2020A Question 08

Describe the process by which increased tissue demand for oxygen leads to an increase in cardiac output.

Examiner Report

This question was poorly answered by the majority of candidates. It revealed widely held errors in understanding about core cardiovascular physiology.

A passing answer should have contained the following points, with explanation. Increased oxygen consumption in tissues leads to local vasodilation (i.e. metabolic autoregulation). This reduction in local vascular resistance causes an increase in local flow for the same MAP. In addition, there is a slight reduction in afterload, which increases stroke volume. Both of the above lead to an increase in flow from the arterial to the venous side of the circulation. This increase in venous return then increases right atrial pressure and stroke volume, via the Frank-Starling mechanism.

The sympathetic nervous system is not directly involved in the above processes. Effectively, cardiac output is “controlled” by the tissues. With exercise, sympathetic tone does increase, and this causes a rise in cardiac output which is additional to the above. It should be noted that in the absence of increased preload, simply increasing heart rate does not reliably lead to increased cardiac output.

The following were common errors:

  • “Local vasodilation causes hypotension, which is sensed by baroreceptors, and causes increased sympathetic tone, which increases CO”.
    This is incorrect. Hypotension is not required as an initial ‘step’ in order for cardiac output to increase. During exercise the BP increases.
  • “Increased oxygen consumption / metabolism leads to a fall in PaO2 / rise in PaCO2 / fall in arterial pH, which then activates the sympathetic nervous system via the chemoreceptors”.
    This is incorrect. Even during strenuous exercise, people do not normally become hypoxaemic or hypercarbic. It has been postulated that there are chemoreceptors within tissue beds (especially muscle), but these have never been identified.
  • “The heart is a demand pump, which means that it will pump enough blood to match tissue demand”.
    This is oversimplified. When we refer to the heart as a demand pump, this means that the forward cardiac output is matched to the venous return.

Several high scoring answers were able to use Guyton curves to add more detail to their answer. However, the majority of candidates who attempted to incorporate Guyton curves only became more confused. This material is well covered in the essential core textbook: Pappano and Weir, Cardiovascular Physiology (11th edition), especially Chapters 9, 10 and 13. For those interested, Guyton’s original article is well worth reading: Guyton A. Regulation of cardiac output. Anesthesiology, 1968, 29(2): 314-326.

Model Answer


  • Summary
  • Tissue activity
  • Respiratory muscle pump
  • Skeletal muscle pump
  • Sympathetic nervous system
  • Intracardiac reflexes

Summary: Cardiac Output

Term Detail
Definition Volume of blood ejected from LV into aorta per unit time

Cardiac factors:

 - Heart rate

 - Contractility

Coupling factors:

 - Preload

 - Afterload


- Most important: Tissue activity ∝ Venous return ∝ Cardiac output

- i.e. Negative feedback loop

- i.e. Cardiac output (CO) is a slave to venous return (VR)

Matching of Supply to Demand

System Mechanism
Tissue Activity

Metabolic autoregulation:

- ↑ Tissue metabolic activity

- ↑ VO2, ↑ VCO2, ↑ H+, K+, adenosine, lactate

- Local vasodilatation

→ ↑ Rate of flow from arterial to venous circulation → ↑ VR
→ ↓ Afterload → ↑ CO (minor effect)

Heterometric autoregulation (Frank-Starling relationship):

- ↑ VR to RV

- ↑ VR to LV

- ↑ Preload

- ↑ Sarcomere stretch

- ↑ Ca2+ sensitisation

- ↑ Force of contraction

→ ↑ Cardiac output


- ↑ CO

- ↓ CVP

- ↓ Preload

→ New equilibrium with ↑ CO, ↑ VR and slight ↑ CVP


Respiratory Muscle Pump

- ↑ Tissue activity

- ↑ VO2

- ↑ VCO2 (Krebs cycle)

- ↑ PaCO2

- ↑ Activation of peripheral and central chemoreceptors

- ↑ Frequency and amplitude of breathing

- ↑ -ve pressure during inspiration → ↑ VR to RV

- ↑ +ve pressure during expiration → ↑ VR to LV

- ↑ CO

VR during spont vent exceeds VR during apnoea

→ Important during exercise

Skeletal Muscle Pump

- ↑ Muscle isometric contraction

- ↑ Compression of capacitance vessels

- ↑ VR

- ↑ CO

*→ Important during exercise*

Sympathetic nervous system

- ↑ Skeletal muscle activity

- Multiple reflex pathways (central, vascular, skeletal)

- ↓↓ SVR, ↑ HR, ↑ contractility, constrict capacitance vessels → ↑ VR

- ↑ CO

→ Important during exercise

Cardiac Reflexes

Bainbridge effect:

- ↑ VR

- ↑ Atrial stretch

- ↑ HR

- ↑ CO

Bowditch effect:

- ↑ HR

- ↑ ICF [Ca2+]

- ↑ Contractility

- ↑ CO

Last updated 2021-08-23

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