Cardiac Output

Definition

• CO = HR × SV
• Normal: 5 L/min (at rest)
• Normal HR: 72 bpm | Normal SV: 70 mL

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Determinants of Stroke Volume

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Frank-Starling Law

• ↑ EDV → ↑ stretch → ↑ force of contraction → ↑ SV
• Operates up to an optimal sarcomere length (~2.2 µm)

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Factors Affecting CO

↑ CO: Exercise, pregnancy, anxiety, fever, hyperthyroidism, AV fistula, anaemia (chronic)

↓ CO: Heart failure, cardiac tamponade, hypovolaemia, arrhythmias

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Measurement Methods

• Fick’s Principle → CO = O₂ consumption ÷ A-V O₂ difference (GOLD STANDARD)
• Thermodilution → most clinically used (Swan-Ganz catheter)
• Dye dilution → indocyanine green

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Cardiac Index

• CO corrected for body surface area
• CI = CO ÷ BSA
• Normal: 2.5–4 L/min/m²

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Venous Return

• VR = CO at steady state
• Guyton’s concept: Mean Systemic Filling Pressure (MSFP) drives VR
• ↑ Blood volume → ↑ MSFP → ↑ VR → ↑ CO

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High-Yield Exam Points

• Starling’s law = heterometric autoregulation
• Anrep effect = homeometric autoregulation (↑ afterload → ↑ contractility)
• Bowditch/Treppe effect = ↑ HR → ↑ contractility
• Exercise: CO can reach 20–25 L/min in trained athletes

Cardiac Output

Cardiac Output (CO) is the volume of blood pumped by each ventricle per minute.

CO = Heart Rate (HR) × Stroke Volume (SV)

• Normal resting CO: 4.5–5.5 L/min
• Normal HR: 72 bpm
• Normal SV: ~70 mL

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Stroke Volume

Stroke volume is the volume ejected per beat.

SV = EDV − ESV

• EDV (End-Diastolic Volume): ~120–130 mL
• ESV (End-Systolic Volume): ~50–60 mL
• Ejection Fraction (EF) = SV/EDV × 100 → Normal: 55–70%

Three Determinants of SV

1. Preload

• Defined as ventricular wall tension at end of diastole
• Clinically approximated by EDV or LVEDP
• Governed by Frank-Starling Law: greater stretch → greater force of contraction
• Factors that increase preload: increased venous return, increased blood volume, bradycardia (longer filling time)

2. Afterload

• The resistance the ventricle must overcome to eject blood
• For LV: approximated by aortic pressure / TPR
• For RV: approximated by pulmonary artery pressure
• ↑ Afterload → ↓ SV (if contractility unchanged)
• In hypertension: chronically ↑ afterload → LV hypertrophy

3. Contractility (Inotropy)

• The intrinsic ability of myocardium to generate force, independent of preload/afterload
• Reflected by the slope of the Frank-Starling curve

Positive inotropes (↑ contractility):

• Sympathetic stimulation (β₁ agonists)
• Catecholamines (adrenaline, noradrenaline)
• Digitalis (↓ Na⁺/K⁺ ATPase → ↑ intracellular Ca²⁺)
• ↑ Heart rate (Bowditch/Treppe effect)

Negative inotropes (↓ contractility):

• β-blockers
• Calcium channel blockers
• Heart failure
• Hypoxia, acidosis

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Frank-Starling Law

Within physiological limits, the force of contraction is proportional to the initial length of the cardiac muscle fibre.

• Mechanism: ↑ sarcomere stretch → ↑ troponin-C affinity for Ca²⁺ → ↑ cross-bridge cycling
• Optimal sarcomere length: 2.0–2.2 µm
• Descending limb of the curve is not normally reached in the healthy heart
• Also called: Heterometric autoregulation or Starling’s Law of the Heart

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Cardiac Index

Cardiac Index (CI) = CO ÷ Body Surface Area (BSA)

• Normal: 2.5–4.0 L/min/m²
• Used to compare CO across individuals of different body sizes
• CI < 2.2 L/min/m² → Cardiogenic shock

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Measurement of Cardiac Output

Fick’s Principle (Gold Standard)

