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USMLE Step 1 Exam Practice

Cardiovascular Physiology for USMLE Step 1

Cardiovascular physiology is one of the highest-yield systems on USMLE Step 1, and Step 1 tests it mostly through curves, equations and cause-and-effect reasoning rather than recall. These notes cover cardiac output and its determinants, the cardiac cycle and heart sounds, pressure-volume loops, cardiac and pacemaker action potentials, the electrocardiogram, haemodynamics and vascular resistance, the pressure-flow relationships in the circulation, blood pressure regulation by baroreceptors and the renin-angiotensin-aldosterone system, coronary and other special circulations, and the classic exam applications in shock, heart failure and valve disease. A 20-question practice set follows.

Cardiac Output and Its Determinants

Cardiac output equals stroke volume multiplied by heart rate. Stroke volume is set by three variables: preload, afterload and contractility. Almost every Step 1 cardiovascular vignette can be reduced to asking which of these three has changed and in which direction.

  • Cardiac output equals stroke volume times heart rate; normal resting value is about 5 litres per minute.
  • By the Fick principle, cardiac output equals oxygen consumption divided by the arteriovenous oxygen content difference.
  • Stroke volume equals end-diastolic volume minus end-systolic volume. Ejection fraction equals stroke volume divided by end-diastolic volume, normally 55 percent or more.
  • Preload is end-diastolic volume, approximated by ventricular end-diastolic pressure; it is raised by volume loading and lowered by venodilators such as nitroglycerin.
  • Afterload is the resistance the ventricle works against, approximated by mean arterial pressure or aortic systolic pressure; it is lowered by arteriodilators such as hydralazine.
  • Contractility (inotropy) is raised by catecholamines acting on beta 1 receptors, digoxin and increased intracellular calcium; it is lowered by beta blockers, non-dihydropyridine calcium channel blockers, acidosis and hypoxia.
  • The Frank-Starling relationship states that greater sarcomere stretch at end-diastole produces greater force of contraction, so venous return and cardiac output are matched beat by beat.
  • Mean arterial pressure is approximately diastolic pressure plus one third of the pulse pressure, and it also equals cardiac output times total peripheral resistance.

Cardiac Cycle, Heart Sounds and Pressure-Volume Loops

The cardiac cycle is a sequence of pressure changes that open and close valves. Valves open and close passively, purely because of pressure gradients, and each closure generates a heart sound. In the pressure-volume loop, the two vertical limbs are the isovolumetric phases and the two horizontal limbs are filling and ejection.

  • Phases: atrial contraction, isovolumetric contraction, rapid ejection, reduced ejection, isovolumetric relaxation, rapid filling, reduced filling (diastasis).
  • S1 is mitral and tricuspid closure at the start of systole; S2 is aortic and pulmonic closure at the end of systole.
  • S3 occurs in early diastole with rapid ventricular filling; it is normal in children and pregnancy and pathological in dilated ventricles and volume overload.
  • S4 occurs in late diastole as the atrium contracts against a stiff ventricle; it suggests ventricular hypertrophy and reduced compliance.
  • Jugular venous pulse: a wave equals atrial contraction, c wave equals tricuspid bulging during isovolumetric contraction, v wave equals atrial filling against a closed tricuspid valve. Cannon a waves occur in complete heart block; the a wave disappears in atrial fibrillation.
  • Physiological splitting of S2 widens on inspiration because increased venous return delays pulmonic closure. Wide fixed splitting is characteristic of an atrial septal defect; paradoxical splitting occurs in left bundle branch block and aortic stenosis.
  • On a pressure-volume loop, increased preload widens the loop to the right; increased afterload raises the top of the loop and reduces stroke volume; increased contractility raises the end-systolic pressure-volume relationship and reduces end-systolic volume.

Electrophysiology and the Electrocardiogram

Ventricular myocytes and pacemaker cells have different action potentials, and confusing them is a common error. Ventricular myocytes have a fast sodium upstroke and a calcium plateau; sinoatrial and atrioventricular nodal cells have no fast sodium channels and depolarise through calcium.

