14.2: Alveolar–Arterial PO₂ Difference and its Diagnostic Value
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Not only knowing what the alveolar and arterial PO2s are, but by how much they differ can tell us where a problem in the process of gas exchange might be occurring. So the PAO2–PaO2 difference has great diagnostic value. Let us return to our schematic of a lung with a ventilated and perfused lung unit and look at a few scenarios, starting with the normal state.
Normal lung: With a well-ventilated and perfused lung (figure 14.2), alveolar PO2 is normal, and when there are no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).
Hypoventilation: Now let us look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2 and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.
Impaired diffusion: Now let us look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and an increased difference between the two.
Inadequate perfusion: Now let us look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.
So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar–arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is not hypoventilation. If there is no increase in A–a difference, you know it is neither a diffusion problem nor a V/Q mismatch.
Summary
These examples to illustrate the point are rather specific, but generally knowing the alveolar and arterial PO2s and calculating A–a PO2 difference allows you to distinguish whether a decline in arterial PO2 is due to a problem getting oxygen down into the lung, or a problem getting oxygen from lung to blood. So the alveolar equation is a simple equation, but it forms a powerful tool.
| State | Effect on PAO2 | Effect on PaO2 | Effect on A–a PO2 |
| Normal | Normal | Normal | Normal (5–10 mmHg) |
| Hypoventilation | Decrease | Decrease | No change |
| Diffusion abnormality | Normal | Decrease | Increase |
| Lack of perfusion | Normal | Decrease | Increase |
References, Resources, and Further Reading
Text
Levitsky, Michael G. "Chapter 3: Alveolar Ventilation." In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.
West, John B. "Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange." In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.
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