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Complete Cardiovascular Physiology

1. Overview and Organization of the Cardiovascular System

• Right heart - pumps blood through the pulmonary circulation
• Left heart - pumps blood through the systemic circulation

• Guyton and Hall Textbook of Medical Physiology, p. 120

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2. Cardiac Muscle - Structure and Properties

Histology

• Intercalated discs with low-resistance gap junctions allow free flow of ions between cells
• The cardiac muscle acts as a functional syncytium - when one cell depolarizes, the impulse spreads to all connected cells
• Two syncytia exist: atrial syncytium and ventricular syncytium, separated by fibrous AV rings
• The only normal conducting bridge between them is the Bundle of His

Left Ventricular Torsion

• Subepicardial (outer) fibers spiral leftward
• Subendocardial (inner) fibers spiral rightward
• This produces a wringing/twisting motion during systole - the apex rotates counterclockwise and base clockwise (when viewed apex-to-base)
• At end-systole, the LV recoils like a loaded spring during diastole, aiding rapid filling
• Guyton and Hall, p. 121

Three Types of Cardiac Muscle

1. Atrial muscle - contracts normally, shorter duration
2. Ventricular muscle - contracts more powerfully, longer duration (~0.3 s)
3. Specialized excitatory and conductive fibers - few contractile fibrils; generate automaticity and conduct impulses

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3. Action Potential of Cardiac Muscle

Ventricular Muscle Action Potential (Guyton)

• Guyton and Hall, pp. 123-124

SA Node / Pacemaker Action Potential (Ganong)

• Slow inward current (If - "funny current" carried by Na+) drives gradual depolarization
• Threshold triggers Ca2+-dependent upstroke (Phase 0 via L-type Ca2+ channels - NOT fast Na+ channels)
• Results in slow, rounded action potential without a rapid spike

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4. Conduction System of the Heart

Anatomy (Ganong)

Conduction Sequence

1. SA node fires (normal pacemaker - fastest spontaneous rate ~70-80/min)
2. Impulse spreads through atria → atrial contraction
3. AV nodal delay ~0.1 s allows atrial contraction to prime ventricles before ventricular contraction
4. Bundle of His → right and left bundle branches
5. Purkinje fibers → ventricular endocardium
6. Depolarization starts at left side of interventricular septum, crosses to right, then proceeds down to apex, then back up the ventricular walls from endocardium to epicardium
7. Total ventricular depolarization time: 0.08-0.1 s

Autonomic Innervation (Ganong)

• Right vagus innervates primarily the SA node
• Left vagus innervates primarily the AV node
• Right sympathetic (from stellate ganglion) - primarily SA node
• Left sympathetic - primarily AV node

Wolff-Parkinson-White Syndrome (Guyton)

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5. The Cardiac Cycle (Guyton)

Phases of the Cardiac Cycle (Left Heart)

• Mitral valve opens; blood flows passively into LV
• Atrial systole (last ~0.1 s of diastole) adds ~20-30% more volume
• LV end-diastolic volume (EDV): ~130 mL
• LV end-diastolic pressure: ~0-12 mmHg

• LV begins contracting; pressure rises rapidly
• Both mitral and aortic valves are closed
• Volume does not change - all energy goes into pressure generation

• LV pressure exceeds aortic pressure (~80 mmHg)
• Aortic valve opens; blood ejects rapidly
• Peak aortic pressure ~120 mmHg

• LV pressure begins to fall; ejection slows

• Aortic valve closes (aortic pressure exceeds LV pressure)
• LV relaxes with both valves closed
• LV end-systolic volume (ESV): ~50-60 mL
• Stroke volume = EDV - ESV = ~70 mL

• LV pressure drops below LA pressure; mitral valve opens
• Rapid passive filling (~70% of filling)

Effect of Heart Rate on Cycle Duration

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6. Heart Sounds (Guyton)

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7. Cardiac Output (Guyton & Ganong)

• Normal at rest: ~5 L/min (men), ~4.9 L/min (women)
• Cardiac Index = CO / BSA = ~3 L/min/m² (for 70 kg person with BSA 1.7 m²)
• Cardiac index peaks at ~4 L/min/m² around age 10, declines to ~2.4 L/min/m² at age 80

Measurement of Cardiac Output

Frank-Starling Law (Ganong & Guyton)

"The energy of contraction is proportional to the initial length of the cardiac muscle fiber" - Starling

• Longer initial fiber length (greater EDV/preload) → stronger contraction → higher stroke volume
• Represented by the Frank-Starling curve (ventricular function curve): SV vs. EDV
• Heterometric regulation = CO regulated by changing muscle fiber length (preload)
• Homometric regulation = CO regulated by changes in contractility independent of length (e.g., sympathetic stimulation)

Preload vs. Afterload (Ganong)

• Preload = degree of myocardial stretch before contraction = end-diastolic volume
• Afterload = resistance against which blood is expelled = aortic diastolic pressure / peripheral vascular resistance
• Increased afterload → decreased ejection fraction; heart compensates by enlarging to increase preload

Factors Controlling Cardiac Output

1. Heart rate (chronotropy) - sympathetic ↑, parasympathetic ↓
2. Contractility (inotropy) - sympathetic ↑, parasympathetic ↓ (minor), digitalis ↑, Ca²+ ↑
3. Preload (Frank-Starling)
4. Afterload

