The alveolar partial pressure of CO₂ (P_ACO₂) varies directly with the body’s production of CO₂ () and inversely with alveolar ventilation (). The relationship is expressed by the following formula:

< ?xml:namespace prefix = "mml" />PACO2=V˙CO2×0.863V˙A

Where:

Because is expressed as a flow of dry gas at 0° C and 760 mm Hg, and is reported as saturated gas at body temperature and ambient pressure, the factor 863 is employed to correct the measurement for comparison under the same conditions. It confers the units of pressure to the resulting dimensionless ratio of flow rates.

As an example, given of 200 ml/min and alveolar ventilation of 4315 ml/min, application of this formula yields a P_ACO₂ of approximately 40 mm Hg:

PACO2=(863mm Hg×200ml/min)÷4315ml/min=40mm Hg

P_ACO₂ increases above this level if CO₂ production increases while alveolar ventilation remains constant or if alveolar ventilation decreases while remains constant. An increase in dead space, the portion of inspired air that is exhaled without being exposed to perfused alveoli, can also lead to an increased P_ACO₂:

V˙=(VT−VD)×f

Where:

Likewise, P_ACO₂ decreases if CO₂ production decreases or alveolar ventilation increases. Normally, complex respiratory control mechanisms maintain P_ACO₂ within a range of 35 to 45 mm Hg under various conditions (see Chapter 14). If CO₂ production increases, as with exercise or fever, ventilation automatically increases to maintain P_ACO₂ within normal range.

Alveolar Oxygen Tensions

Many factors determine the alveolar partial pressure of O₂ (P_AO₂). Most important is PiO₂. In addition, when O₂ is in the lungs, it is diluted by both water vapor and CO₂. To account for all these factors, the following alveolar air equation is applied:

PAO2=FiO2×(PB−47)−(PACO2÷0.8)

Where:

FiO₂ = Fraction of inspired O₂ (decimal)

P_B = Barometric pressure (mm Hg)

47 = Water vapor tension (in mm Hg) at 37° C

P_ACO₂ = Alveolar PCO₂

0.8 = Normal respiratory exchange ratio (R)

The equation component FiO₂ × (P_B − 47) is a simple application of Dalton’s law:

Partial pressure=Fractional concentration×Total pressure

However, under BTPS conditions in the lungs, the total pressure available for O₂ is reduced by an amount equal to the saturated water vapor pressure at 37° C, or 47 mm Hg.

The equation component (PaCO₂ ÷ 0.8) accounts for the alveolar CO₂. However, PaCO₂ cannot simply be subtracted, as was done for water vapor. Instead, the equation must be corrected for the difference between O₂ and CO₂ movement into and out of the alveoli, which is done by dividing the P_ACO₂ by R. R is the ratio of CO₂ excretion to O₂ uptake, which normally averages 0.8 throughout the lung. In addition, because PaCO₂ nearly equals P_ACO₂, PaCO₂ can be substituted for P_ACO₂. For example, if FiO₂ is 0.21, P_B is 760 mm Hg, and PaCO₂ is 40 mm Hg, the normal alveolar partial pressure of O₂ can be estimated as follows:

PAO2=0.21×(760mm Hg−47)−(40mm Hg÷0.8)=99.73mm Hg

In clinical practice, if a patient is breathing 60% or more O₂ (FiO₂ ≥ 0.60), the correction for R can be dropped because the magnitude of the correction to PaCO₂ falls below significance relative to the much larger calculated FiO₂ (P_B − 47). This yields the following simplified form of the alveolar air equation:

PAO2=FiO2(PB−47)−PaCO2

The accompanying Mini Clini provides an example of how to use the alveolar air equation.

Mini Clini

Alveolar-Arterial PO₂ Difference and a/A Ratio

Not all of the O₂ from the alveoli gets into the blood. Why this occurs is discussed later in this chapter. This Mini Clini considers how the efficiency of O₂ transfer from the alveoli to the blood can be computed.

Several bedside computations can be used to estimate the efficiency of pulmonary O₂ transfer. The most common computation is the difference between the alveolar and arterial PO₂, called the A-a gradient (P[A−a]O₂). Normally, this difference is small—only 5 to 10 mm Hg when air is breathed and no more than 65 mm Hg when 100% O₂ is breathed.

Another common bedside computation is the ratio of arterial to alveolar PO₂, called the a/A ratio. The a/A ratio should be thought of as the proportion of O₂ getting from the alveoli to the blood. Normally, this proportion is at least 90% (a ratio of 0.9).

 Problem

Compute and interpret the P(A−a)O₂ and a/A ratio for a 45-year-old woman breathing 70% O₂ at sea level, with the following blood gas values: PaO₂, 50 mm Hg; PaCO₂, 50 mm Hg.

Discussion

1. Compute P_AO₂ using one form of the alveolar O₂ equation as follows: P_AO₂ = FiO₂ × (P_B − 47) − P_ACO₂ (patient breathing >60% O₂)

P_AO₂ = Alveolar O₂ tension (mm Hg)

FiO₂ = Inspired O₂ fraction (decimal)

P_ACO₂ = Alveolar CO₂ tension (mm Hg, often estimated by arterial CO₂ tension)

P_AO₂ = 0.7 × (760 mm Hg − 47 mm Hg) − 50 mm Hg

P_AO₂ = 449 mm Hg

2. Compute P(A−a)O₂ as follows:

P(A−a)O₂ = P_AO₂ − PaO₂

PaO₂ = Arterial O₂ tension (mm Hg)

P(A−a)O₂ = 449 mm Hg − 50 mm Hg

P(A−a)O₂ = 399 mm Hg

3. Compute a/A ratio as follows:

a/A = PaO₂/P_AO₂

a/A = 50 mm Hg/449 mm Hg

a/A = 0.11

Discusson

Both the P(A−a)O₂ and the a/A ratio are abnormal. Compared with a normal value of 65 mm Hg or less, the P(A−a)O₂ of nearly 400 mm Hg is very high. This P(A−a)O₂ indicates a large difference between the alveolar and arterial PO₂ values (i.e., inefficient O₂ transfer). Likewise, the a/A ratio of 0.11 indicates that only approximately 11% of the O₂ in the alveoli is getting into the blood. Although the patient is receiving a high FiO₂ (0.70), she has a severe problem getting O₂ into her blood and needs immediate evaluation by a critical care physician.

