Stroke volume definition/ formula

Answer 8

SV: volume of blood ejected from ventricle during systole.

SV= EDV- ESV

Question 9

Afterload

Answer 9

The ventricular wall tension during contraction; the force that must be overcome for the ventricle to eject its contents. Often approximated by systolic ventricular pressure or mean arterial pressure.

Question 10

Axes on Frank-Starling Curve

Answer 10

Vertical axis: Measurement of cardiac performance (e.g. cardiac output or stroke volume)

Horizontal axis: Function of preload (e.g. ventricular end diastolic volume or pressure)

Question 11

In a frank-starling curve in a normal patient, where is the normal resting length, optimal sarcomere length, and suboptimal sarcomere length?

Answer 11

Normal resting sarcomere length would lie in the middle of the curve. Optimal sarcomere length is to the right, in which there is large ventricular EDV (large preload) and increased stroke volume. Suboptimal sarcomere length is to the left, in which there is small ventricular EDV (muscle fibers are too scrunched up) and therefore the stroke volume is decreased.

Question 12

How is the Frank-Starling curve shifted when there is increased contractility or heart failure compared to a normal pt?

Answer 12

In states of increased cardiac contractility (e.g. norepi infusion), there is an increased stroke volume at any level of preload. Therefore, the curve is shifted upwards. In heart failure (decreased contractility), there is a lower stroke volume for any preload or EDV compared to normal pt. Thus, the curve is shifted downwards.

Question 13

What are the different factors that increase stroke volume?

Answer 13

Increasing EDV (preload) will increase stroke volume. Moreover, decreasing ESV will also result in an increase in stroke volume. ESV can be decreased by increasing inotropy.

Question 14

What are the different factors that will decrease stroke volume?

Answer 14

An increase in ESV (w/ EDV constant) means that ventricle hasn’t fully emptied → decrease in stroke volume. Increased afterload will result in an increase in ESV, decreasing SV.

Question 15

Ejection fraction definition/ formula

Answer 15

The fraction of EDV ejected from ventricle during each systolic contraction (normal range= 55-75%).

EF= Stroke volume / EDV

Question 16

What does Frank-Starling Curve represent

Answer 16

Describes inc in stroke volume/ cardiac output that occur in response to an increase in venous return or end diastolic volume. Increases in EDV cause an increase in ventricular fiber legnth → increase in tension. Thus, it indicates that cardiac output matches venous return (greater the venous return, greater the cardiac output).

Question 17

What is preload related to besides end-diastolic volume?

Answer 17

Right atrial pressure, since EDV is related to right atrial pressure.

Question 18

What is afterload for left ventricle related to?

Answer 18

Aortic pressure; increases in aortic pressure cause an increase in afterload of left ventricle.

Question 19

What is afterload related to for the right ventricle?

Answer 19

Pulmonary artery pressure. Increases in pulmonary artery pressure cause an increase in afterload on the right ventricle.

Question 20

Mechanism of parasympathetic action on heart rate

Answer 20

Parasympathetic has a negative chronotropic effect. ACh is released by vagus nerve, which binds muscarinic (M2) receptor. This activate inhibitory G protein system, which inhibits adenylate cyclase / reduces cAMP formation. Ultimately, it reduces heart rate by acting at the SA node, which affects phase 4 (slow depolarization stage) of the SA node by decreasing funny current (I_f), so that there is decreased inward Na+ current. As a result, there are fewer action potentials per unit time bc the threshold potential is reached more slowly (decreased slope of phase 4) and therefore fires less frequently.

Question 21

Chronotropic vs. Dromotropic effects

Answer 21

Chronotropic effects: produces changes in HR by acting at the SA node

Dromotropic effects: produce changes in conduction velocity primarily by acting in the AV node.

Question 22

Mechanism of parasympathetic action on conduction velocity

Answer 22

Parasympathetic has a negative dromotropic effect. ACh is released by vagus nerve, which binds muscarinic (M2) receptor. This activate inhibitory G protein system, which inhibits adenylate cyclase / reduces cAMP formation. Ultimately, it reduces conduction velocity by acting at the AV node, specifically by decreasing inward Ca2+ current. As a result, APs are conducted more slowly from atria to ventricles.

Question 23

What is the upstroke of AP in AV node?

Answer 23

Result of inward Ca+ current

Question 24

What is SNS effect on heart rate?

