09. Physiology - Cardiac Function

LaPlace's Law

• Relates pressure within a sphere to wall stress.
• Equation: Wall stress (σ) = Pressure (P) * Radius (r) / Thickness (u).
• Increased wall tension corresponds to increased pressure, like inflating a balloon.

Wiggers' Diagram

• Illustrates the sequence of events in the cardiac cycle by linking pressure and volume (or flow) changes.
• Starts with action potentials triggering contraction (Excitation-Contraction Coupling).
• Contraction increases tension, leading to increased pressure via LaPlace's Law.

Phases of the Cardiac Cycle

Systole

• Mitral valve closure to aortic valve closure.
• Contraction and ejection of blood.

Diastole

• Aortic valve closure to mitral valve closure.
• Relaxation and filling of the heart.

ECG Correlation with Ventricular Events

• P-wave: Atrial depolarization and contraction.
  • Represents atrial contraction and filling of the ventricle.
  • There's a delay between the P-wave and changes in flow due to excitation-contraction coupling.
• QRS complex: Ventricular depolarization and contraction.
  • Ventricular pressure rises, closing the mitral valve.
  • All valves are closed during the isovolumic contraction phase.
  • There's a delay between the QRS complex and mitral valve closure.
• Ventricular Ejection: LV pressure exceeds aortic pressure, opening the aortic valve.
  • Blood leaves the heart, reducing its volume.
• Isovolumic Relaxation: Aortic valve closes as the heart relaxes, pressure falls despite no open valves.
• Early Rapid Filling: LV pressure drops below atrial pressure, opening the mitral valve.
  • Rapid filling of the heart begins.
  • E-wave on transmitral Doppler echocardiography.
• Diastasis: A period of "rest" with minimal flow when the heart rate is slow.
• Late Atrial Filling (Atrial Systole): A new P-wave occurs, causing additional atrial filling.
  • A-wave on transmitral Doppler echocardiography.

Right vs Left Ventricle

• RV wall is thinner than LV wall.
• RV generates less pressure than LV.
  • Peak RV pressure ~25 mmHg.
  • Peak LV pressure ~120 mmHg.
• RV and LV contract at slightly different times, usually with some overlap.

Auscultation

• Listening to body sounds.
• Common sounds: heart, lung, pulse pressure.

Heart Sounds

• Generated by valve closures and blood deceleration.
• 1st heart sound: Mitral valve closure/aortic valve opening ("Lub").
• 2nd heart sound: Aortic valve closure/mitral valve opening ("Dub").
• 3rd heart sound: Blood deceleration during early rapid filling.
• 4th heart sound: Blood deceleration during late atrial filling.

Splitting of Heart Sounds

• Normally, sounds from the left and right ventricles overlap.
• If RV doesn't close the pulmonary valve at the same time the LV closes the aortic valve, the 2nd heart sound may "Split".
  • A2, P2 for an aortic and pulmonary sound.

Pressure-Volume Loop

• Traces the cardiac cycle in a counter-clockwise direction.
• "Corners" defined by valve closures.

Important Measurements and Indexes

• EDV (End Diastolic Volume): Volume of blood when mitral valve closes.
• ESV (End Systolic Volume): Volume of blood in the heart when aortic valve closes.
• SV (Stroke Volume): Difference between EDV and ESV.
• EF (Ejection Fraction): Percentage of blood ejected, (100 * SV / EDV) or (100 * (EDV - ESV) / EDV).
  • Normal EF is >50%.

Afterload, Preload, and Contractility

• Changing afterload (systemic/aortic blood pressure) alters aortic valve opening but not mitral valve closure (preload).
• Afterload impacts aortic valve closure/ESV and allows calculation of contractility or inotropy.
• Connecting end-systolic points with different afterloads creates a line whose slope indicates contractility.

Factors Reducing Contractility

• Reduced calcium release from the sarcoplasmic reticulum.
• Decreased thin filament activation.
• Slowed or inhibited myosin ATPase.

Preload and Frank-Starling Law

• Increased preload generally leads to increased stroke volume.
• Frank-Starling Law: Myocytes contract more vigorously at longer lengths/higher volumes.
• Length-dependent activation can be broken in a sick heart, leading to reduced EF.

Pressure-Volume Loops Reflecting Heart Function

• Normal Heart: Myocardium generates more tension at longer lengths, leading to increased stroke volume.
• Dysfunctional Heart: Myocardium generates the same force at all lengths, limiting contractility and reducing EF.

