---

Q2: Conduction System of Heart | Cardiac Action Potential | Heart Block

---

PART 1: CONDUCTION SYSTEM OF THE HEART

Components and Sequence of Activation

---

• Located in the posterior wall of the right atrium, near the opening of the superior vena cava
• Acts as the dominant pacemaker of the heart (intrinsic rate: 60-100 beats/min)
• Fires spontaneously due to its unstable resting membrane potential (automaticity)
• Has the fastest rate of phase 4 (spontaneous) depolarization of all conducting cells
• Suppresses all other latent pacemakers via overdrive suppression

• Impulse spreads from the SA node to the right and left atria via the internodal tracts (anterior, middle, and posterior)
• The atria depolarize and contract
• Simultaneously, the impulse travels to the AV node

• Located in the lower interatrial septum, above the tricuspid valve
• Conduction velocity here is very slow: 0.01-0.05 m/s (slowest in the heart)
• This AV delay (~100 ms) is physiologically important - it ensures the ventricles have enough time to fill with blood before they are activated
• Intrinsic rate if it acts as pacemaker: 40-60 beats/min
• Acts as the only normal electrical bridge between atria and ventricles

• Arises from the AV node and passes through the fibrous skeleton of the heart
• Divides into the right bundle branch (for right ventricle) and left bundle branch (for left ventricle)

• Run along the interventricular septum toward the apex
• The left bundle branch further divides into the left anterior fascicle and left posterior fascicle

• Fine network of fibers spreading from the bundle branches to the subendocardial myocardium
• Conduction velocity is the fastest: 2-4 m/s
• Rapidly and simultaneously distribute impulses to the ventricular myocardium from the apex upward, ensuring efficient ventricular contraction and blood ejection

Summary of Intrinsic Rates (Latent Pacemakers)

The pacemaker with the fastest rate controls heart rate. Under normal conditions, the SA node dominates. If the SA node fails, a latent pacemaker (ectopic focus) takes over.

---

PART 2: CARDIAC ACTION POTENTIAL

A. Action Potential of Ventricular Muscle (Fast-Response)

• Triggered when threshold (~-70 mV) is reached
• Rapid opening of voltage-gated fast Na+ channels → massive Na+ influx (INa)
• Membrane potential rapidly rises from -90 mV to approximately +20 mV
• This is the fastest phase; rate of rise (dV/dT) is highest when the resting potential is most negative

• Brief, rapid repolarization immediately after the upstroke
• Caused by: (a) inactivation of Na+ channels (inactivation gates close) and (b) transient outward K+ current (K+ leaves cell down its electrochemical gradient)

• Unique feature of cardiac action potential (absent in nerve/skeletal muscle)
• Lasts 150-200 ms; membrane potential remains stably depolarized (~0 mV)
• Maintained by a balance: inward Ca2+ current (via L-type Ca2+ channels) = outward K+ current
• The Ca2+ entry during this phase triggers Ca2+-induced Ca2+ release from the sarcoplasmic reticulum, initiating contraction (excitation-contraction coupling)
• L-type Ca2+ channels are blocked by nifedipine, diltiazem, and verapamil

• Gradual then rapid return to resting potential
• Caused by: (a) decrease in Ca2+ conductance (gCa falls → inward Ca2+ current stops) and (b) increase in K+ conductance (gK rises → large outward K+ current, IK)
• Membrane potential returns to -90 mV

• Stable at approximately -90 mV in ventricular cells
• High K+ conductance (IK1) drives membrane toward K+ equilibrium potential
• Inward Na+ and Ca2+ currents balance the outward K+ current
• No spontaneous depolarization in ventricular cells (unlike SA node)

B. Action Potential of SA Node (Slow-Response / Pacemaker Potential)

• The maximum diastolic potential is approximately -65 mV
• There is slow, spontaneous depolarization caused by:
  • Opening of funny current (If) channels (also called HCN channels): carry inward Na+ current
  • Gradual decrease in K+ conductance (as K+ channels close after repolarization)
  • Gradual increase in T-type Ca2+ current
• This slow depolarization brings the membrane to threshold (~-40 mV), triggering the next action potential automatically
• This is the basis of automaticity - the heart's ability to beat without external input

Refractory Periods

• Absolute Refractory Period (ARP): Spans phases 0, 1, 2, and most of phase 3. No stimulus can trigger another action potential. Most Na+ channels are inactivated. Prevents tetanic contraction of cardiac muscle.
• Relative Refractory Period (RRP): Late phase 3. A stronger-than-normal stimulus can trigger an action potential. Some Na+ channels have recovered.
• Supranormal Period: Brief period after RRP where a weaker-than-normal stimulus can trigger an action potential.