Changes in Alveolar Gas Partial Tensions

In addition to CO₂, O₂, and water vapor, alveoli normally contain nitrogen. Nitrogen is inert and plays no role in gas exchange; however, it occupies space and exerts pressure. According to Dalton’s law, the partial pressure of alveolar nitrogen (P_AN₂) must equal the pressure it would exert if it alone were present. To compute P_AN₂, subtract the pressures exerted by all the other alveolar gases, as follows:

PAN2=PB−(PAO2+PACO2+PH2O)

PAN2=760mm Hg−(100mm Hg+40mm Hg+47mm Hg)

PAN2=760mm Hg−187mm Hg

PAN2=573mm Hg

Because both water vapor tension and P_AN₂ remain constant, the only partial pressures that change in the alveolus are O₂ and CO₂. Based on the alveolar air equation, if FiO₂ remains constant, P_AO₂ must vary inversely with P_ACO₂.2–4

 Rule of Thumb

When the patient is breathing room air, the sum of P_AO₂ and P_ACO₂ equals about 140 mm Hg (100 mm Hg and 40 mm Hg). Changes in ventilation that cause P_ACO₂ to vary also vary the resulting P_AO₂ to keep the total at 140 mm Hg. If P_ACO₂ of a patient breathing room air increases from 40 mm Hg to 60 mm Hg (an increase of 20 mm Hg), P_AO₂ should decrease by approximately 20 mm Hg. This equation assumes a constant value for R.

P_ACO₂ itself varies inversely with the level of alveolar ventilation. For a constant CO₂ production, a decrease in simultaneously increases P_ACO₂ and decreases P_AO₂, whereas an increase in has the opposite effect (Figure 11-2). However, ventilation can be increased only so much. Neural control mechanisms and the increased work of breathing prevent decreases in P_ACO₂ much below 15 to 20 mm Hg. Whenever a patient is breathing room air at sea level, the RT should not expect to see a PaO₂ greater than 120 mm Hg during hyperventilation. PaO₂ values greater than 120 mm Hg indicate that the patient is breathing supplemental O₂. The accompanying Mini Clini presents a clinical application of these principles.

Mini Clini

Assessing Arterial Gas Partial Pressures

 Problem

The RT is given the following arterial blood gas report for a patient who was just admitted to the emergency department: PaO₂ = 170 mm Hg; PaCO₂ = 23 mm Hg. Without additional data, what conclusions can the RT draw about the FiO₂ in this case?

Discussion

In room air, the total pressure exerted by O₂ and CO₂ in the alveoli (and blood) should be approximately 140 mm Hg. In this case, the total is 170 mm Hg (PaO₂) + 23 mm Hg (PaCO₂), or 193 mm Hg. Whenever total pressure significantly exceeds 140 mm Hg and PaO₂ is greater than 120 mm Hg, the RT can be assured that the patient is breathing supplemental O₂.

Mechanism of Diffusion

As described in Chapter 6, diffusion is the process whereby gas molecules move from an area of high partial pressure to an area of low partial pressure. To diffuse into and out of the lung and tissues, O₂ and CO₂ must move through significant barriers.

Fick’s First Law of Diffusion

The bulk movement of a gas through a biologic membrane () is described by Fick’s first law of diffusion:

V˙gas=[(A×D)÷T](P1−P2)

In this formula, A is the cross-sectional area available for diffusion, D is the diffusion coefficient of the gas, T is the thickness of the membrane, and (P₁ − P₂) is the partial pressure gradient across the membrane.

According to Fick’s law, the greater the surface area, diffusion constant, and pressure gradient, the more diffusion occurs. Conversely, with greater the distance across the membrane (thickness), less diffusion occurs. Given that the area of and distance across the alveolar-capillary membrane are constant in healthy people, diffusion in the normal lung mainly depends on gas pressure gradients.

Pulmonary Diffusion Gradients

For gas exchange to occur between the alveoli and pulmonary capillaries, a difference in partial pressures (P₁ − P₂) must exist. Figure 11-3 shows the size and direction of these gradients for O₂ and CO₂. In the normal lung, the alveolar PO₂ averages approximately 100 mm Hg, whereas the mean PCO₂ is approximately 40 mm Hg. Venous blood returning to the lungs has a lower PO₂ (40 mm Hg) than alveolar gas. The pressure gradient for O₂ diffusion into the blood is approximately 60 mm Hg (100 mm Hg − 40 mm Hg). As blood flows past the alveolus, it takes up O₂ and moves to the left atrium with a PO₂ close to 100 mm Hg in healthy people.

Because venous blood has higher PCO₂ than alveolar gas (46 mm Hg vs. 40 mm Hg), the pressure gradient for CO₂ causes it to diffuse in the opposite direction, from the blood into the alveolus. This diffusion continues until capillary PCO₂ equilibrates with the alveolar level, at approximately 40 mm Hg.

Although the pressure gradient for CO₂ is approximately one-tenth of the pressure gradient for O₂, CO₂ has little difficulty diffusing across the alveolar-capillary membrane. CO₂ diffuses approximately 20 times faster across the alveolar-capillary membrane than O₂ because of its much higher solubility in plasma. Disorders that impair the diffusion capacity of the lung (D_L) can affect O₂ movement into the blood, especially when blood flow through the lung is rapid because the time the RBCs are in contact with the alveoli is reduced.

Time Limits to Diffusion

For blood leaving the pulmonary capillary to be adequately oxygenated, it must spend sufficient time in contact with the alveolus to allow equilibration.5,8 If the time available for diffusion is inadequate, blood leaving the lungs may not be fully oxygenated. The diffusion time in the lung depends on the rate of pulmonary blood flow. As depicted in Figure 11-4, blood normally takes approximately 0.75 second to pass through the pulmonary capillary. This time is more than enough to ensure complete diffusion of O₂ across the alveolar-capillary membrane normally.

If blood flow increases, such as during heavy exercise, capillary transit time can decrease to 0.25 second. This short time frame is adequate to ensure that equilibration occurs as long as no other factors impair diffusion. However, in the presence of a diffusion limitation, rapid blood flow through the pulmonary circulation can result in inadequate oxygenation. High fever and septic shock, which often cause increased cardiac output, are good examples of conditions that limit diffusion time because of increased blood flow.

In clinical practice, knowledge of D_L can be helpful in evaluating certain diseases. D_L is the bulk flow of gas (ml/min) that diffuses into the blood for each 1-mm Hg difference in the pressure gradient. Although O₂ can be used to measure D_L, low concentrations (0.1% to 0.3%) of carbon monoxide are used more commonly. Chapter 19 provides details on the technique for measuring D_L and its diagnostic use.

Systemic Diffusion Gradients

Partial pressure gradients in the tissues are the opposite of the partial pressure gradients in the lung. As cellular metabolism depletes its O₂, intracellular PO₂ decreases to less than PO₂ of the blood entering the tissue capillary. O₂ diffuses from the tissue capillary blood (PO₂ = 100 mm Hg) to the cells (PO₂ < 40 mm Hg). Simultaneously, CO₂ diffuses from the cells (PCO₂ > 46 mm Hg) into the capillary blood (PCO₂ = 40 mm Hg). After equilibration, blood leaves the tissue capillaries with PO₂ of approximately 40 mm Hg and PCO₂ of approximately 46 mm Hg.