Answer 24

Has positive chronotropic effect; Sympathetic nervous system releases catecholamines (Norepi), which binds and stimulates B1 adrenergic receptor. This is coupled to Gs protein, which stimulates adenyl cyclase to stimulate cAMP production. The cAMP signaling cascade leads to increased funny current (I_f), the inward Na+ current in phase 4 of SA node depolarization. As a result, the threshold potential is reached more quickly (decreased slope of phase 4) adn therefore more frequently.

Question 25

What is SNS effect on conduction velocity of the heart?

Answer 25

Has positive dromotropic effect; Sympathetic nervous system releases catecholamines (Norepi), which binds and stimulates B1 adrenergic receptor. This is coupled to Gs protein, which stimulates adenyl cyclase to stimulate cAMP production. The cAMP signaling cascade leads to increased calcium current (upstroke) of AV node. As a result, action potentials are conducted more rapidly from atria to ventricles.

Question 26

How does SNS affect inotropy (contractility)?

Answer 26

Norepi from SNS binds B1 receptor, which activates Gs, stimulating adenylate cyclase and cAMP production. Cyclic AMP signaling has the following effects:

1) Phosphorylation of Ca2+ channels causes Ca2+ channels to remain open longer (increased inward Ca2+ current during plateau phase)
2) Phosphorylation of proteins in the SR enhances release of Ca2+
3) Phosphorylation of myosin increases myosin ATPase, which increases the speed of cross-bridge cycling.
4) Phosphorylation of Ca2+ pumps in the SR increases the speed of calcium re-uptake and relaxation.

Question 27

What factors will increase stroke volume?

Answer 27

1) Increased inotropy
2) Increased preload
3) Decreased afterload.

Question 28

Factors that increase contractility (and SV)

Answer 28

1) Sympathetic Stimulation (catecholamines) via B1 receptors– cause increased intracellular Ca2+ current in plateau phase of cardiac action potential.
2) Increased HR– more AP per unit time → more Ca2+ enters myocardial cells during AP plateaus → more Ca2+ stored in SR → more Ca2+ released from SR and greater tension produced during contraction.
3) Digitalis (Digoxin)/ decreased extracellular Na+– diminish Na+ gradient across cell membrane (Na+ - Ca2+ exchange) depends on this gradient and when diminished, produces increase in intracellular Ca2+, since Ca2+ can’t get out.

Question 29

Factors that decrease contractility/ SV

Answer 29

1) Beta blockade
2) Heart failure
3) Acidosis
4) Hypoxia
5) Parasymathetic stimulation (ACh) via muscarinic receptors/ Ca2+ channel blockers

Question 30

Parasympathetic effect on contractility

Answer 30

Negative inotropy; ACh binds muscarinic receptors only on atria and decreases inotropy by decreasing inward Ca2+ current during plateau phase of action potential.

Question 31

Function of Sodium-calcium exchanger (NCX) and consequence of dysfunction.

Answer 31

Removes calcium from cells by using electrochemical gradient of sodium. If exchanger works poorly, Ca2+ stays in the myocyte → enhanced inotropy

Question 32

Mechanism of Digitalis (Digoxin)

Answer 32

Competes with K+ for binding to the Na+/K+ ATPase. As a result, Na+ can’t get out/ K+ can’t get in, resulting in a buildup of Na+ inside the cell. When intracellular Na+ increases, Na+ gradient diminishes, and NCX cannot work, as it needs Na+ gradient to bring Ca2+ out of the cell. As a result, Ca2+ cannot get out of the cell, builds up within the cell, and increases inotropy.

Question 33

Why can hypokalemia increase risk for Digitalis toxicity?

Question 34

Effect of ACE inhibitors and ARBs on preload and afterload

Answer 34

Preload and afterload

Question 35

What is SNS effect on vascular smooth muscle in skeletal muscle vs. everywhere else?

Answer 35

In skeletal muscle, catecholamines preferentially binds B2 receptors and cause vasodilation. However, in every other bed (e.g. skin, kidney, etc.) the catecholamines bind alpha-1 receptors and cause vasoconstriction.

Question 36

Myocardial oxygen consumption (MVO2) is directly related to what feature of the heart? And how is this feature increased??

Answer 36

MyoCARDial oxygen consumption (MVO2) is directeld related to wall tension, which is increased by contractility, afterload, heart rate, and ventricular diameter.

Question 37

Wall tension formula (Laplace’s law)

Answer 37

Wall tension= (Pressure x radius)/ (2 x thickness)

Question 38

How does increase in SV affect wall tension?

