Cardiovascular physiology,
the pump, the circuit and its control.

The volume of blood ejected by one ventricle per minute — the product of heart rate and stroke volume. Normally about 5 L min⁻¹ in a 70 kg adult; indexed to body surface area, a cardiac index of 2.5–4.0 L min⁻¹ m⁻².

Start with the equation, then take each term. Heart rate is set by the balance of vagal and sympathetic tone at the sinoatrial node, and its effect is not monotonic: beyond about 150 min⁻¹ diastolic filling time is so curtailed that stroke volume falls faster than rate rises, so output falls. Stroke volume depends on preload, afterload and contractility.

The mark that is most often dropped is on the determinants of preload. Do not stop at venous return: add intrathoracic pressure, ventricular compliance, the atrial contribution, heart rhythm and the competence of the atrioventricular valve.

Cardiovascular physiology →

No, and the distinction is worth marks. Preload is the load on the myocyte at the end of diastole — strictly the end-diastolic sarcomere length, and in practice the end-diastolic volume, or the wall stress that volume produces.

Venous return is only one of its determinants. For a given venous return, preload also depends on ventricular compliance (a stiff ventricle reaches a higher pressure at a smaller volume), on the atrial kick, on heart rhythm and rate, and on the atrioventricular valve. That is why a raised central venous pressure does not reliably mean a well-filled ventricle.

Note also that filling pressure is a surrogate for filling volume, and the two diverge exactly where it matters most — the stiff, the hypertrophied and the tamponaded ventricle.

Cardiovascular physiology →

The force of contraction of cardiac muscle is proportional to its initial fibre length, within physiological limits.

Three mechanisms, and the second and third are what separate a good answer:

• Actin–myosin overlap. Stretching toward the optimal sarcomere length of about 2.2 µm increases the number of available cross-bridges.
• Length-dependent calcium sensitivity. Stretch increases the affinity of troponin C for calcium, so the same calcium transient produces more force. This is the dominant mechanism in cardiac muscle, and it is why the cardiac length–tension relationship is far steeper than the skeletal one.
• Titin transmits the stretch and contributes to restoring force, and reducing lattice spacing brings the filaments closer together.

The functional point: it lets the ventricle match its output to its filling beat by beat, and it is what keeps the outputs of the two ventricles equal without any nervous control.

Cardiovascular physiology →

The wall stress the ventricle must develop to eject blood — the load opposing contraction, into the systemic circulation. It is not the volume in the ventricle, and an answer that says it is scores nothing.

Determinants, best built from two equations:

• Laplace’s law, σ = P·r / 2h. Wall stress rises with intraventricular pressure and with radius, and falls with wall thickness — which is why a dilated ventricle is at a mechanical disadvantage and why hypertrophy is initially compensatory.
• Hagen–Poiseuille, R = 8ηl / πr⁴. Systemic vascular resistance is dominated by arteriolar radius; viscosity contributes, so polycythaemia raises afterload; length is anatomically fixed.

Add aortic valve area and aortic input impedance — arterial compliance and reflected pressure waves matter, which is why afterload is not simply “systemic vascular resistance”.

Cardiovascular physiology →

Because it is load-dependent. Ejection fraction is stroke volume divided by end-diastolic volume, and both change with preload and afterload without any change in the contractile state. Reduce afterload and ejection fraction rises; give a fluid bolus and it barely moves although stroke volume has risen.

The clearest clinical example is mitral regurgitation: the ventricle unloads into a low-pressure atrium, so an ejection fraction of 60% already represents impaired contractility, and a fall below 60% is an indication for surgery.

The load-independent index is end-systolic elastance, the slope of the end-systolic pressure–volume relation, because it describes the line the ventricle must end on whatever load it faces. Others include dP/dt_max (preload-dependent) and the preload-recruitable stroke work relation.

Cardiovascular physiology →

Because they move different curves. Plot cardiac output and venous return against the variable they share — right atrial pressure — and the circulation settles where they cross.

A fluid bolus raises mean systemic filling pressure, shifting the vascular function curve to the right. The new intersection lies at a higher output and a higher right atrial pressure.

An inotrope lifts the cardiac function curve. The heart now pumps a given volume at a lower filling pressure, so the new intersection lies at a higher output and a lower right atrial pressure.

The clinical corollary is worth stating: right atrial pressure is not an independent variable that anyone sets — it is the price the heart charges for accepting blood. A rising central venous pressure with a falling cardiac output points at the heart, not at the volume state.

Cardiovascular physiology →

Venous return = (mean systemic filling pressure − right atrial pressure) / venous resistance. Everything below acts on one of those three terms, and each needs a clause saying how — naming the factor alone does not score.