Energy Utilization by the Heart

• Requires significant energy, using oxygen for mitochondrial respiration.
• Myosin ATPase is a primary ATP user, requiring a shift from fatty acid to glucose utilization when ATP availability is reduced.
• ATP is crucial for relaxation as it detaches the myosin from the rigor state. Reduced ATP impairs relaxation.

Work of the Heart

• Work is the effort used to move blood out of the left ventricle.
• Work = Area of the Pressure-Volume loop, approximated as a rectangle.
• Top = Mean Arterial Pressure (MAP).
• Bottom = Diastolic Pressure.
• Work = Stroke Volume x (MAP - Diastolic Pressure).

Fick's Method

• Gold standard for quantifying oxygen utilization.
• CO (Cardiac Output) = O2 Uptake (ml O2/min) / A-V O2 Difference (ml O2/L blood).
• Represents the rate of oxygen consumption divided by the difference between arterial and venous oxygen content.
• Relates oxygen use to cardiac output - the amount of blood pumped through the body.

Cardiac Output

• Represents blood delivered to the body.
• Calculated as: CO = SV x HR (Heart Rate).

Sequence of Events in Cardiac Function

1. Myocyte action potential driven by sodium, potassium, etc.
2. Excitation spreads via gap junctions.
3. Electrocardiogram tracks depolarization.
4. Calcium-induced calcium release by RyR increases cytosolic calcium.
5. Increased cytosolic calcium allows troponin/tropomyosin movement, enabling myosin binding.
6. Myosin ATPase generates force.
7. Cardiac structure transmits force into pressure.
8. Cardiac output is generated, influenced by all prior steps.

Laplace’s Law

• Laplace’s Law describes the relationship between pressure, wall tension, radius, and thickness of a sphere.
• The heart can be approximated as a sphere.
• A larger radius requires less pressure to be generated.
• Laplace's Law can be used to understand dilated cardiomyopathies and hypertension.

Wiggers’ Diagram

• Wiggers’ Diagram describes the relationship between the electrocardiogram (ECG), ventricular pressure, volume, and valve activity during the cardiac cycle.
• The P-wave corresponds to atrial depolarization and contraction, resulting in atrial filling of the ventricle.
• The QRS complex corresponds to ventricular depolarization and contraction, causing ventricular pressure to rise and close the mitral valve, resulting in isovolumic contraction.
• When the ventricular pressure exceeds aortic pressure, the aortic valve opens, allowing blood to exit the ventricle and reducing its volume (ejection).
• As contraction fades and the heart relaxes, the aortic valve closes, leading to a decrease in pressure despite closed valves (isovolumic relaxation).
• Once ventricular pressure falls below atrial pressure, the mitral valve opens, allowing for rapid filling of the ventricle (early rapid filling).
• Diastasis is a period of low blood flow during periods of slow heart rate, occurring following early rapid filling.
• Late atrial filling or atrial systole occurs following diastasis, when a new P-wave causes further atrial filling.
• Systole refers to ventricular contraction and ejection, while diastole refers to ventricular relaxation and filling.

Pressure-Volume Relationships

• Frank-Starling Mechanism: A larger preload (end-diastolic volume, end-diastolic pressure, or right atrial pressure) results in a larger stroke volume.
• Length Dependent Activation: The relationship between sarcomere length and muscle tension, explaining how increasing preload can increase contractility.
• Inotropy: Increased inotropy (contractility) leads to a greater increase in stroke volume.
• Myosin ATPase: Is the primary consumer of ATP in the heart, and, therefore, the primary driver of oxygen consumption by the heart.
• Diastolic Function: Refers to the ability of the heart to relax and fill.
• Diastolic Dysfunction: Is now more common than systolic dysfunction and relates to the heart’s ability to relax and fill passively.

Cardiac Output

• Cardiac Output (CO) is the amount of blood pumped by the heart per minute. It can be calculated using Fick’s method or by multiplying stroke volume (SV) and heart rate (HR): CO = SV * HR.

Final Integration

• Cardiac Function. Cardiac function is a complex interplay of various cellular and structural mechanisms.
• L6 (Myocyte Action Potential): The myocyte action potential is initiated by sodium influx, followed by potassium efflux, and is propagated via gap junctions.
• L7 (Electrocardiogram): The electrocardiogram tracks the path of depolarization across the heart.
• L8 (Calcium-Induced Calcium Release): Calcium-induced calcium released by the ryanodine receptor (RyR) causes an increase in cytosolic calcium.
• L9 (Cardiac Structure): Cardiac structure helps to transmit force (tension/stress) into pressure.
• Integration of Concepts: The integration of action potential, calcium dynamics, muscle contraction, and cardiac structure creates the heart’s ability to generate and control cardiac output.