Question 16

Describe the role of carbon dioxide in the control of alveolar ventilation.

[Click here to toggle visibility of the answers]

College Answer

Better answers considered the role of CO2 in the control of alveolar ventilation in terms of sensors, central processing and effectors - with an emphasis on sensors. Features of central and peripheral chemoreceptors should have been described in detail. The PCO2/ventilation response curve is best described using a graph, with key features of the curve identified (including gradient and axes). Various factors affecting the gradient of this curve and how CO2 affects the response to hypoxic drive should be described.


In brief summary:

  • Increasing PaCO2 causes an increase in minute ventilation.
  • This is mediated by peripheral chemoreceptors over the timescale of seconds, and by central chemoreceptors over minutes.
    • Peripheral chemoreceptors are the carotid glomus cells, which sense PaCO2 as well as PaO2, pH, temperature and blood pressure
    • Central chemoreceptor areas are found in multiple areas of the brain, but are generally said to concentrate in the ventral medulla
  • The relationship between PaCOis fairly linear in the range of 45-80 mmHg; the rate of minute volume increases by 2-5L/min per every 1mm Hg of CO2 increase.

    Effects of physiological and pathological changes on the ventilatory response to CO2 can be graphically represented thus:
    ventilatory response to CO2 under different conditions
    • The CO2/ventilation response curve is shifted to the left by metabolic acidosis and hypoxia
    • Sleep, sedation, anaesthesia and opiates shift the curve to the right and decrease the slope of the curve (i.e. the increase in minute ventilation is reduced per unit rise of CO2)
    • Age decreases the ventilatory response to CO2
    • A high level of physical fitness also diminishes hypercapnic respiratory drive
  • The response to raised PaCO2 is rapid; about 75% of the maximum minute volume change is achieved over minutes
  • At a stable metabolic rate and with minimal inspired CO2 the relationship between minute volume and PaCO2 is described by a hyperbolic curve.


Haldane, John Scott, and James Lorrain Smith. "The physiological effects of air vitiated by respiration"  Journal of Pathology and Bacteriology, Volume 1, Issue 2 fmi, 123-255 (1892)

Haldane, J. S.; Priestley, J. G.;  "The regulation of the lung-ventilation." Journ. of Physiol 32 (1905).

Schaefer, Karl Ernst. "Respiratory pattern and respiratory response to CO2." Journal of Applied Physiology 13.1 (1958): 1-14.

Berger, Albert J., Robert A. Mitchell, and John W. Severinghaus. "Regulation of respiration." New England Journal of Medicine 297.4 (1977): 194-201.

Mohan, Ravi, and James Duffin. "The effect of hypoxia on the ventilatory response to carbon dioxide in man." Respiration physiology 108.2 (1997): 101-115.

Douglas, Neil J., et al. "Hypercapnic ventilatory response in sleeping adults." American Review of Respiratory Disease126.5 (1982): 758-762.

Pattinson, Kyle TS. "Opioids and the control of respiration." British journal of anaesthesia 100.6 (2008): 747-758.

Gross, Jeffrey B. "When you breathe in you inspire, when you don't breathe, you… expire: new insights regarding opioid-induced ventilatory depression." Anesthesiology: The Journal of the American Society of Anesthesiologists 99.4 (2003): 767-770.

Romberg, Raymonda, et al. "Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers." Anesthesiology: The Journal of the American Society of Anesthesiologists 99.4 (2003): 788-798.

Munson, Edwin, et al. "The effects of halothane, fluroxene and cyclopropane on ventilation: a comparative study in man." Anesthesiology 27.6 (1966): 716-728.

Fencl, V., T. B. Miller, and Ja R. Pappenheimer. "Studies on the respiratory response to disturbances of acid-base balance, with deductions concerning the ionic composition of cerebral interstitial fluid.American Journal of Physiology-Legacy Content 210.3 (1966): 459-472.

Tansley, John G., et al. "Human ventilatory response to 8 h of euoxic hypercapnia." Journal of Applied Physiology 84.2 (1998): 431-434.

Kronenberg, Richard S., and Charles W. Drage. "Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men." The Journal of clinical investigation 52.8 (1973): 1812-1819.

Byrne-Quinn, Edward, et al. "Ventilatory control in the athlete." Journal of Applied Physiology 30.1 (1971): 91-98.