• Blood volume and venous tone raise mean systemic filling pressure. Sympathetically mediated venoconstriction recruits the unstressed volume of the splanchnic and cutaneous beds into the stressed compartment.
• The skeletal muscle pump with competent venous valves intermittently raises pressure in the deep veins and imposes one-way flow.
• The respiratory (thoracic) pump. Inspiration lowers intrathoracic and therefore right atrial pressure while raising intra-abdominal pressure, so the gradient widens.
• The cardiac pump. Descent of the atrioventricular ring in systole enlarges the atrium and lowers its pressure — the x descent — and rapid ventricular relaxation contributes diastolic suction.
• Gravity below the level of the heart, and a negative right atrial pressure, both widen the gradient — though the second is self-limiting because the great veins collapse as they enter the thorax.

Cardiovascular physiology →

Give it as a gradient, not as an assertion. Positive intrathoracic pressure is transmitted to the right atrium, so right atrial pressure rises; the gradient between mean systemic filling pressure and right atrial pressure narrows, venous return falls, and right ventricular preload falls with it.

Two further mechanisms complete the answer. Lung inflation raises pulmonary vascular resistance by compressing alveolar vessels — worst at volumes above functional residual capacity — so right ventricular afterload rises. And ventricular interdependence means that a distended right ventricle shifts the septum leftwards and impairs left ventricular filling.

The left ventricle is affected differently: raised intrathoracic pressure reduces its transmural pressure and therefore its afterload, which is why continuous positive airway pressure can help in acute left ventricular failure.

Cardiovascular physiology →

It is a pressure comparison, not an anatomical difference. Coronary perfusion pressure is aortic root pressure minus the pressure in the tissue the vessel supplies.

Left ventricular pressure in systole equals or exceeds aortic pressure, so intramyocardial vessels are compressed, flow falls to near zero and briefly reverses; about 80% of left coronary flow occurs in diastole. Right ventricular systolic pressure is only about 25 mmHg against the same aortic driving pressure, so the right coronary artery is perfused in both phases and is merely modulated.

The subendocardium is the most vulnerable layer because it experiences the highest compressive pressure. Two consequences follow: tachycardia shortens diastole disproportionately and cuts supply, and a raised left ventricular end-diastolic pressure reduces the subendocardial gradient even in diastole.

Cardiovascular physiology →

Take supply and demand in turn — the reasoning, not a list.

Demand rises. Concentric hypertrophy increases muscle mass. By Laplace’s law the high intraventricular systolic pressure raises wall stress despite the thicker wall. Ejection takes longer, so the tension–time index is greater.

Supply falls. Coronary perfusion pressure is aortic root pressure minus intraventricular pressure: the stenosis lowers the first while hypertrophy raises the second, and the subendocardium suffers most. Capillary density does not keep pace with the increase in muscle mass.

The compensations make it worse. A fall in cardiac output provokes tachycardia, which shortens diastole — the only period in which the left ventricle is perfused. Hence the haemodynamic goals: slow, sinus rhythm, adequately filled, and systemic vascular resistance maintained.

Cardiovascular physiology →

The stimulus first. On standing, 500–800 mL pools in the dependent veins. Venous return falls, so stroke volume and cardiac output fall and mean arterial pressure transiently falls. In the supine position pressure is roughly uniform at 95–100 mmHg; erect, it falls above and rises below the heart by about 0.77 mmHg per cmH₂O of blood column.

The sensor. Carotid sinus and aortic arch stretch receptors are unloaded, so their firing falls — the direction candidates most often get wrong.

The afferent and integrator. Reduced traffic in the glossopharyngeal (carotid sinus) and vagus (aortic arch) nerves reaches the nucleus tractus solitarius, which withdraws its inhibition of the sympathetic outflow.

The efferent response, and it must be linked back to the equation: increased heart rate and contractility raise cardiac output; arteriolar constriction raises systemic vascular resistance; venoconstriction raises mean systemic filling pressure and restores venous return; and noradrenaline is released from the adrenal medulla. Since MAP = CO × SVR + RAP, all three limbs defend the pressure.

Cardiovascular physiology →

Forced expiration against a closed glottis at about 40 mmHg for 10 seconds. Each phase is a mechanical effect followed by a reflex correction.