---

PART 3: NOTE ON HEART BLOCK

Causes

1. Ischemia of the AV node or bundle (e.g., coronary artery disease)
2. Compression by scar tissue or calcified cardiac structures
3. Inflammation - rheumatic fever, myocarditis, diphtheria
4. Vagal overstimulation (carotid sinus syndrome)
5. Degenerative changes in the elderly
6. Drugs - digitalis, beta-blockers, calcium channel blockers

Classification of AV (Heart) Block

• Definition: Delayed but uninterrupted conduction through the AV node
• ECG: P-R interval prolonged to >0.20 sec (normal: 0.16 sec)
• Every P wave is followed by a QRS complex
• Usually benign; often requires no treatment

• Progressive prolongation of P-R interval with each beat until one QRS is dropped (non-conducted P wave)
• After the dropped beat, P-R interval resets and the cycle repeats
• Caused by abnormality of the AV node
• Usually benign

• P-R interval remains fixed, but periodically a P wave is not followed by a QRS (e.g., 2:1, 3:1 block)
• Caused by abnormality of the Bundle of His-Purkinje system
• More serious; may progress to complete heart block
• Pacemaker implantation often required

• No conduction from atria to ventricles
• Atria and ventricles beat independently (AV dissociation)
• ECG: P waves and QRS complexes are completely dissociated
• Ventricular rate is driven by a ventricular escape pacemaker: 20-40 beats/min
• Patient presents with syncope, dizziness, or Stokes-Adams attacks
• Definitive treatment: Permanent pacemaker implantation

ECG Summary

---

---

Q3: Cardiac Output — Definition, Factors, and Measurement

---

DEFINITION

Cardiac Output = Stroke Volume × Heart Rate

• End-Diastolic Volume (EDV): Volume in ventricle at end of diastole (~140 mL)
• End-Systolic Volume (ESV): Volume remaining after ejection (~70 mL)
• Stroke Volume = EDV - ESV

---

FACTORS AFFECTING CARDIAC OUTPUT

---

A. FACTORS AFFECTING STROKE VOLUME

1. PRELOAD (End-Diastolic Volume / Venous Return)

• Preload is the degree of stretching of the ventricular muscle fibers just before contraction - it corresponds to the end-diastolic volume (EDV)
• The relationship between preload and stroke volume is explained by the Frank-Starling Law of the Heart

The volume ejected by the ventricle in systole is directly proportional to the end-diastolic volume (venous return).

• As venous return increases → EDV increases → ventricular fibers are stretched → increased overlap of actin-myosin filaments → greater cross-bridge formation → greater force of contraction → increased stroke volume and cardiac output
• This ensures cardiac output equals venous return in the steady state
• In the physiologic range, the relationship is nearly linear; only at very high EDV does the curve flatten

• Increased venous return (exercise, lying down, IV fluids)
• Increased blood volume
• Venoconstriction

• Hemorrhage, dehydration
• Standing up (venous pooling)
• Vasodilators (nitrates)

---

2. AFTERLOAD (Aortic Pressure / Resistance to Ejection)

• Afterload is the resistance or pressure against which the ventricle must pump to eject blood - essentially the aortic pressure / total peripheral resistance (TPR)
• An increase in afterload increases the work the ventricle must do to open the aortic valve

• ↑ Afterload → ↑ ESV (less blood ejected) → ↓ Stroke Volume → ↓ Cardiac Output
• ↓ Afterload → ↓ ESV (more blood ejected) → ↑ Stroke Volume → ↑ Cardiac Output

• In hypertension, high afterload reduces cardiac output over time
• Vasodilator drugs (e.g., ACE inhibitors) reduce afterload and improve CO in heart failure

---

3. CONTRACTILITY (Inotropy)

• Contractility (inotropic state) is the intrinsic ability of the myocardium to develop force and shorten, independent of preload and afterload
• It is determined by intracellular Ca²+ concentration - more Ca²+ → more cross-bridge cycling → greater force

• Sympathetic stimulation / Catecholamines (norepinephrine, epinephrine) - act via β1 receptors → ↑ cAMP → ↑ Ca²+
• Digitalis (cardiac glycosides) - inhibit Na⁺/K⁺ ATPase → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²+ exchange → ↑ Ca²+
• Increased heart rate itself (Treppe/Staircase phenomenon)