Answer 38

It increases wall tension because stroke volume is equivalent to radius and wall tension= (pressure x radius)/ (2 x thickness)

Question 39

What is a drug that decreases preload?

Answer 39

Venodilators (e.g. nitroglycerin)

Question 40

What is a decreases afterload?

Answer 40

Aterial vasodilators (e.g. hydralazine)

Question 41

How does increase in afterload increase wall tension?

Answer 41

Increase in afterload → increase in pressure → increase in wall tension (Laplace law) .

Question 42

How does the left ventricle compensate for increased afterload in order to decrease wall tension?

Answer 42

LV compensates for increased afterload by thickening (hypertrophy) in order to decrease wall tension (think of Laplace law)

Question 43

What is concentric LV hypertrophy and what is it a result of?

Answer 43

New sarcomeres are in parallel—LV will form thick walls with relatively small cavity and EDV decreases. It occurs in response to pressure overload bc in response to increased LV wall stress, wall thickens and LV chamber radius decreases to try to reduce wall stress. (T=Pr/2h)

Question 44

What is eccentric LV hypertrophy and what is it a result of?

Answer 44

It is when new sarcomeres form in series, resulting in left ventricle becoming dilated (increase radius) with thin (but still thicker than normal), flabby walls. This results from volume overload, which leads to an increase in chamber radius. As a result, it increases its thickness to reduce wall tension. (T= Pr/2h)

Question 45

Example of eccentric LVH

Answer 45

Mitral regurgitation- Left ventricle gets overloaded because it has too much blood → eccentric LVH.

Question 46

What type of hypertrophy (eccentric of concentric) is seen in physiologic cardiac hypertrophy such as in response to pregnancy or endurance training? How does the cell grow in length and width?

Answer 46

Physiologic hypertrophy relating to pregnancy/ endurance training induces eccentric hypertrophy. The cell grows in legnth but also increases somewhat in width.

Question 47

What type of hypertrophy (eccentric vs. concentric) occurs to cardiac cells due to valvular regurgitation? How do they grow in regard to legnth and width?

Answer 47

Eccentric hypertrophy. The cells grow in length and shrink in width.

Question 48

What type of hypertropy (eccentric vs. concentric) is seen in phsyiologic hypertrophy seen in isometric exercise training (e.g. weight lifting)? How does it grow in regards to length and width?

Answer 48

Concentric hypertrophy. Grows mainly in width.

Question 49

What type of hypertropy (eccentric vs. concentric) is seen in pathologic hypertrophy such as chronic HTN or aortic stenosis? How does it grow in regards to length and width?

Answer 49

Concentric hypertrophy. Growht of width and length

Question 50

Two equations for mean arterial pressure

Answer 50

MAP= CO x TPR

MAP= 2/3 diastrolic pressure + 1/3 systolic pressure

Question 51

During early stages of exercise, why does CO need to be increased and how does the body do this?

Answer 51

There is arteriolar dilation in the legs to provide blood to the muscles, decreasing TPR. MAP= CO x TPR; thus, if nothing happens, MAP decreases and person will just fall. Body compensates by increasing CO, which can be done by increasing HR and SV. SV is increased by venoconstricting the legs; as a result, all the blood that the leg receives will be able to get up to the right atrium to increase CO.

Question 52

How is CO increased during late stages of exercise?

Answer 52

By increasing HR only; stroke volume plateus because there is only so much that the heart can pump.

Question 53

Why does very high HR reduce SV and CO? What is an example of this?

Answer 53

During very high heart rate, there is no time to fill the heart during diastole. As a result, SV and CO decreases. An example is Vtach.

Question 54

Difference between O2 content and HbO2 saturation. Which depends on the amount of Hgb? How is PO2?

Answer 54

Content is how much oxygen is in the blood, while saturation is how much oxygen (% wise) is bound to Hgb. O2 content depends on the amount of Hgb; for ex, if 1 molecule of Hgb is present and is saturated, it is 100% saturated. Same with if there is 1000 molecules of Hgb that are saturated with oxygen, it is 100% saturated. However, 1000 molecules of Hgb has more oxygen content.

PO2 is not determined by content or saturation; it is determined by the pressure of gas that’s dissolved in sample.