• I — onset of strain. Raised intrathoracic pressure is transmitted to the aorta and squeezes the pulmonary vessels, so arterial pressure rises briefly with a reflex slowing of the heart.
• II — sustained strain. Venous return is obstructed, so stroke volume and arterial pressure fall; unloaded baroreceptors produce tachycardia and vasoconstriction that partly restore the pressure.
• III — release. Intrathoracic pressure falls and the pulmonary bed re-expands, so pressure dips further for one or two beats.
• IV — venous return is restored into a still-vasoconstricted circulation, so pressure overshoots above baseline and the loaded baroreceptors produce a reflex bradycardia.

Phase IV is the therapeutic phase: that vagal surge is what may break a supraventricular tachycardia by increasing atrioventricular nodal refractoriness. Two abnormal patterns are worth naming — the square wave response of a raised filling pressure, as in left ventricular failure, where there is no phase II fall and no phase IV overshoot; and autonomic failure, where the phase II reflex recovery and the phase IV overshoot are both absent while the mechanical phases persist.

Cardiovascular physiology →

Three positive waves and two descents, with a normal mean of 3–5 mmHg. Label them against the ECG, not against the clock.

• a — atrial contraction, following the P wave.
• c — the closed tricuspid valve bulging into the atrium during isovolumetric contraction, following the QRS.
• x descent — atrial relaxation and downward displacement of the atrioventricular ring during ejection.
• v — atrial filling against a closed tricuspid valve, peaking near the end of the T wave.
• y descent — the tricuspid valve opens and the atrium empties.

Abnormalities follow from the mechanism: no a wave in atrial fibrillation; cannon a waves when the atrium contracts against a shut valve in complete heart block or junctional rhythm; a large fused cv wave with a lost x descent in tricuspid regurgitation; a steep, deep y descent in constriction against a blunted y in tamponade.

Cardiovascular physiology →

It attacks both sides of the oxygen balance at once, which is why it is the single most important variable to control.

Demand rises roughly in proportion to rate: more contractions per minute, each with its own tension–time cost, and increased calcium cycling.

Supply falls. Increasing heart rate shortens diastole far more than systole, and diastole is when the left ventricle is perfused. At 60 min⁻¹ diastole is roughly two-thirds of the cycle; at 150 min⁻¹ it is closer to a third of a much shorter cycle.

There is a limited counter-argument worth acknowledging: metabolic autoregulation vasodilates the coronary bed as work rises, and in a healthy young heart coronary flow does increase with rate. It is the stenosed vessel, already maximally dilated distally with no coronary reserve left, that cannot do this.

Cardiovascular physiology →

Organise it by timescale — that structure alone earns marks.

Seconds. Loss of volume lowers mean systemic filling pressure, so venous return, stroke volume and arterial pressure fall. Unloaded arterial baroreceptors and cardiopulmonary low-pressure receptors withdraw inhibition of the sympathetic outflow: tachycardia, increased contractility, arteriolar constriction and venoconstriction, with flow redistributed to brain and heart, whose beds autoregulate.

Minutes to hours. Reduced capillary hydrostatic pressure shifts interstitial fluid into the circulation — transcapillary refill, several hundred millilitres per hour. Renin–angiotensin–aldosterone is activated, antidiuretic hormone is released from the posterior pituitary at pressures low enough to be a vasoconstrictor as well as an antidiuretic, and cortisol and catecholamines raise plasma glucose and so plasma osmolality, drawing in more water. Thirst appears.

Days to weeks. Albumin is resynthesised by the liver over several days; erythropoietin restores red cell mass over weeks.

Add the decompensation: with severe or continuing loss, sympathetic drive fails, paradoxical vasodilatation and bradycardia appear, and the fall becomes irreversible.

Cardiovascular physiology →

Systolic function is only half of the ventricle’s job. This is diastolic dysfunction: reduced compliance, so the end-diastolic pressure–volume relation is steep and a high filling pressure is required to achieve even a modest end-diastolic volume. That filling pressure is transmitted back to the left atrium and pulmonary veins, and the result is pulmonary congestion in a ventricle that empties perfectly well.

Causes: hypertensive or hypertrophic remodelling with interstitial fibrosis, ischaemia (relaxation is an active, ATP-dependent process, so it fails early), ageing, and external constraint such as constriction or tamponade.

Three practical consequences. The atrial kick contributes far more than its usual 20%, so loss of sinus rhythm is poorly tolerated. Filling is time-dependent, so tachycardia is harmful. And the ventricle sits on a steep part of its own curve, so it is intolerant of both under- and over-filling — a narrow therapeutic window in either direction.

Cardiovascular physiology →

Severe preload loss limits stroke volume; extreme tachycardia also shortens filling time.

Physiology SAQ Paper 1 · Q1 →

Stroke volume falls, so systolic pressure falls more than diastolic pressure maintained by vasoconstriction.

Physiology SAQ Paper 1 · Q1 →