• Parasympathetic stimulation (acetylcholine)
• Beta-blockers, calcium channel blockers
• Heart failure, myocardial ischemia, acidosis, hypoxia

---

B. FACTORS AFFECTING HEART RATE

1. Autonomic Nervous System

• Sympathetic stimulation (β1 receptors): ↑ heart rate (positive chronotropy) → ↑ CO
• Parasympathetic (vagal) stimulation: ↓ heart rate (negative chronotropy) → ↓ CO

2. Hormones

• Epinephrine, norepinephrine: ↑ heart rate and contractility
• Thyroid hormones: ↑ heart rate (hyperthyroidism → ↑ CO)

3. Temperature

• Fever / hyperthermia: ↑ heart rate → ↑ CO
• Hypothermia: ↓ heart rate → ↓ CO

4. Starling's Law on Heart Rate

• At very high heart rates, diastolic filling time decreases → EDV falls → stroke volume falls → CO may actually decrease (inverse relationship at extremes)

5. Age and Physical Fitness

• Athletes have higher stroke volume (due to cardiac hypertrophy) with lower resting heart rate but normal or higher CO
• CO declines with age due to reduced compliance and contractility

---

Summary Table: Factors Affecting Cardiac Output

---

WAYS TO MEASURE CARDIAC OUTPUT

1. Fick's Principle (Direct Fick Method)

Cardiac Output = O₂ Consumption / (O₂ content of pulmonary vein - O₂ content of pulmonary artery)

CO = O₂ Consumption / (Arterial O₂ content - Venous O₂ content)

• O₂ consumption = 250 mL/min
• Arterial O₂ content = 0.20 mL/mL blood
• Venous O₂ content = 0.15 mL/mL blood

CO = 250 / (0.20 - 0.15) = 250 / 0.05 = 5000 mL/min

• Right heart catheterization (to sample mixed venous blood from pulmonary artery)
• Measurement of O₂ consumption (spirometry)

---

2. Indicator Dilution Method

CO = Amount of indicator injected / (Mean concentration × Duration of curve)

• The area under the concentration-time curve is used to calculate CO
• Thermodilution is the most widely used clinical variant - cold saline (indicator) is injected into right atrium, temperature change detected in pulmonary artery by a thermistor (Swan-Ganz catheter)
• Limitation: Errors with intracardiac shunts, tricuspid regurgitation, rapid IV fluids

---

3. Echocardiography (Non-Invasive)

• 2D echocardiography: Measures EDV and ESV; calculates stroke volume and ejection fraction
• Doppler echocardiography: Measures blood flow velocity in the aorta; CO = Velocity Time Integral × Aortic cross-sectional area × Heart Rate
• Advantage: Non-invasive, bedside, widely available

---

4. Pulse Contour Analysis / Arterial Waveform Analysis

• Continuous CO measurement from the arterial pressure waveform
• Based on the principle that pulse pressure (systolic - diastolic) is proportional to stroke volume
• Devices: PiCCO, LiDCO, FloTrac
• Minimally invasive

---

5. Impedance Cardiography (Thoracic Bioimpedance)

• Measures changes in thoracic electrical impedance caused by pulsatile aortic blood flow
• Non-invasive, continuous measurement
• Less accurate in critical illness

---

6. Magnetic Resonance Imaging (MRI)

• Most accurate non-invasive method for measuring stroke volume and CO
• Phase-contrast MRI measures flow velocity in the aorta
• Used as a reference standard in research

---

---

Cardiac Cycle: Phases with Pressure-Volume Curve

---

DEFINITION

• Duration: ~0.8 seconds at a heart rate of 75 beats/min
• Systole (contraction): ~0.3 seconds
• Diastole (relaxation): ~0.5 seconds

---

WIGGERS DIAGRAM

---

THE SEVEN PHASES OF THE CARDIAC CYCLE

PHASE A — Atrial Systole

• The atria contract following the P wave
• Atrial contraction actively ejects blood into the ventricle through the open mitral valve
• This contributes the final ~20% of ventricular filling (called the "atrial kick")
• Ventricular volume rises to its maximum = End-Diastolic Volume (EDV ~140 mL)
• Left atrial pressure briefly rises, seen as the "a" wave of the venous pulse
• The ventricular pressure shows a small "blip" due to this added volume