Question 55

CO equations (2)

Answer 55

CO = SV x HR

CO= rate of O2 consumption/ (arterial O2 content- venous O2 content)

Question 56

Pulse pressure equation

Answer 56

Pulse pressure = systolic pressure - diastolic pressure

Question 57

What situations increase pulse pressure? What are examples?

Answer 57

Situations in which systolic pressure goes up. Most important determinant of pulse pressure is SV.

Ex: Hyperthyroidism, aortic regurgitation, aortic stiffening (arteriosclerosis/ systolic HTN), exercise (transient)

Question 58

What situations decrease pulse pressure? What are some examples?

Answer 58

Decrease pulse pressure in situations in which systolic pressure decreases.

Ex: Aortic stenosis- can’t get blood out, Cardiogenic shock- doesn’t generate any pressure, Cardiac tamponade- blood around the heart keeps it small and quiet, HF.

Question 59

Where is the greatest drop in vascular pressure?

Answer 59

Across the arterioles

Question 60

What type of blood vessel has the greatest resistance?

Answer 60

Arterioles

Question 61

Blood flow equation

Answer 61

Q= change in P/R

Question 62

Equation for blood flow velocity

Answer 62

v= Q/A (Q= blood flow mL/min, A= cross sectional area)

Question 63

How is resistance related to viscosity, length of blood vessel, and radius of blood vessel?

Answer 63

Resistance is directly proportional to the viscosity of the blood and length of vessel. It is inversely proprortional to the fourht power of the vessel radius.

Question 64

What feature of blood/blood vessel has the greatest influence on resistance?

Answer 64

Radius of blood vessel, since it is inversely proportional to the fourth power. For ex, if blood vessel decreases by factor of 2, then resistance increases by factor of 16 (2⁴).

Question 65

Total resistance in series and what is an example?

Answer 65

R_T= R₁ + R₂ + R3…etc.

Example is the arrangement of BVs in a given organ since each organ is supplied by a large artery, smaller arteries, arterioles, capillaries, and veins arranged in series.

Question 66

Total resistance in parallel arrangement and what is an example?

Answer 66

1/R_T= 1/R₁ + 1/R₂ + 1/R₃ … etc.

Example is the systemic circulation, as each organ is supplied by an artery that branches off the aorta. R1, R2, and R3 can be resistances of renal, hepatic and other circulations. Each artery in parallel receives a fractoin of the total blood flow, and total resistance is less than resistance of any of the individual arteries.

Question 67

What is autoregulation?

Answer 67

How blood flow to an organ remains constant over a wide range of perfusion pressures or metabolic needs

Question 68

What is unique about pulmonary vasculature in regards to hypoxia?

Answer 68

Hypoxia causes vasoconstriction in pulmonary vasculature so that only well-ventilated areas are perfused. In other organs, hypxia causes vasodilation.

Question 69

Why isn’t MAP not a simple average of diastolic and systolic pressures?

Answer 69

Because a greater fraction of cardiac cycle is spent in diastole.

Question 70

What is pulmonary capillary wedge pressure (PCWP)? How is this determined?

Answer 70

Good approximation of left atrial pressure. PCWP is measured with pulmonary artery catheter (Swan-Ganz catheter). A catheter, inserted into smallest branches of pulmonray artery, makes almost direct contact with the pulmonary capillaries. The measured pulmonary capillary pressure is approximately equal to the LAP.

Question 71

How does the vascular function graph shift when mean systemic pressure increases? What changes are required for this to occur?

Answer 71

The vascular function graph shifts right. This occurs when there is more volume of blood in the system (e.g. fluid infusion or sympathetic activity) or an increase in venous tone (which increases RAP). Due to these changes, for any EDV or RAP, the cardiac output is increased compared to the normal.

Question 72

What is mean systemic pressure?

Answer 72

Point at which the vascular function curve intersects the x-axis. This is the measure of how much pressure is in the periphery to push blood back to right atrium in which the venous return will be zero. For instance, if RAP = +7 and pressure in periphery is also +7 to push blood back to RA, the venous return will be 0 because there is too much RAP.

Question 73

Steps in pacemaker (SA node) action potential

Answer 73

Phase 0: Upstroke; caused by increase inward Ca2+ current (I_Ca2+)

Phase 3: Repolarization; caused by increase in outward K+ current

Phase 4: Slow depolarization; accounts for automaticity of SA node; due to inward Na+ current (I_f). This current is turned on by repolarization of membrane potential of preceding action potential.

Phase 1 +2: not present in SA node action potential.