Carbon Dioxide Toxicity: Respiratory Physiology

Carbon dioxide (CO2) is normally present in the atmosphere in a concentration of 0.03 to 0.04 per cent by volume of dry air. This represents a partial pressure (PCO2) of 0.23 to 0.30 mm Hg. It is one of the products of metabolism of protein, carbohydrates and fats produced in the mitochondria in roughly the same volume as oxygen is consumed. For example:

Glucose (a carbohydrate) + oxygen = carbon dioxide + water + energy

The resultant CO2 has to be transported from the tissues by the circulation and eliminated by exhalation from the lungs.

The normal PCO2 in arterial blood (PaCO2) is about 40 mm Hg and for mixed venous blood is about 46 mm Hg. Some factors that determine arterial PCO2 are summarised in Figure 18.1. PCO2 in the alveolar gas (PaCO2) is in equilibrium with that of the pulmonary veins and is therefore also about 40 mm Hg. Being a product of metabolism, the amount of CO2 produced is unchanged, so the PaCO2 is constant irrespective of depth (unlike oxygen and nitrogen, which reflect the pressures in the inspired gas).

Some factors that influence the partial pressure of carbon dioxide (PCO2). V/Q, ventilation-perfusion. (Adapted from Nunn JF. Applied Respiratory Physiology. 3rd ed. London: Butterworth; 1987.)
Figure 18.1 Some factors that influence the partial pressure of carbon dioxide (PCO2). V/Q, ventilation-perfusion. (Adapted from Nunn JF. Applied Respiratory Physiology. 3rd ed. London: Butterworth; 1987.)

CO2 is the most potent stimulus to respiration. The central medullary chemoreceptors in the brain are stimulated by increases in arterial CO2 and acidosis. In normal conditions, adjustments in ventilation keep the arterial and alveolar CO2 partial pressure remarkably constant. The peripheral chemoreceptors (carotid and aortic bodies) are primarily responsive to hypoxaemia (increasing respiration) but also respond to increases in acidosis and CO2 concentration.

The solubility of CO2 is about 20 times that of oxygen so there is considerably more CO2 than oxygen in simple solution (most of the oxygen is transported bound to haemoglobin). CO2 is transported in the blood in both plasma and red cells. In each 100 ml of arterial blood, 3 ml are dissolved, 3 ml are in carbamino compounds (with haemoglobin and plasma proteins) and 44 ml are carried as bicarbonate (HCO3−).

At rest, approximately 5 ml of CO2 per 100 ml blood are given up from the tissues and liberated in the lungs. About 200 ml of CO2 are produced and excreted per minute. If this CO2 is retained in the body (e.g. from rebreathing), the PaCO2 will climb at the rate of 3 to 6 mm Hg per minute.

With exercise, much larger amounts of CO2 are produced. The working diver can produce more than 3 litres of CO2 per minute for short periods, and 2 litres per minute for more than half an hour, usually without serious alteration in PaCO2 – as a result of a concomitant increase in respiration.

Because ventilation matches any increased CO2 production, while diving, the arterial and hence alveolar CO2 tensions should be maintained at approximately 40 mm Hg despite increasing environmental pressure. Therefore, the alveolar CO2 percentage decreases with increased depths. In contrast, because the source is from the inspired gas, the alveolar partial pressure of oxygen (PO2) and the partial pressure of nitrogen (PN2) increase with depth, but the percentages show little change.

PaCO2 is the primary drive to respiration, as discussed earlier, and it is intimately related to alveolar ventilation. As every breath-hold diver knows, deliberate hyperventilation can drive the PaCO2 down and extend breath-hold time (see Chapters 16 and 61). The exact relationship between PaCO2 and alveolar ventilation is shown in the following equation:

Where k is a conversion factor to convert conditions at STPD (standard temperature and pressure, dry) to BTPS (body temperature and pressure, saturated); VCO2 is the CO2 production in litres per millimetre STPD; Va is the alveolar ventilation in litres per minute BTPS; and PICO2 is the inspired carbon dioxide partial pressure.

Alterations in PaCO2 have widespread effects on the body, especially on the respiratory, circulatory and nervous systems. Apart from the hypocapnia produced by hyperventilation, the more frequent derangement in diving is hypercapnia, an elevation of CO2 in blood and tissues. This may be an acute effect or chronic. Where hypercapnia produces pathophysiological changes dangerous to the diver, the term ‘CO2 toxicity’ (or CO2 poisoning) is used.