Just as arterial blood reflects pulmonary gas exchange, venous blood reflects events occurring in the tissues. The use of venous blood to assess tissue oxygenation is discussed in Chapter 46.

Anatomic Shunts

A shunt is the portion of the cardiac output that returns to the left heart without being oxygenated by exposure to ventilated alveoli. Two right-to-left anatomic shunts exist in normal humans: (1) bronchial venous drainage and (2) thebesian venous drainage (see Chapters 8 and 9). A right-to-left shunt causes poorly oxygenated venous blood to move directly into the arterial circulation (venous admixture), reducing the O₂ content of arterial blood. Together, these normal shunts account for approximately three-fourths of the normal difference between P_AO₂ and PaO₂. The remaining difference is a result of normal inequalities in pulmonary ventilation and perfusion.⁵

Regional Inequalities in Ventilation and Perfusion

The normal respiratory exchange ratio of 0.8 assumes that ventilation and perfusion in the lung are in balance, with every liter of alveolar ventilation () matched by approximately 1 L of pulmonary capillary blood flow (). Any variation from this perfect balance alters gas tensions in the affected alveoli. As previously discussed, changes in affect P_ACO₂, which alters P_AO₂. Changes in blood flow also alter alveolar gas pressures. If blood flow to an area of the lung increases, CO₂ coming from the tissues is delivered faster, causing an increase in P_ACO₂ if minute ventilation remains the same. At the same time, O₂ is taken up by the capillaries faster than restored by ventilation, causing a decrease in alveolar P_AO₂. Decrease in pulmonary capillary blood flow has the opposite effect (i.e., decrease in P_ACO₂ and increase in P_AO₂) assuming minute ventilation remains the same.5,7,8

Effect of Alterations in Ventilation/Perfusion Ratio

Figure 11-5 shows graphs of the effect of changes on the respiratory exchange ratio (R), plotting all possible values of P_AO₂ and P_ACO₂. When ventilation and perfusion are in perfect balance ( = 0.99), R equals 0.8. At this point, P_AO₂ and P_ACO₂ values equal the ideal values of 100 mm Hg and 40 mm Hg.

As the increases above 1.0 (following the curve to the right), R increases. The result is a higher P_AO₂ and lower P_ACO₂. At the extreme right of the graph, perfusion is zero ( = ∞). Areas with ventilation but no blood flow represent alveolar dead space (see Chapter 10). The makeup of gases in these areas is similar to that of inspired air (PO₂ = 150 mm Hg; PCO₂ = 0 mm Hg).

As the decreases below 1.0 (following the curve to the left), R decreases. The result is a lower P_AO₂ and higher P_ACO₂. At the extreme left of the graph, there is perfusion but no ventilation ( = 0). With no ventilation to remove CO₂ and restore fresh O₂, the makeup of gases in these areas is similar to mixed venous blood ( = 40 mm Hg; = 46 mm Hg).

Venous blood entering areas with values of zero cannot pick up O₂ or unload CO₂ and leave the lungs unchanged. As this venous blood returns to the left side of the heart, it mixes with well-oxygenated arterial blood, diluting its O₂ contents in a manner similar to that described for a right-to-left anatomic shunt. To distinguish such areas from true anatomic shunts, exchange units with values of zero are called alveolar shunts. Although small anatomic shunts are normal, alveolar shunts are not.

Causes of Regional Differences in Ventilation/Perfusion Ratio

Regional variations in in a normal lung are mainly caused by gravity and are most evident in the upright posture. Because the pulmonary circulation is a low-pressure system, blood flow in the upright lung varies considerably from top to bottom (see Chapter 8). Farther down the lung, perfusion increases linearly in proportion to the hydrostatic pressure so that the lung bases receive nearly 20 times as much blood flow as the apexes.

Regional differences in ventilation throughout the lung also occur, but they are less drastic than the differences in perfusion. Similar to perfusion, ventilation also is increased in the lung bases, with approximately four times as much ventilation going to the bases than to the apexes of the upright lung. These regional differences in ventilation are caused by the effect of gravity on pleural pressures (see Chapter 10).

Table 11-1 summarizes the relationships between ventilation and perfusion by lung region.⁸ At the lung apexes, ventilation exceeds blood flow, resulting in a high (approximately 3.3), high PO₂ (132 mm Hg), and low PCO₂ (32 mm Hg). Farther down the lung, blood flow increases more than ventilation owing to gravity. Toward the middle, the two are approximately equal ( = 1.0). At the bottom of the lung, blood flow is greater than ventilation, resulting in a low (approximately 0.66), low PO₂ (89 mm Hg), and slightly higher PCO₂ (42 mm Hg).

TABLE 11-1

Summary of Variations in Gas Exchange in the Upright Lung, by Region

Lung Region	Ratio	Mean PAO2 (mm Hg)	Mean PACO2 (mm Hg)	Blood Flow
Apexes	3.3	132	32	Low
Middle	1.0	100	40	Moderate
Bases	0.66	89	42	High

As shown in Table 11-1, because of gravity, most blood flows to the lung bases, where PO₂ is less than normal and PCO₂ is greater than normal. After leaving the lung, this large volume of blood combines with the smaller volume coming from the middle and apical regions. The result is a mixture of blood with less O₂ and more CO₂ than would come from an ideal gas exchange unit.

Physically Dissolved Oxygen

As gaseous O₂ diffuses into the blood, it immediately dissolves in the plasma and erythrocyte fluid. By applying Henry’s law (see Chapter 6), the amount of dissolved O₂ in the blood (at 37° C) can be computed with the following simple formula:

Dissolved O2(ml/dl)=PO2×0.003

This equation is plotted in Figure 11-6, which shows that the relationship between partial pressure and dissolved O₂ is direct and linear. In normal arterial blood with PaO₂ of approximately 100 mm Hg, there is approximately 0.3 ml/dl of dissolved O₂. However, if an individual with normal arterial blood breathes pure O₂, PaO₂ increases to approximately 670 mm Hg. In this case, the dissolved O₂ would increase to approximately 2.0 ml/dl. The blood of someone breathing pure O₂ in a hyperbaric chamber at 3 atm (2280 mm Hg) would carry nearly 6.5 ml/dl dissolved O₂ in the plasma. This amount is enough to supply most tissue needs at rest by itself.

Most blood O₂ is transported in chemical combination with Hb in the erythrocytes. Hb is a conjugated protein, consisting of four linked polypeptide chains (the globin portion), each of which is combined with a porphyrin complex called heme. The four polypeptide chains of Hb are coiled together into a ball-like structure, the shape of which determines its affinity for O₂.5,8

As shown in Figure 11-7, each heme complex contains a centrally located ferrous iron ion (Fe⁺⁺). When Hb is not carrying O₂, this ion has four unpaired electrons. In this deoxygenated state, the molecule exhibits the characteristics of a weak acid. Deoxygenated Hb serves as an important blood buffer for hydrogen ions, a crucial factor in CO₂ transport.