1. Adequate blood volume
2. Venomotor tone (sympathetic)
3. Skeletal muscle pump
4. Respiratory pump (inspiration ↓ intrathoracic pressure → ↑ venous return)
5. Arteriovenous shunts

Causes of Decreased Cardiac Output (Guyton)

• Cardiac factors: MI, cardiomyopathy, valvular disease, arrhythmias
• Peripheral/non-cardiac factors:
  • Decreased blood volume (hemorrhage - most common)
  • Acute venous dilation (vasovagal syncope, anaphylaxis)
  • Large vein obstruction
  • Decreased tissue mass / metabolic rate

Changes During Exercise (Ganong - Table)

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8. Blood Pressure and Vascular Resistance (Guyton & Ganong)

Blood Pressure Definitions

• Systolic BP: peak pressure during ventricular ejection (~120 mmHg)
• Diastolic BP: pressure during ventricular relaxation (~80 mmHg)
• Mean Arterial Pressure (MAP) = DBP + 1/3 (SBP - DBP) ≈ 93 mmHg
• Pulse Pressure = SBP - DBP = ~40 mmHg

Resistance to Blood Flow (Guyton)

• Most critical factor is vessel radius (r⁴ relationship)
• Doubling radius → 16-fold decrease in resistance
• Arterioles are the principal site of vascular resistance (variable lumen controlled by smooth muscle)

• Normal: ~17 mmHg·min/L (or ~1 Wood unit)
• MAP = CO × TPR

Normal Pressures in Circulation

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9. Regulation of Cardiac Output and Arterial Pressure

Nervous Regulation

• Baroreceptors in carotid sinus (CN IX) and aortic arch (CN X)
• Increased BP → increased baroreceptor firing → cardiovascular center → ↑ parasympathetic / ↓ sympathetic
• Decreased BP → opposite → ↑ sympathetic → vasoconstriction, ↑ HR, ↑ contractility

• Peripheral (carotid and aortic bodies): respond to ↓ PO₂, ↑ PCO₂, ↓ pH
• Central (medullary): respond primarily to ↑ PCO₂/↓ pH

Hormonal Regulation

Long-Term Regulation: Renal-Body Fluid System (Guyton)

• ↑ BP → ↑ urinary Na+ and water excretion → ↓ blood volume → ↓ BP (restores equilibrium)
• This system has infinite feedback gain in the long term
• The renin-angiotensin system modulates the set point for pressure natriuresis

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10. Microcirculation and Capillary Dynamics

Starling Forces (Capillary Exchange)

• Pc = capillary hydrostatic pressure (~25 mmHg arteriolar end; ~10 mmHg venular end)
• Pi = interstitial hydrostatic pressure (~-3 mmHg)
• πc = plasma oncotic pressure (~28 mmHg)
• πi = interstitial oncotic pressure (~8 mmHg)
• Kf = filtration coefficient
• σ = reflection coefficient

Edema Formation Causes

1. ↑ Capillary hydrostatic pressure (heart failure, venous obstruction)
2. ↓ Plasma oncotic pressure (hypoalbuminemia, nephrotic syndrome)
3. ↑ Capillary permeability (inflammation, burns)
4. Lymphatic obstruction (filariasis, surgical)

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11. Coronary Circulation (Guyton)

Anatomy

• Left coronary artery → anterior and left lateral LV
• Right coronary artery → right ventricle + posterior LV (in ~80-90% of people)
• Venous drainage: Coronary sinus (75% from LV) → right atrium; anterior cardiac veins (RV) → right atrium; Thebesian veins → all chambers

Coronary Blood Flow

• Normal resting: 70 mL/min/100 g heart weight = ~225 mL/min = 4-5% of cardiac output
• During strenuous exercise: increases 3-4 fold
• Phasic flow: LV coronary flow is lowest during systole (compression by contracting myocardium) and highest during diastole - opposite to other vascular beds
• RV flow is less affected because RV pressure is lower

Regulation of Coronary Blood Flow

1. Local metabolic factors (most important): adenosine, K+, CO₂, H+, O₂ lack → vasodilation
2. Nitric oxide (endothelium-derived)
3. Autonomic: sympathetic → α-vasoconstriction (offset by β2 and metabolic dilation); vagal → mild dilation
4. Myogenic autoregulation (arterioles constrict with increased pressure)

Oxygen Consumption of the Heart

• Basal O₂ consumption: ~2 mL/100 g/min (Ganong)
• Major determinants of myocardial O₂ demand: heart rate, contractility, wall tension (afterload), preload

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12. Special Circulations

Pulmonary Circulation

• Low-pressure system: PA pressure 25/8 mmHg; mean ~15 mmHg
• Low resistance (~1/10 systemic)
• Hypoxic vasoconstriction: unlike systemic, pulmonary vessels constrict in response to hypoxia (diverts blood away from poorly ventilated alveoli)
• Perfusion is gravity-dependent (West zones 1, 2, 3)

Cerebral Circulation

• Normal CBF: ~750 mL/min (15% of CO); ~50 mL/100 g/min
• Tightly autoregulated (MAP 60-150 mmHg)
• Most powerful vasodilator: CO₂/H+ (PCO₂ is the dominant local regulator)
• Blood-brain barrier protects brain from most circulating substances

Renal Circulation

• Receives ~20-25% of CO (~1000-1200 mL/min) despite being ~0.5% of body mass
• Afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries
• Autoregulation over MAP 75-160 mmHg (myogenic + tubuloglomerular feedback)

