Overall V˙A/Q˙C Ratio

Normal gas exchange between air and blood can occur only if pulmonary blood flow perfuses ventilated alveoli. Thus the V˙A/Q˙C ratio is critical in maintaining normal gas exchange. The V˙A/Q˙C ratio may refer to ventilation and blood flow in a single alveolus, all alveoli in a single lobe, or all 300 million plus alveoli in the lung. The average resting V˙A (alveolar ventilation) for the lung is about 4 L per minute, and the resting Q˙C (pulmonary capillary blood flow) is about 5 L per minute. The overall average V˙A/Q˙C is about 0.8 for the lung as a whole.¹ However, the overall V˙A/Q˙C ratio reveals little about the lung’s ability to function as a gas-exchange organ. For example, consider the hypothetical extreme situation in which 5 L per minute of pulmonary blood perfuses a nonventilated left lung and 4 L per minute of gas ventilates a nonperfused right lung. The overall average V˙A/Q˙C would be normal (4 L/min ÷ 5 L/min = 0.8), but gas exchange would be impossible.

V˙A/Q˙C Ratio as a Determinant Of Alveolar PO₂

The model of the lung and its pulmonary blood flow in Figure 12-1 shows that ventilation continually adds atmospheric oxygen to the alveoli, whereas pulmonary blood flow continually removes oxygen from the alveoli. If blood flow ceases and ventilation continues, oxygen builds up in the alveoli until alveolar PO₂ equals the inspired PO₂. If ventilation ceases and blood flow continues, P_AO₂ decreases until it is equal to the PO₂ of venous blood. Thus, the balance between the addition of oxygen (V˙A) and its removal (Q˙C) determines P_AO₂. Decreased V˙A relative to Q˙C decreases the V˙A/Q˙C ratio and reduces P_AO₂ (blood removes oxygen more rapidly than it is replenished). Decreased Q˙C relative to V˙A increases the V˙A/Q˙C ratio and increases P_AO₂ (ventilation adds oxygen more rapidly than it is removed). In the same way, the V˙A/Q˙C ratio also determines P_ACO₂. In this instance, blood flow adds carbon dioxide to alveoli, whereas ventilation removes it.

Alveolar Oxygen–Carbon Dioxide Diagram

Figure 12-2 is a theoretical model of three alveoli with three different V˙A/Q˙C relationships. The inspired PO₂ and PCO₂ for all alveoli are 150 mm Hg and 0 mm Hg (breathing room air at sea level). The middle alveolus has a normal V˙A/Q˙C ratio, maintaining a P_AO₂ equal to 100 mm Hg and a P_ACO₂ equal to 40 mm Hg. Incoming mixed venous blood with a PO₂ of 40 mm Hg and a PCO₂ of 45 mm Hg takes on alveolar PO₂ and PCO₂ values as diffusion and equilibrium occur between the blood and alveolar gas pressures.

If ventilation gradually decreases with no change in blood flow, the V˙A/Q˙C ratio decreases until it eventually equals 0 when ventilation ceases (left alveolus, Figure 12-2). This condition is called absolute shunt. Because no ventilation exists, P_AO₂ and P_ACO₂ levels eventually equalize with the levels of mixed venous blood (i.e., P_AO₂ becomes 40 mm Hg, and P_ACO₂ becomes 45 mm Hg). This condition is called shunt because blood leaving unventilated alveoli is identical in composition to the mixed venous blood entering the alveoli, as though blood flow took a detour around the lung, bypassing it altogether. (In reality, a completely blocked alveolus would collapse because blood flow would continually absorb oxygen and shrink the alveolus until it collapsed.)

The alveolus on the right (see Figure 12-2) shows the other extreme. Blood flow is completely blocked, but ventilation persists unchanged. Because no carbon dioxide can enter the alveolus and no oxygen can be taken up by the blood, P_ACO₂ and P_AO₂ take on values identical to room air. This alveolus has exactly the same PO₂ and PCO₂ as the conducting airways (i.e., the anatomical dead space). This alveolus represents absolute dead space; the V˙A/Q˙C equals ∞ (infinity) because blood flow is zero. The horizontal double arrow below the three alveolar units represents a V˙A/Q˙C continuum of all possibilities ranging from absolute shunt to absolute dead space (from V˙A/Q˙C = 0 to V˙A/Q˙C = 8).