O₂ molecules bind to Hb by way of the ferrous iron ion, one for each protein chain. With complete O₂ binding, all electrons become paired, and Hb is converted to its oxygenated state (oxyhemoglobin [HbO₂]).

In whole blood, 1 g of normal Hb can carry approximately 1.34 ml of O₂. Given an average blood Hb content of 15 g/dl, the O₂-carrying capacity of the blood can be calculated as follows:

1.34ml/g×15g/dl=20.1ml/dl

The addition of Hb increases the O₂-carrying capacity of the blood nearly 70-fold compared with plasma alone. The amount of O₂ bound to Hb depends on its level of saturation with O₂ (see later).

Hemoglobin Saturation

Saturation is a measure of the proportion of available Hb that is carrying O₂. Saturation is computed as the ratio of HbO₂ (content) to total Hb (capacity). Hb arterial oxygen saturation (SaO₂) is always expressed as a percentage of this ratio and calculated according to the following formula:

SaO2=[HbO2÷Total Hb]×100

Where [HbO₂] equals the oxyhemoglobin content. If there were a total of 15 g/dl Hb in the blood, of which 7.5 g was HbO₂, the SaO₂ would be calculated as follows:

SaO2(%)=[7.5÷15]×100=50%

In this example, Hb is said to be 50% saturated: Only half of the available Hb is carrying O₂, and the remainder is unoxygenated. In clinical practice, both SaO₂ and total Hb content are measured directly to derive the HbO₂. Normal SaO₂ is 95% to 100% depending on the age of the patient.

Oxyhemoglobin Dissociation Curve

Hb saturation with O₂ varies with changes in PO₂. Plotting the saturation (y-axis) against PO₂ (x-axis) yields the HbO₂ dissociation curve (Figure 11-8). In contrast to dissolved O₂, Hb saturation is not linearly related to PO₂.⁴ Instead, the relationship forms an S-shaped curve. The flat upper part of this curve represents the normal operating range for arterial blood. Because the slope is minimal in this area, minor changes in PaO₂ have little effect on SaO₂, indicating a strong affinity of Hb for O₂. With a normal PaO₂ of 100 mm Hg, SaO₂ is approximately 97%. If some abnormality (e.g., lung disease) reduced PaO₂ to 65 mm Hg, SaO₂ would still be approximately 90%.

However, with PO₂ less than 60 mm Hg, the curve steepens dramatically, which is why it is beneficial to keep PaO₂ greater than 60 mm Hg in clinical practice. With PO₂ less than 60 mm Hg, a small decrease in PO₂ causes a large increase in SaO₂, indicating a lessening affinity for O₂. This normal decrease in the affinity of Hb for O₂ helps release large amounts of O₂ to the tissues, where PO₂ is low.

Total Oxygen Content of the Blood

Total O₂ content of the blood equals the sum of O₂ dissolved and chemically combined with Hb.2,7 For total O₂ content to be calculated, the following three values must be known: (1) PO₂, (2) total Hb content (g/dl), and (3) Hb saturation. Given these values, the following equation can be applied:

CaO2=(0.003×PO2)+(Hbtot×1.34×SO2)

Where:

Typically, clinicians want to know the O₂ content of arterial blood (CaO₂). The (0.003 × PO₂) component of the equation represents dissolved O₂, whereas the (Hb_tot × 1.34 × SO₂) component represents the chemically combined oxyhemoglobin. For example, the RT obtains a sample of normal arterial blood with PO₂ of 100 mm Hg containing 15 g/dl of Hb that is 97% saturated with O₂. To compute the total O₂ content, the RT can apply the aforementioned equation as follows:

CaO2=(0.003×PaO2)+(Hbtot×1.34×SaO2)

CaO2=(0.003ml×100mm Hg)+(15g/dl×1.34×0.97)

CaO2=(0.3ml)+(19.5g/dl)

CaO2=19.8ml/dl

The normal CaO₂ concentration is 16 to 20 ml/dl.

Normal Loading and Unloading of Oxygen (Arteriovenous Differences)

Figure 11-9 uses the oxyhemoglobin dissociation curve to show the effects of O₂ loading and unloading in the lungs and tissues. Point A represents freshly arterialized blood leaving the pulmonary capillaries, with PO₂ of approximately 100 mm Hg and Hb saturation of approximately 97%. As blood perfuses body tissues, O₂ uptake causes a decrease in both PO₂ and saturation, such that venous blood leaving the tissues (point V) has PO₂ of approximately 40 mm Hg, with Hb saturation of approximately 73%.

Using a normal Hb content of 15 g/dl and knowing the saturation at each possible PO₂, the total O₂ content can be calculated at any PO₂ in the manner previously described. The y-axis of Figure 11-9 provides this information in SaO₂ increments of 10%. Table 11-2 summarizes the difference between the O₂ content of these normal arterial and venous points.

As indicated in Table 11-2, the difference between the arterial and venous O₂ contents is normally approximately 5 ml/dl. This is the arterial-to-mixed venous O₂ content difference (C()O₂). C()O₂ is the amount of O₂ given up by every 100 ml of blood on each pass through the tissues.

Fick Equation

C()O₂ indicates O₂ extraction in proportion to blood flow. If this measure is combined with total-body O₂ consumption, cardiac output can be calculated. The basis for this calculation is the classic Fick equation:

Q˙t=V˙O2÷[C(a−v¯)O2×10]

In this equation, is cardiac output (L/min), is the whole-body O₂ consumption (ml/min), and C()O₂ is the arteriovenous O₂ content difference (ml/dl). The factor of 10 converts ml/dl to ml/L. Given a normal of 250 ml/min and a normal C()O₂ of 5 ml/dl, a normal cardiac output is calculated as follows:

Q˙t=200ml/min÷(5ml/dl×10)

Q˙t=250ml/min÷5ml/L

Q˙t=5.0L/min

Normal cardiac output is 4 to 8 L/min in an adult patient.

Factors Affecting Oxygen Loading and Unloading

In addition to the shape of the HbO₂ curve, many other factors affect O₂ loading and unloading. Among the most important factors in clinical practice are blood pH, body temperature, and erythrocyte concentration of certain organic phosphates.⁵ Variations in the structure of Hb also affect O₂ loading and unloading, as can chemical combinations of Hb with substances other than O₂, such as carbon monoxide.

pH (Bohr Effect)

The impact of changes in blood pH on Hb affinity for O₂ is called the Bohr effect. As shown in Figure 11-10, the Bohr effect alters the position of the HbO₂ dissociation curve. A low pH (acidity) shifts the curve to the right, whereas a high pH (alkalinity) shifts it to the left. These changes are a result of variations in the shape of the Hb molecule caused by fluctuations in pH.

