The cardiac pressure-volume cycle & ions and action potentials Flashcards
What is the name of the circle of arteries on the underside of the base of the brain AND what is its physiological function?
- The Circle of Willis
- It provides redundancies in arterial blood supply to the brain, vouchsafing consistent perfusion to all regions (and protection from ischaemia) in cases where one major artery supplying the brain was temporarily blocked or narrowed
Name TWO plasma secretions of the kidney that are central to the RAAS.
- Angiotensin converting enzyme
- Renin
Name THREE aspects of the circulation of large skeletal muscles that make it a “special circulation”.
- Can use up to 80% of cardiac output during exercise
- Arterial supply vasodilates in response to sympathetic stimulation
- Muscle pump contributes directly to venous return.
Name TWO aspects of the circulation of the brain that make it a “special circulation”.
- Auto-regulation (constancy of flow and pressure)
- Circle of Willis
Name FOUR aspects of the special circulation of the skin that make it well-suited for thermo-regulation.
- Can regulate blood perfusion by up to 100-fold
- Arterio-venous anastomoses allow for thermal exchange without the resistance of a capillary bed
- Sweat glands turn fluid ultrafiltrate from plasma into a rapid heat loss system.
Name THREE reactions of the special circulation of the skin that make its inflammatory response to trauma unique.
- Red reaction
- Flare
- Wheal.
Draw a ventricular action potential. Include axes, units, and approximate values.
List the heart valves, and for each one state the type of valve it is, and the regions it separates.
- Tricuspid Valve: AV valve, Right Atrium from Right Ventricle
- Pulmonic Valve: semilunar, Right ventricle from Pulmonary Arteries
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- Mitral (bicuspid) Valve: AV valve, Left Atrium from left Ventricle
- Aortic Valve: semilunar, left ventricle from aorta
Name the valve sounds and when they can appear in the cardiac cycle.
•S1: First heart sound (lub)
–When Mitral & Tricuspid Close
–during systole
–
•S2: Second heart sound (dub)
–When Aortic & pulmonic valves Close
–during diastole
–Diastole is longer than systole
Align an ECG in time directly underneath a ventricular action potential
QRS complex lines up with depolarisation of ventricular AP
T wave lines up with repolarisation of ventricular AP
Draw a nodal action potential. Include axes, units, and approximate values.
Nodal AP is in red
Align an ECG in time directly underneath a nodal action potential
P wave lines up with depolarisation of SA Node
List the phases of the ventricular action potential and state for each what channel is responsible for conducting that current.
0 Depolarisation: Na+ gates open in response to wave of excitation from pacemaker
1 Transient Outward Current: tiny amount of K+ leaves cell, this leads to a small amount of repolarisation
2 Plateau phase: Inflow of Ca2+ just about balances outflow of K+
3 Rapid repolarisation phase: Membrane potential falls as K+ leaves cell
4 Back to resting potential
List the phases of the cardiac nodal action potential and state for each what channel is responsible for conducting that current.
0 Depolarisation: Ca2+ channels open in response to automaticity
3 Rapid repolarisation phase: Membrane potential falls as K+ leaves cell
4 Pacemaker potential
Name 3 types of potassium channel that are important in cardiac rhythmic activity AND for each name its primary function.
- Delayed rectifier: repolarises the action potential
- Inward rectifier: clamps voltage near resting potential (in non-nodal myocytes). Also contributes to late repolarisation of AP
- Ach-activated K+ channel: slows down heart rate in response to vagal stimulation by decreasing the pacemaker potential’s slope upward.
- Could also mention:
- K(ATP) channels
What is tetany, and why does it not occur in cardiac muscle?
Tetany is a state of maximal contraction in a skeletal muscle cell in which a high stimulation frequency is too rapid for recovery and relaxation, so the contractions effectively become continuous and stronger than possible with a single twitch. It occurs because calcium builds up in the cytosol due to the lack of time to pump it back into the SR. This does not happen in cardiac muscle because an extended contraction without relaxation would effectively stop the beating of that cell and prevent relaxation/diastole.
What is the pacemaker potential and how does it come about?