  • Ventricular myocyte: phase 0 rapid sodium influx, phase 1 transient potassium efflux, phase 2 plateau from calcium influx balancing potassium efflux, phase 3 repolarisation from potassium efflux, phase 4 resting potential maintained by inward rectifier potassium current.
  • Pacemaker cell: phase 4 slow depolarisation driven by the funny current (If, a sodium influx), phase 0 upstroke driven by calcium through L-type channels, phase 3 repolarisation by potassium efflux. There is no phase 1 or 2.
  • Intrinsic rates: sinoatrial node about 60 to 100 per minute, atrioventricular node about 40 to 60, His-Purkinje about 25 to 40.
  • Conduction speed is fastest in the Purkinje system and slowest in the atrioventricular node; nodal delay allows atrial emptying before ventricular contraction.
  • Electrocardiogram: P wave equals atrial depolarisation, PR interval equals conduction from atrium through the atrioventricular node (normal 120 to 200 milliseconds), QRS equals ventricular depolarisation (normal under 120 milliseconds), QT interval covers depolarisation plus repolarisation, T wave equals ventricular repolarisation.
  • Atrial repolarisation is hidden within the QRS complex and is not separately visible.
  • Hyperkalaemia gives peaked T waves then widened QRS; hypokalaemia gives flattened T waves and U waves; hypocalcaemia prolongs the QT interval.

Haemodynamics, Vascular Function and Special Circulations

Flow through a vessel is driven by the pressure gradient and opposed by resistance. Because resistance varies with the fourth power of the radius, small changes in arteriolar diameter dominate control of both regional blood flow and total peripheral resistance.

  • Flow equals pressure gradient divided by resistance. By Poiseuille's law, resistance is proportional to viscosity and vessel length and inversely proportional to the fourth power of the radius.
  • Arterioles are the main site of resistance and the main determinant of total peripheral resistance; veins are the main capacitance vessels and hold about 65 to 70 percent of the blood volume.
  • Capillaries have the largest total cross-sectional area and therefore the slowest linear velocity of flow, which favours exchange.
  • Resistances in series add directly; resistances in parallel add as reciprocals, so total resistance is always less than the smallest single resistance.
  • Starling forces: net filtration equals the filtration coefficient times the difference between the hydrostatic pressure gradient and the oncotic pressure gradient. Oedema results from raised capillary hydrostatic pressure (heart failure), reduced plasma oncotic pressure (nephrotic syndrome, liver failure), increased permeability (sepsis, burns) or impaired lymphatic drainage.
  • Coronary flow occurs mainly in diastole because systolic compression obstructs the subendocardial vessels; tachycardia shortens diastole and can precipitate ischaemia. The main local metabolic vasodilator in the heart is adenosine, with nitric oxide contributing.
  • Autoregulation: the brain responds mainly to carbon dioxide and hydrogen ion, the lungs are unique in vasoconstricting in response to hypoxia, skeletal muscle responds to adenosine, lactate and potassium, and the kidney uses myogenic and tubuloglomerular feedback.
  • Local metabolic control dominates in the heart and brain; sympathetic alpha 1 tone dominates in skin and splanchnic beds.

Regulation of Blood Pressure and High-Yield Clinical Correlations

Short-term blood pressure regulation is neural through the baroreceptor reflex, and long-term regulation is hormonal and renal, mainly through the renin-angiotensin-aldosterone system and pressure natriuresis. Step 1 usually tests these by asking how a given lesion or drug shifts cardiac and vascular function curves.

  • Carotid sinus afferents run in the glossopharyngeal nerve, aortic arch afferents in the vagus; both project to the nucleus tractus solitarius. A rise in pressure increases firing, raises vagal tone and lowers sympathetic tone.
  • Carotid sinus massage increases baroreceptor firing and slows the heart, which is why it can terminate supraventricular tachycardia.
  • Peripheral chemoreceptors in the carotid and aortic bodies respond to low oxygen tension, high carbon dioxide and low pH; central chemoreceptors in the medulla respond to carbon dioxide and pH but not directly to oxygen.
  • Renin is released from juxtaglomerular cells in response to low renal perfusion pressure, sympathetic beta 1 stimulation and low sodium delivery to the macula densa. Angiotensin II constricts arterioles, constricts the efferent arteriole preferentially, stimulates aldosterone, and increases thirst and antidiuretic hormone release.
  • Atrial natriuretic peptide is released from atrial myocytes in response to volume overload; it dilates vessels and promotes sodium excretion, opposing the renin-angiotensin-aldosterone system.
  • Hypovolaemic and cardiogenic shock share low cardiac output with high systemic vascular resistance; distributive (septic, anaphylactic, neurogenic) shock shows high cardiac output with low systemic vascular resistance. Cardiogenic shock differs from hypovolaemic shock by having a high, not low, pulmonary capillary wedge pressure.
  • Aortic stenosis produces a crescendo-decrescendo systolic murmur, pressure overload and concentric hypertrophy; aortic regurgitation produces volume overload, wide pulse pressure and eccentric hypertrophy.
  • Handgrip increases afterload and so increases the murmurs of mitral regurgitation, aortic regurgitation and ventricular septal defect, while decreasing those of aortic stenosis and hypertrophic cardiomyopathy. Standing or the Valsalva strain reduces preload and increases the hypertrophic cardiomyopathy murmur.

