The physiology under load
Applied cardiovascular physiology
What you should already have
About 60 minutes
Plus the time it takes to redraw this lesson’s figures from memory, which is the fastest way to find out what you have not understood.
Where this shows up
Everything in the first three lessons was the normal system. This one perturbs it — standing up, straining, exercising, bleeding, growing old, and being anaesthetised — and each perturbation is read the same way: name the curve that moved, and the direction.
Learning outcomes
By the end of this lesson you should be able to:
- Read posture, the Valsalva manoeuvre, exercise and haemorrhage as changes to a named curve, and predict the reflex response and its time course.
- Describe the cardiovascular changes of ageing and of obesity, separating what ageing does from what its comorbidities do.
- Predict the cardiovascular effect of the induction agents and the vasoactive drugs from their action on preload, afterload, contractility and rate.
- State the haemodynamic goals for each valve lesion, and derive them rather than recalling them.
- Draw the relations this topic is built on with labelled and scaled axes, and distinguish the four that are commonly substituted for one another.
Standing up
| Stage | Stimulus | Response | Timescale |
|---|---|---|---|
| Immediate, mechanical | 500–800 mL pools below the heart | Venous return, stroke volume and cardiac output fall; MAP falls transiently | Within one or two beats |
| Arterial baroreflex | Carotid sinus and aortic arch unloaded; firing falls; sympathetic outflow disinhibited | Heart rate and contractility rise, arterioles and veins constrict, noradrenaline released from the adrenal medulla | Seconds |
| Cardiopulmonary receptors | Low-pressure atrial and ventricular receptors also unloaded | Reinforces the sympathetic response; reduces atrial natriuretic peptide release | Seconds |
| Muscle and respiratory pumps | Postural muscle activity and respiration | Restore venous return mechanically | Seconds to minutes |
| Humoral | Renin–angiotensin–aldosterone and antidiuretic hormone | Fluid retention and vasoconstriction | Minutes to hours |
Quantitatively: supine, arterial pressure is roughly uniform at 95–100 mmHg, because every vessel is near the level of the heart. Erect, gravity adds a hydrostatic column, so pressure falls above the heart and rises below it by about 0.77 mmHg for every cmH₂O of vertical distance. Mean arterial pressure at the ankle may exceed 180 mmHg while pressure at the head falls, and it is the fall at the carotid sinus that the reflex responds to.
The Valsalva manoeuvre
Exercise
| Variable | Change | Mechanism |
|---|---|---|
| Cardiac output | Rises 4–6 fold; up to 8 fold in the trained | Rate rises about 3 fold, stroke volume about 1.5 fold; rate contributes more |
| Heart rate | Rises early | First by vagal withdrawal, then by sympathetic drive. Maximum ≈ 220 − age, or 208 − 0.7 × age above 40 |
| Stroke volume | Rises, then plateaus around 40–50% of maximum effort | Increased venous return by the muscle and respiratory pumps, plus increased contractility; limited thereafter by filling time |
| Systemic vascular resistance | Falls substantially | Metabolic vasodilatation in exercising muscle overwhelms sympathetic constriction elsewhere — functional sympatholysis |
| Mean arterial pressure | Rises modestly | Output rises more than resistance falls. Systolic rises, diastolic changes little in dynamic exercise |
| Muscle blood flow | Rises more than twentyfold | Local metabolites: adenosine, K⁺, H⁺, CO₂, hyperosmolarity, nitric oxide |
| Coronary blood flow | Rises up to fivefold | Metabolic autoregulation matched to cardiac work. A common error is to attribute the local metabolic vasodilatation of exercise to the coronary bed rather than to the exercising muscle |
| Splanchnic and renal flow | Fall to as little as a quarter | Sympathetic constriction of beds that can tolerate it |
The distinction between dynamic and static exercise is worth a sentence. In dynamic exercise the metabolic vasodilatation of large muscle groups lowers systemic vascular resistance, so output rises greatly and diastolic pressure changes little: a volume load on the heart. In static (isometric) exercise, sustained contraction compresses the muscle vasculature so resistance rises and both systolic and diastolic pressure rise steeply: a pressure load, which is why isometric effort is poorly tolerated in aortic stenosis and in heart failure.
