Cardiovascular Physiology

Cardiovascular Circuits and Pressure-Driven Flow

The cardiovascular system consists of two main circuits: the pulmonary and systemic circuits. Blood flows through these circuits in a continuous loop, driven by pressure gradients generated by the heart's pumping action.

• Pulmonary Circuit: Carries deoxygenated blood from the right ventricle to the lungs via pulmonary arteries and returns oxygenated blood to the left atrium via pulmonary veins.

• Systemic Circuit: Delivers oxygenated blood from the left ventricle through the aorta to systemic tissues and returns deoxygenated blood to the right atrium via systemic veins.

• Two-Pump System: The heart's right side pumps blood to the lungs (pulmonary), while the left side pumps blood to the body (systemic).

• Pressure-Driven Flow: Blood moves from regions of higher pressure to lower pressure. Valves ensure unidirectional flow by opening when pressure behind them exceeds pressure ahead and closing when the gradient reverses.

• Heart Valves:

  • Atrioventricular (AV) Valves: Tricuspid (right) and mitral (left) valves separate atria from ventricles.

  • Semilunar Valves: Pulmonary and aortic valves separate ventricles from major arteries.

Example: During ventricular contraction, the left ventricular pressure exceeds aortic pressure, opening the aortic valve and allowing blood ejection.

The Cardiac Cycle: Stages, Pressures, Volumes, and Heart Sounds

The cardiac cycle describes the sequence of mechanical and electrical events during one heartbeat. It consists of five main stages, each characterized by specific valve states, pressure changes, and volume shifts.

• Late Diastole: Both atria and ventricles are relaxed; AV valves open, semilunar valves closed; passive ventricular filling occurs.

• Atrial Systole: Atria contract, pushing additional blood into ventricles; ventricular volume reaches end-diastolic volume (EDV).

• Isovolumic Ventricular Contraction: Ventricular pressure rises above atrial pressure, closing AV valves (first heart sound, S1); semilunar valves remain closed; ventricular volume is constant.

• Ventricular Ejection: Ventricular pressure exceeds arterial pressure, opening semilunar valves; blood is ejected, ventricular volume decreases toward end-systolic volume (ESV).

• Isovolumic Ventricular Relaxation: Ventricular pressure falls below arterial pressure, closing semilunar valves (second heart sound, S2); both valve sets closed; ventricular volume remains constant until AV valves reopen.

Stroke Volume (SV): The amount of blood ejected per beat, calculated as:

For example, if and , then .

• Pressure-Volume Relationships: Left ventricular and aortic pressures track closely during ejection due to the open aortic valve, while atrial and ventricular pressures are similar during filling with an open AV valve.

• Heart Sounds: S1 ("lub") marks AV valve closure; S2 ("dub") marks semilunar valve closure.

Example: During isovolumic contraction, both AV and semilunar valves are closed, and ventricular pressure rises rapidly without a change in volume.

Contractile Myocardial Cells: Structure and Electrical Behavior

Cardiac muscle contains two main cell types: contractile cells (responsible for force generation) and autorhythmic cells (responsible for initiating electrical impulses).

• Intercalated Disks: Specialized connections between cardiac cells containing desmosomes (mechanical linkage) and gap junctions (electrical communication).

• Action Potential Phases in Contractile Cells:

  1. Rapid depolarization due to Na+ influx.

  2. Na+ channel inactivation.

  3. Plateau phase: Ca2+ entry through L-type channels and altered K+ conductance.

  4. Repolarization as Ca2+ channels close and K+ efflux increases.

  5. Stable resting potential.

• Long Refractory Period: The prolonged action potential prevents summation and tetanus, ensuring rhythmic contractions.

Comparison: Skeletal muscle can undergo tetanus due to short refractory periods, but cardiac muscle cannot, which is essential for effective pumping.

Cardiac Excitation–Contraction Coupling and Relaxation

Excitation–contraction (EC) coupling links the electrical action potential to mechanical contraction in cardiac muscle.

• Sequence of Events:

  1. Action potential spreads into T-tubules of the myocyte.

  2. Voltage-gated L-type Ca2+ channels open, allowing extracellular Ca2+ entry.

  3. Ca2+-induced Ca2+ release: Incoming Ca2+ triggers RyR2 channels on the sarcoplasmic reticulum (SR) to release stored Ca2+.

  4. Local Ca2+ sparks sum to create a cytosolic Ca2+ signal.

  5. Ca2+ binds troponin, initiating actin–myosin crossbridge cycling and contraction.

  6. Relaxation: Ca2+ is pumped back into the SR and removed via the Na+/Ca2+ exchanger (NCX); Na+/K+-ATPase maintains the Na+ gradient.

