Physiology of the Heart

Question 1

What are the four basic phases of the cardiac cycle?

Answer 1

(1) period of filling
(2) period of isovolumetric contraction
(3) period of ejection
(4) period of isovolumetric relaxation

Question 2

Describe the ventricular events during the cardiac cycle.

Answer 2

The cardiac cycle is the events that occur in the heart from the beginning of one heartbeat to the next. It is divided into systole and diastole. During diastole there is first isovolumetric relaxation and then a filling phase. Isovolumetric relaxation - ventricles begin to relax and the intraventricular pressure decreases rapidly –> aortic and pulmonary valves are forced closed –> but at this stage the AV valves remain closed also so there is change in pressure without change in volume until the pressure decreases sufficiently for the AV valves to open. Filling phase: as the AV valves open blood is able to flow from the atria in to the ventricles; just before systole the atria contract and there is an additional thrust of blood into the ventricles. This is followed by systole - first there is isovolumetric contraction, followed by an ejection phase. Isovolumetric contraction: the ventricles begin to contract, and the pressure rises in the ventricles –> forces the AV valves to close. However, there pressure is not yet sufficient to force the aortic and pulmonary valves open. Ejection phase: the pressure continues to rise and the semilunar valves open –> blood is pumped from the heart.

Question 3

What are the pressures and volumes in the ventricles through the cardiac cycle?

Answer 3

At the beginning of diastole the aortic valve closes - at this stage the pressure is approx. 100mmHg and the volume is about 50mL (end systolic volume). Pressure decreases rapidly during isovolumetric relaxation while volume remains the same. The mitral as the period of ventricular filling begins - at the beginning of this stage the volume is still 50mL and the pressure has dropped to 2-3mmHg. The volume increases to an end diastolic volume of approx. 120mL. The ventricles begin to contract and the mitral valve closes –> during isovolumetric contraction pressure rises abruptly to about 80mmHg and this causes the aortic valve to open. Pressure increases further as the ventricle continue to contract and blood is forced from the heart into the aorta. About 70mL is ejected - this is the stroke volume. The cycle then repeats.

Question 4

What is happening in the atria during the cardiac cycle?

Answer 4

There are several pressure waves that are seen in the atria through the cardiac cycle. At the beginning of systole the ventricles begin to contract and there is closure of the AV valves –> this causes a slight bulging of the valves into the atria resulting in the ‘c wave’. During systole blood accumulates in the atria and the pressure and volume increases –> creates the ‘v wave’. Then the ventricles relax and the AV valves open in diastole –> the blood flows from the atria into the ventricles and pressure initially decreases. At the end of diastole, the atria contract and this causes the ‘a wave’.

Question 5

What are the events in the aorta during the cardia cycle?

Answer 5

During systole, the left ventricle contracts and as ventricular pressure reaches approx. 80mmHg the aortic valve is forced open –> blood is forced into the aorta and aortic pressures rises. As systole comes to an end, the ventricles relax and the ventricular pressures fall below the aortic pressure –> the aortic valve closes and aortic pressures also fall as they are no longer receiving blood from the ventricles - however there is a ‘dicrotic notch’ (slight upstroke) in the aortic pressure - it is thought to be caused by a backflow of blood in the aorta.

Question 6

What do the heart sounds represent?

Answer 6

First heart sound = ‘lub’ caused by the closure of the mitral and tricuspid valves.
Second heart sound = ‘dub’ caused by closure of the aortic and pulmonary valves.

Question 7

What are the two key phases of the cardiac cycle?

Answer 7

Systole and diastole

Question 8

What is preload?

Answer 8

The degree of tension placed on the heart when it begins to contract - it is the end-diastolic pressure.

Question 9

What is afterload?

Answer 9

The load against which the heart must pump - it is the pressure in the aorta.

Question 10

Explain the Frank-Starling Mechanism.

Answer 10

The heart matches its output with venous return, and the ability to do this is explained by the Frank-Starling Mechanism. When extra blood flows in to the ventricles the cardiac muscle is stretched to a greater length –> this stretching brings the actin and myosin filaments into a more optimal degree of overlap –> able to generate more force –> increases contractility –> increases stroke volume.