As blood pH decreases and the curve shifts to the right, the Hb saturation for a given PO₂ decreases (decreased Hb affinity for O₂). Conversely, as blood pH increases and the curve shifts to the left, the Hb saturation for a given PO₂ increases (increased affinity of Hb for O₂).4,5,8

These changes enhance O₂ loading in the lungs and O₂ unloading in the tissues. As blood in the tissue picks up CO₂, pH decreases from 7.40 to approximately 7.37. The HbO₂ curve shifts to the right, lowering the affinity of Hb for O₂. With lower affinity for O₂, Hb more readily gives up O₂ to the tissues. Conversely, when venous blood returns to the lungs, the pH increases again to 7.40. This change in pH shifts the HbO₂ curve back to the left, increasing the affinity of Hb for O₂ and enhancing its uptake from the alveoli.

Body Temperature

Variations in body temperature also affect the HbO₂ dissociation curve. As shown in Figure 11-11, a decrease in body temperature shifts the curve to the left, increasing Hb affinity for O₂. Conversely, as body temperature increases, the curve shifts to the right, and the affinity of Hb for O₂ decreases. As with the Bohr effect, these changes enhance normal O₂ uptake and delivery. At the tissues, temperature changes are directly related to metabolic rate, such that areas of high metabolic activity have higher temperatures. In exercising muscle, higher temperatures decrease Hb affinity for O₂, enhancing its release to the tissues. Conversely, in hypothermia, the O₂ demands of the tissues are greatly reduced, and Hb need not give up as much of its O₂.²

Measurement of Hemoglobin Affinity for Oxygen

Variations in the affinity of Hb for O₂ are quantified by a measure called the P₅₀.2,8 The P₅₀ is the partial pressure of O₂ at which the Hb is 50% saturated, standardized to a pH level of 7.40. A normal P₅₀ is approximately 26.6 mm Hg. Conditions that cause a decrease in Hb affinity for O₂ (a shift of the HbO₂ curve to the right) increase the P₅₀ to a value higher than normal. Conditions associated with an increase in affinity (a shift of the HbO₂ curve to the left) decrease the P₅₀ to lower than normal. With 15 g/dl Hb, a 4-mm Hg increase in P₅₀ results in approximately 1 to 2 ml/dl more O₂ being unloaded in the tissues than when the P₅₀ is normal. Figure 11-12 shows the effect of changes in P₅₀ and summarizes how the major factors previously discussed affect Hb affinity for O₂.

Transport Mechanisms

Approximately 45 to 55 ml/dl of CO₂ is normally carried in the blood in the following three forms: (1) dissolved in physical solution, (2) chemically combined with protein, and (3) ionized as bicarbonate.5,7

Chemically Combined With Protein

Molecular CO₂ has the capacity to combine chemically with free amino groups (NH₂) of protein molecules (Prot), forming a carbamino compound:

Prot-NH2+CO2⇔Prot-NHCOO−+H+

A small amount of the CO₂ leaving the tissues combines with plasma proteins to form these carbamino compounds. A larger fraction of CO₂ combines with erythrocyte Hb to form a carbamino compound called carbaminohemoglobin. As indicated in the previous equation, this reaction produces H⁺ ions. These H⁺ ions are buffered by the reduced Hb, which is made available by the concurrent release of O₂.

The availability of additional sites for H⁺ buffering increases the affinity of Hb for CO₂. Because reduced Hb is a weaker acid than HbO₂, pH changes associated with the release of the H⁺ ions in the formation of carbaminohemoglobin are minimized. Carbaminohemoglobin constitutes approximately 12% of the total CO₂ transported.

Ionized as Bicarbonate

Approximately 80% of CO₂ in the blood is transported as bicarbonate. Of the CO₂ that dissolves in plasma, a small portion combines chemically with water in a process called hydrolysis. Hydrolysis of CO₂ initially forms carbonic acid, which quickly ionizes into hydrogen and bicarbonate ions:

CO2+H2O⇔H2CO3⇔HCO3−+H+

The H⁺ ions produced in this reaction are buffered by the plasma proteins in much the same way as Hb buffers H⁺ in the RBC. However, the rate of this plasma hydrolysis reaction is extremely slow, producing minimal amounts of H⁺ and HCO₃⁻.

Most CO₂ undergoes hydrolysis inside the erythrocyte. This reaction is greatly enhanced by an enzyme catalyst called carbonic anhydrase. The resulting H⁺ ions are buffered by the imidazole group (R-NHCOO⁻) of the reduced Hb molecule. The concurrent conversion of HbO₂ to its deoxygenated form helps buffer H⁺ ions, enhancing the loading of CO₂ as carbaminohemoglobin.

As the hydrolysis of CO₂ continues, HCO₃⁻ ions begin to accumulate in the erythrocyte. To maintain a concentration equilibrium across the cell membrane, some of these anions diffuse outward into the plasma. Because the erythrocyte is not freely permeable by cations, electrolytic equilibrium must be maintained by way of an inward migration of anions. This migration is achieved by the shifting of chloride ions (Cl⁻) from the plasma into the erythrocyte—a process called the chloride shift, or the Hamburger phenomenon.

Carbon Dioxide Dissociation Curve

As with O₂, CO₂ has a dissociation curve. The relationship between blood PCO₂ and CO₂ content is depicted in Figure 11-14. The first point to note is the effect of Hb saturation with O₂ on this curve. As previously discussed, CO₂ levels, through their influence on pH, modify the O₂ dissociation curve (Bohr effect). Figure 11-14 shows that oxyhemoglobin saturation also affects the position of the CO₂ dissociation curve. The influence of oxyhemoglobin saturation on CO₂ dissociation is called the Haldane effect. As previously explained, this phenomenon is a result of changes in the affinity of Hb for CO₂, which occur as a result of its buffering of H⁺ ions.^4–7

Figure 11-14, A shows CO₂ dissociation curves for three levels of blood O₂ saturation. The first two are physiologic values, and the third extreme value is provided for contrast. Figure 11-14, B amplifies selected segments of these curves in the physiologic range of PCO₂. Note first the arterial point “a” lying on the curve representing SaO₂ of 97.5%. At this point, PCO₂ is 40 mm Hg, and CO₂ content is approximately 48 ml/dl. The venous point “v” falls on the curve, representing SaO₂ of approximately 70%. At this point, PCO₂ is 46 mm Hg, and CO₂ content is approximately 52 ml/dl. Because O₂ saturation changes from arterial to venous blood, the true physiologic CO₂ dissociation curve must lie somewhere between these two points. This physiologic curve is represented as the dashed line in Figure 11-14, B.

