Cardiac Physiology, Cycle, Valves & Murmurs — USMLE Step 1 Notes

Cardiac output & the core formulas

• Cardiac output (CO) = heart rate × stroke volume. Also (Fick): CO = rate of O2 consumption ÷ (arterial O2 − venous O2 content).
• Stroke volume (SV) = end-diastolic volume − end-systolic volume. SV is set by preload, afterload and contractility (mnemonic: SV CAP — Contractility, Afterload, Preload).
• Ejection fraction (EF) = SV ÷ EDV (normal ≥55%). EF is preserved in diastolic failure (HFpEF) and reduced in systolic failure (HFrEF).
• Mean arterial pressure (MAP) = CO × total peripheral resistance, and approximately MAP = diastolic + ⅓(pulse pressure).
• Pulse pressure = systolic − diastolic. It rises with aortic regurgitation, stiff arteries, hyperthyroidism and anaemia; it falls in aortic stenosis, tamponade, cardiogenic shock and heart failure.
• Preload approximates end-diastolic volume/ventricular filling (raised by volume, venoconstriction; lowered by venodilators such as nitroglycerin). Afterload approximates aortic pressure/systemic resistance (lowered by arterial dilators such as hydralazine, ACE inhibitors).
• Contractility rises with sympathetic tone, catecholamines, digoxin and calcium; it falls with beta-blockade, heart failure, acidosis and hypoxia.
• Myocardial oxygen demand rises with heart rate, contractility, afterload and wall tension (wall tension = pressure × radius ÷ 2 × wall thickness, by Laplace). This is why beta-blockers and nitrates relieve angina.

Starling curves

• The Frank-Starling relationship: greater end-diastolic sarcomere stretch → greater force of contraction, so the heart ejects whatever venous return delivers.
• A curve shifted up and left = increased contractility (sympathetic stimulation, digoxin, inotropes); down and right = reduced contractility (heart failure, beta-blockade, ischaemia).
• In failure, the same preload yields a smaller stroke volume — so filling pressures rise and congestion develops.

The cardiac cycle & heart sounds

• Phases: atrial contraction → isovolumetric contraction (all valves shut, highest O2 consumption) → rapid then reduced ejection → isovolumetric relaxation → rapid then reduced filling.
• S1 = mitral and tricuspid closure at the start of systole (loud in mitral stenosis, soft in mitral regurgitation).
• S2 = aortic and pulmonary closure at the start of diastole.
• S3 = early diastolic filling sound: normal in children/pregnancy, otherwise suggests volume overload (heart failure, mitral regurgitation, dilated cardiomyopathy).
• S4 = late diastolic atrial kick against a stiff ventricle (hypertension, hypertrophy, ischaemia, HFpEF); always abnormal in older adults.

Jugular venous pressure waveform

• a wave = atrial contraction (absent in atrial fibrillation; giant/cannon in tricuspid stenosis and complete heart block).
• c wave = tricuspid bulging into the atrium during ventricular contraction.
• x descent = atrial relaxation/downward pull (lost in tricuspid regurgitation).
• v wave = atrial filling against a closed tricuspid valve (large in tricuspid regurgitation).
• y descent = tricuspid opening and rapid filling (steep in constrictive pericarditis; absent in tamponade).
• Kussmaul sign (JVP rises on inspiration) suggests constrictive pericarditis, right heart failure or restrictive cardiomyopathy.

Pressure-volume loops

• Read the loop anticlockwise: filling (bottom, along the end-diastolic pressure-volume relationship) → isovolumetric contraction (vertical rise) → ejection (top) → isovolumetric relaxation (vertical fall). Loop width = stroke volume; loop area = stroke work.
• Increased preload: loop widens to the right (bigger SV). Increased afterload: loop gets taller and narrower (smaller SV, higher end-systolic volume). Increased contractility: steeper end-systolic line, loop widens with a smaller end-systolic volume.
• Aortic stenosis: tall, narrow loop (high pressure generated, reduced SV). Aortic regurgitation: no true isovolumetric relaxation, wide loop shifted right. Mitral regurgitation: no true isovolumetric contraction, loop shifted left with a large total SV but reduced forward flow. Mitral stenosis: small, narrow loop with reduced filling.

Valvular disease

• Aortic stenosis: crescendo-decrescendo systolic murmur at the right 2nd ICS radiating to the carotids, with a soft S2 and pulsus parvus et tardus. Triad of syncope, angina and dyspnoea. Causes: age-related calcification, bicuspid valve (younger), rheumatic. Treat with valve replacement once symptomatic.
• Aortic regurgitation: early decrescendo diastolic murmur at the left sternal border, wide pulse pressure with bounding (water-hammer) pulses, head bobbing and an Austin Flint rumble. Causes: aortic root dilatation, bicuspid valve, endocarditis, rheumatic.
• Mitral stenosis: opening snap then a low-pitched mid-diastolic rumble at the apex, loud S1; almost always rheumatic. Causes left atrial enlargement → atrial fibrillation, dysphagia, hoarseness.
• Mitral regurgitation: holosystolic murmur at the apex radiating to the axilla, soft S1, often an S3. Causes: mitral prolapse, ischaemia/papillary rupture, LV dilatation, endocarditis, rheumatic.
• Mitral valve prolapse: mid-systolic click then a late systolic murmur; associated with connective-tissue disease (Marfan, Ehlers-Danlos). The click moves earlier with standing/Valsalva.

Splitting of S2

• Physiological: inspiration increases venous return, delaying pulmonary valve closure — splitting appears on inspiration and disappears on expiration.
• Wide: anything delaying right ventricular emptying — pulmonary stenosis, right bundle branch block; splitting persists but still widens with inspiration.
• Fixed: atrial septal defect — the shunt equalises the effect of respiration, so the split does not vary at all.
• Paradoxical (reversed): delayed left ventricular emptying — aortic stenosis, left bundle branch block; the split is heard on expiration and closes on inspiration.

