13.6 Cardiac Anatomy, Electrophysiology, the Cardiac Cycle & Cardiac Output

13.6 Cardiac Anatomy, Electrophysiology, the Cardiac Cycle & Cardiac Output

The circulatory system couples metabolic demand to perfusion pressure. To understand its regulation, one must integrate electrical impulse propagation through myocardial tissue with mechanical valve gating, fluid shear dynamics, and hematologic biochemistry.

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Heart Anatomy & Dual-Circuit Circulatory Architecture

The mammalian heart consists of four muscular chambers operating across two circulations arranged in series:

• Pulmonary Circuit (Low Pressure, Low Resistance): Deoxygenated systemic venous blood returns to the right atrium via the superior vena cava, inferior vena cava, and coronary sinus. Blood flows through the tricuspid valve (right AV valve) into the right ventricle. During ventricular systole, the right ventricle contracts, pumping blood through the pulmonary semilunar valve into the pulmonary trunk and pulmonary arteries to the pulmonary capillary beds for gas exchange. Typical peak systolic pressure in the pulmonary circuit is only ~25 mmHg (25/10 mmHg).
• Systemic Circuit (High Pressure, High Resistance): Oxygenated blood returns from the lungs via four pulmonary veins into the left atrium. Blood passes through the mitral valve (bicuspid / left AV valve) into the thick, muscular left ventricle. Left ventricular contraction generates high pressure (~120/80 mmHg), pumping blood through the aortic semilunar valve into the ascending aorta for systemic arterial distribution.

Valvular Anatomy and Structural Integrity

• Atrioventricular (AV) Valves (Tricuspid & Mitral): Prevent backflow of blood from ventricles into atria during ventricular systole. The valve leaflets are tethered to fibrous chordae tendineae, which anchor to specialized myocardial projections called papillary muscles. During ventricular systole, papillary muscles contract synchronously, tensing the chordae tendineae to prevent valve prolapse or eversion into the lower-pressure atria.
• Semilunar Valves (Aortic & Pulmonary): Composed of three crescent-shaped pocket-like cusps lacking chordae tendineae. When ventricular pressure exceeds arterial diastolic pressure, the cusps are forced flat against the vessel walls. When ventricles relax and pressure drops, blood briefly flows backward, filling the cusps, snapping the valves shut, and sealing the orifices.

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Cardiac Electrophysiology & the Conduction Pathway

Myocardial contraction is coordinated by specialized non-contractile autorhythmic cardiac cells that generate and distribute action potentials across the syncytium via intercalated discs containing gap junctions (connexin-43):

1. Sinoatrial (SA) Node: The primary physiological pacemaker of the heart, located in the posterior wall of the right atrium near the superior vena cava orifice. SA nodal cells have no stable resting membrane potential. Instead, they exhibit spontaneous diastolic depolarization (pacemaker potential) driven by:
   • Funny Sodium Current ($I_f$): Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that open at negative potentials (-60 mV), permitting inward $Na^+$ leak.
   • T-Type Calcium Channels ($I_{Ca,T}$): Transient low-voltage activated calcium channels opening near -50 mV.
   • L-Type Calcium Channels ($I_{Ca,L}$): At threshold (-40 mV), massive opening of long-lasting L-type $Ca^{2+}$ channels drives the Phase 0 depolarizing upstroke (unlike neurons and ventricular myocytes, Phase 0 is calcium-dependent, not sodium-dependent!). Intrinsic firing rate is 60-100 bpm.
2. Atrioventricular (AV) Node: Located in the inferior interatrial septum above the tricuspid valve. As the action potential propagates through the atria via internodal tracts, it reaches the AV node, which introduces a critical ~0.1-second delay. This delay is caused by smaller fiber diameters and fewer gap junctions, ensuring that the atria completely finish contracting and emptying blood into the ventricles before ventricular systole begins.
3. Bundle of His (AV Bundle): Emerges from the AV node and penetrates the non-conductive dense fibrous skeleton of the heart (which electrically insulates atria from ventricles).
4. Right and Left Bundle Branches: Travel down the interventricular septum toward the cardiac apex.
5. Purkinje Fibers: Large-diameter cells with high conduction velocity (2-4 m/s) that arborize upward through the ventricular myocardium from the apex toward the base. This anatomical arrangement ensures that ventricular contraction begins at the apex and sweeps upward toward the base, squeezing blood toward the outflow tracts (aorta and pulmonary artery).

