Carriage Of Carbon Dioxide
Carbon dioxide (CO2) is produced by tissues and transported in the blood to the lungs, where it is expired. The amount of CO2 that can be carried in the blood is much greater than that of O2, as seen in the CO2 dissociation curve (Fig. 9a). The CO2 dissociation curve is also more linear and does not reach a plateau. CO2 is transported in the blood as bicarbonate ions, as carbamino compounds combined with proteins or simply dissolved in the plasma (Fig. 9b).
Bicarbonate: In mixed venous blood about 60% of CO2 is trans- ported in the form of bicarbonate. CO2 and water combine to form carbonic acid (H2CO3) and thence bicarbonate (HCO3−):
The left-hand side of the equation proceeds slowly in plasma, but is accelerated dramatically by the enzyme carbonic anhydrase (CA), which is present in red blood cells. Ionization of carbonic acid to bi- carbonate and H+ is rapid in the absence of any enzyme. Bicarbonate is therefore formed preferentially in the red cells, from which it easily diffuses out into the plasma. The red cell membrane is however impermeable to H+ ions and they remain within the cell. To maintain electrical neutrality, Cl- ions diffuse into the cell to replace bicarbonate, an effect known as the chloride shift (Fig. 9c). A build-up of H+ in the red blood cell would impair further movement of Equation 1 to the right, thus limiting formation of bicarbonate. However, H+ binds avidly to reduced (deoxygenated) haemoglobin; i.e. haemoglobin acts as a buffer, so the rise in H+ concentration is limited and more bicarbonate can be formed. Oxygenated haemoglobin does not bind H+ so well, as it is more acidic. This contributes to the Haldane effect, which states that, for any given Pco2, the CO2 content of deoxygenated blood is greater than that of oxygenated blood. As a result, when blood gives up oxygen to respiring tissues, i.e. becomes deoxygenated, it is able to take up more of the CO2 that the tissues are producing. Conversely, oxygenation of haemoglobin in the lung assists the unloading of CO2 from the blood so it can be expired. This is illustrated in Fig. 9a and Equation 2.
H+ + haemoglobin · O2 ⇔ haemoglobin · H + O2 (2)
Note that as a consequence of all the above, deoxygenated red blood cells have a higher intracellular osmolality and water enters, causing them to swell slightly. In the lung, CO2 is given off, osmolality falls and the red cells shrink again.
Carbamino compounds: CO2 combines rapidly with terminal amino groups on proteins to form carbamino compounds:
CO2 + protein · NH2 ⇔ protein · NH · COOH (3)
In blood, the most prevalent protein is haemoglobin, which combines with CO2 to form carbaminohaemoglobin. Reduced haemo- globin forms carbamino compounds more readily than oxygenated haemoglobin, and this also contributes to the Haldane effect (Fig. 9b). About 30% of the CO2 expired is carried to the lungs as carbamino compounds.
CO2 in solution: CO2 is approximately 20 times more soluble in water than O2. A significan proportion ( 10%) of the CO2 exhaled is therefore carried to the lung dissolved in the plasma.
Because of the Haldane effect, the proportion of CO2 that is carried in the blood as bicarbonate, carbamino compounds and simply dissolved differs between oxygenated arterial blood and deoxygenated mixed venous blood (Fig. 9b).
Hypoventilation and hyperventilation Ventilation is normally closely matched to the metabolic requirements of the body, and this can be estimated from the rate of CO2 production (Chapter 11). The partial pressure of CO2 in the alveoli (PAco2) is proportional to the amount of CO2 exhaled per minute (Vco2) as a fraction of total alveolar ventilation (VA), i.e. PAco2 ∝ Vco2IVA. The gas in the alveoli is in equilibrium with arterial blood, so PAco2 estimates the partial pressure in the blood (Paco2). At any given metabolic rate, doubling the alveolar ventilation halves alveolar and arterial Pco2, and halving alveolar ventilation doubles PAco2 and Paco2. Changes in alveolar ventilation also affect alveolar Po2, but the relationship is not as simple because O2 is present in both inspired and expired gas. Thus, doubling alveolar ventilation will halve the difference between the inspired and alveolar O2 fraction. Hypoventilation (underventilation) and hyperventilation (overventilation) are therefore define in terms of Paco2, so that a patient is hypoventilating when Paco2 is more than 45 mmHg (5.9 kPa) and hyperventilating when the Paco2 is less than 40 mmHg (5.3 kPa). Note that the CO2 content of the blood will be affected more slowly by hypo or hyperventilation than the O2 content, as the CO2 stores in the body (e.g. as HCO3−) are approximately 75 times greater than those for O2 (e.g. haemoglobin and myoglobin). Also, al- though hyperventilation increases arterial Po2, in a healthy patient it has little effect on O2 content as arterial haemoglobin is normally close to saturation (Chapter 8).
Hypoventilation may occur when the respiratory drive is impaired by head injury, or drugs such as morphine or barbiturates which sup- press the respiratory centres. It may also be caused by respiratory muscle weakness or severe chest trauma. Hypoventilation is sometimes a feature of severe chronic obstructive airways disease (COPD; Chapter 26), but is not usually a feature of asthma (Chapter 25) unless the attack is severe or prolonged enough to lead to exhaustion. Hypoventilation is diff cult to achieve voluntarily, as the respiratory centres create an overwhelming desire to breathe.
Hypoventilation leads to hypercapnia (high Paco2) and hypoxia (low Pao2). Increasing severity of hypercapnia causes peripheral vasodilatation, muscle twitching and hand fap, confusion, drowsiness and eventually coma; there is a concomitant respiratory acidosis (Chapter 10). The effects of hypoxia are dealt with elsewhere (Chapter 8). Hyperventilation can be induced voluntarily and in states of high anxiety (e.g. panic attacks) or pain. It results in a low Paco2 (hypocapnia), which can cause light-headedness, visual disturbances due to cerebral vasoconstriction, paraesthesia ('pins and needles') and muscle cramps, especially carpopedal spasm; there is a concomitant respiratory alkalosis (Chapter 10).
Respiratory gas exchange ratio
Respiratory gas exchange ratio (R) is the ratio of CO2 production to O2 consumption as measured at the mouth. In the steady state, CO2 production and O2 consumption reflec tissue metabolism. Metabolizing carbohydrates produces a volume of CO2 equal to the volume of O2 consumed, whereas metabolizing fats and proteins produces a smaller volume of CO2 than O2 consumed. For an average mixed diet R ∞ 0.8.