CO = O₂ consumption (mL/min) ÷ (Arterial O₂ content − Venous O₂ content)

• Requires: arterial and mixed venous blood samples + O₂ consumption measurement
• Accurate but invasive and cumbersome

Thermodilution Method (Most Commonly Used Clinically)

• Cold saline injected into right atrium via Swan-Ganz catheter
• Temperature change measured in pulmonary artery
• CO calculated from temperature-time curve
• Principle: Stewart-Hamilton equation
• Overestimates CO in: low-output states, tricuspid regurgitation

Dye Dilution Method

• Indicator: Indocyanine green
• Dye injected IV; concentration measured in arterial blood over time
• CO = Amount of dye ÷ (Mean concentration × Time)

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Regulation of Cardiac Output

Intrinsic Regulation

• Frank-Starling mechanism — responds to changes in venous return automatically
• Anrep effect — ↑ afterload → transient ↓ SV followed by recovery via ↑ contractility (homeometric autoregulation)
• Bowditch/Treppe effect — ↑ HR → ↑ contractility (force-frequency relationship)

Extrinsic Regulation

• Sympathetic nervous system: ↑ HR (chronotropy) + ↑ contractility (inotropy) + ↑ conduction velocity (dromotropy)
• Parasympathetic nervous system: ↓ HR via vagus nerve (dominant at rest)
• Hormones: Adrenaline, thyroid hormone, glucagon → ↑ CO

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Venous Return and CO

At steady state: Venous Return = Cardiac Output

Guyton’s Concept

• Mean Systemic Filling Pressure (MSFP): pressure throughout systemic circuit when heart is stopped (~7 mmHg)
• VR = (MSFP − RAP) ÷ Resistance to venous return
• Factors increasing VR: ↑ blood volume, venoconstriction, muscle pump, respiratory pump, ↓ RAP

Veno-Arterial Coupling

• Heart and vasculature function together
• Illustrated by cardiac function curve (Frank-Starling) and vascular function curve (Guyton’s VR curve)
• Intersection = operating point of the cardiovascular system

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Cardiac Output in Physiological States

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High-Output vs Low-Output States

High-Output States (CO elevated)

• Anaemia, AV fistula, Paget’s disease, Beriberi (thiamine deficiency), hyperthyroidism, pregnancy

Low-Output States (CO reduced)

• Cardiomyopathy, myocardial infarction, cardiac tamponade, hypovolaemia, severe arrhythmias

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Oxygen Delivery and CO

DO₂ = CO × CaO₂

• CaO₂ = (Hb × 1.34 × SaO₂) + (0.003 × PaO₂)
• Normal DO₂: ~1000 mL/min
• Normal VO₂: ~250 mL/min
• O₂ extraction ratio = VO₂/DO₂ ≈ 25%

When CO falls, the body compensates by ↑ O₂ extraction → ↑ A-V O₂ difference.

1. Frank-Starling Curve

Plots Stroke Volume (or CO) against EDV (or Preload). Shows how increasing ventricular filling increases stroke volume up to an optimal point. Multiple curves illustrate the effect of changing contractility. Essential for understanding heart failure and inotropic drugs.

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2. Guyton’s Cardiac and Vascular Function Curves

Superimposed plot of the cardiac function curve (Frank-Starling) and the vascular function curve (venous return vs. right atrial pressure). The intersection point represents the steady-state operating point of the cardiovascular system. Shifting either curve demonstrates the effect of drugs, volume loading, or heart failure.

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3. Fick’s Principle — Cardiac Output Measurement

Schematic of the pulmonary circuit showing oxygen consumption, arterial O₂ content, and mixed venous O₂ content. Illustrates how CO is calculated using: CO = VO₂ ÷ (CaO₂ − CvO₂). Foundational diagram for understanding invasive haemodynamic monitoring.