These three hypothetical alveolar units do not represent the only possibilities. Alveolar V˙A/Q˙C ratios may be located anywhere on the continuum, representing V˙A/Q˙C relationships that are lower than normal or higher than normal. Alveoli with abnormally high V˙/Q˙ ratios, but still less than infinity, produce relative dead space; blood flow is present but is abnormally low with respect to ventilation. Alveoli with abnormally low V˙/Q˙ ratios, but still greater than zero, produce relative shunt; ventilation is present but is abnormally low with respect to blood flow. A high V˙/Q˙ ratio generally implies a blood flow deficiency, whereas a low V˙/Q˙ ratio generally implies a ventilatory deficiency. The terms relative dead space and relative shunt are equivalent to the terms dead space effect and shunt effect, or simply high V˙/Q˙ and low V˙/Q˙. Either way, these terms refer to conditions in which blood flow or ventilation is low but not completely absent.

Figure 12-3 illustrates the positions of the three hypothetical alveoli in Figure 12-2 on the oxygen–carbon dioxide diagram.¹ P_ACO₂ is plotted on the vertical (y) axis, and P_AO₂ is plotted on the horizontal (x) axis. Gas pressures in the normal alveolus (V˙/Q˙ = 1) are represented by a point on the oxygen–carbon dioxide diagram where P_AO₂ and P_ACO₂ are 100 mm Hg and 40 mm Hg. This point also indicates PO₂ and PCO₂ values for end-capillary blood leaving the normal alveolus because capillary blood equilibrated with alveolar gas. The absolute shunt alveolus (V˙/Q˙ = 0) takes on P_AO₂ values identical to values of mixed venous blood (note the mixed venous symbol, v¯). Gas pressures in this alveolus are plotted on the oxygen–carbon dioxide diagram showing that PO₂ equals 40 mm Hg and PCO₂ equals 45 mm Hg. The absolute dead space alveolus (V˙/Q˙=∞ ∞) takes on a P_AO₂ equal to 150 mm Hg and a P_ACO₂ equal to 0 mm Hg, values identical to inspired atmospheric gas (note the inspired symbol, I, on the x axis). The curved line passing through these three points is the V˙A/Q˙C line. It represents all possible gas compositions in a single alveolus (breathing room air) supplied by mixed venous blood with a PO₂ equal to 40 mm Hg and a PCO₂ equal to 45 mm Hg. Because end-capillary blood leaving the alveoli equilibrated with alveolar gas, the V˙A/Q˙C line also represents all possible PO₂ and PCO₂ combinations of end-capillary blood from a single alveolus.

Figure 12-3 shows that a P_AO₂ of 50 mm Hg and P_ACO₂ of 80 mm Hg cannot coexist in a single alveolus while the patient is breathing room air because this point does not lie on the V˙A/Q˙C line. However, this alveolar gas composition can exist if the mixed venous blood composition changes greatly, creating a new V˙A/Q˙C line passing through different points. For example, a greatly increased metabolic rate would produce more carbon dioxide, increasing Pv¯CO₂ and decreasing Pv¯O₂, especially if cardiac output cannot increase appropriately. A new V˙A/Q˙C line would be created, beginning at much higher carbon dioxide and lower oxygen values on the left end (see Figure 12-3) but curving down to the same inspired point (PCO₂ = 0 mm Hg and PO₂ = 150 mm Hg) on the right end. The gas composition of any single alveolus and thus of its end-capillary blood depends on the PO₂ and PCO₂ of its mixed venous blood and its V˙/Q˙ ratio.