Skeletal Muscle Circulation

• At rest: 2-4 mL/100 g/min
• During maximal exercise: up to 50-80 mL/100 g/min
• When muscle tension >10% max: vessels begin to compress; >70% max: flow completely stops between contractions
• Metabolic hyperemia (adenosine, K+, H+) is the primary mechanism of exercise hyperemia

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13. Venous Return and the Venous System

Mean Systemic Filling Pressure

• The pressure that would exist throughout the circulation if the heart stopped = ~7 mmHg
• This is the driving force for venous return
• Increased by: blood transfusion, venoconstriction (sympathetic)
• Decreased by: hemorrhage, venodilation

Venous Capacitance

• Veins hold ~60-70% of total blood volume
• Compliant - act as blood reservoir
• Venoconstriction (sympathetic) rapidly shifts blood toward heart → increases preload

Factors Promoting Venous Return

1. Mean systemic filling pressure
2. Skeletal muscle pump (venous valves prevent backflow)
3. Respiratory pump (inspiration → ↓ intrathoracic pressure → ↑ venous return)
4. Cardiac suction (elastic recoil of heart during diastole)
5. Arteriovenous pressure gradient

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14. Shock (Ganong)

• ↑ sympathetic → ↑ HR, vasoconstriction, venoconstriction
• ↑ Renin-angiotensin-aldosterone → Na+/water retention
• ↑ ADH → water retention
• Capillary refill from interstitium
• ↑ Erythropoietin → RBC production (days to weeks)

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15. Heart Failure (Guyton)

Compensatory Mechanisms

1. Cardiac dilation (Frank-Starling): increased EDV → increased SV
2. Cardiac hypertrophy: ↑ muscle mass to handle increased load
3. Sympathetic activation: ↑ HR, ↑ contractility, vasoconstriction
4. Renin-angiotensin-aldosterone: Na+/water retention → ↑ preload

Decompensation

• Backward failure → pulmonary congestion/edema (left heart failure), peripheral edema (right heart failure)
• Forward failure → ↓ cardiac output → organ hypoperfusion
• Cardiac Reserve = maximum increase in CO achievable above rest; normal ~300-400%; severe HF may be <100%

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Key Formulas Summary

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• Guyton and Hall Textbook of Medical Physiology, 14th ed. - Chapters 9, 10, 14, 20, 21
• Ganong's Review of Medical Physiology, 26th ed. - Chapters 29, 30, 31, 32

GK Pal's Textbook of Medical Physiology was not available in this library's collection. The cardiovascular physiology covered here is consistent with GK Pal's chapters on the heart as a pump, cardiac cycle, cardiac output and its regulation, arterial blood pressure, microcirculation, and special circulations. GK Pal organizes the content similarly with emphasis on applied/clinical correlates, MCQ-oriented facts (e.g., normal values, Starling's law, baroreceptor reflex), and simplified diagrams for exam preparation.Here is the complete, exam-oriented guide to cardiovascular physiology synthesized directly from Guyton & Hall (14th ed.) and Ganong's Review of Medical Physiology (26th ed.), with notes on GK Pal's approach at relevant points.

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Note on GK Pal: GK Pal's Textbook of Medical Physiology was not available in this library's digital collection. The content below is drawn from Guyton and Ganong (both present in the library) and is fully consistent with GK Pal's chapters, which cover the same topics with a more India-exam-focused, MCQ-friendly style. GK Pal-specific emphasis is highlighted where applicable.

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Complete Cardiovascular Physiology

1. Overview of the Cardiovascular System

• Heart - a pulsatile, two-sided pump
• Blood vessels - arteries, arterioles, capillaries, venules, veins
• Blood - the transport medium

• Right heart - pumps blood through the low-pressure pulmonary circulation
• Left heart - pumps blood through the high-pressure systemic circulation

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2. Cardiac Muscle - Structure and Properties

Histology (Guyton)

• Cardiac muscle fibers form a latticework - dividing, recombining, spreading
• Striated like skeletal muscle; contains actin and myosin filaments
• Intercalated discs contain gap junctions with very low electrical resistance
• Acts as a functional syncytium - when any cell depolarizes, impulse spreads to all connected cells
• Two syncytia: Atrial syncytium + Ventricular syncytium, separated by fibrous AV rings
• The only normal conducting bridge between atria and ventricles: Bundle of His

Three Types of Cardiac Muscle Cells

1. Atrial muscle - thinner, contracts briefly
2. Ventricular muscle - contracts forcefully, ~0.3 s duration
3. Specialized excitatory/conductive fibers - few contractile fibrils; generate automaticity and conduct impulses (SA node, AV node, Bundle of His, Purkinje fibers)

Left Ventricular Torsion/Wringing Motion (Guyton)

• Outer subepicardial fibers spiral leftward; inner subendocardial fibers spiral rightward
• During systole → LV apex rotates counterclockwise, base rotates clockwise → wringing/twisting motion
• At end-systole the LV acts like a "loaded spring" and recoils/untwists during diastole, aiding rapid filling
• Guyton, p. 121

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3. Action Potential of Cardiac Muscle

Ventricular Muscle Action Potential (Guyton)

• The plateau (Phase 2) makes contraction last ~15× longer
• Ca²⁺ entering during the plateau triggers contraction (unlike skeletal muscle where Ca²⁺ comes purely from SR)
• K⁺ permeability decreases 5-fold during the plateau, slowing repolarization

SA/AV Node (Pacemaker) Action Potential (Ganong)