At point “a,” the high SaO₂ decreases the capacity of the blood to hold CO₂, helping unload this gas at the lungs. At point “v,” the lower mixed venous O₂ saturation () increases the capacity of the blood for CO₂, aiding uptake at the tissues.

The total CO₂ content of arterial and venous blood is compared in Table 11-4. The amounts of CO₂ are expressed in gaseous volume equivalents (ml/dl) and as millimoles per liter (mmol/L). This latter measure of the chemical combining power of CO₂ in solutions is critical in understanding the role of this gas in acid-base balance.

Impaired Oxygen Delivery

O₂ delivery () to the tissues is a function of arterial O₂ content (CaO₂) times cardiac output ():

D˙O2=CaO2×Q˙t

When O₂ delivery is inadequate for cellular needs, hypoxia occurs. According to the preceding equation, hypoxia occurs if (1) the arterial blood O₂ content is decreased, (2) cardiac output or perfusion is decreased (shock or ischemia), or (3) abnormal cellular function prevents proper uptake of O₂. Table 11-5 summarizes causes, common clinical indicators, mechanisms, and examples of hypoxia.

TABLE 11-5

Causes of Hypoxia

Cause	Primary Indicator	Mechanism	Example
Hypoxemia
Low PiO2	Low PAO2	Reduced PB	Altitude
	Low PaO2
Hypoventilation	High PaCO2	Decreased	Drug overdose
imbalance	Low PaO2	Decreased relative to perfusion	COPD, aging
	High P(A−a)O2 on air; resolves with O2
Anatomic shunt	Low PaO2	Blood flow from right to left side of heart	Congenital heart disease
	High P(A−a)O2 on air; does not resolve with O2
Physiologic shunt	Low PaO2	Perfusion without ventilation	Atelectasis
	High P(A−a)O2 on air; does not resolve with O2
Diffusion defect	Low PaO2	Damage to alveolar-capillary membrane	ARDS
	High P(A−a)O2 on air; resolves with O2
Hb deficiency
Absolute	Low Hb content	Loss of Hb	Hemorrhage
	Reduced CaO2
Relative	Abnormal SaO2	Abnormal Hb	Carboxyhemoglobin
	Reduced CaO2
Low blood flow	Increased C()O2	Decreased perfusion	Shock, ischemia
Dysoxia	Normal CaO2	Disruption of cellular enzymes	Cyanide poisoning
	Decreased C()O2

ARDS, Acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease.

Hypoxemia

Hypoxemia occurs when the partial pressure of O₂ in the arterial blood (PaO₂) is decreased to less than the predicted normal value based on the age of the patient. Impaired O₂ delivery also occurs in the presence of abnormalities that prevent saturation of Hb with O₂ (see subsequent discussion).

Decreased Partial Pressure of Oxygen in Arterial Blood

Decreased PaO₂ may be caused by a low ambient PO₂, hypoventilation, impaired diffusion, imbalances, and right-to-left anatomic or physiologic shunting. PO₂ also decreases normally with aging. The normal predicted PaO₂ decreases steadily with age, and the average is approximately 85 mm Hg at age 60 years (see later discussion).

Breathing gases with a low O₂ concentration at sea level or breathing air at pressures less than atmospheric lowers the alveolar O₂ tension, decreasing PaO₂. A common example of this problem occurs during travel to high altitudes, where the visitor often experiences the ill effects of hypoxia for several days. This condition is called mountain sickness. In such cases, although PaO₂ is reduced, the pressure gradient between the alveoli and the arterial blood for O₂ (P[A−a]O₂) remains normal.

Assuming a constant FiO₂, alveolar PO₂ varies inversely with alveolar PCO₂. An increase in the alveolar PCO₂ (hypoventilation) is always accompanied by a proportionate decrease in alveolar PO₂. P(A−a)O₂ is normal in such cases. Conversely, hyperventilation decreases P_ACO₂ and helps compensate for hypoxemia.

Even when alveolar PO₂ is normal, disorders of the alveolar-capillary membrane may limit diffusion of O₂ into the pulmonary capillary blood, decreasing PaO₂. Examples are pulmonary fibrosis and interstitial edema. However, as previously noted, a pure diffusion limitation is an uncommon cause of hypoxemia at rest.

imbalances are the most common cause of hypoxemia in patients with lung disease. A imbalance is an abnormal deviation in the distribution of ventilation to perfusion in the lung. The normal lung has some mismatch; however, in disease states, the degree of imbalances becomes much greater.

A physiologic shunt is the portion of venous blood that travels from the right heart to the left heart without being involved in adequate gas exchange with ventilated portions of the lung. This includes capillary or absolute anatomic shunts and relative shunts where perfusion exceeds ventilation as seen in disease states that diminish pulmonary ventilation. Relative shunts can be caused by chronic obstructive pulmonary disease (COPD), restrictive disorders, or any condition resulting in hypoventilation.

The shunt equation quantifies the portion of blood included in the mismatch. It is usually expressed as a percentage of the total cardiac output:

Q˙sQ˙t=Cc′O2−CaO2Cc′O2−Cv¯O2

Where:

 = Blood entering systemic blood without being oxygenated in the lungs

 = Total cardiac output

Cc′O₂ = O₂ content at the end of the ventilated and perfused pulmonary capillaries

CaO₂ = Arterial O₂ content

 = Mixed venous O₂ content

Although arterial O₂ content can be directly measured from a systemic artery and mixed venous O₂ content can be directly measured from the pulmonary artery, the end capillary content must be derived from an additional calculation requiring use of the alveolar air equation and the Hb concentration.

Conversely, dead space ventilation refers to ventilation that does not participate in gas exchange. This can be considered wasted ventilation because it consumes energy to move gases into and out of the lung but without any resulting gas exchange. Dead space ventilation can be separated into two categories: alveolar and anatomic.

Alveolar dead space is ventilation that enters into alveoli that are without any perfusion or without adequate perfusion. Conditions that can lead to alveolar dead space include pulmonary emboli, partial obstruction of the pulmonary vasculature, destroyed pulmonary vasculature (as can occur in COPD), and reduced cardiac output.

Anatomic dead space is the portion of inspired ventilation that never reaches the alveoli for gas exchange. Normal individuals have a portion of inspired gases that never reach the alveoli before exhalation. This is usually a fixed volume. It becomes problematic in conditions where tidal volumes decrease to the point where a significant percentage of the inspired gas remains in the anatomic dead space.