Positive pressure ventilation
Take it as a gradient, not as an assertion. Positive intrathoracic pressure is transmitted to the right atrium, so right atrial pressure rises and the gradient between mean systemic filling pressure and right atrial pressure narrows. Venous return falls, and right ventricular preload falls with it. In addition, lung inflation compresses alveolar vessels and raises pulmonary vascular resistance, increasing right ventricular afterload; and a distended right ventricle shifts the interventricular septum leftwards, impairing left ventricular filling by ventricular interdependence.
The left ventricle is affected in the opposite direction: raised intrathoracic pressure reduces its transmural pressure and therefore its afterload, which is the basis for using continuous positive airway pressure in acute left ventricular failure. PEEP adds a fall in mean arterial pressure, and therefore in renal perfusion pressure and glomerular filtration; the redistribution of the reduced output to vital organs reduces splanchnic perfusion.
Pneumoperitoneum and the head-down position
Insufflation to 12–15 mmHg has a biphasic effect on preload: at low pressures the splanchnic reservoir is squeezed and venous return transiently rises, while at higher pressures inferior vena caval compression reduces it. Systemic vascular resistance rises, from mechanical compression and from a neurohumoral response including vasopressin and the renin–angiotensin system, so afterload and mean arterial pressure rise while cardiac output usually falls. Absorbed carbon dioxide adds a sympathetic stimulus. Peritoneal stretch can produce a vagally mediated bradycardia. Trendelenburg increases venous return and central blood volume, which the healthy heart handles and the failing heart does not.
Haemorrhage and shock
| Class | Blood loss | Pulse (min⁻¹) | Systolic BP | Pulse pressure | Respiratory rate | Urine output | Mental state |
|---|---|---|---|---|---|---|---|
| Class I | < 750 mL (< 15%) | < 100 | Normal | Normal or raised | 14–20 | > 30 mL h⁻¹ | Slightly anxious |
| Class II | 750–1500 mL (15–30%) | 100–120 | Normal | Narrowed | 20–30 | 20–30 mL h⁻¹ | Mildly anxious |
| Class III | 1500–2000 mL (30–40%) | 120–140 | Reduced | Narrowed | 30–40 | 5–15 mL h⁻¹ | Anxious, confused |
| Class IV | > 2000 mL (> 40%) | > 140 | Reduced | Narrowed | > 35 | Negligible | Confused, lethargic |
Note what changes first. Pulse pressure narrows before systolic pressure falls, because the early response is vasoconstriction with a reduced stroke volume: diastolic pressure is maintained or rises while systolic falls. A normal systolic pressure is therefore compatible with a 30% loss, especially in the young.
The compensations, in order of speed:
- Seconds. Reduced mean systemic filling pressure lowers venous return and stroke volume. Arterial baroreceptors and cardiopulmonary receptors are unloaded; sympathetic outflow rises. Tachycardia, increased contractility, arteriolar constriction, venoconstriction, and redistribution to the autoregulated cerebral and coronary beds at the expense of skin, muscle, splanchnic and renal circulations.
- Minutes to hours. Reduced capillary hydrostatic pressure shifts interstitial fluid into the vasculature — transcapillary refill, several hundred millilitres per hour. Renin–angiotensin–aldosterone activation, antidiuretic hormone release, cortisol and catecholamine-driven hyperglycaemia raising plasma osmolality and drawing in further water, and thirst.
- Days to weeks. Hepatic albumin synthesis restores oncotic pressure over about four to six days; erythropoietin restores red cell mass over weeks.
Decompensation. Beyond about 40% loss, or with continuing haemorrhage, sympathetic drive fails: paradoxical vasodilatation and bradycardia appear, tissue acidosis blunts the response to catecholamines, and the fall becomes self-sustaining.
