The Cardiac Cycle

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Wiggers Diagram (Pressures and Volumes)

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Flowchart

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The 7 Phases in Detail

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SYSTOLE (3 phases)

Phase A - Atrial Systole

The ventricle was already filling passively before atrial systole; atrial contraction adds the final "top-up."

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Phase B - Isovolumetric Ventricular Contraction (IVC)

"Iso" = same; "volumetric" = volume. Volume cannot change because all valves are shut. - Costanzo Physiology 7th Edition

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Phase C - Rapid Ventricular Ejection

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Phase D - Reduced Ventricular Ejection

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DIASTOLE (3 phases)

Phase E - Isovolumetric Ventricular Relaxation (IVR)

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Phase F - Rapid Ventricular Filling

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Phase G - Reduced Ventricular Filling (Diastasis)

Then the cycle repeats with the next P wave and atrial systole.

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Summary Table

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Key Values to Remember

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Effect of Heart Rate on Cycle Duration

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Cardiac Output and Its Regulation

Definition

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Formula

• SV = EDV - ESV = 140 - 70 = 70 mL
• CO = 70 mL × 75 bpm = 5,250 mL/min (~5.25 L/min)
• Ejection Fraction (EF) = SV / EDV = 70/140 = 0.50 (50%)
• Costanzo Physiology 7th Edition

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Cardiac Index

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Regulation of Cardiac Output

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A. Regulation of Stroke Volume

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1. Preload

"The volume of blood ejected by the ventricle depends on the volume present in the ventricle at the end of diastole."

• As venous return increases → EDV increases → myocardial fibers stretch → they contract with greater force → SV increases → CO increases
• This is a direct consequence of the length-tension relationship in cardiac muscle
• In the physiologic range the relationship is nearly linear; at excessive EDV the curve flattens
• The Frank-Starling mechanism ensures that cardiac output automatically matches venous return in steady state
• Costanzo Physiology 7th Edition

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2. Afterload

• As afterload increases → ventricle must generate more pressure before ejection can begin → ejection slows → ESV increases → SV decreases → CO falls
• Cardiac output declines in response to large increases in afterload; modest changes may have no effect on CO
• The right ventricle (thinner wall) is more sensitive to afterload changes than the left ventricle
• In heart failure, CO becomes highly sensitive to afterload - hence vasodilators (ACE inhibitors, nitrates) improve CO by reducing SVR
• Morgan and Mikhail's Clinical Anesthesiology, 7th Edition

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3. Contractility (Inotropy)

Sympathetic fibers innervate both atrial and ventricular muscle. Norepinephrine enhances contractility primarily via β₁-receptor activation. - Morgan and Mikhail's Clinical Anesthesiology, 7th Edition

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B. Regulation of Heart Rate (Chronotropy)

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C. Extrinsic Regulatory Mechanisms

1. Autonomic Nervous System

• Sympathetic activation (exercise, stress, hemorrhage): releases norepinephrine → β₁ receptor activation → positive chronotropy (↑ HR) + positive inotropy (↑ contractility) → ↑ CO
• Parasympathetic (vagal) activation (rest, valsalva): releases acetylcholine → negative chronotropy (↓ HR) + mild negative inotropy → ↓ CO

2. Baroreceptor Regulation

• High-pressure baroreceptors (carotid sinus, aortic arch) sense arterial pressure - not CO directly
• A fall in BP → baroreceptor firing decreases → sympathetic output increases → HR and SV increase → CO rises
• Importantly: baroreceptors do not correct changes in CO that occur without a change in MAP (e.g., if CO rises but SVR falls proportionally, MAP is unchanged and baroreceptors do not respond)
• Medical Physiology (Boron & Boulpaep)