Question 11

Describe the cardiac conduction system.

Answer 11

The cardiac action potential originates at the sinoatrial node, which is located at the junction of the SVC with the right atrium. The cells of the SA node depolarise spontaneously between 60-100 times/minute. This action potential spreads through the right and left atria and then arrives at the AV node. It cannot pass directly from the atria into the ventricles due ot the fibrous atrioventricular ring. Instead it passes through the AV node –> bundle of His –> right and left bundle branches –> Purkinje fibres –> ventricular myocardium, depolarising ventricular myocytes from the endocardium to the epicardium (inside to outside).

Question 12

What ionic events are occurring in a pacemaker cell through the action potential?

Answer 12

Phase 0 = upstroke; caused by a slow influx of calcium ions (there are no fast Na+ channels in cardiac pacemaker cells).
Phase 1 = rapid repolarisation; caused by an inactivation of the Ca current and a transient K+ efflux.
Phase 2 = plateau; this is poorly sustained in the pacemaker cells.
Phase 3 = repolarisation; this is caused by K+ efflux.
Phase 4 = diastolic potential; in pacemaker cells this potential is unstable - there is a low decay of the K+ efflux with an influx of Ca ions and the funny current, which leads to another depolarisation when the potential reaches threshold.

Question 13

What ionic events are occurring in the ventricular myocyte during an action potential?

Answer 13

Phase 0 = upstroke; caused by a rapid sodium influx with a slower calcium influx.
Phase 1 = rapid repolarisation; caused by inactivation of the Na and Ca currents with a transient K+ efflux.
Phase 2 = plateau; this is sustained in the ventricular myocyte with entry of Ca ions via L-type channels.
Phase 3 = repolarisation; caused by K+ efflux.
Phase 4 = the cell returns until approx. -80mV until it is stimulated again.

Question 14

What are the structural and functional properties of cardiac muscle?

Answer 14

Cardiac muscle is striated, and contains actin and myosin filaments in the same way as skeletal muscle. Unlike skeletal muscle, it is arranged in a lattice and fibres are separated by intercalated discs containing gap junctions, which allows rapid diffusion of ions so that the muscle acts as a syncytium.

Question 15

Outline the differences between skeletal and cardiac muscle.

Answer 15

Skeletal = arranged in fibres; Cardiac = arranged as a lattice.
Skeletal = sarcomeres separated by Z bands; Cardiac = separated by intercalated discs and acts as a syncytium.
Skeletal = activated by neurons releasing ACh at the NMJ; Cardiac = activated by pacemaker cells. 
Skeletal = T tubules for a triad at the A-I junction; Cardiac = T tubules form a diad at the Z disk. 
Skeletal = action potential is a spike; Cardiac = action potential is a spike followed by a plateau. 
Skeletal = depolarisation causes L-type Ca channels to mechanically activate the release of Ca from the SR; Cardiac = depolarisation causes L-type Ca channels to let Ca ions into the cell, and this causes Ca-activated Ca release from the SR.

Question 16

Explain the events of contraction in a cardiac myocyte.

Answer 16

Cardiac pacemaker cell initiates an action potential –> it is passed along the cardiac conducting system to the ventricular myocyte –> passes along T-tubules –> causes depolarisation of the ventricular myocyte –> L-type calcium channels open –> calcium flows into the sarcoplasm –> leads to calcium-induced calcium release from the SR –> calcium binds to troponin C, inducing a conformational change in the troponin complex –> allows actin and myosin to interact –> cross-bridge cycling occurs –> actin and myosin are pulled across each other and the heart contracts. After the cell repolarises, calcium is (1) sequestered into the SR (80%) or (2) extruded from the cell (20%) –> this decreases the calcium concentration –> calcium dissociates from troponin C –> cross-bridge cycling cannot occur –> heart relaxes.

Question 17

Explain the process of cross-bridge cycling.