Ageing
| Change | Mechanism | Consequence |
|---|---|---|
| Arterial stiffening | Elastin fragmentation and collagen deposition | Reduced Windkessel effect: widened pulse pressure, isolated systolic hypertension, raised afterload |
| Ventricular hypertrophy | Myocyte number falls 30–35%; the survivors enlarge | Reduced compliance, so a higher filling pressure for the same volume |
| Diastolic dysfunction | Slowed active relaxation and increased passive stiffness | The atrial contribution to filling rises from about 20% to as much as 40%, so sinus rhythm becomes critical |
| Blunted β-adrenergic response | Receptor downregulation and reduced post-receptor coupling | Circulating catecholamines are higher but the response is smaller. Maximum heart rate falls; the response to a fall in pressure is less brisk |
| Sinoatrial node atrophy | By 70, about 10% of pacemaker cells remain | Conduction disease and arrhythmia become common |
| Blunted baroreflex | Reduced arterial distensibility and receptor sensitivity | Postural hypotension; exaggerated pressure swings at induction |
Obesity
| Change | Mechanism | Note |
|---|---|---|
| Blood volume and cardiac output | Rise roughly in proportion to lean and adipose mass | Stroke volume rather than heart rate is the main contributor, which is the part most often assumed the other way round |
| Systemic vascular resistance | Often falls in the young obese | Capillary beds in adipose tissue are arranged in parallel, so total resistance falls — which is why a young obese patient is frequently normotensive despite a high output |
| Later hypertension | Renin–angiotensin activation, sympathetic overactivity, and adipose tissue acting as an autocrine organ (leptin, resistin, adipokines, plasminogen activator inhibitor 1) | Systemic vascular resistance rises over time, on top of atherosclerosis |
| Ventricular remodelling | Eccentric hypertrophy from chronic volume overload, later concentric from pressure overload | Reduced compliance, raised end-diastolic filling pressure, increased cardiac workload |
| Cardiac index | Often normal or low when indexed | Absolute output is high; indexing to body surface area is what makes the comparison meaningful |
Why it matters at induction
Anaesthetic implications
Induction and maintenance agents
| Agent or technique | Blood pressure | Vascular effect | Cardiac effect | Mechanism and note |
|---|---|---|---|---|
| Propofol | ↓↓ (20–40%) | ↓↓ arteriolar and venous tone | ↓ direct myocardial depression | Blunts the baroreflex, so the compensatory tachycardia is lost. Venodilatation reduces mean systemic filling pressure and therefore preload. The commonest cause of hypotension after induction, and worst in the hypovolaemic and the elderly |
| Thiopentone | ↓ | ↓ mainly venodilatation | ↓ direct depression | Baroreflex largely preserved, so heart rate rises |
| Ketamine | ↑ or unchanged | ↑ via central sympathetic stimulation | ↓ direct depression, unmasked when catecholamines are depleted | Useful in hypovolaemia, but pressure may fall in the catecholamine-depleted patient |
| Etomidate | ≈ unchanged | Minimal | Minimal | The most haemodynamically stable induction agent; adrenocortical suppression is the trade-off |
| Volatile agents | ↓ | ↓↓ (isoflurane, sevoflurane, desflurane) | ↓ dose-dependent, greatest with halothane | Depress the baroreflex; desflurane can cause a sympathetic surge if the concentration is raised rapidly |
| Neuraxial block | ↓ | ↓↓ sympathetic block below the level | Unchanged unless T1–T4 cardioaccelerators are blocked | Venodilatation dominates. A high block removes the cardioaccelerator fibres, so bradycardia accompanies hypotension |
Haemodynamic goals in valvular disease
| Lesion | Rate | Rhythm | Preload | Afterload | Rationale |
|---|---|---|---|---|---|
| Aortic stenosis | Slow | Sinus rhythm essential | Full | Maintain — coronary perfusion depends on it | Avoid tachycardia and vasodilatation; the hypertrophied ventricle is preload-dependent and the atrial kick may contribute 40% |
| Aortic regurgitation | Fast | Less critical | Full | Reduce | A shorter diastole gives less time to regurgitate; low resistance favours forward flow |
| Mitral stenosis | Slow | Sinus rhythm essential | Full but avoid overload | Maintain | Filling is time-dependent; avoid anything that raises pulmonary vascular resistance |
| Mitral regurgitation | Fast | Less critical | Full | Reduce | Avoid raising systemic vascular resistance, which increases the regurgitant fraction |
| Hypertrophic obstructive cardiomyopathy | Slow | Sinus rhythm essential | Full | Maintain | Avoid inotropes: increased contractility worsens dynamic outflow obstruction |
Vasoactive drugs
| Drug | Receptor activity | Haemodynamic effect | Clinical note |
|---|---|---|---|
| Noradrenaline | α₁ ≫ β₁ | ↑↑ SVR, modest ↑ contractility, reflex ↓ HR | Vasodilatory shock; maintains coronary and cerebral perfusion pressure |