---

PHASE B — Isovolumetric Ventricular Contraction

• Ventricular contraction begins with the QRS complex
• As ventricular pressure rises and exceeds left atrial pressure, the mitral valve snaps shut - producing S1
• The aortic valve remains closed because ventricular pressure has not yet reached aortic pressure (~80 mmHg)
• Volume remains constant (all valves closed) - hence "isovolumetric"
• Ventricular pressure rises dramatically from ~0 to ~80 mmHg

---

PHASE C — Rapid Ventricular Ejection

• When ventricular pressure exceeds aortic pressure (~80 mmHg), the aortic valve opens
• Blood is rapidly ejected into the aorta - most of the stroke volume (~70%) is ejected here
• Left ventricular pressure and aortic pressure both rise to their maximum (~120 mmHg = systolic pressure)
• Ventricular volume falls steeply
• Atrial filling begins: left atrial pressure starts slowly rising as pulmonary venous return enters the atrium

---

PHASE D — Reduced Ventricular Ejection

• Ventricular repolarization begins (T wave on ECG)
• Ventricle begins relaxing → ventricular pressure falls
• Blood continues to be ejected (aortic valve still open), but at a slower rate
• Ventricular volume reaches its minimum = End-Systolic Volume (ESV ~70 mL)
• Aortic pressure begins to fall as blood runs off into the peripheral arteries faster than it is being added

Stroke Volume = EDV - ESV = 140 - 70 = 70 mL

---

PHASE E — Isovolumetric Ventricular Relaxation

• When ventricular pressure falls below aortic pressure, the aortic valve closes → produces S2
  • The aortic valve closes slightly before the pulmonic valve
  • During inspiration, splitting of S2 is heard (P2 delayed due to ↑ right heart filling)
  • Dicrotic notch (incisura) appears on the aortic pressure curve at the moment of aortic valve closure
• Both valves are now closed → ventricular volume is constant (isovolumetric)
• Ventricular pressure falls rapidly from ~80 mmHg to near zero
• The mitral valve will open once ventricular pressure falls below atrial pressure

---

PHASE F — Rapid Ventricular Filling

• When ventricular pressure falls below left atrial pressure, the mitral valve opens
• Blood rushes rapidly from the left atrium into the relaxed, compliant ventricle
• Ventricular volume increases rapidly - this is the most rapid phase of filling (~70-80% of filling occurs here)
• Ventricular pressure remains low due to high compliance
• S3 is caused by this rapid rush of blood into the ventricle
  • S3 in adults: suggests volume overload (heart failure, mitral regurgitation)
• Aortic pressure continues to fall as blood runs off into the arterial tree

---

PHASE G — Reduced Ventricular Filling (Diastasis)

• This is the longest phase of the cardiac cycle
• Ventricular filling continues at a slow rate as atrial and ventricular pressures equilibrate
• Ventricular volume gradually increases toward EDV
• At the end of this phase, atrial systole (Phase A) occurs again → the cycle repeats
• Important: With tachycardia (↑ heart rate), diastasis is the first phase to be shortened, which reduces EDV and stroke volume

---

Summary Table of the Cardiac Cycle

---

LEFT VENTRICULAR PRESSURE-VOLUME (P-V) LOOP

Understanding the Loop (Counter-clockwise traversal):

• Starts at Point 1 = End of diastole (EDV = 140 mL, pressure ~5 mmHg)
• All valves closed → ventricular pressure rises sharply with no change in volume
• Represented as a vertical line going upward on the right side of the loop
• Ends at Point 2 when ventricular pressure = aortic pressure (~80 mmHg) → aortic valve opens

• Aortic valve opens → blood ejected into aorta
• Volume decreases from 140 mL (EDV) to 70 mL (ESV)
• Pressure rises to peak (~120 mmHg) then falls
• Represented as the curved top portion of the loop
• Ends at Point 3 = End of systole (ESV ~70 mL) - this point touches the systolic pressure-volume curve (dashed line)
• The width of the loop = Stroke Volume (70 mL)

• Aortic valve closes → both valves closed → pressure falls sharply with no change in volume
• Represented as a vertical line going downward on the left side of the loop
• Ends at Point 4 when ventricular pressure falls below atrial pressure → mitral valve opens

• Mitral valve opens → ventricle fills passively then actively (atrial systole)
• Volume increases from ESV (70 mL) back to EDV (140 mL) at low pressure
• Represented as the flat bottom portion of the loop

Key Information from the P-V Loop:

Effects on the P-V Loop:

---