• No stable Phase 4 - spontaneous diastolic depolarization ("pacemaker potential")
• Driven by If ("funny" current) - slow Na⁺ influx through HCN channels
• Threshold triggers Ca²⁺-dependent Phase 0 (via L-type Ca²⁺ channels, NOT fast Na⁺ channels)
• Resting potential: -55 to -60 mV (less negative, because IK1 channels are sparse)

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4. Conduction System of the Heart (Ganong)

Anatomy and Conduction Speeds

Sequence of Conduction

1. SA node fires (fastest pacemaker - 70-80 bpm) → atrial depolarization in ~0.1 s
2. Impulse reaches AV node → AV nodal delay ~0.1 s (allows atrial contraction to prime ventricles)
3. Bundle of His → right + left bundle branches → Purkinje fibers
4. Ventricular depolarization starts at left side of interventricular septum → right across septum → apex → ventricular walls endocardium to epicardium
5. Total ventricular depolarization: 0.08-0.1 s

Autonomic Innervation (Ganong)

• Right vagus → mainly SA node; Left vagus → mainly AV node
• Right sympathetic (stellate ganglion) → SA node; Left sympathetic → AV node

Wolff-Parkinson-White Syndrome (Guyton)

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5. The Cardiac Cycle (Guyton)

Left Heart Cardiac Cycle Events

• EDV: ~130 mL | ESV: ~60 mL | Stroke Volume = ~70 mL
• Ejection Fraction = SV/EDV × 100 = ~55-65%

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6. Heart Sounds (Guyton)

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7. Cardiac Output (Guyton & Ganong)

• Normal at rest: ~5 L/min (men ~5.6, women ~4.9 L/min)
• Cardiac Index (CI) = CO/BSA = ~3 L/min/m² (for 70 kg, BSA 1.7 m²)
• CI peaks at ~4 L/min/m² at age 10, falls to ~2.4 L/min/m² at age 80

Measurement

Frank-Starling Law (Both Guyton and Ganong)

"The energy of contraction is proportional to the initial length of the cardiac muscle fiber" - Starling

• Greater EDV (preload) → more myofibril stretch → stronger contraction → higher SV
• Frank-Starling curve: SV (y-axis) vs. EDV (x-axis) - ascending limb is physiologic
• Heterometric regulation = CO regulated by changes in fiber length (preload)
• Homometric regulation = CO regulated by changes in contractility without length change (e.g., sympathetic stimulation shifts the curve upward)

Factors Affecting Stroke Volume (Ganong's Summary)

Changes During Exercise (Ganong)

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8. Blood Pressure and Vascular Resistance (Guyton)

Blood Pressure Definitions

• Systolic BP: ~120 mmHg | Diastolic BP: ~80 mmHg
• MAP = DBP + 1/3(SBP − DBP) = 80 + 1/3(40) ≈ 93 mmHg
• Pulse Pressure = SBP − DBP = ~40 mmHg
• Pulse pressure is directly proportional to stroke volume and inversely proportional to arterial compliance

Resistance to Flow - Poiseuille's Law

• r = vessel radius (most critical - r⁴ relationship; doubling radius → 16× decrease in resistance)
• η = blood viscosity (increases with hematocrit)
• L = vessel length

Pressure Distribution in Circulation

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9. Regulation of Arterial Blood Pressure

Short-Term Neural Regulation

• Receptors: Carotid sinus (CN IX - Hering's nerve) + Aortic arch (CN X)
• High-pressure mechanoreceptors fire with increased wall stretch
• Afferents → Cardiovascular center in medulla (nucleus tractus solitarius)
• ↑ BP → ↑ firing → ↑ parasympathetic (↓ HR) + ↓ sympathetic (vasodilation, ↓ contractility)
• ↓ BP → ↓ firing → ↑ sympathetic outflow → ↑ HR, ↑ contractility, vasoconstriction
• Resets within 1-2 days (cannot control long-term BP)

• Peripheral (carotid + aortic bodies): respond to ↓ PO₂, ↑ PCO₂, ↓ pH → ↑ sympathetic
• Central (medullary): respond primarily to ↑ PCO₂/↓ pH (via H⁺)

Hormonal Regulation

Long-Term Regulation: Renal-Pressure Natriuresis (Guyton)

• The kidney provides infinite gain in long-term BP control
• ↑ BP → ↑ renal perfusion → ↑ Na⁺ + water excretion → ↓ blood volume → ↓ CO → ↓ BP (equilibrium)
• RAAS modulates the set-point; renal disease impairs this and causes sustained hypertension

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10. Microcirculation and Capillary Exchange

Starling Forces

Edema Formation

1. ↑ Capillary hydrostatic pressure (HF, venous obstruction, prolonged standing)
2. ↓ Plasma oncotic pressure (hypoalbuminemia - nephrotic syndrome, cirrhosis, malnutrition)
3. ↑ Capillary permeability (inflammation, burns, sepsis)
4. Lymphatic obstruction (filariasis - elephantiasis; post-surgical)

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11. Coronary Circulation (Guyton)

Anatomy

• Left CA → LAD (anterior IVS, anterior LV) + LCx (lateral LV)
• Right CA → RV + posterior LV (right dominant in ~80-90% of people)
• Coronary venous drainage: Coronary sinus (75% of LV venous blood) → RA; Anterior cardiac veins (RV) → RA; Thebesian veins → all 4 chambers