Where to listen

Murmurs by timing

• Systolic: aortic stenosis (crescendo-decrescendo, radiates to carotids), mitral regurgitation (holosystolic, radiates to axilla), tricuspid regurgitation (holosystolic, louder on inspiration), mitral valve prolapse (click then late systolic), ventricular septal defect (harsh holosystolic at the left lower sternal border).
• Diastolic: aortic regurgitation (early decrescendo), mitral stenosis (opening snap then mid-diastolic rumble).
• Continuous: patent ductus arteriosus (machine-like, below the left clavicle).

Manoeuvres

• Increase preload (squatting, leg raise, expiration for left-sided): most murmurs get louder — but hypertrophic cardiomyopathy gets softer and mitral prolapse clicks later.
• Decrease preload (standing, Valsalva strain): most murmurs get softer — but hypertrophic cardiomyopathy gets louder and mitral prolapse clicks earlier. This pair is the classic exam discriminator.
• Increase afterload (handgrip): mitral regurgitation, aortic regurgitation and VSD get louder; aortic stenosis and hypertrophic cardiomyopathy get softer.
• Inspiration increases venous return to the right heart, so right-sided murmurs get louder (mnemonic: RILE — Right-sided Inspiration, Left-sided Expiration).

Myocardial vs pacemaker action potentials

• Ventricular myocyte: phase 0 rapid depolarisation (fast Na influx) → phase 1 brief repolarisation (K efflux, Na channels close) → phase 2 plateau (Ca influx balances K efflux — this triggers calcium-induced calcium release and contraction) → phase 3 repolarisation (K efflux) → phase 4 resting potential (K permeability).
• Pacemaker (SA/AV nodal) cell: no fast Na channels. Phase 4 spontaneous slow depolarisation via the funny current (I_f, Na influx) sets the heart rate; phase 0 upstroke is calcium-driven (slow, hence slow conduction through the AV node); phase 3 is K efflux. Sympathetic tone steepens phase 4 (faster rate); vagal tone flattens it.
• Conduction speed: His-Purkinje fastest, AV node slowest (allowing atrial contribution to filling). Order: SA node → atria → AV node → bundle of His → bundle branches → Purkinje.

The ECG — what it measures

• The ECG records the summed electrical activity of the myocardium from the body surface; each lead views that vector from a different angle. It shows rhythm and electrical events, not contraction directly.
• P wave = atrial depolarisation; PR interval (120-200 ms) = AV nodal delay; QRS (<120 ms) = ventricular depolarisation (atrial repolarisation is hidden within it); ST segment = plateau/phase 2; T wave = ventricular repolarisation; QT interval = total depolarisation plus repolarisation.
• At standard speed, one small square = 0.04 s and one large square = 0.20 s, so rate = 300 ÷ number of large squares between R waves.
• Territory follows blood supply: II, III, aVF inferior (RCA); V1-V4 anterior/septal (LAD); I, aVL, V5-V6 lateral (LCx). Work through real traces in the ECGs tab.

Natriuretic peptides

• ANP is released by atrial myocytes and BNP by ventricular myocytes in response to stretch (volume overload).
• Both cause vasodilatation, natriuresis and diuresis, and oppose the renin-angiotensin-aldosterone system — a natural counter-regulatory brake in heart failure.
• Clinically, BNP/NT-proBNP is used to rule out heart failure in breathless patients (a normal level makes it unlikely). Sacubitril blocks neprilysin, the enzyme that degrades these peptides, raising their levels.

Baroreceptors & chemoreceptors

• Carotid sinus baroreceptor: afferent via the glossopharyngeal nerve (CN IX) to the medulla; responds to increased stretch by reducing sympathetic and increasing vagal output (rate and pressure fall). Aortic arch baroreceptor: afferent via the vagus (CN X); responds only to increased pressure.
• Efferent limbs are the sympathetic chain and the vagus. Carotid massage raises carotid sinus pressure → reflex bradycardia. In haemorrhage, reduced stretch removes inhibition → tachycardia and vasoconstriction.
• Peripheral chemoreceptors (carotid and aortic bodies) respond to low PO2 (<60 mmHg), high PCO2 and low pH. Central chemoreceptors in the medulla respond to CSF pH/CO2 (not directly to O2).

Normal resting pressures & autoregulation

• Approximate pressures (mmHg): right atrium <5; right ventricle 25/5; pulmonary artery 25/10 (mean <20); pulmonary capillary wedge ≈ left atrium 4-12; left ventricle 120/10; aorta 120/80.
• A wedge pressure above left ventricular diastolic pressure suggests mitral stenosis.
• Autoregulation keeps organ flow constant across a range of pressures, by local metabolites: heart — adenosine, NO, hypoxia; brain — CO2/pH; kidney — myogenic and tubuloglomerular feedback; lungs are the exception, where hypoxia causes vasoconstriction to divert blood to ventilated alveoli; skeletal muscle — lactate, adenosine, K+.

Capillary fluid exchange (Starling forces)

• Net filtration = K_f × [(P_capillary − P_interstitial) − (π_capillary − π_interstitial)] — hydrostatic pressure pushes fluid out, oncotic pressure pulls it back in.
• Oedema results from raised capillary hydrostatic pressure (heart failure, venous obstruction), reduced plasma oncotic pressure (nephrotic syndrome, liver failure, malnutrition), increased permeability (sepsis, burns, histamine) or impaired lymphatic drainage (lymphoedema, filariasis).

High-yield revision notes and original diagrams; verify against a primary source before clinical use.