Dead space is generally expressed as a ratio to total tidal volume:

VDVT=PaCO2−PE¯CO2PaCO2

Where:

V_D = Physiologic dead space (anatomic + alveolar)

V_T = Tidal volume

PaCO₂ = Partial pressure of arterial CO₂

P_ĒCO_2 = Mean partial pressure of exhaled CO₂

The clinical significance of increased physiologic dead space is that it is wasted ventilation in that, by definition, it does not contribute to gas exchange. In the face of increased dead space, normal ventilation must increase to achieve homeostasis. This additional ventilation comes at a cost with an increase in the work of breathing, which consumes additional O₂ further adding to the burden of external ventilation.

Figure 11-15 shows the possible range of . As shown in the top two units, when ventilation is greater than perfusion (high ), there is wasted ventilation, or alveolar dead space. Conversely, when ventilation is less than perfusion, is low (bottom two lung units). In this case, blood leaves the lungs with an abnormally low O₂ content. In lung disease, imbalances usually cause both excess wasted ventilation and poor oxygenation. Because imbalance impairs O₂ exchange, PaO₂ is reduced.

To understand how imbalance causes hypoxemia, reinspect the normal oxyhemoglobin dissociation curve, with PO₂ plotted against O₂ content (Figure 11-16). The curve is nearly flat in the physiologic range of PaO₂ (>70 mm Hg) but falls steeply when PaO₂ is less than 60 mm Hg. Points representing O₂ content of three separate lung units also are shown. These units have of 0.1, 1.0, and 10.0.

Blood leaving the normal unit ( = 1) has a normal O₂ content (19.5 ml/dl). Blood leaving the unit with poor ventilation ( = 0.1) has a low O₂ content (16.0 ml/dl). Because Hb is almost fully saturated at a normal PO₂ of 100 mm Hg, blood leaving the over ventilated unit ( = 10) has an O₂ content that is just slightly greater than normal (20.0 ml/dl). When the blood from all three units mixes together, the result is O₂ content that is reduced (18.5 ml/dl). The decrease in oxygenation caused by the poorly ventilated unit is not fully compensated for by the high unit.

of zero represents a special type of imbalance. When is zero, there is blood flow but no ventilation. The result is equivalent to a right-to-left anatomic shunt, shown at the bottom of Figure 11-15. Venous blood bypasses ventilated alveoli and mixes with freshly oxygenated arterial blood, resulting in what is called a venous admixture. Right-to-left physiologic shunting results in a more severe form of hypoxemia than a simple imbalance, as seen in conditions such as pulmonary edema, pneumonia, and atelectasis.

 Rule of Thumb

Although imbalances are the most common cause of hypoxemia in patients with respiratory diseases, physiologic shunting also can occur commonly, especially in patients who are critically ill. To differentiate between hypoxemia caused by a imbalance and hypoxemia caused by shunting, apply the following 50/50 rule: If O₂ concentration is greater than 50 (%) and PaO₂ is less than 50 (mm Hg), significant shunting is present; otherwise, the hypoxemia is mainly caused by a simple imbalance.

When a low PaO₂ is observed, the RT must take into account the normal decrease in arterial O₂ tension that occurs with aging. As shown in Figure 11-17, for an individual breathing air at sea level, the “normal” P(A−a)O₂ increases in a near-linear fashion with increasing age (shaded area). This increase in P(A−a)O₂ results in a gradual decline in PaO₂ over time and is probably caused by reduced surface area in the lung for gas exchange and increases in mismatching. PaO₂ of 85 mm Hg in a 60-year-old adult would be interpreted as normal, but the same PaO₂ in a 20-year-old adult would indicate hypoxemia. The expected PaO₂ in older adults may be estimated by using the following formula:

Expected PaO2=100.1−(0.323×Age in years)

Hemoglobin Deficiencies

Normal PaO₂ does not guarantee adequate arterial O₂ content or delivery. For arterial O₂ content to be adequate, there also must be enough normal Hb in the blood. If the blood Hb is low—even when PaO₂ is normal—hypoxia can occur because of low O₂ content in the arterial blood.

Hb deficiencies, or anemias, can be either absolute or relative. Absolute Hb deficiency occurs when the Hb concentration is lower than normal. Relative Hb deficiencies are caused by either the displacement of O₂ from normal Hb or the presence of abnormal Hb variants. A low blood Hb concentration may be caused either by a loss of RBCs, as with hemorrhage, or by inadequate erythropoiesis (formation of RBCs in the bone marrow). Regardless of the cause, a low Hb content can seriously impair the O₂-carrying capacity of the blood, even in the presence of a normal supply (PaO₂) and adequate diffusion.⁵

Figure 11-18 plots the relationship between arterial O₂ content and PaO₂ as a function of Hb concentration. As can be seen, progressive decreases in blood Hb content cause large decreases in arterial O₂ content (CaO₂). A 33% decrease in Hb content (from 15 g/dl to 10 g/dl) reduces CaO₂ as much as would a decrease in PaO₂ from 100 mm Hg to 40 mm Hg.

Relative Hb deficiencies are caused by abnormal forms of Hb. As previously discussed, both carboxyhemoglobinemia and methemoglobinemia can cause abnormal O₂ transport, as can abnormal Hb variants. In carboxyhemoglobinemia and methemoglobinemia, each 1 g of affected Hb is comparable to the loss of 1 g of normal Hb. Abnormal hemoglobins have variable effects on O₂ transport. Hemoglobins causing left shifts in the dissociation curve impede O₂ unloading and are most likely to cause hypoxia.

Mini Clini

Effect of Anemia on Oxygen Content

In its most common form, anemia is a clinical disorder in which the number of RBCs is decreased. Because RBCs carry Hb, anemia decreases the amount of this O₂-carrying protein.

 Problem

What effect would anemia that causes a progressive decrease in Hb from (1) 15 g/dl to (2) 12 g/dl to (3) 8 g/dl to (4) 4 g/dl have on the amount of O₂ carried in a patient’s blood? Assume that PO₂ and saturation stay normal at 100 mm Hg and 97%.

Discussion

1. Calculate dissolved O₂ the same way for all four examples as follows:

Dissolved O2=100×0.003=0.30ml/dl

2. Compute chemically combined O₂ as follows: Chemically combined O₂ = Hb (g/dl) × 1.34 ml/g × SaO₂

a. 15 g/dl × 1.34 ml/g × 97% = 19.50 ml/dl

b. 12 g/dl × 1.34 ml/g × 97% = 15.60 ml/dl

c. 8 g/dl × 1.34 ml/g × 97% = 10.40 ml/dl

d. 4 g/dl × 1.34 ml/g × 97% = 5.20 ml/dl

3. Compute total O₂ content as follows:

CaO2=Dissolved O2+Chemically combined O2

a. 0.30 + 19.50 = 19.80 ml/dl

b. 0.30 + 15.60 = 15.90 ml/dl

c. 0.30 + 10.40 = 10.70 ml/dl

d. 0.30 + 5.20 = 5.50 ml/dl

Loss of Hb decreases the amount of O₂ carried in a patient’s blood, even though PO₂ and saturation remain normal. With Hb concentration of 4 g/dl, the amount of O₂ carried in a patient’s blood is only approximately one-fourth the normal concentration (5.50 vs. 19.80 ml/dl).

