The importance of CO2 Metabolism Alveolar ventilation Gas exchangeHyper/hypoventilation


Hyperventilation probably isn’t what you think it is. Hyperventilation is when ventilation exceeds metabolic demands and PaCO2 drops below 5 kPa. The result will be an alkalosis that affects the function of every protein in the body, producing a confusing spectrum of symptoms with a single cause. Shallow, rapid breathing is probably just that, not necessarily hyperventilation.

The importance of CO2

The body’s main mechanism for altering breathing patterns uses CO2 as the trigger, not O2. It sounds counterintuitive, like many topics in physiology, but because CO2 levels determine blood pH and changes in pH fundamentally alter biochemical processes, it’s the thing the body is most interested in regulating. Oxygen comes second.

Whether someone is adequately ventilated can be determined from the partial pressure of CO2 in arterial blood (PaCO2), not from how they appear to be breathing. A patient might appear to be hyperventilating, but in fact be taking lots of shallow breaths and actually hypoventilating. Similarly, when we exercise, breathing increases to get rid of excess CO2; this increase is appropriate (hyperpnoea), since the body is producing increased CO2 that needs to be “blown off”. Ventilation comes down to metabolism: how much CO2 is the body producing, and what alveolar ventilation is required to blow it off to keep PaCO2 at 5 kPa.


If you fuelled the body exclusively with glucose, the amount of O2 consumed and CO2 produced would be the same. This is due to the stoichiometry of burning glucose in O2:

For every molecule of glucose (C6H12O6), six molecules of O2 are required, and six molecules of CO2 are produced. We don’t live on pure glucose though. Imagine if we lived on pure fat instead. The chemistry is rather different (this is palmitin, a common plant and animal fat):

In this case, the ratio of CO2 to O2 is 102÷140 or 0.73. We call this ratio the respiratory exchange ratio. For glucose it is 1.0, for fats it is closer to 0.7. On a mixed diet, it’s fair to assume that this ratio is around 0.8; we normally produce around 250 mL/min CO2, burning 300 mL/min O2 in the process. Adequate ventilation is a matter of getting those gas flow rates working, and it’s the CO2 that the body is keeping an eye on the most, because (PaCO2) regulates pH and every process in the body is altered by pH disturbances.

Alveolar ventilation (V̇A)

Breathing in and out doesn’t completely replenish the stale air in the lungs. In fact most of the volume of the lungs stays in the lungs, and each breath dilutes fresh air in the functional residual capacity (FRC) of the lung. Furthermore, the air in the conducting airways doesn’t contribute to gas exchange at all and constitutes dead space. At rest, with a typical tidal volume VT; the depth of each breath) of around 500 ml, 150 ml is lost in dead space (VD), and the remaining 350 mL is mixed into the much larger 2350 mL existing FRC. So, it’s not a matter of breathing in, exchanging gases and breathing out. The process of gas exchange goes on continuously, and breathing is just the mechanism for removing a little stale air and adding a little fresh stuff. If we treat the lung as one big alveolus connected to a single airway it works out as shown in Figure 1.

alveolar air

Figure 1: Gas exchange is a continuous process, breathing just tops up the alveoli with a bit of fresh air from time to time. At the end of expiration the lungs still contain over 2 litres of air (this represents the functional residual capacity, or FRC), and inspiration during normal breathing at rest only adds 500 mL to the volume of air in the lungs. Approximately 150 mL of each breath is wasted in the conducting airways as dead space (VD), leaving 350 ml to contribute to the volume ventilating the alveoli (VA).

The actual volume of air that reaches the alveoli is tidal volume (VT) minus the dead space (VD):

That’s just thinking about volumes (L) though. We need to think in terms of flow: L per minute (L/min). This is simple enough. Say you take 12 breaths per minute (your respiratory frequency, or f), each of 500 ml VT. From this we can calculate your minute ventilation (V̇E, in mL/min) by multiplying the two:

minute ventilation

Note that we use expiratory volume/min (V̇E) as a convention. Also, note the accent over the V indicates flow, rather than volume.
Of course, not all that ventilation reaches the alveoli because some of it is lost in dead space, so if we wanted to calculate the true alveolar ventilation we’d have to factor VD into the equation:

alveolar ventilation

The natural reaction to seeing someone breathe at, say, 40 breaths per minute, with a VT of 150 mL might be to think that they are hyperventilating. To be sure, we’d need to see their PaCO2 to see if they were hypocapnic. Repeating the above calculations with those values should give you a clue about the degree of alveolar ventilation in such a person. Their V̇E would be 6000 mL/min, but their V̇A would have to be zero, so they must be hypoventilating.

Gas exchange:

By the time fresh air is diluted down in the somewhat staler alveolar environment (and water vapour is added), PAO2 is 14 kPa, and is mixed with 6 kPa CO2 (equal to PvO2). In fact, you can calculate what the PAO2 should be based on PaCO2 using the alveolar gas equations. If the airways become obstructed, the alveoli become less ventilated and the air in them is staler as a result: PAO2 will drop and PACO2 will rise closer to venous blood levels. Indeed, if the airway leading to a series of alveoli becomes completely obstructed, the partial pressures of O2 and CO2 in those alveoli will equilibrate with venous blood. The process of gas exchange is summarised in Figure 2 below:

alveolar gas exchange

Figure 2: Venous blood is depleted of O2 by the tissues and has usually has an extra kPa of CO2 compared with arterial blood. During gas exchange in the alveoli, some venous CO2 is lost into the alveoli, while O2 is absorbed into blood. The difference between PAO2 and PaO2 can be 1-2 kPa; water vapour accounts for 1 kPa of partial pressure, another 1kPa less reflects the slightly imperfect exchange of O2, which is not particularly water-soluble.

Hyperventilation and hypoventilation

Figure 3 below illustrates the relationship between alveolar ventilation (V̇A) and the partial pressure of CO2 (PO2) in the alveoli (PACO2). Remember, under normal circumstances the (PACO2) will be equal to the arterial partial pressure of CO2 (PaCO2)

hyperventilation hypoventilation

Figure 3: The relationship between alveolar ventilation (V̇A) and the partial pressure of CO2 in alveolar air (PACO2). Typical values are shown by the dashed lines.

Hyperventilation is excessive V̇A such that too much CO2 is blown out of the body, not breathing too quickly as the word is commonly (mis)used. Hypoventilation is the opposite; you retain too much CO2. So:

[Note that although we often lazily interchange acidaemia/acidosis and alkalaemia/alkalosis, the meanings of these words are slightly different. Alkalosis refers to the body being alkaline; alkalemia refers specifically to blood being alkaline.]

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