3. Chemoreceptor Regulation

• Peripheral chemoreceptors detect ↓ PO₂, ↑ PCO₂, ↓ pH
• Low CO → low tissue perfusion → ↓ PO₂, ↑ PCO₂ → chemoreceptor stimulation → reflex tachycardia → ↑ CO (a negative-feedback correction)
• Note: high PCO₂ also directly depresses myocardial contractility (via intracellular acidosis reducing troponin C sensitivity to Ca²⁺); the reflex tachycardia counterbalances this direct depressant effect

4. Low-Pressure (Atrial) Baroreceptors

• Located in pulmonary artery, atrial-venous junctions, atria, and ventricles
• Detect "fullness" of the circulation (venous return)
• When activated by increased venous pressure → trigger Bainbridge reflex: tachycardia + renal vasodilation + diuresis (to reduce volume load)

5. Local Metabolic Autoregulation

"The venous return to the heart is the sum of all the local blood flows through all the individual tissue segments." - Guyton and Hall Textbook of Medical Physiology

• Tissues with increased metabolic demand (e.g., exercising muscle) release vasodilatory metabolites (CO₂, adenosine, H⁺, K⁺, lactic acid) → local arteriolar dilation → ↑ local blood flow → ↑ venous return → Frank-Starling raises CO
• This is why CO can rise from 5 L/min at rest to 20-25 L/min during strenuous exercise in trained athletes

6. Hormonal Regulation

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Summary - Determinants of Cardiac Output

CARDIAC OUTPUT = STROKE VOLUME × HEART RATE
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          ____________|____________
         |            |            |
      PRELOAD      AFTERLOAD   CONTRACTILITY
         |            |            |
    Frank-Starling  SVR/MAP    Sympathetic/Ca²+
    Venous return   Aortic     Catecholamines
    Blood volume    impedance  Inotropic drugs

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Key Normal Values

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Systemic Vascular Resistance (SVR)

Definition

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Formula

Worked Example

• Harrison's Principles of Internal Medicine 22E

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SVR Index (SVRI)

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What Determines SVR?

1. Arteriolar diameter - the most important factor (resistance ∝ 1/r⁴ by Poiseuille's Law)
2. Vessel length
3. Blood viscosity (e.g., rises with polycythemia, falls with anemia)
4. Number of parallel vessels (more vessels = lower total resistance)

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Factors That Change SVR

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SVR vs. CO Relationship

• If CO falls (e.g., heart failure) → SVR rises compensatorily to maintain MAP
• If SVR falls (e.g., septic shock) → CO must rise to maintain MAP
• This is why septic shock presents with low SVR + high CO (hyperdynamic state), while cardiogenic shock presents with high SVR + low CO

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Limitations of SVR as Afterload

• Arterial wall compliance and elasticity
• Pulsatile (frequency-dependent) nature of blood flow
• Arterial wave reflection
• Blood viscosity and density
• These factors become especially important in elderly patients or those with atherosclerosis, where pulsatile load on the LV is significant even if SVR is "normal"

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Pulmonary Vascular Resistance (PVR) - Comparison

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Blood Pressure - Definition, Determinants, and Regulation

Definition

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Types of Arterial Blood Pressure

MAP Formula

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The Fundamental Equation of Blood Pressure

Blood pressure is the product of Cardiac Output and Systemic Vascular Resistance. All determinants of BP ultimately act through one or both of these two variables.

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Determinants of Blood Pressure

I. Cardiac Output (CO)

A. Heart Rate

• Controlled by the autonomic nervous system
• Sympathetic (β₁) → ↑ HR
• Parasympathetic (vagal) → ↓ HR

B. Stroke Volume - determined by three factors:

C. Blood Volume

• The most important determinant of stroke volume is filling pressure, which is regulated by sodium homeostasis
• Sodium balance controls water retention → blood volume → venous return → EDV → SV
• Regulated mainly by renal sodium excretion/resorption via aldosterone and ANP - Robbins, Cotran & Kumar Pathologic Basis of Disease

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II. Systemic Vascular Resistance (SVR / Peripheral Resistance)

• Regulated predominantly at the level of arterioles by neural and hormonal inputs
• Vascular tone = balance between vasoconstrictors and vasodilators

