PreClinical Insight: Respiratory Physiology

The capillaries of the unit deliver mixed venous blood with a low partial pressure of O2 (Pv¯O2). The partial pressure of O2 (PO2) in the alveolar gas (PAO2) is much higher than in the capillary blood and O2 diffuses passively from the alveolar space into the blood during passage through the capillaries. The membrane separating the alveolar gas and blood compartments causes little resistance to diffusion so the PO2 in end-capillary blood (PecO2) equilibrates with PAO2 well before the blood leaves the unit. Oxygenation of arterial blood is, therefore, primarily dependent on the PAO2. Note that in this idealised lung unit there is no difference between PAO2 and PO2 in arterial blood (PaO2). For reasons explained later, the alveolar–arterial O2 tension difference (PA–aO2) is very helpful when assessing the causes of gas exchange problems in clinical medicine. The partial pressure of CO2 (PCO2) is greater in mixed venous blood (Pv¯CO2) than in the alveolar gas (PACO2) and diffusion over the alveolar–capillary membrane, therefore, results in a net flow in a direction opposite to that of O2, from blood to alveolar gas. The result is again an equal PCO2 in alveolar gas and end-capillary blood (PecCO2) because the resistance for diffusion is even less for CO2 than for O2. Due to differences in the relationship between partial pressures and blood content for O2 and CO2, there is approximately as much CO2exchanged for a partial pressure difference between mixed venous and arterial blood of 5 mmHg (0.7 kPa) as there is O2 exchanged with a difference of 60 mmHg (6.7 kPa). The amount of O2carried in the blood is determined by the haemoglobin concentration, the fraction of haemoglobin binding O2 and the PaO2. It is important to understand that the end-capillary blood O2 content (CecO2), rather than the PecO2, from different units are additive.

Diffusion limitation as a cause of Arterial Hypoxemia

In case 1, a 25-year-old male elite cyclist who undergoes a cardiopulmonary exercise study is noted to have progressively worsening arterial hypoxaemia with increasing workload (a response not seen in normal individuals). Arterial blood gases (ABGs) at end-exercise are: pH 7.18, PCO2 in arterial blood (PaCO2) 30 mmHg (4.0 kPa), PaO2 81 mmHg (10.8 kPa) and arterial haemoglobin O2saturation 88%.Exercise increases the amount of O2 extracted from arterial blood in the systemic circulation, which tends to reduce Pv¯O2. Therefore, more O2 needs to be taken up in the lung to reach normal oxygenation of arterial blood. Exercise also increases pulmonary blood flow, which shortens the time that the blood is exposed to alveolar gas. The combined effect is that more O2 needs to be taken up in less time. At very high cardiac outputs, the transit time might be too short for complete equilibration between PAO2 and PecO2. This represents diffusion limitation as a cause of hypoxaemia in athletes achieving extremely high cardiac outputs. Hypoxaemia due to diffusion limitation can also be seen in normal individuals during exercise at altitude. In this setting, the driving pressure for O2 diffusion is decreased due to the lower PO2 in inspired air (PIO2) at altitude and the transit time of blood through the alveolar capillaries is shorter due to higher cardiac outputs. A diffusion limitation can also occur in patients with interstitial lung diseases. Patients with these diseases might have a normal PaO2 at rest but develop hypoxaemia during exercise, which can be explained by the combined effect of increased resistance to diffusion through the thickened alveolar–capillary membrane, reduced Pv¯O2 and a shortened transit time. Oxygenation of capillary blood as a function of time under different conditions. The panel illustrates how PecO2 and hence PaO2 fail to reach PAO2 due to low Pv¯O2 and short transit time during extreme exercise at sea level (solid curve) and moderate exercise at altitude (dashed curve).