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Diagram Checklist

• Frank-Starling Curve — SV vs EDV with shifted contractility curves
• Guyton’s Vascular Function Curve — intersection operating point
• Fick’s Principle schematic — pulmonary circuit O₂ calculation

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Diagram-Based Viva Questions

1. Draw a Frank-Starling curve and show the effect of positive and negative inotropes.
2. On Guyton’s curve, what happens to the operating point when blood volume is increased?
3. How would the Frank-Starling curve shift in a patient with dilated cardiomyopathy?
4. Using Fick’s principle, calculate CO if VO₂ is 250 mL/min and A-V O₂ difference is 50 mL/L.
5. What is the significance of the descending limb of the Starling curve? Is it seen clinically?

Long Essays

1. [KUHS 2023] [Repeated] Describe cardiac output — definition, normal values, determinants, and regulation. Add a note on measurement of cardiac output by Fick’s principle.

2. [KUHS 2022] [Repeated] Explain Frank-Starling’s law of the heart. Describe the factors affecting venous return and their role in regulating cardiac output.

3. [KUHS 2021] [Repeated] Define cardiac output. Discuss the factors that regulate stroke volume. Explain the concept of cardiac index and its clinical significance.

4. [KUHS 2019] [Repeated] Describe the methods of measurement of cardiac output. Explain Fick’s principle in detail with relevant calculations.

5. [RGUHS 2022] [Repeated] Write about the regulation of cardiac output. Explain intrinsic and extrinsic mechanisms with appropriate diagrams.

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Short Essays

1. [KUHS 2024] [Repeated] Frank-Starling law of the heart.

2. [KUHS 2024] [New] Cardiac index — definition and clinical significance.

3. [KUHS 2023] [Repeated] Thermodilution method of measuring cardiac output.

4. [KUHS 2023] [Repeated] Factors increasing venous return.

5. [KUHS 2022] [Repeated] Ejection fraction — normal value and clinical relevance.

6. [KUHS 2022] [New] Anrep effect and Bowditch effect.

7. [KUHS 2021] [Repeated] High output cardiac failure — causes and mechanism.

8. [KUHS 2021] [Repeated] Role of sympathetic nervous system in regulation of cardiac output.

9. [KUHS 2020] [Repeated] Preload and afterload — definitions and clinical importance.

10. [RGUHS 2023] [Repeated] Guyton’s venous return curve and its significance.

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Short Notes

1. [KUHS 2024] [Repeated] Fick’s principle.

2. [KUHS 2024] [New] Stroke volume — determinants.

3. [KUHS 2024] [Repeated] Mean systemic filling pressure.

4. [KUHS 2023] [Repeated] End-diastolic volume.

5. [KUHS 2023] [New] Heterometric autoregulation.

6. [KUHS 2023] [Repeated] Dye dilution method.

7. [KUHS 2022] [Repeated] Cardiac output during exercise.

8. [KUHS 2022] [Repeated] Homeometric autoregulation.

9. [KUHS 2022] [New] Oxygen delivery (DO₂).

10. [KUHS 2021] [Repeated] Treppe effect / Bowditch phenomenon.

11. [KUHS 2021] [Repeated] Cardiac output in pregnancy.

12. [KUHS 2021] [New] A-V oxygen difference.

13. [KUHS 2020] [Repeated] Swan-Ganz catheter.

14. [KUHS 2020] [Repeated] Factors affecting heart rate.

15. [RGUHS 2022] [Repeated] Cardiogenic shock — definition and CO changes.

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Viva Questions

1. What is the normal cardiac output at rest?
2. How is stroke volume calculated from EDV and ESV?
3. What is the normal ejection fraction? When is it reduced?
4. State Frank-Starling law in one sentence.
5. What is heterometric autoregulation?
6. What is homeometric autoregulation? Give an example.
7. Differentiate preload and afterload.
8. What is the effect of increasing preload on stroke volume?
9. Name four positive inotropic agents.
10. What is the Bowditch (Treppe) effect?
11. What is the Anrep effect?
12. What is cardiac index? What is its normal range?
13. How does the body compensate for a fall in cardiac output?
14. Name the gold standard method for measuring cardiac output.
15. State Fick’s principle for CO measurement.
16. What is thermodilution? Which catheter is used?
17. What is mean systemic filling pressure?
18. How does exercise affect cardiac output?
19. Name four causes of high-output cardiac failure.
20. What is the relationship between venous return and cardiac output at steady state?