| Adrenaline | β₁ = β₂ ≥ α₁ | ↑↑ HR and contractility; α₁ dominates at higher doses | Cardiac arrest, anaphylaxis, low-output states; arrhythmogenic and raises lactate |
| Dobutamine | β₁ > β₂ | ↑ contractility and HR, mild ↓ SVR | Low-output states with adequate pressure; increases myocardial oxygen demand |
| Dopamine | Dose-dependent D → β₁ → α₁ | Variable | Largely superseded; no proven renal benefit at low dose |
| Phenylephrine | α₁ only | ↑ SVR, reflex ↓ HR, ↓ CO if the ventricle is impaired | Hypotension from vasodilatation, especially under spinal anaesthesia |
| Metaraminol | α₁, some indirect | As phenylephrine | Convenient bolus agent for spinal-induced hypotension |
| Ephedrine | Indirect (noradrenaline release) plus weak direct | ↑ HR, contractility and SVR | Tachyphylaxis with repeated doses; traditionally favoured in obstetrics, though phenylephrine causes less fetal acidosis |
| Milrinone | Phosphodiesterase-3 inhibition | ↑ contractility, ↓ SVR and PVR, lusitropy | An inodilator; useful in right ventricular failure and pulmonary hypertension |
| Vasopressin | V₁ receptors | ↑ SVR without β effects | Catecholamine-resistant vasoplegia; spares pulmonary vasoconstriction |
| Glyceryl trinitrate | Nitric oxide donor | Venodilatation ≫ arteriolar; ↓ preload | Reduces wall tension and therefore myocardial oxygen demand |
Drawing it, and the distinctions it turns on
The diagrams of this topic, and the confusions they expose
The diagrams, and what each must show
| Diagram | Axes | Must be labelled | Common errors |
|---|---|---|---|
| Wiggers diagram | Aortic, ventricular and atrial pressure on one axis; ventricular volume below; ECG below that; heart sounds | Axes with units and a time scale; the four valve events marked on the pressure traces; EDV and ESV labelled | Aortic pressure never falling to zero; the two isovolumetric phases flat on the volume trace |
| Pressure–volume loop | Volume on x (0–160 mL), pressure on y (0–160 mmHg) | Four corners labelled by valve event, plus the ESPVR and the EDPVR | Drawing the loop as a mirror image; omitting the two relations; wrong axis scale |
| Frank–Starling curve | End-diastolic volume or pressure on x, stroke volume or stroke work on y | A family of three curves, and the normal operating point on the steep part | Drawing one curve only, which cannot show the difference between preload and contractility |
| Cardiac and vascular function curves | Right atrial pressure on x, flow on y | Both curves, their intersection, and the mean systemic filling pressure intercept | Drawing curves that do not cross, or that cross where the stated operating point is not |
| Coronary flow | Time over one cycle on x, flow on y, with aortic pressure above | Separate left and right traces; systole shaded; the brief systolic reversal in the left | Drawing right coronary flow with the same systolic dip as the left |
| Venous pressure waveform | Time on x, pressure 0–10 mmHg on y, with the ECG beneath | a, c and v waves and x and y descents, with the pressure range labelled | Drawing it on a ventricular pressure scale, where it is invisible |
| Compliance and elastance curves | Volume on y for compliance; pressure on y for elastance | Both artery and vein on the same axes; state which quantity is which | Confusing the two orientations, or drawing a pressure–volume loop instead |
The distinctions that are most often collapsed
| The confusion | The correct position | Why it matters |
|---|---|---|
| Afterload defined as a volume | It is the pressure, force or wall tension opposing ejection | An incorrect definition propagates — every quantity derived from it inherits the error |
| Preload equated with venous return | Preload is end-diastolic fibre length; venous return is one determinant of it | Compliance, the atrial kick, rhythm and intrathoracic pressure all change preload without changing venous return |
| Vasoconstriction confused with venoconstriction | Arteriolar constriction raises resistance and afterload; venoconstriction raises mean systemic filling pressure and preload | They have opposite effects on the two function curves |
| Coronary flow confused with coronary perfusion pressure | Pressure is aortic root minus intraventricular; flow is pressure divided by resistance | The two are separated by coronary resistance, and neither can be substituted for the other |
| Listing without mechanism | Where the question says 'describe' or 'explain', a list of determinants earns little | A determinant named without its mechanism does not explain the change it is invoked for |
| Drawing the wrong diagram | A pressure–volume loop, a Frank–Starling curve or a venous return curve where an elastance or compliance curve was asked for | They are four different relations; which applies depends on which variable is being held and which is free |
| Unlabelled or unscaled axes | Every graph needs both axes named, with units and a plausible scale | An unlabelled curve states a shape but no quantity, so nothing can be read off it |