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TRANSPORT OF CARBON DIOXIDE

Carbon dioxide is the primary product of the oxidative processes taking place in the body cells, and is removed form the tissues by the blood. On average, a person uses about 300 ml/min of O2 and produces about 250 ml/min of CO2 at rest. These numbers can go up 20 times during heavy exercise. CO2  is carried in the blood in three forms: physically dissolved, as bicarbonate, and in combination with Hb as carbamino compound (HbCO2). At the Hb molecule, CO2 combines with globin, hence, does not compete with O2. According to Henry's law, CO2 from the tissues diffuses to the plasma where it is physically dissolved. It combines with H2O to produce carbonic acid. But in plasma this reaction is very slow. From plasma, CO2 diffuses to the red blood cells where :

CO2 + H2O ® H2CO3 is facilitated by the enzyme carbonic anhydrase.

H2CO3 ionizes into bicarbonate and H+ ion: H2CO3 ® HCO3- + H+ (Fig. 13).

 

Fig.13
Fig. 13.  CO2 transport. In the tissue capillaries CO2 difuses along the pressure gradient from the tissues into plasma. Part of the CO2 remains physically disolved and other part combines with water in plasma. However, in plasma this reaction is very slow. In the red bloodcells, it is facilitated by enzyme, carbonic anhydrase. Thus, as soon as CO2 diffuses from plasma to red blood cells it combines with water to produce carbonic acid.  Carbonic acid dissociates to hydrogen ion and hicarbonate. Some of bicarbonate diffuses out into plasma changing electrical charge of the cell membrane. In order to maintain electrical neutrality (the cell membrane is relatively impermeable to cations), Cl- diffuses into the cell plasma.  The Cl- diffusion in (or out) of the cell is called the chloride shift.  In the pulmonary capillaries all reactions follow  the pressure gradient in the reverse directions.
 

In the tissue capillaries, Hb free of O2 (O2 diffused to the tissues) may combine with H+ (H+ + HbO2 ® H+Hb + O2). This is because reduced Hb is less acid than HbO2. Therefore, Hb acts as a buffer. Consequently, the presence of reduced Hb in the tissue capillaries helps with the loading of CO2. This is known as the Haldane effect. As the result, for a given PCO2, more CO2 is carried in deoxygenated blood than in oxygenated blood (Fig.14).

Fig.14

Fig. 14.  CO2 dissociation curve. A: CO2 content in blood. At PCO2 above 25 mmHg, CO2 content - PCO2 relationship is almost linear. B. "Physiological" part of the CO2 dissociation curve shows that CO2 content in blood depends on %HbO2. Mixed venous blood (%Hb=75) can carry more CO2 that arterial blood (%Hb=97.5). The dependence of the CO2 content in blood on %HbO2 is called the Haldane effect. C: Comparison of CO2 and O2 content in blood in relation to their partial pressures.
 

The total amount of CO2 in blood, by approximation, is composed of:

1) 10% of CO2 physically dissolved in the plasma and red blood cells.

2) 79% of CO2 converted into bicarbonate and hydrogen ions. This reaction occurs primarily in the red blood cells because they contain large amounts of the enzyme carbonic anhydrase, although bicarbonate diffuses in plasma.

3) 11% of CO2 combined with Hb (HbCO2).

 If there is more CO2 , the production of all the substances: HbCO2, HCO3-, H+ increases, while a sudden lowering of blood PCO2 results in H2CO3- going to H2CO3 and further into CO2 and H2O, HbCO2 generates Hb and CO2. This is precisely what happens as venous blood flows through the lung capillaries:
H+ + HCO3-® H2CO3 ® H2O + CO2, and
HbCO2 ® Hb + CO2

Because the blood PCO2 is higher than alveolar PCO2, a net diffusion of CO2 from the blood lowers the blood PCO2. Normally, as fast as CO2 is generated from HCO3- and H+ from HbCO2, it diffuses into the alveoli. Reduced Hb readilly bonds O2.

Unlike the HbO2 curve, the CO2 dissociation curve (Fig. 14) has no steep portion or a flat or nearly horizontal portion, thus the relationship between CO2 content and PCO2 is almost linear. This means that if we hypoventilate and alveolar PCO2 rises, then arterial, capillary, tissue and venous CO2 also rises. Doubling alveolar ventilation halves alveolar PCO2. This means that an increase in alveolar ventilation proportionaly increases CO2 removal.

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Respiratory Failure - Some Definitions

Respiratory failure occurs when there are abnormalities in arterial blood gas tensions resulting from failure of:
 
                                        1) the lungs as a gas exchanging organ

2) the ventilatory control mechanism

3) the neuromuscular breathing apparatus
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Arterial Hypoxia

Blood hypoxia refers to deficient blood oxygenation, i.e. low PaO2 and low %Hb saturation. In a hypoxic condition, if PaO2 decreases to or below 60 mmHg, O2 content in arterial and venous blood are lower than the normal values at sea level.

There are five general causes of hypoxia:

1. Inhalation of low O2 mixture (e.g. high altitude).

2. Hypoventilation. PaO2 decreases and PaCO2 increases. It means that alveolar ventilation in
    relation to the metabolic CO2 production is reduced. Examples of hypoventilation include:
 

a) diseases affecting the central nervous system.

b) neuromuscular diseases.

c) barbiturates, and other drugs and narcotics.
 

 3. Ventilation/perfusion imbalance within the lungs.

4. Shunts: venous blood bypasses the gas exchange area in the lungs and returns to systemic
    circulation.

5. O2 diffusion impairment (e.g. pulmonary edema).