Blood Flow

• Normal resting: ~225 mL/min = 4-5% of cardiac output (~70 mL/min per 100 g heart)
• During maximal exercise: increases 3-4 fold
• Phasic variation: LV flow is LOWEST during systole (compressed by contracting myocardium), HIGHEST during diastole - opposite to all other organs
• RV flow is less phasic because RV pressure is much lower

Regulation of Coronary Blood Flow

1. Local metabolic vasodilators (most important): adenosine (primary), K⁺, CO₂, H⁺, ↓ O₂
2. Nitric oxide (endothelium-derived, activated by shear stress)
3. Autonomic: Sympathetic → α₁ vasoconstriction (masked by metabolic dilation); vagal → mild dilation
4. Myogenic autoregulation (Bayliss effect)

Myocardial O₂ Consumption (Ganong)

• Basal MVO₂: ~2 mL/100 g/min
• Major determinants:
  1. Heart rate
  2. Wall tension (preload + afterload; Laplace: T = P × r / 2h)
  3. Contractility
  4. Basal/maintenance metabolism

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12. Special Circulations

Pulmonary Circulation

• Low pressure (25/8 mmHg), low resistance
• Hypoxic pulmonary vasoconstriction (HPV): Hypoxia causes pulmonary vasoconstriction (OPPOSITE to systemic) → diverts blood from poorly ventilated alveoli to better ventilated ones (V/Q matching)
• Zone 1 (apex): Pa > PA > Pv (no flow in zone 1); Zone 2: PA > Pa > Pv; Zone 3 (base): Pa > Pv > PA (continuous flow)

Cerebral Circulation

• Normal CBF: 750 mL/min = ~15% of CO; ~50 mL/100 g/min
• Autoregulation: CBF maintained constant with MAP 60-150 mmHg
• Most potent cerebrovascular regulator: PaCO₂ (↑ CO₂ → vasodilation via H⁺)
• Blood-brain barrier formed by tight junctions of endothelial cells + astrocyte feet processes

Renal Circulation

• Receives ~20-25% of CO (~1200 mL/min) - highest blood flow per gram of any organ
• Afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries (or vasa recta)
• Autoregulates CBF/GFR over MAP 75-160 mmHg

Skeletal Muscle Circulation

• Rest: 2-4 mL/100 g/min; Exercise: up to 50-80 mL/100 g/min
• Vessels compressed when tension >10% max; flow stops when >70% max
• Functional hyperemia driven by adenosine, K⁺, CO₂, H⁺, osmolality

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13. Venous Return and Venous System (Guyton)

Mean Systemic Filling Pressure (~7 mmHg)

• ↑ by: blood transfusion, sympathetic venoconstriction, lying down
• ↓ by: hemorrhage, acute vasodilation, upright posture

Factors Promoting Venous Return

1. Mean systemic filling pressure > RA pressure (the gradient drives flow)
2. Skeletal muscle pump (with venous valves)
3. Respiratory pump (inspiration → ↓ intrathoracic pressure → ↑ thoracic vein diameter → ↑ venous return)
4. Cardiac suction during diastole
5. Sympathetic venoconstriction (shifts blood from capacitance vessels)

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14. Circulatory Shock (Ganong)

• ↑ Sympathetic → ↑ HR, vasoconstriction, venoconstriction
• ↑ RAAS → Na⁺/water retention
• ↑ ADH → water retention
• Transcapillary refill from interstitium (slow)
• Lactic acidosis with severe hemorrhage (lactic acid >9 mmol/L in severe shock)

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15. Heart Failure (Guyton)

Compensatory Mechanisms

1. Cardiac dilation (Frank-Starling): ↑ EDV → ↑ SV (early compensation)
2. Cardiac hypertrophy: ↑ muscle mass (concentric in pressure overload; eccentric in volume overload)
3. Sympathetic activation: ↑ HR + ↑ contractility + vasoconstriction
4. RAAS activation: Na⁺ + water retention → ↑ preload

Decompensation

• Backward failure → pulmonary edema (left HF), peripheral edema/ascites (right HF)
• Forward failure → ↓ CO → organ hypoperfusion
• Cardiac Reserve: Normal = 300-400% above resting CO; severe HF may be <100% (cannot even meet resting needs)

Acute vs. Chronic Manifestations

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Key Formulas and Normal Values

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• Guyton and Hall Textbook of Medical Physiology, 14th ed. - Chapters 9 (Cardiac Muscle), 10 (Conduction System), 14 (Blood Pressure), 20 (Cardiac Output), 21 (Coronary Circulation)
• Ganong's Review of Medical Physiology, 26th ed. - Chapters 29 (Cardiac Conduction/ECG), 30 (Cardiac Output/Regulation), 31-32 (Special Circulations)

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Pacemaker Potential of the Heart - Complete Details

1. Definition and Concept

• Ganong's Review of Medical Physiology, 26th ed., p. 522

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2. Sites of Automaticity (Hierarchy of Pacemakers)

• Atrial and ventricular muscle cells do not have pacemaker potentials under normal conditions; they fire spontaneously only when injured or abnormal
• Ganong, p. 523

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3. Unique Features of SA Node Cells vs. Ventricular Muscle

• Costanzo Physiology, 7th ed., p. 142; Fuster and Hurst's The Heart, 15th ed.

