Question 21

Describe the physiological consequences of a progressive rise in blood carbon dioxide levels.

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College Answer

Candidates were expected to present a mechanistic description the neuro-cellular events 
following a rise in PaCO2 such as changes in H+ in CSF, stimulation of central and peripheral 
chemoreceptors and neural pathways that lead to stimulation of respiratory centre. A 
systematic approach to the question with in-depth details of direction and magnitude of 
physiologic changes were required. Most candidates presented graphs of cerebral blood 
flow and tidal volume changes with increasing PaCO2. Common omissions included other 
important points,such as the cardiovascular and respiratory effects of rising CO2 and the 
rightward shift of oxygen haemoglobin curve.


The following is a short list of the physiological consequences of hypercapnia. Theoretically, it could be possible to graph all of these physiological changes along an axis of increasing CO2, but these graphs would probably have little additional information to add to the statement "it gets worse". Acidosis gets worse, CNS depression gets worse, ICP gets worse, sympathetic overactivation gets ore overactivated, etc. 

The physiological consequences of hypercapnia are:

  • Depressed airway reflexes with severe hypercapnia
  • Changes in respiratory drive:
    • Increased respiratory drive with mild hypercapnia
    • Depressed respiratory drive with severe hypercapnia
    • These changes are controlled by central chemoreceptors
    • The chemoreceptors are sensitive to changes in the pH of CSF
    • Their output is maximal with a PaCO2 of 60-65 mmHg
    • With extremely high PaCO2, the neurodepressant effect of hypercapnia actually depresses the respiratory drive
  • Changes in respiratory function:
    • Bronchodilation
    • Right shift of the oxygen-haemoglobin dissociation curve
  • Cardiovascular stimulation:
    • Sympathetic overactivity, thus:
    • Hypertension
    • Tachycardia
    • Serum catecholamine excess
    • Increase in cardiac output
    • Prolonged QT interval
  • Vasoactive effects:
    • Systemic arterial vasodilation
    • Pulmonary arterial vasoconstriction
  • CNS effects
    • Progressively increasing sedation
    • Increased intracranial pressure
  • Acid-base effects
    • Acidosis
    • Increased serum bicarbonate
  • Other organ system effects
    • Increased renal vascular resistance
    • Decreased GFR
    • Decreased urine output
    • Increased portal venous pressure and vascular resistance


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Brackett Jr, Newton C., Jordan J. Cohen, and William B. Schwartz. "Carbon dioxide titration curve of normal man: Effect of increasing degrees of acute hypercapnia on acid-base equilibrium." New England Journal of Medicine 272.1 (1965): 6-12.

Van den Elshout, F. J., C. L. Van Herwaarden, and H. T. Folgering. "Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects." Thorax 46.1 (1991): 28-32.

Richardson, D. W., A. J. Wasserman, and J. L. Patterson. "General and regional circulatory responses to change in blood pH and carbon dioxide tension." The Journal of clinical investigation 40.1 (1961): 31-43.

Kiely, David G., Robert I. Cargill, and Brian J. Lipworth. "Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans." Chest 109.5 (1996): 1215-1221.

Trethewie, E. R., and Margaret M. Hodgkinson. "The influence of carbon dioxide and pH on the electrocardiogram of the isolated perfused heart." Experimental Physiology 40.1 (1955): 1-11.

Sarubbi, Berardo, et al. "Effect of blood gas derangement on QTc dispersion in severe chronic obstructive pulmonary disease: evidence of an electropathy?." International journal of cardiology 58.3 (1997): 287-292.