The pacemaker potential is the upward drift in voltage that occurs between action potentials, which occurs in myocytes of SA node, AV node, and conduction system only. Also called: diastolic potential. It occurs instead of the resting potential (because these cells lack the inward rectifier K+ channels that would clamp the cell to the resting potential). The slope of PP determines the automatic rate of firing of the cell.
Draw a graph of the pressure volume loop of a cardiac cycle of the left ventricle (ie graph pressure vs volume). Label the axes (including units and approximate values), and label each phase of the cardiac cycle. Draw arrows where each set of valves open and close.
4-1: Filling
1-2: isovol contr
2-3: ejection
3-4: isovol relax
AV valves
Open at 4
Close at 1
Semilunar valves
Open at 2
Close at 3
Under what circumstances would you expect a systolic murmur? Or a diastolic murmur?
Systolic murmur: semilunar insufficiency/stenosis, AV valve regurgitation
Diastolic murmur: semilunar regurgitation, AV valve insufficiency/stenosis
What is the molecular basis of cardiac muscle contraction?
This is the sliding filament model (explained in detail in module 102) where thick filaments pull on thin filaments from two opposing z-lines, thus shortening the sarcomere. The thick filaments are mostly made up of myosin (a “motor protein”) and the thin filaments are structurally based on actin. The thin filaments also have on them the regulatory proteins tropomyosin and troponin, which are essential in converting the calcium signal in the cytoplasm into contraction.
In the Wiggers plot above:
Identify systole and diastole
Identify the four phases of the cardiac pressure cycle.
Identify when each pair of valves opens and closes.
Draw an ECG that aligns in time with the pressure plots.
IVC is defined as the time between when the mitral valve closes and the aortic valve opens. During this time the “contraction” of the left ventricle generates increasing pressure but without changing volume (ie there is force generation without extensive contraction in size because the blood fluid is not compressible, and the aortic valve has not yet opened). You can tell when the mitral valve is closed because the atrial pressure (red at bottom) and the ventricular pressure (black) are identical. When the mitral valve closes, the ventricular pressure become independent of the atrial pressure. Likewise, you can tell when the aortic valve is open because the aortic pressure (red, upper) and the ventricular pressure (black) become identical. When the aortic valve closes (as the ventricle starts to relax), the aortic pressure and the ventricular pressure split apart. At the end of IVR the mitral valve opens and the ventricle and the atrium have identical pressures.
Given the normal ventricular pressure-volume (grey), explain what type of valve dysfunction is shown in red (at X) and explain the mechanism for why the valve changes result in the pressure-volume changes?
This aortic valve stenosis.
There is high afterload because the valve creates resistance during systole that obstructs blood from leaving. No change in preload
The high afterload manifests as very high pressure during ejection, and high volumes during isovolumic relaxation (because the stenotic valve interferes with ejection
Given the normal ventricular pressure-volume (grey), explain what type of valve dysfunction is shown in red (at X) and explain the mechanism for why the valve changes result in the pressure-volume changes?
This is mitral stenosis.
The stenotic mitral valve interferes with filling (and thus reduces preload), so volume during isovolumic contraction is low..
Because preload is so much lower, afterload is lowered (because the ventricle generates so much less pressure) due to reduced Starling forces.
The lower afterload manifests as a low isovlumic relaxation. It also results in the lack of a corner because the previous systole did not pump so much blood, so there is less systemic back pressure on the aortic valve
Given the normal ventricular pressure-volume (grey), explain what type of valve dysfunction is shown in red (at X) and explain why its pressure-volume relationship is round rather than square-ish?
This is aortic regurgitation.
The preload is much higher than normal (ie the right edge of the red curve is shifted leftward).
Preload is higher in all regurgitating valve anomalies. In aortic regurgitation, during diastole the aortic valve allows fluid to back-flow into the left ventricle, added to the fluid coming from the left atrium.
Both regurgitating valve pathologies have rounded PV curves (ie they do not have corners, or IVC and IVR phases). The straight lines of IVC and IVR occur when both valves are closed and the left ventricle is a sealed unit. In regurgitating valves, there is never a time when both valves are completely closed – one valve is always leaking
Given the normal ventricular pressure-volume (grey), explain what type of valve dysfunction is shown in red (at X) and explain the mechanism for these changes in terms of preload and afterload.
