The Gas Exchanger: Matching Ventilation and Perfusion
Physiology of the Pulmonary Vasculature: Where Does the Blood Go?
From Chapter 2, we recall that the pulmonary vasculature takes deoxygenated blood from the right ventricle to the alveolar capillaries, where gas exchange occurs. The capillaries join to form pulmonary veins, which ultimately return the oxygenated blood to the left atrium and ventricle from where the oxygenated blood is pumped to the body. The pulmonary circulation is a high-compliance, low-resistance system. This means that it is able to adjust to large changes in flow, or cardiac output, with little change in resistance.
Effect of Gravity on Pulmonary Blood Flow ↑
Under conditions of normal cardiac output with an individual at rest, pulmonary blood flow is directed by gravity to the more dependent portions of the lung, that is, the portions of lung that are lower or oriented in the inferior aspects of the thorax with respect to gravity. Consequently, not all pulmonary vessels may receive blood and, thus, do not participate in gas exchange (recall that alveoli that do not receive blood flow constitute part of the dead space). Under conditions of high cardiac output or increased pulmonary vascular resistance, vessels that previously were not receiving blood are now recruited and participate in the gas exchange process. Nevertheless, as a general principle, the most dependent portions of the lung receive the greatest amount of pulmonary blood flow under normal conditions.
Effect of the Alveoli on Pulmonary Blood Flow ↑
The extent that pulmonary capillaries are in intimate contact with the alveoli, the pressure within the alveolus may alter the flow of blood through the adjacent capillary. If the alveolar pressure exceeds the pulmonary capillary pressure, the capillary will be squeezed and blood flow to that alveolus will diminish or cease.
Three types of pressure must be considered when assessing blood flow to a region of the lung: pulmonary arterial pressure, pulmonary venous pressure, and alveolar pressure (Quick Check 5-1). As discussed in Chapter 4, flow is normally expressed as a pressure differential divided by resistance:
One might think that the pulmonary artery pressure (Pa) and the pulmonary venous pressure (Pv) are all that need to be considered when assessing flow through vessels with a given resistance. However, the pulmonary capillaries, as they course alongside the alveoli, appear to behave in a manner similar to the Starling resistors discussed in Chapter 4. As seen in Animated Figures 4-10A and B, if the vessel travels through an environment in which the pressure outside the vessel is greater than inside (i.e., a negative transmural pressure) and the vessel wall is very compliant, the vessel will collapse, and flow will cease (Fig. 5-4).
The relationship between these pressures and blood flow in the lungs can be characterized by thinking of the lungs as being composed of three zones, first postulated by John West (Fig. 5-5). In the most superior zone (highest region with respect to gravity), zone I, Palv > Pa and there is no flow of blood to this region of the lung. Thus, the alveoli in this zone do not participate in gas exchange and are part of the lung's dead space. In zone II, Pa > Palv > Pv. There is some blood flow to the alveolus throughout the zone, and the amount of flow increases as one moves down the top to the bottom of the lung and the pressure differential between Pa and Palv increases. In zone III, Pa > Pv > Palv, and alveolar pressure has no effect on the flow of blood throughout the region.
Pulmonary Vascular Resistance and Distribution of Flow ↑
Because flow is inversely related to resistance, we also need to consider factors that will alter the resistance within the pulmonary circulation. Although the pulmonary arteries are relatively thin-walled structures, they do have smooth muscle within their walls. The tone of the muscle plays a role in modulating the diameter of the vessel and, hence, the resistance to flow. Unlike the systemic circulation, in which resistance is largely determined by the balance between the sympathetic and parasympathetic nervous systems, the pulmonary circulation does not appear to respond significantly to these inputs.
When exposed to low levels of oxygen, the pulmonary vessels constrict. The exact mechanism by which hypoxic vasoconstriction occurs is not well understood, but hypoxia is a very potent vasoconstrictor for the pulmonary circulation. Again, this is in contrast to the systemic circulation, which responds to localized tissue hypoxia with vasodilation. In the case of the systemic circulation, tissue hypoxia is often a sign of insufficient blood flow to that region; vasodilation in that setting makes sense as a way of delivering more blood and oxygen to sustain metabolic activities in the tissue. However, in the lungs, local hypoxia generally reflects a problem with the airways or alveoli; either ventilation is diminished because of obstruction airflow or the alveoli are filled with fluid, thereby preventing gas from coming into contact with the pulmonary capillaries. In either event, it would be counterproductive, from a survival standpoint, to send blood to regions of lung that are not receiving oxygen. The blood would exit that region of lung without having been able to eliminate carbon dioxide or pick up a fresh supply of oxygen. Rather, hypoxic vasoconstriction occurs, increasing local resistance in those vessels and resulting in a redistribution of pulmonary blood flow to the regions of lung that are well ventilated.
Two chemicals produced locally in the pulmonary circulation, nitric oxide (NO) and prostacyclin, also contribute to the tone and resistance of the pulmonary vessels. Nitric oxide, produced by nitric oxide synthase in the endothelial cell membrane, is the most potent endogenous vasodilator discovered. Its half-life is extremely short; it is produced locally and acts locally in the vessel. Mechanical stimuli can increase production of NO. Rapid flow through the vessel, for example, increases shear stress that appears to stimulate production of nitric oxide synthase. Thus, as flow increases, NO production also increases to dilate the pulmonary vessel and diminish resistance, thereby allowing for an increase in flow with a minimal increase in pressure. Biochemical stimulation of nitric oxide synthase results from a variety of materials, including acetylcholine, bradykinin, substance P, serotonin, and adenosine triphosphate (ATP).
Prostacyclins, a form of prostaglandin, are produced in the lungs and act as vasodilators in the pulmonary circulation. Also, to the extent that calcium influx into muscle cells is important for muscle contraction, pharmacologic blockage of calcium channels with drugs such as nifedipine and verapamil may lead to mild pulmonary vasodilatation.
Matching of Ventilation and Perfusion in the Lungs ↑
We have outlined the key physiological principles that govern the distribution of ventilation and perfusion in the lungs. For optimal gas exchange to occur, new gas from the atmosphere must travel to regions of lung that are also receiving blood flow from the pulmonary circulation. For the most part, both ventilation and perfusion are greatest at the bases of the lung in an upright person; thus, the match between ventilation and perfusion is generally quite good, although not perfect. There is relatively more ventilation than perfusion to the apices of the lungs, and relatively more perfusion than ventilation at the bases. When diseases affect either the distribution of ventilation (