Key Terms

Preload
Ventricular end-diastolic volume, that is the degree of sarcomere stretch before contraction; approximated clinically by end-diastolic or wedge pressure.
Ejection fraction
Stroke volume divided by end-diastolic volume, normally 55 percent or higher; it is an index of contractility and is reduced in systolic heart failure.
Funny current
The slow inward sodium current of pacemaker cells that produces spontaneous phase 4 depolarisation and therefore sets heart rate; it is the target of ivabradine.
Pulmonary capillary wedge pressure
A catheter-measured estimate of left atrial pressure, used to separate cardiogenic shock (high) from hypovolaemic shock (low).

Practice Quiz — 20 Questions

correct out of 20

  1. A patient has a stroke volume of 70 millilitres and a heart rate of 80 beats per minute. Cardiac output is:

    • A.4.2 litres per minute
    • B.5.6 litres per minute
    • C.7.0 litres per minute
    • D.8.4 litres per minute
    B. 5.6 litres per minute — Cardiac output equals stroke volume times heart rate: 70 millilitres times 80 equals 5600 millilitres, or 5.6 litres per minute.

  2. Nitroglycerin lowers myocardial oxygen demand mainly by:

    • A.Reducing preload through venodilation
    • B.Reducing afterload through arteriolar dilation
    • C.Increasing contractility
    • D.Blocking beta 1 receptors
    A. Reducing preload through venodilation — Nitrates act predominantly on veins, reducing venous return and therefore preload and wall stress.

  3. Which change shifts the Frank-Starling curve upward and to the left?

    • A.Beta blockade
    • B.Increased contractility
    • C.Increased afterload
    • D.Hypovolaemia
    B. Increased contractility — Positive inotropy produces a greater stroke volume at any given end-diastolic volume, shifting the curve up and to the left.

  4. The fourth heart sound (S4) is produced by:

    • A.Rapid passive ventricular filling
    • B.Atrial contraction against a stiff ventricle
    • C.Mitral valve closure
    • D.Aortic valve opening
    B. Atrial contraction against a stiff ventricle — S4 is a late diastolic sound of atrial systole against a non-compliant, usually hypertrophied ventricle.

  5. Wide, fixed splitting of the second heart sound is characteristic of:

    • A.Aortic stenosis
    • B.Atrial septal defect
    • C.Left bundle branch block
    • D.Mitral stenosis
    B. Atrial septal defect — An atrial septal defect equalises right and left atrial filling across the respiratory cycle, so the split does not vary with inspiration.

  6. During isovolumetric contraction:

    • A.The aortic valve is open and the mitral valve is closed
    • B.Both valves are closed and volume is constant
    • C.Both valves are open
    • D.The mitral valve is open and the aortic valve is closed
    B. Both valves are closed and volume is constant — All four valves are shut, pressure rises steeply and ventricular volume does not change.

  7. In sinoatrial nodal cells, the upstroke of the action potential (phase 0) is caused by:

    • A.Fast sodium influx
    • B.Calcium influx through L-type channels
    • C.Potassium efflux
    • D.Chloride influx
    B. Calcium influx through L-type channels — Nodal cells lack functional fast sodium channels; their upstroke is calcium-dependent, which is why they are slowed by verapamil and diltiazem.

  8. The plateau phase (phase 2) of the ventricular action potential results from:

    • A.Sodium influx alone
    • B.Calcium influx balanced by potassium efflux
    • C.Potassium influx
    • D.Closure of all ion channels
    B. Calcium influx balanced by potassium efflux — Inward calcium current through L-type channels offsets outward potassium current, sustaining depolarisation and triggering calcium-induced calcium release.