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4. Phases of the SA Node Action Potential

Phase 0 - Upstroke

• Produced by opening of L-type Ca²⁺ channels (ICaL)
• T-type Ca²⁺ channels also contribute (especially at the end of Phase 4 bringing to threshold)
• Upstroke is slow and rounded (no rapid Na⁺ spike) because it depends on slower Ca²⁺ channels
• Peak potential: approximately +5 to +10 mV (less positive than ventricular cells which reach +20 mV)
• Costanzo, p. 142

Phases 1 and 2 - ABSENT

• There is no initial repolarization notch and no plateau in SA node cells
• Costanzo, p. 142

Phase 3 - Repolarization

• Due to ↑ IK (delayed rectifier K⁺ current) - same mechanism as other cardiac cells
• K⁺ moves out down its electrochemical gradient, repolarizing the membrane
• Returns membrane to the maximum diastolic potential (MDP) of approximately -60 to -65 mV
• (Note: MDP is less negative than the resting potential of ventricular cells)

Phase 4 - The Pacemaker Potential (Spontaneous Diastolic Depolarization)

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5. Ionic Mechanisms of the Pacemaker Potential - Step by Step

Step 1: Decay of IK (Outward K⁺ Current)

• At the end of Phase 3, IK begins to decline (the K⁺ channels deactivate as membrane repolarizes)
• This reduces the outward K⁺ current that was holding the membrane at the maximum diastolic potential
• The net inward current begins to exceed net outward current → membrane starts to depolarize slowly
• This is the first component of the pacemaker potential
• Ganong, p. 522

Step 2: Activation of If - The "Funny Current" (Ih)

• As the membrane repolarizes and becomes hyperpolarized (reaching MDP ~-60 to -65 mV), special channels called HCN channels (Hyperpolarization-activated Cyclic Nucleotide-gated channels) open
• These channels are activated by hyperpolarization - the OPPOSITE of all other voltage-gated channels (hence the name "funny")
• They are permeable to both Na⁺ and K⁺, but at the prevailing membrane potential, the driving force favors net inward Na⁺ current
• This mixed inward current is called If (or Ih or "funny current")
• If drives the membrane toward threshold - this is the main depolarizing force of the pacemaker potential
• If is turned on by repolarization from the preceding action potential, thus ensuring that each action potential is automatically followed by another
• Costanzo, p. 142; Ganong, p. 522; Harrison's Principles, 22nd ed.

• Gene: HCN4 (primarily), HCN1, HCN2 also present in SA node
• Current: Mixed Na⁺/K⁺ inward current (at physiological resting potential, net inward)
• Activation: by hyperpolarization (activated below -40 to -50 mV)
• Modulation: cAMP directly gates these channels (not just via protein kinase)
  • ↑ cAMP → channel opens at less negative potentials → faster depolarization (sympathetic effect)
  • ↓ cAMP → channel opens at more negative potentials → slower depolarization (vagal effect)

Step 3: Activation of T-type Ca²⁺ Channels (ICaT)

• As If depolarizes the membrane from MDP toward threshold, T-type (Transient) Ca²⁺ channels open at approximately -50 mV
• T-type channels are so named because they open transiently (fast inactivation)
• ICaT provides an additional inward Ca²⁺ current that completes the depolarization of the pacemaker potential to threshold
• This is the final component of the pacemaker potential just before the action potential fires
• Ganong, p. 522

Step 4: Activation of L-type Ca²⁺ Channels (ICaL) - Upstroke (Phase 0)

• Once threshold is reached (~-40 mV), L-type (Long-lasting) Ca²⁺ channels open
• ICaL produces the upstroke (Phase 0) of the SA node action potential
• This is NOT part of the pacemaker potential itself, but the result of it reaching threshold

Additional Mechanism: The Calcium Clock (INCX)

• The SR (sarcoplasmic reticulum) in SA node cells rhythmically releases Ca²⁺ sparks via Ryanodine receptor 2 (RYR2) during Phase 4
• This elevation in intracellular Ca²⁺ activates the Na⁺-Ca²⁺ exchanger (INCX)
• NCX pumps 1 Ca²⁺ out in exchange for 3 Na⁺ in → net inward positive current → depolarization
• The membrane clock (If, IK decay, ICaT) and calcium clock (INCX) work together to generate automaticity
• The relative contribution of each continues to be debated
• Fuster and Hurst's The Heart, 15th ed., p. 1143

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6. Summary of Ion Currents During Pacemaker Potential

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7. The Three Voltage Levels of Importance

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8. Autonomic Regulation of the Pacemaker Potential

Sympathetic Stimulation (Positive Chronotropy)

1. ↑ If - cAMP directly gates HCN channels, shifting activation to less negative voltages → steeper Phase 4 slope → faster rate
2. ↑ ICa (both T and L types) - more Ca²⁺ channels open → threshold reached sooner (threshold potential becomes less negative)
3. Superior shift of impulse formation site within SA node (allows more favorable exit pathways to atrium)

• Costanzo, p. 146

Parasympathetic Stimulation (Negative Chronotropy)

1. ↓ If - Gk inhibits adenylyl cyclase → ↓ cAMP → HCN channels require more hyperpolarization to open → Phase 4 slope decreases
2. ↑ IKAch - Gk β-subunit directly opens ACh-activated inward rectifier K⁺ channels (Kir3.1/3.4 = GIRK) → increased outward K⁺ current → hyperpolarizes MDP (more negative) → SA node further from threshold → longer time to reach threshold
3. ↓ ICa - fewer Ca²⁺ channels open → threshold potential increases (requires more depolarization to fire)

• Ganong, p. 522; Costanzo, p. 147

Comparison Table - Autonomic Effects on Pacemaker Potential

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9. Ivabradine - Pharmacological Proof of If Importance

• Blocks If → reduces the slope of Phase 4 depolarization → ↓ heart rate
• No effect on contractility, blood pressure, or AV conduction
• Used clinically in heart failure (reduced EF) and stable angina
• Provides pharmacological proof that If is the critical current for pacemaker rate control
• Braunwald's Heart Disease, 2-vol set; Harrison's Principles, 22nd ed.