• Key Distinction: In cardiac muscle, extracellular Ca2+ entry is essential for triggering SR Ca2+ release, unlike in skeletal muscle.

Example: If Ca2+ reuptake into the SR is slowed, relaxation is delayed, potentially impairing cardiac function.

Pacemaker Action Potential and the Cardiac Conduction System

Autorhythmic (pacemaker) cells generate spontaneous action potentials that coordinate the heartbeat. The conduction system ensures rapid and organized spread of excitation.

• Pacemaker Potential: Gradual depolarization due to "funny" (If) Na+ channels, followed by Ca2+ influx for the upstroke, and K+ efflux for repolarization.

• Comparison: Pacemaker cells have no stable resting potential and rely on Ca2+-dependent upstroke, while contractile cells have a stable resting potential and a fast Na+-dependent upstroke.

• Conduction Pathway:

  1. Sinoatrial (SA) node (primary pacemaker, ~70 bpm)

  2. Atrial pathways

  3. Atrioventricular (AV) node (delay, ~50 bpm)

  4. AV bundle (bundle of His) and bundle branches

  5. Purkinje fibers (~30 bpm)

  6. Ventricular myocardium (activation from apex upward)

• Hierarchy: The fastest pacemaker (usually the SA node) sets the heart rate; lower pacemakers can take over if higher ones fail.

Example: SA node failure leads to slower pacing by the AV node or Purkinje fibers.

Electrocardiogram (ECG): Electrical Signals and Pathology Patterns

An ECG records the summed electrical activity of the heart as detected by skin electrodes. It provides information about the timing and sequence of cardiac electrical events.

• Key ECG Components:

  • P wave: Atrial depolarization

  • QRS complex: Ventricular depolarization

  • T wave: Ventricular repolarization

• Interpretation: Electrical events precede mechanical contraction; ECG does not directly indicate valve states or pressure changes.

• Pathology Patterns:

  • Sinus Tachycardia: Normal conduction, increased SA-node rate.

  • Atrial Fibrillation: Uncoordinated atrial electrical activity.

  • AV Conduction Block: Impaired conduction from atria to ventricles.

Example: In AV block, P waves may not always be followed by QRS complexes, indicating failed conduction to the ventricles.

Cardiac Output and Autonomic Control of Heart Rate

Cardiac output (CO) is the volume of blood pumped by each ventricle per minute. It is determined by stroke volume (SV) and heart rate (HR).

Units: mL/beat × beats/min = mL/min

• Autonomic Regulation:

  • Sympathetic Stimulation: Increases If-associated Na+ and Ca2+ permeability, steepens pacemaker depolarization, increases HR.

  • Parasympathetic Stimulation: Increases K+ permeability, decreases Ca2+ permeability, hyperpolarizes cells, slows HR.

• Effect on Pacemaker Cells: Sympathetic input shortens time to threshold (increases rate); parasympathetic input lengthens it (decreases rate).

• Distinction: Changes in HR are separate from changes in ventricular contractile force.

Example: During exercise, sympathetic activity increases both HR and contractility, raising CO.

Intrinsic and Extrinsic Control of Stroke Volume

Stroke volume is regulated by both intrinsic (within the heart) and extrinsic (neural/hormonal) mechanisms.

• Intrinsic Control (Frank–Starling Law): Increased ventricular filling (EDV/preload) stretches cardiac muscle, enhancing contractile force and increasing SV within physiological limits.

• Extrinsic Control: Sympathetic stimulation increases contractility by enhancing Ca2+ signaling, leading to greater force at a given initial length.

• Integration: CO depends on both HR and SV; increasing HR does not always increase CO if SV decreases.

Example: If EDV rises but ESV remains constant, SV increases. If HR rises while SV falls, total CO may remain unchanged or require calculation.

Key Equations and Concepts

• Stroke Volume:

• Cardiac Output:

• Frank–Starling Mechanism: Increased preload (EDV) leads to increased SV due to optimal sarcomere length for force generation.

Summary Table: Cardiac Cycle Phases and Valve States

Additional info:

• "Preload" refers to the initial stretching of cardiac myocytes prior to contraction, closely related to EDV.

• "Ca2+-induced Ca2+ release" is a unique feature of cardiac EC coupling, not present in skeletal muscle.

• "Dicrotic notch" on the aortic pressure curve marks closure of the aortic valve.