This is mitral valve regurgitation.
This red graph shows low afterload (i.e. top is shifted down, and left side is shifted further left).
There is low afterload because during systole the blood can be ejected into the left atrium (through the regurgitating mitral valve), as well as into the aorta. This lowers the resistance against pumping.
There is much higher preload (right edge is shifted rightward). This happens because the excess blood in the left atrium (from the previous beat) is under high pressure, and it adds to the filling of the left ventricle, creating volume overload
How is the rhythm of the heartbeat initiated and maintained?
Specialised nodal cells (in SA and AV node) have autorhythmicity. Instead of remaining at a resting potential between APs, they undergo a pacemaker potential, which is a slow depolarisation toward threshold due to net inward current of the funny current (If: Na+ inward AND K+ outward) . From the SA node signals are sent (via four branches) throughout the atria, and to the AV node, where the signal is delayed ~150 ms. The signal is then conducted via specialised conducting tissue in the His-Purkinje system, inferiorly toward the apex of the heart, and then superiorly and laterally back toward the base.
How do the atria beat before the ventricles?
The entire heart is driven by the first cell to depolarize after the previous beat. The fastest cells to recover are (in a healthy heart) in the SA node. The impulse is then sent to the AV node via the atrial bundles, and there is a lengthy delay of the signal while it traverses the AV node. The His-Purkinje system then allows for relatively synchronous activity of the ventricles. Since contraction follows electrical activity, the atria contract first, and the electrical delay in the AV node leads to a contraction delay for the ventricle.
What is the funny current, what effect does it have on nodal cells, and what ions mediate it?
The funny current is an inward ionic current found in nodal (and His-Purkinje) cells that has the unusual property that it is greatest (ie has the highest conductance) when the transmembrane voltage (Vm) is most negative.
This means that it drives the cell to depolarise when it is in diastole – this effect is called the Pacemaker Potential.
The ions conducted by the funny current are Na+ inward AND K+ outward, but the net effect is an inward current because the Na+ in is greater than the K+ out when Vm is close to EK. The reversal potential of the funny current is typically ~ -10 mV
What is the dicrotic notch, and what does it represent?
The dicrotic notch is a sudden dip in pressure that can be seen in a Wiggers plot (in the graph of aortic pressure versus time) at the moment that ejection (during systole) ends. It represents the moment when LV pressure diminishes below aortic back pressure, leading to temporary back flow and closure of the aortic valve.
Draw a graph showing left ventricular pressure vs. time. Include axes, units and approximate values. On that graph, draw where valve activity can be heard, and where the Isovolumetric relaxation occurs. Finally, on the same graph, draw a line showing aortic pressure vs. time
What is the difference between the refractory period and the after-hyperpolarisation?
- The after-hyperpolarisation = a description of the membrane voltage
- The refractory period = a description of the cell’s functional state, i.e. whether the cell is ready to fire again.
- Usually the refractory period (a functional state) corresponds to the after-hyperpolarisation (a set of voltages), but technically these are two different issues.
What channels are missing from the nodal action potential that make it so different in timing and shape from a ventricular action potential?
Inward rectifier potassium channels.
Why does amlodipine overdose sometimes cause very high heart rates? Why doesn’t it does slow the heart down?
Amlodipine is a dihyropyridine Ca2+ blocker that is targeted more to the calcium channels of the vessels than to the channels of the heart. Because it does not target cardiac calcium channels, it does not substantially slow down the heart rate. The main effect of amlodipine is vasodilatation, and in cases of overdose the vasodilatation leads to severely low peripheral resistance and low blood pressure. This low BP is detected by baroreceptors, which homeostatically increase heart rate to attempt to correct the low blood pressure.
Quinidine is antiarrhythmic drug (use prophylactically) whose main action is to block Na+ channels. In most patients it results in an increase in the rate of sinus rhythm. Why doesn’t it slow down the heart rate?
The main effect of Na+ channel blockers on the heart is to slow down conduction velocity between different regions of the heart; this happens because the reduced Na+ influx slows down depolarisation in the His-Purkinje system.
Sinus rate, which is controlled by cells in the SA node, is highly dependent on calcium influx for depolarisation. A Na+ channel blocker would not effect the SA node activity directly.