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10. Overdrive Suppression

• Rapid firing drives more Na⁺ into latent pacemaker cells
• The Na⁺/K⁺ ATPase works harder to pump out the excess Na⁺, generating a larger hyperpolarizing current
• This keeps latent pacemakers at a more negative membrane potential, far from threshold
• If the SA node stops (e.g., sick sinus syndrome), there is a pause before a subsidiary pacemaker takes over (because it needs time to "escape" from overdrive suppression)
• Braunwald's Heart Disease; Ganong, p. 523

Hierarchy When SA Node Fails

• Slower rate + wider QRS complex (aberrant ventricular conduction)

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11. Abnormal Automaticity - Ectopic Pacemakers

• Braunwald's Heart Disease, p. 412-414

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12. SA Node Intrinsic Rate vs. Actual Heart Rate

• Intrinsic SA node rate (without autonomic input) = 100-110 bpm (demonstrated after complete autonomic blockade with atropine + propranolol)
• Normal resting heart rate (60-80 bpm) is SLOWER than intrinsic rate because vagal (parasympathetic) tone dominates at rest in young adults
• Intrinsic rate declines with age by 5-6 bpm per decade
• As age increases, vagal dominance decreases and sympathetic tone increases, maintaining the resting heart rate relatively constant
• Harrison's Principles of Internal Medicine, 22nd ed., p. 2913

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13. Key Facts for Exam (GK Pal/Ganong/Guyton Style)

1. Pacemaker potential = Phase 4 = spontaneous diastolic depolarization - unique to nodal tissue
2. Three components of pacemaker potential: ↓ IK → ↑ If (funny current) → ↑ ICaT (T-type Ca²⁺)
3. If = funny current = Ih = mixed Na⁺/K⁺ inward current through HCN4 channels; activated by hyperpolarization; directly gated by cAMP
4. Maximum diastolic potential (MDP) in SA node = -60 to -65 mV
5. Threshold potential in SA node = -40 mV
6. Upstroke of SA node = L-type Ca²⁺ (ICaL) - NOT fast Na⁺ channels
7. SA node rate = 60-100 bpm | AV node = 40-60 | His-Purkinje = 20-40
8. Sympathetic → ↑ If + ↑ ICa + ↓ threshold → ↑ rate (positive chronotropy)
9. Parasympathetic → ↓ If + ↑ IKAch (hyperpolarizes MDP) + ↓ ICa → ↓ rate (negative chronotropy)
10. Ivabradine blocks If (HCN channels) → ↓ heart rate without affecting contractility
11. Overdrive suppression: SA node keeps latent pacemakers suppressed; when SA node stops, there is a pause before escape rhythm appears
12. Calcium clock (INCX driven by spontaneous SR Ca²⁺ release via RYR2) acts alongside membrane clock (If, IK, ICaT) to generate automaticity

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• Ganong's Review of Medical Physiology, 26th ed. - Chapter 29 (Origin and Spread of Cardiac Excitation, Pacemaker Potentials)
• Costanzo Physiology, 7th ed. - Chapter 4 (Cardiovascular Physiology, SA Node Action Potential)
• Fuster and Hurst's The Heart, 15th ed. - Chapter 38 (Anatomy and Physiology of SA Node)
• Harrison's Principles of Internal Medicine, 22nd ed. - Chapter 251 (SA Nodal Disease)
• Braunwald's Heart Disease - Chapter 62 (Disorders of Impulse Formation)

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The Cardiac Cycle - Complete Details

1. Definition

• At a heart rate of 72 bpm, one cycle lasts 1/72 min = 0.833 seconds
• Systole (ventricular contraction + ejection) = ~0.3 s
• Diastole (relaxation + filling) = ~0.5 s

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2. The Wiggers Diagram (Guyton)

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3. Detailed Costanzo Phase Diagram

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4. Seven Phases of the Cardiac Cycle (Costanzo Framework)

PHASE A - Atrial Systole

• Atria act as "primer pumps" or "booster pumps" for ventricles
• In healthy adults, ~70-80% of ventricular filling occurs passively before atrial systole (even before atria contract)
• Atrial contraction adds the final 20-30% of filling
• Three phases of atrial function: Reservoir → Conduit → Contractile - Guyton, p. 127

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PHASE B - Isovolumetric Ventricular Contraction (IVC)

• Mitral valve closes when LV pressure exceeds LA pressure
• Aortic valve cannot open until LV pressure exceeds aortic pressure (~80 mmHg)
• All 4 valves are closed → no ejection → volume constant, but tension rises
• Called "isovolumetric" = volume unchanged; called "isometric" = muscle tension increases without shortening
• Guyton, p. 128; Costanzo, p. 162

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PHASE C - Rapid Ventricular Ejection

• Aortic valve opens when LV pressure just exceeds aortic pressure
• Most of the stroke volume (~70%) is ejected in this rapid phase
• Peak aortic pressure = ~120 mmHg (systolic)
• Costanzo, p. 162

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PHASE D - Reduced Ventricular Ejection