The Surface Electrocardiogram (ECG / EKG)

• P Wave: Represents atrial depolarization initiated by the SA node.
• PR Interval: Measures the time from the onset of atrial depolarization to the onset of ventricular depolarization, capturing the transit through the AV node (normal 0.12-0.20 s). Prolongation reflects first-degree AV block.
• QRS Complex: Represents rapid ventricular depolarization (normal duration <0.10-0.12 s). Atrial repolarization occurs simultaneously but its electrical signal is buried within the massive QRS complex.
• ST Segment: Isoelectric plateau corresponding to the Phase 2 $Ca^{2+}$ plateau of the ventricular myocyte action potential. ST-elevation indicates transmural myocardial infarction (STEMI).
• T Wave: Represents ventricular repolarization.
• QT Interval: Total electrical systole of the ventricles (depolarization plus repolarization).

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The Cardiac Cycle & Ventricular Volume Mechanics

The cardiac cycle describes the alternating phases of muscular contraction (systole) and relaxation (diastole):

Heart Sounds

• $S_1$ ("Lub"): Produced by the sudden deceleration of blood and reverberation of heart walls following closure of the AV valves (mitral and tricuspid) at the onset of isovolumetric contraction.
• $S_2$ ("Dub"): Produced by the sudden closure of the semilunar valves (aortic and pulmonary) at the onset of isovolumetric relaxation.

Cardiac Output, Stroke Volume & The Frank-Starling Law

Core Mathematical Formulations

• Cardiac Output ($CO$): The volume of blood ejected by each ventricle per unit time (typically ~5.0 L/min at rest): $$CO = HR \times SV$$ (where $HR$ is heart rate in beats per minute, and $SV$ is stroke volume in mL/beat).
• Stroke Volume ($SV$): The volume of blood pumped from a ventricle during a single contraction: $$SV = EDV - ESV$$
  • End-Diastolic Volume ($EDV$): Blood volume in the ventricle at the end of diastole (typically ~120 mL).
  • End-Systolic Volume ($ESV$): Residual blood volume remaining in the ventricle after systole (typically ~50 mL).
  • Typical $SV = 120\text{ mL} - 50\text{ mL} = 70\text{ mL}$.
• Ejection Fraction ($EF$): The fraction of end-diastolic volume ejected per beat, serving as a primary clinical marker of myocardial contractile performance (normal = 55-70%): $$EF = \frac{SV}{EDV} \times 100\% = \frac{70}{120} \times 100\% \approx 58.3\%$$

The Three Determinants of Stroke Volume

1. Preload: The resting tension or stretch on the ventricular myocardium immediately prior to contraction, clinically indexed by End-Diastolic Volume ($EDV$) or end-diastolic pressure. Preload is governed by the Frank-Starling Law of the Heart: the energy of contraction is proportional to the initial muscle fiber length. Mechanistically, increased venous return stretches ventricular myocytes, moving sarcomeres from an under-stretched state (1.8 micrometers) toward the optimal length ($l_0 \approx 2.2\,\mu\text{m}$). This optimizes actin-myosin overlap and increases the affinity of troponin C for $Ca^{2+}$, generating greater cross-bridge cycling and force of contraction. This mechanism intrinsically balances the output of the right and left ventricles.
2. Afterload: The load or impedance against which the ventricles must pump to eject blood into the systemic circulation. It is determined primarily by aortic pressure and Systemic Vascular Resistance (SVR). Pathological elevations in afterload (e.g., chronic systemic hypertension, aortic stenosis) increase $ESV$ and decrease $SV$, forcing the ventricle to hypertrophy.
3. Inotropy (Contractility): The intrinsic contractile strength of the myocardium at any given preload and afterload, independent of muscle fiber length. Governed by intracellular free calcium availability. Sympathetic stimulation (norepinephrine/epinephrine acting on $\beta_1$ adrenergic receptors) activates the $G_s \to \text{cAMP} \to \text{PKA}$ cascade, which phosphorylates L-type $Ca^{2+}$ channels (increasing $Ca^{2+}$ influx) and phospholamban (disinhibiting SERCA to accelerate $Ca^{2+}$ re-uptake into the sarcoplasmic reticulum, enhancing both contraction force and the rate of relaxation [lusitropy]).

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