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Regulation of Blood Pressure

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SHORT-TERM REGULATION (Seconds - Minutes)

1. Baroreceptor Reflex (Most Important Rapid Mechanism)

• Location: Carotid sinus (CN IX) and aortic arch (CN X)
• Mechanism: Stretch-sensitive mechanoreceptors that fire in proportion to arterial pressure
• Pathway: Baroreceptors → Nucleus of the Tractus Solitarius (NTS) in medulla → vasomotor center

• Allows rapid adjustment to postural changes (standing up), hemorrhage, and exercise
• In chronic hypertension, the baroreceptor reflex is "reset" to maintain the elevated pressure rather than correct it - Ganong's Review of Medical Physiology, 26th Edition

2. Chemoreceptor Reflex

• Peripheral chemoreceptors (carotid/aortic bodies) detect ↓ PO₂, ↑ PCO₂, ↓ pH
• Hypoxia/hypercapnia → sympathetic activation → ↑ HR, vasoconstriction → ↑ BP

3. CNS Ischemic Response (Cushing Reflex)

• When cerebral perfusion pressure falls critically → massive sympathetic discharge → ↑↑ BP
• A last-resort emergency mechanism

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INTERMEDIATE REGULATION (Minutes - Hours)

4. Renin-Angiotensin-Aldosterone System (RAAS)

Low BP / Low Na⁺ / ↑ Catecholamines
              ↓
    Juxtaglomerular cells (kidney)
              ↓ release
            RENIN
              ↓ cleaves
       Angiotensinogen (liver)
              ↓
        Angiotensin I
              ↓ ACE (lung endothelium)
        Angiotensin II
         /          \
Vasoconstriction    Adrenal cortex
 (↑ SVR → ↑ BP)         ↓
                   ALDOSTERONE
                        ↓
              ↑ Na⁺ reabsorption (kidney)
                        ↓
              ↑ Blood volume → ↑ CO → ↑ BP

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LONG-TERM REGULATION (Hours - Days)

5. Renal Pressure-Diuresis / Natriuresis (Most Important Long-term Mechanism)

"The kidney is the ultimate long-term regulator of blood pressure." - Guyton and Hall Textbook of Medical Physiology

• When BP ↑ → kidneys excrete more Na⁺ and water (pressure diuresis/natriuresis) → ↓ blood volume → ↓ CO → BP returns to normal
• When BP ↓ → kidneys retain Na⁺ and water → ↑ blood volume → ↑ CO → BP rises
• This mechanism has infinite gain over the long term - no other mechanism can permanently change BP without also altering the renal set-point

6. Atrial Natriuretic Peptide (ANP) and BNP

• Released from atrial myocardium (ANP) and ventricular myocardium (BNP) in response to volume overload
• Lower BP by:
  • Systemic vasodilation (↓ SVR)
  • Inhibiting Na⁺ reabsorption in distal renal tubules → natriuresis and diuresis (↓ blood volume)
  • Antagonizing RAAS and sympathetic activity
• Elevated ANP/BNP = hypervolemia, most commonly seen in congestive heart failure - Robbins, Cotran & Kumar Pathologic Basis of Disease

7. Vascular Autoregulation (Local)

• Tissues regulate their own blood flow to match metabolic demand
• Increased blood flow → myogenic vasoconstriction (Bayliss effect) → protects against hyperperfusion
• Metabolic signals (↓ pH, ↑ CO₂, ↑ adenosine, ↓ O₂) → local vasodilation → ↓ local SVR

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Summary Table

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Key Takeaway

• Short-term: Baroreceptors and the autonomic nervous system provide rapid second-to-second adjustments
• Medium-term: RAAS adjusts blood volume and vascular tone over minutes to hours
• Long-term: The kidneys (pressure diuresis) are the ultimate arbiters of chronic blood pressure, setting the equilibrium point that all other mechanisms revolve around