  9. The PR interval mainly reflects:

    • A.Ventricular depolarisation
    • B.Atrioventricular nodal conduction delay
    • C.Ventricular repolarisation
    • D.Atrial repolarisation
    B. Atrioventricular nodal conduction delay — The bulk of the PR interval is conduction delay at the atrioventricular node, allowing atrial emptying before ventricular systole.

  10. If the radius of an arteriole is halved, resistance to flow increases by a factor of approximately:

    • A.2
    • B.4
    • C.8
    • D.16
    D. 16 — Resistance varies inversely with the fourth power of the radius, so halving the radius multiplies resistance by two to the fourth power, that is 16.

  11. Which vessels contain the largest fraction of total blood volume at rest?

    • A.Arteries
    • B.Arterioles
    • C.Capillaries
    • D.Veins
    D. Veins — The venous system is the capacitance reservoir and holds roughly 65 to 70 percent of the circulating volume.

  12. Blood flow velocity is slowest in capillaries because:

    • A.Their individual radius is smallest
    • B.Their total cross-sectional area is largest
    • C.Blood viscosity is highest there
    • D.Their walls are thinnest
    B. Their total cross-sectional area is largest — For a constant total flow, velocity is inversely proportional to total cross-sectional area, which is greatest in the capillary bed.

  13. Nephrotic syndrome causes oedema chiefly by:

    • A.Raising capillary hydrostatic pressure
    • B.Lowering plasma oncotic pressure
    • C.Blocking lymphatic drainage
    • D.Raising interstitial oncotic pressure
    B. Lowering plasma oncotic pressure — Heavy urinary protein loss lowers plasma albumin and therefore plasma oncotic pressure, favouring net filtration.

  14. Coronary blood flow occurs predominantly during:

    • A.Systole
    • B.Diastole
    • C.Isovolumetric contraction
    • D.Rapid ejection
    B. Diastole — Systolic myocardial compression obstructs the subendocardial vessels, so most perfusion happens in diastole; tachycardia shortens diastole and worsens ischaemia.

  15. The pulmonary circulation is unique because alveolar hypoxia causes:

    • A.Vasodilation
    • B.Vasoconstriction
    • C.No change in tone
    • D.Loss of autoregulation
    B. Vasoconstriction — Hypoxic pulmonary vasoconstriction diverts blood away from poorly ventilated alveoli, improving ventilation-perfusion matching.

  16. The main local metabolite responsible for coronary vasodilation is:

    • A.Adenosine
    • B.Histamine
    • C.Bradykinin
    • D.Serotonin
    A. Adenosine — Adenosine, produced from adenosine triphosphate breakdown during increased work or hypoxia, is the principal coronary metabolic vasodilator.

  17. Carotid sinus massage slows the heart because it:

    • A.Decreases baroreceptor firing
    • B.Increases baroreceptor firing and vagal outflow
    • C.Stimulates peripheral chemoreceptors
    • D.Blocks the atrioventricular node directly
    B. Increases baroreceptor firing and vagal outflow — Mechanical stretch mimics a pressure rise, increasing afferent firing, raising vagal tone and slowing atrioventricular conduction.

  18. Angiotensin II preserves glomerular filtration rate in hypovolaemia mainly by:

    • A.Dilating the afferent arteriole
    • B.Constricting the efferent arteriole
    • C.Constricting the afferent arteriole
    • D.Increasing renal blood flow
    B. Constricting the efferent arteriole — Preferential efferent arteriolar constriction maintains glomerular capillary hydrostatic pressure, which is why angiotensin converting enzyme inhibitors can drop filtration in renal artery stenosis.

  19. A hypotensive patient has warm extremities, high cardiac output and low systemic vascular resistance. The most likely diagnosis is:

    • A.Cardiogenic shock
    • B.Hypovolaemic shock
    • C.Septic shock
    • D.Obstructive shock from tamponade
    C. Septic shock — Distributive shock, of which sepsis is the commonest cause, produces vasodilation with a compensatory rise in cardiac output.

  20. The murmur of hypertrophic cardiomyopathy becomes louder with:

    • A.Handgrip
    • B.Squatting
    • C.Passive leg raise
    • D.Standing up from squatting
    D. Standing up from squatting — Standing reduces preload and ventricular cavity size, worsening outflow obstruction and intensifying the murmur; manoeuvres that increase preload or afterload soften it.

References