Reciprocal Relationship between Alveolar Carbon Dioxide Pressure and Alveolar Oxygen Pressure Breathing Room Air

The V˙A/Q˙C line in Figure 12-3 is drawn as though the mixed venous blood gas composition does not change as V˙A/Q˙C changes. Although this statement is essentially true if the V˙/Q˙ of only one alveolus changes, it is not true if the collective V˙/Q˙ of all alveoli uniformly change. Chapter 4 explains that V˙A and P_ACO₂ are reciprocally related. For example, if V˙A decreases to half normal, P_ACO₂ increases from 40 mm Hg to 80 mm Hg. The corresponding P_AO₂ while breathing room air can be calculated with the alveolar air equation (see Chapter 7), yielding the following result:

PAO2=0.21(713)−80(1.2)PAO2=53.7or54mm Hg

Thus, the decrease in P_AO₂ is about the same as the increase in P_ACO₂ in uniform alveolar hypoventilation with room air (i.e., P_ACO₂ and P_AO₂ are reciprocally related).

This reciprocal relationship is not shown on the oxygen–carbon dioxide diagram in Figure 12-3 because this diagram represents a hypothetical change in the V˙/Q˙ of one alveolus out of millions of alveoli; a V˙/Q˙ change in one alveolus would not affect mixed venous blood composition. (The P_AO₂ of 54 mm Hg and P_ACO₂ of 80 mm Hg in the example do not define a point on the V˙/Q˙ curve.) In reality, mixed venous blood gases do change when the entire lung hypoventilates. For example, if all 300 million alveoli uniformly hypoventilate, the average P_ACO₂ increases, producing an equal increase in the average end-capillary PCO₂. As a result, arterial PCO₂ increases. When this arterial blood with an increased PCO₂ passes through tissue capillaries, tissue PCO₂ builds up until a diffusion gradient from tissues to blood is created; this increases mixed venous PCO₂. By increasing P_ACO₂, overall hypoventilation ultimately also increases the mixed venous PCO₂. The end result is a new P_ACO₂-P_AO₂ combination, identifying a point on a new V˙A/Q˙C line in the oxygen–carbon dioxide diagram. The important point illustrated by Figure 12-3 is that the gas composition of any alveolus is determined by its incoming venous gas composition and V˙/Q˙ ratio.

V˙A/Q˙C RATIO Distribution in Normal Lung

Chapter 6 describes why the V˙A/Q˙C ratio increases from the lung base to the lung apex (see Figure 6-11). Similar to blood flow, ventilation is greatest in the lung base and least in the apex. However, from the base to apex, blood flow decreases at a more rapid rate than ventilation, which means that apical regions are relatively overventilated with respect to blood flow (high V˙A/Q˙C), whereas basal regions are relatively underventilated with respect to blood flow (low V˙A/Q˙C). Figure 12-4 illustrates these regional differences in V˙A/Q˙C with respect to the oxygen–carbon dioxide diagram. (In this figure, P_AO₂ decreases by 40 mm Hg from the lung apex to the lung base, whereas P_ACO₂ increases only about 15 mm Hg from apex to base.²)

Because P_AO₂ and P_ACO₂ are different in different regions of the lungs, similar regional differences exist in alveolar end-capillary blood oxygen and carbon dioxide contents. Arterial blood is a mixture of these end-capillary contents. Arterial oxygen and carbon dioxide contents are an average of the alveolar end-capillary oxygen and carbon dioxide contents. Similarly, expired gas at the end of a tidal exhalation is a mixture of alveolar gas pressures from differing V˙A/Q˙C regions. Thus, end-tidal PO₂ and PCO₂ reflect the overall averages of the lungs’ P_AO₂ and P_ACO₂.

Figure 12-4 shows that the normal lung is not a perfect gas-exchange organ. End-capillary blood from low V˙A/Q˙C basal regions has a decreased PO₂ and submaximal oxygen content. End-capillary blood from normal V˙A/Q˙C regions has near-maximal oxygen content (PO₂ = 100 mm Hg; hemoglobin saturation = 98.5%). Blood from high V˙A/Q˙C apical regions carries only slightly more oxygen per 100 mL than blood from normal units because blood from normal V˙A/Q˙C regions already has near-maximal oxygen content.

