---

1. Ventricular Muscle Action Potential

---

Phase 4 - Resting Membrane Potential

• Value: approximately -90 mV
• Maintained primarily by a high K+ conductance (gK); the membrane is most permeable to K+ at rest
• K+ moves out down its concentration gradient, leaving net negative charge inside
• Unlike SA/AV nodal cells, ventricular muscle shows no spontaneous depolarization (no "funny current" / If) - it is a stable flat line

---

Phase 0 - Upstroke (Rapid Depolarization)

• Triggered when an arriving impulse depolarizes the membrane to threshold (~-70 mV)
• Sudden opening of fast voltage-gated Na+ channels (activation gates open rapidly)
• Large inward Na+ current (INa) rapidly drives membrane toward ENa (+65 mV)
• Peak of upstroke reaches approximately +20 mV
• Na+ channels then close as inactivation gates respond to depolarization
• Rate of rise = dV/dT; greatest when resting membrane potential is most negative (-90 mV), because more Na+ channels have open inactivation gates

---

Phase 1 - Initial (Brief) Repolarization

• Short, transient dip after the upstroke peak
• Two mechanisms:
  1. Closure of Na+ channel inactivation gates → inward Na+ current ceases
  2. Transient outward K+ current (Ito) - at peak upstroke, large electrochemical driving force pushes K+ out of cell

---

Phase 2 - Plateau

• Duration: 150-200 ms - unique to cardiac muscle (absent in nerve/skeletal muscle)
• Maintained by a balance of inward and outward currents (net current ≈ 0):
  • Inward: L-type Ca2+ channels open → slow inward Ca2+ current (ICa-L) - also called "slow inward current"
    • Blocked by: nifedipine, diltiazem, verapamil
  • Outward: sustained K+ current (IK), driven by electrochemical gradient
• The Ca2+ influx during Phase 2 triggers Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (CICR) - essential for excitation-contraction coupling
• Physiological importance: the plateau creates a long absolute refractory period, preventing re-stimulation of the ventricle before it has relaxed - the heart cannot tetanize

---

Phase 3 - Rapid Repolarization

• Inward Ca2+ current decreases (gCa falls as L-type channels inactivate)
• Simultaneously, K+ conductance increases further (IK rises) → large outward K+ current
• Net outward current drives membrane potential back toward resting level (~-90 mV)
• As repolarization proceeds, driving force on K+ decreases (approaching EK), so IK gradually lessens

---

Phase 4 - Resting (Restored)

• Membrane returns to -90 mV
• Na+/K+ ATPase restores ionic gradients; Na+/Ca2+ exchanger removes Ca2+ that entered during Phase 2

---

---

2. Conducting System of the Heart

Components (in order of impulse travel)

• Location: beneath the epicardium on the posterior wall of the right atrium, near the opening of the superior vena cava, in the sulcus terminalis cordis (Keith-Flack node)
• Size: ~10 mm long, spindle-shaped
• Intrinsic rate: 60-80 impulses/minute (fastest of all pacemaker cells)
• Generates spontaneous action potentials due to the "funny current" (If) causing slow Phase 4 depolarization
• Sets the normal heart rate (sinoatrial nodal rhythm)

• Impulse spreads from the SA node through the working myocardium of the right atrium to the AV node via preferential intra-atrial pathways with higher conduction velocity
• Simultaneously activates both atria

• Location: at the atrioventricular septum in the interatrial septum (Koch's triangle), between the coronary sinus opening and septal cusp of the tricuspid valve (Aschoff-Tawara node)
• Size: ~5 mm long
• Intrinsic rate: 50-60 impulses/minute (overridden by SA node normally)
• Key functional property: AV nodal delay (approx. 0.1 s) - slows conduction to allow ventricular filling before contraction
• Only normal electrical connection between atria and ventricles (the fibrous annulus electrically insulates the rest)
• Action potential: relies on L-type Ca2+ channels (ICa-L) for Phase 0 (no fast Na+ channels); slow upstroke; Phase 4 depolarization present

• Extends from the AV node through the central fibrous body (cardiac skeleton) into the muscular interventricular septum
• Penetrating bundle traverses the annulus fibrosis; insulated from surrounding myocardium
• Blood supply: AV nodal artery (from RCA in 80-90%) and first septal perforator of LAD

• Curves down the right side of the interventricular septum, enters the septomarginal trabecula (moderator band), reaches the anterior papillary muscle
• Peripheral branches form a subendocardial plexus, terminating at papillary muscles and ventricular myocardium near the apex

• Fans out as flat broad bundles along the left side of the interventricular septum
• Divides into anterior fascicle and posterior fascicle, proceeding toward the papillary muscle bases
• Blood supply: dual (from LAD and posterior descending artery branches)

• Terminal subendocardial network from both bundle branches
• Fastest conduction in the heart: 1-3 m/s
• Action potential: rapid upstroke (fast Na+ channels), prolonged plateau, modest Phase 4 automaticity
• Transmit impulses rapidly to ventricular myocardium from apex toward base