Dysoxia

Dysoxia is a form of hypoxia in which the cellular uptake of O₂ is abnormally decreased. The best example of dysoxia is cyanide poisoning. Cyanide disrupts the intracellular cytochrome oxidase system, preventing cellular use of O₂. Dysoxia also may occur when tissue O₂ consumption becomes dependent on O₂ delivery.

Figure 11-19 plots tissue O₂ consumption () against O₂ delivery () in both normal and pathologic states. Normally, the tissues extract as much O₂ as they need from what is delivered, and O₂ consumption equals O₂ demand (flat portion of solid line). However, if delivery decreases, conditions begin to change (solid line). At a level called the point of critical delivery, tissue extraction reaches a maximum. Further decreases in delivery result in an O₂ “debt,” which occurs when O₂ demand exceeds O₂ delivery. Under conditions of O₂ debt, O₂ consumption becomes dependent on O₂ delivery (sloped line). This dependence leads to lactic acid accumulation and metabolic acidosis.

In pathologic conditions such as septic shock and acute respiratory distress syndrome (dotted line), this critical point may occur at levels of O₂ delivery considered normal. In addition, the slope of the curve below the point of critical delivery may be less than normal, indicating a decreased extraction ratio ().⁶ In combination, these findings indicate that O₂ demands are not being met and that a defect exists in the cellular mechanisms regulating O₂ uptake.

Impaired Carbon Dioxide Removal

Any disorder that decreases alveolar ventilation () relative to metabolic need impairs CO₂ removal. Impaired CO₂ removal by the lung causes hypercapnia and respiratory acidosis (see Chapter 13). A decrease in alveolar ventilation occurs when (1) the minute ventilation is inadequate, (2) the dead space ventilation per minute is increased, or (3) a imbalance exists.^4–8

Ventilation/Perfusion Imbalances

Theoretically, any imbalance should cause an increase in PaCO₂. However, PaCO₂ does not always increase in these cases. Many patients who are hypoxemic because of a imbalance have a low or normal PaCO₂. This common clinical finding suggests that imbalances have a greater effect on oxygenation than on CO₂ removal.

Careful inspection of the O₂ and CO₂ dissociation curves supports this finding. The O₂ and CO₂ dissociation curves are plotted on the same scale in Figure 11-20. The upper CO₂ curve is nearly linear in the physiologic range. The lower O₂ curve is almost flat in the physiologic range. Point “a” on each curve is the normal arterial point for both content and partial pressure. To the right of the graph are two lung units, one with a low and the other with a high . The blood O₂ and CO₂ contents from each unit are plotted on the curves.

The final CO₂ content, arrived at by averaging the high and low points, is shown as point “a” on the CO₂ curve. This point is the same as the normal arterial point for CO₂.

The final O₂ content, also arrived at by averaging the high and low points, is shown as point “X” on the O₂ curve. Although the averaged value for CO₂ was normal, the PaO₂ resulting from averaging the O₂ content of the high and low units is well below normal (point “a” on the O₂ curve).

The effect of low units is decreased PaO₂ and increased PaCO₂. The effect of high units is the opposite (i.e., increased PO₂ and decreased PCO₂). However, the shape of the dissociation curves dictates that a high unit can reverse the high PCO₂ but not the low PO₂. Any increase in PCO₂ from low units can be corrected by a reduction in PCO₂ from high units. However, these same high units cannot compensate for the reduced O₂ content because the O₂ curve is nearly flat when PO₂ is higher than normal.

Patients with imbalances still must compensate for high PCO₂ coming from underventilated units. To compensate for these high PCO₂ values, the patient’s minute ventilation must increase (Figure 11-21). Patients who can increase their minute ventilation tend to have either normal or low PaCO₂, combined with hypoxemia.

Conversely, patients with a imbalance who cannot increase their minute ventilation are hypercapnic. Hypercapnia generally occurs only when the imbalance is severe and chronic, as in COPD. Such a patient must sustain a higher than normal minute ventilation just to maintain normal PaCO₂. If the energy costs required to sustain a high minute ventilation are prohibitive, the patient opts for less work—and hence elevated PaCO₂.

Summary Checklist

• Movement of gases between the lungs and the tissues depends mainly on diffusion.

• P_ACO₂ varies directly with CO₂ production and inversely with alveolar ventilation.

• P_AO₂ is computed using the alveolar air equation.

• With a constant FiO₂, P_AO₂ varies inversely with P_ACO₂.

• Normal P_AO₂ averages 100 mm Hg, with mean P_ACO₂ of approximately 40 mm Hg.

• Normal mixed venous blood has PO₂ of approximately 40 mm Hg and PCO₂ of approximately 46 mm Hg

• Ventilation and perfusion must be in balance for pulmonary gas exchange to be effective. Because of normal anatomic shunts and imbalances, pulmonary gas exchange is imperfect.

• In disease, can range from zero (perfusion without ventilation or physiologic shunting) to infinity (pure alveolar dead space).

• Blood carries a small amount of O₂ in physical solution, and larger amounts are carried in chemical combination with erythrocyte Hb.

• Hb saturation is the ratio of oxyhemoglobin to total Hb, expressed as a percentage.

• To compute total O₂ contents of the blood, add the dissolved O₂ content (0.003 × PO₂) to the product of Hb content × Hb saturation × 1.34.

• C()O₂ is the amount of O₂ given up by every 100 ml of blood on each pass through the tissues. All else being equal, C()O₂ varies inversely with cardiac output.

• Hb affinity for O₂ increases with high PO₂, high pH, low temperature, and low levels of 2,3-DPG.

• Hb abnormalities can affect O₂ loading and unloading and can cause hypoxia.

• Most CO₂ (about 80%) is transported in the blood as ionized bicarbonate; other forms include carbamino compounds in physical solution.

• Changes in CO₂ levels modify the O₂ dissociation curve (Bohr effect). Changes in Hb saturation affect the CO₂ dissociation curve (Haldane effect). These changes are mutually beneficial, assisting in gas exchange at the lung and the cellular level.

• Hypoxia occurs if (1) the arterial blood O₂ content is decreased, (2) blood flow is decreased, or (3) abnormal cellular function prevents proper uptake of O₂.

• Decreased PaO₂ level may be a result of a low ambient PO₂, hypoventilation, impaired diffusion, imbalances, and right-to-left anatomic or physiologic shunting.

• A decrease in alveolar ventilation occurs when (1) the minute ventilation is inadequate, (2) dead space ventilation is increased, or (3) a imbalance exists.