Answer 17

(1) ATP binds to the myosin head, causing the dissociation of actin from myosin.
(2) ATP is broken down into ADP and phosphate –> the myosin head becomes ‘cocked’.
(3) Weak cross bridges form.
(4) The phosphate is released –> strong cross-bridges form.
(5) Power stroke occurs.
(6) ADP is released.

Question 18

What factors determine cardiac output?

Answer 18

CO = stroke volume x heart rate

Question 19

What factors determine stroke volume?

Answer 19

(1) preload: increased preload –> increased stroke volume
(2) afterload: increased afterload –> decreased stroke volume.
(3) contractility - determined by preload, afterload, and the autonomic nervous system. Increased contractility –> increased stroke volume.

Question 20

Explain the process of haemostasis.

Answer 20

When there is vessel injury, haemostasis is the formation of a blood clot that stops the haemorrhage.
Step 1: arteriolar vasoconstriction. Immediately after vessel injury, blood flow to the area is reduced by arteriolar vasoconstriction.
Step 2: Primary haemostasis (formation of a platelet plug). Platelets encounter the constituents of the subendothelial connective tissue including Von Willebrand Factor –> the vWF acts as a bridge between the platelet’s glycoprotein Ib and collagen in the vessel wall –> platelets are able to adhere to the vessel wall. Then, platelets are activated: this process includes a change in shape, alteration to glycoprotein IIb/IIIa to increase affinity for fibrinogen, and movement of phospholipids to the surface of the platelets where they are able to serve as sites for assembly of clotting factors. There is a cycle of activation –> release of granules by the platelets –> further recruitment and activation –> so that a platelet plug is formed.
Step 3: secondary haemostasis (the coagulation cascade). This is a series of reactions that leads to the deposition of a fibrin clot.
Step 4: the fibrinolytic cascade. Once initiated, coagulation must be restricted to the site of vessel injury via the fibrinolytic cascade. It is generated by the conversion of plasminogen –> plasmin, mainly by tissue plasminogen activator produced by the endothelium.

Question 21

Outline the extrinsic pathway of coagulation.

Answer 21

The extrinsic pathway begins with trauma to the vessel wall, which exposes tissue factor –> tissue factor complexes with factor VII –> activates factor X –> activated X combines with factor V –> this forms prothrombin activator –> causes prothrombin to be converted into thrombin –> results in cross-linking of fibrin

Question 22

Outline the intrinsic pathway of coagulation.

Answer 22

The intrinsic pathway begins with trauma to the blood or exposure of the blood to collagen in the vessel wall –> this causes activation of factor XII –> activates factor XI –> activates factor IX –> acts with factor VIII to activate factor X –> combines with factor V to form prothrombin activator –> causes prothrombin to be converted into thrombin –> cross-linking of fibrin

Question 23

What effect does the SNS have on the heart?

Answer 23

Positive inotropic effect = increased force of contraction
Positive chronotropic effect = increased heart rate
Increased automaticity = tendency to generate ectopic beats
Reduced cardiac efficiency = oxygen consumption increase is > than the increase in cardiac work performed
Cardiac hypertrophy

Question 24

What effect does the parasympathetic NS have on the heart?

Answer 24

Negative chronotropic effect = reduced heart rate
Reduced automaticity
Inhibition of conduction through the AV node
BUT has very little effect on contractility because the M2 acetylcholine receptors are only sparsely distributed in the ventricles.

Question 25

What are the main factors that control BP?

Answer 25

BP = Cardiac output x peripheral vascular resistance
In the short term, it is predominantly controlled by the baroreflex.
In the long term, it is controlled predominantly by the RAAS.

Question 26

Explain the baroreflex.

Answer 26

The baroreflex is a negative feedback loop.
Baroreceptors are located in the carotid sinus and aortic arch –> they detect stretch and increased stretch = increased frequency of action potentials –> these are transmitted by the glossopharyngeal and vagus nerves to the medulla (nucleus tractus solitarius) –> from the NTS, neurons project to the RVLM and the DMNV –> RVLM is inhibited by the NTS, and this causes a decrease in sympathetic nervous system activity; The DMNV is excited and this causes an increase in parasympathetic nervous system activity.