Hierarchy of Pacemakers

---

---

3. Types of Heart Block

---

First-Degree AV Block

• Definition: All atrial impulses are conducted to the ventricle, but with abnormal delay
• ECG: PR interval > 200 ms (fixed prolongation), every P wave followed by a QRS
• Location: Delay usually within the AV node (may also be in atria, His bundle, or Purkinje)
• Significance: Generally benign; does not typically warrant pacing
• Note: "block" is a misnomer - conduction is slowed, not interrupted

---

Second-Degree AV Block

• ECG: Progressive lengthening of the PR interval with each beat, until one P wave is not conducted ("dropped" QRS - the "dropped beat")
• Classic feature: PR interval before the dropped beat is longest; first PR after is shortest; RR intervals show progressive shortening
• Location: Typically within the AV node
• Significance: Usually hemodynamically stable; does not typically require pacing in the absence of symptoms
• Common in athletes (high vagal tone) or inferior MI

• ECG: Fixed PR interval (no progressive prolongation) preceding a suddenly non-conducted P wave
• Usually associated with QRS widening (bundle branch block pattern)
• Location: Infranodal (His bundle or bundle branches)
• Significance: More serious - risk of sudden death; permanent pacing required even without symptoms due to unpredictable complete block
• In 2:1 AV block, Type I vs II cannot be distinguished on ECG alone; if PR < 160 ms + wide QRS → infranodal (Type II) more likely

---

Third-Degree AV Block (Complete Heart Block)

• Definition: Complete interruption of conduction between atria and ventricles (AV dissociation)
• ECG: P waves and QRS complexes are independent, with ventricular rate slower than atrial rate
• Ventricular rhythm maintained by an escape pacemaker:
  • Narrow QRS escape rhythm → block in AV node/proximal His (rate ~50-60 bpm; more stable)
  • Wide QRS escape rhythm → block in distal His/bundle branches (rate ~25-45 bpm; unreliable)
• Significance: Life-threatening; permanent pacing is required

Summary Table

---

---

4. Factors Affecting Venous Return

---

1. Mean Systemic Filling Pressure (MSFP)

• The equilibrium pressure in the vascular system when flow is zero
• Increased by: Blood volume transfusion; venoconstriction (sympathetic tone increases venomotor tone, squeezing the unstressed volume into stressed volume)
• Decreased by: Hemorrhage/hypovolemia; venodilation
• A higher MSFP increases the driving pressure gradient for venous return → increases VR

2. Blood Volume

• Direct effect on MSFP: more blood → greater stressed volume → higher MSFP → higher VR
• Volume expansion (e.g., IV fluids, transfusion): shifts vascular function curve right → increases VR
• Volume depletion (e.g., hemorrhage, dehydration): shifts curve left → decreases VR

3. Right Atrial Pressure (RAP / CVP)

• Inverse relationship with VR: as RAP rises, the pressure gradient (MSFP - RAP) falls → VR decreases
• Reduced RAP (e.g., reduced cardiac filling) → increased gradient → increased VR
• Very negative RAP causes venous collapse (veins buckle), creating a "waterfall effect" that limits further increase in VR (the flat "knee" of the vascular function curve)

4. Venomotor Tone (Venoconstriction / Venodilation)

• Most blood volume (~70%) resides in veins; venomotor tone controls how much is in the "unstressed" vs. "stressed" compartment
• Venoconstriction (sympathetic stimulation, epinephrine): decreases venous compliance → shifts blood from unstressed to stressed volume → acts like a transfusion → raises MSFP → increases VR
• Venodilation (nitrates, heat): acts like a blood loss → reduces MSFP → decreases VR

5. Total Peripheral Resistance (TPR) / Arteriolar Tone

• Arterioles contain little of the total blood volume, so they don't affect MSFP much
• However, arteriolar resistance affects the slope of the vascular function curve:
  • Arteriolar dilation → blood redistributes from arterial to venous side → raises capillary venous pressure (CVP) → increases VR (steeper vascular function curve)
  • Arteriolar constriction → lowers CVP → decreases VR (flatter curve)

6. Skeletal Muscle Pump

• Rhythmic contraction of skeletal muscles compresses veins, propelling blood toward the heart
• Venous valves prevent backflow
• Major factor during exercise - dramatically increases VR and cardiac output

7. Respiratory Pump (Thoracic Pump)

• During inspiration: intrathoracic pressure falls → right atrial pressure decreases → pressure gradient increases → VR increases
• During expiration: reverse effect
• Positive pressure ventilation (IPPV) impairs this mechanism → reduces VR

8. Gravity / Body Position

• Standing: hydrostatic pressure increases venous pressure in lower limbs → venous pooling → reduces effective VR (can cause orthostatic hypotension)
• Lying flat or raising legs: reverses pooling → increases VR
• Trendelenburg position increases VR

9. Heart Rate and Cardiac Contractility (Indirect)

• A more vigorously contracting heart empties more completely → reduces RAP → increases the MSFP-RAP gradient → "sucks" more venous return
• Increased cardiac output lowers RAP, which in turn augments VR (Frank-Starling mechanism working in reverse to maintain steady state)

10. Intrapericardial Pressure / Cardiac Tamponade

• Elevated pericardial pressure compresses the heart, raises RAP → reduces VR → reduces cardiac output

---

Summary Table - Factors Affecting Venous Return