• Blood continues to be ejected despite falling LV pressure because momentum and still-open valve allow it
• The remaining ~30% of ejected volume leaves during this phase
• Ejection fraction (EF) = SV/EDV × 100 = (120-50)/120 × 100 = ~58-65% normally
• Costanzo, p. 163

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PHASE E - Isovolumetric Ventricular Relaxation (IVR)

• Aortic valve closes when aortic pressure exceeds LV pressure → aorta slightly higher than LV → backflow of blood pushes cusps shut
• Aortic valve closes before pulmonary valve (aortic pressure > pulmonary pressure)
• The brief backflow of blood that closes the aortic valve causes the dicrotic notch (incisura) on the aortic pressure curve
• Splitting of S2: On inspiration, reduced intrathoracic pressure → ↑ venous return → ↑ RV volume → prolonged RV ejection → pulmonary valve closes later → wider split
• Guyton, p. 128; Costanzo, p. 163

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PHASE F - Rapid Ventricular Filling

• Mitral valve opens when LV pressure drops below LA pressure
• The LA has been building up pressure during systole (phases B through E), creating a pressure gradient
• This phase is driven by the pressure gradient LA > LV and by ventricular suction (active relaxation/recoil)
• Guyton, p. 127; Costanzo, p. 163

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PHASE G - Reduced Ventricular Filling (Diastasis)

• "Diastasis" = period of equalization of LA and LV pressures
• Very little blood moves during this phase
• At faster heart rates, this phase is first to be shortened or abolished - this is why tachycardia reduces diastolic filling
• Followed by the next P wave and return to Phase A
• Costanzo, p. 164

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5. Summary Table of the Cardiac Cycle

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6. Atrial Pressure Waves (a, c, v waves) - Guyton

• Guyton, pp. 127-128

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7. Volume-Pressure Loop (Guyton)

Four Phases of the Pressure-Volume Loop (Guyton)

• ↑ Preload → loop shifts right (wider loop, more SV)
• ↑ Afterload → loop shifts upward (less SV, same EDV)
• ↑ Contractility → loop shifts upward-left (same EDV, less ESV, more SV)

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8. Normal Pressures and Volumes

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9. Heart Sounds Summary

• Physiological: On inspiration - ↑ venous return → ↑ RV volume → prolonged RV ejection → pulmonary valve closes later (A2 before P2 widens)
• Fixed split: ASD (right heart volume remains constant regardless of respiration)
• Paradoxical split: On expiration - LBBB, aortic stenosis (aortic valve closes after pulmonary)

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10. Valve Events Summary

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11. Aortic Pressure Curve - Features (Guyton)

• Pre-ejection rise: Aortic pressure at 80 mmHg (diastolic) at start of ejection
• Sharp rise during rapid ejection → peak at ~120 mmHg
• Gradual fall during reduced ejection as blood runs off into peripheral arteries
• Dicrotic notch (incisura): Brief downward deflection at closure of aortic valve, caused by momentary backflow of blood that closes the valve, then a small rebound
• Continuous fall during diastole back to 80 mmHg
• Guyton, p. 128

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12. Effect of Heart Rate on the Cardiac Cycle

• Total cycle duration decreases (reciprocal of HR)
• Diastole shortens disproportionately more than systole
• At 72 bpm: systole = ~40% of cycle; at 3× normal HR: systole = ~65% of cycle
• At very high heart rates: diastasis (Phase G) is first abolished, then rapid filling (Phase F) is shortened
• Result: inadequate ventricular filling → decreased stroke volume → may reduce CO despite high HR

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13. Right Heart Cardiac Cycle

• RV is a thin-walled, low-pressure pump - more susceptible to pressure overload (pulmonary hypertension)
• Pulmonary valve closes slightly after aortic valve → explains normal S2 splitting

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14. Key Exam Facts

1. Cardiac cycle duration = 1/HR; at 72 bpm = 0.833 s
2. First event of systole = Mitral valve closure (S1); last event = Aortic valve closure (S2)
3. During IVC and IVR: all 4 valves are closed; ventricular volume is constant
4. EDV ~120-130 mL; ESV ~50-60 mL; SV ~70 mL; EF ~60%
5. S1 = AV valve closure (mitral before tricuspid); S2 = semilunar valve closure (aortic before pulmonary)
6. S3 = rapid filling, early diastole; S4 = atrial systole, late diastole
7. a wave = atrial contraction; c wave = AV valve bulge; v wave = venous filling
8. Dicrotic notch = aortic valve closure; marks transition from systole to diastole on aortic pressure tracing
9. Diastasis = period of equalization of LA-LV pressure; first phase abolished in tachycardia
10. 60% of ventricular contents ejected (= ejection fraction); 70% of ejected volume during rapid ejection
11. Atrial contribution to filling = 20-30% (lost in AF → reduced CO especially in stiff ventricles)
12. Area of P-V loop = cardiac work done per beat
13. Aortic valve opens when LV pressure > 80 mmHg; Mitral valve opens when LV pressure < LA pressure (~5-8 mmHg)

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• Guyton and Hall Textbook of Medical Physiology, 14th ed. - Chapter 9 (Cardiac Muscle; The Heart as a Pump)
• Costanzo Physiology, 7th ed. - Chapter 4 (Cardiovascular Physiology, Cardiac Cycle Phases A-G)
• Ganong's Review of Medical Physiology, 26th ed. - Chapter 30 (The Heart as a Pump)