Because end-capillary blood from low V˙A/Q˙C regions is not maximally saturated with oxygen while room air is breathed, arterial blood is also never maximally saturated. This is true because arterial blood is a mixture of end-capillary blood from all V˙A/Q˙C regions. As long as any low V˙A/Q˙C regions exist, low end-capillary oxygen contents mix with and dilute maximally saturated end-capillary blood, causing submaximal arterial oxygen content.

Normal Alveolar-Arterial Oxygen Pressure Difference

To understand how the lung’s normal V˙A/Q˙C imbalances contribute to the normal P(A-a)O₂, one must understand what determines alveolar and arterial oxygen compositions. (Recall from Chapter 1 that another source of the normal P(A-a)O₂ is anatomical shunting, in which bronchial venous blood mixes with freshly oxygenated pulmonary venous blood.) Arterial blood is a mixture of the end-capillary blood from all V˙A/Q˙C regions in the lungs. Alveolar gas, collected at the end of a tidal exhalation, is a mixture of alveolar gases from these same differing V˙A/Q˙C regions. Although alveolar gas is in equilibrium with end-capillary blood, the average P_AO₂ is not the same as the average end-capillary blood PO₂. The oxygen-hemoglobin equilibrium curve illustrates this point (Figure 12-5). For the sake of simplicity, this illustration assumes that equal volumes of end-capillary blood from apical and basal lung regions mix to form arterial blood. (This is not actually true because the lung’s bases receive more blood flow than the apices.) PaO₂ is not determined by an average of the mixed end-capillary PO₂ values; instead, PaO₂ is determined by an average of the mixed end-capillary oxygen contents.

For example, let us assume in Figure 12-5 that 100 mL of end-capillary blood from the lung apex is mixed with 100 mL of end-capillary blood from the lung base. Blood from the apex has a PO₂ equal to 130 mm Hg and an oxygen saturation (SaO₂) of 100%. Blood from the base has a PO₂ of 85 mm Hg and an SaO₂ of about 94%. With a hemoglobin concentration of 15 g/dL, the oxygen content in 100 mL of apical blood is as follows:

(15×1.34×1.0)+(130×0.003)=20.5mL

The oxygen content in 100 mL of basal blood is as follows:

(15×1.34×0.94)+(85×0.003)=19.1mL

Mixing these two samples produces 200 mL of blood containing 39.6 mL of oxygen, or 19.8 mL of oxygen per 100 mL of blood (19.8 mL/dL), corresponding to about 97% saturation on the oxyhemoglobin equilibrium curve (see Figure 12-5). This mixture produces a PaO₂ of about 96 to 97 mm Hg, which is obviously not the average of apical and basal PO₂ values. High V˙A/Q˙C apical units cannot negate the desaturating effect that low V˙A/Q˙C basal units have on mixed end-capillary blood. The desaturating effects of basal alveolar units are even more pronounced than illustrated in this example because basal regions actually receive more blood flow and contribute proportionally more to the arterial blood.

In contrast, mixed expired alveolar gas PO₂ is simply the average of the PO₂ values from all of the differing V˙A/Q˙C regions in the lungs because no hemoglobin is involved. In the example just discussed, the average P_AO₂ is (130 + 85)/2 = 108 mm Hg, producing a P(A-a)O₂ of 12 mm Hg (P_AO₂ of 108 mm Hg − PaO₂ of 96 mm Hg). The differing V˙A/Q˙C ratios in the lung create a normal P(A-a)O₂ of approximately 7 to 14 mm Hg, if room air is breathed (F_IO₂ = 0.21).³ Severely diseased lungs have many abnormally low V˙A/Q˙C regions; in such instances, the P(A-a)O₂ is even higher.

CONCEPT QUESTION 12-5

Why does absolute shunting affect P(A-a)O₂?