This chapter is most relevant to Section F6(viii) from the 2017 CICM Primary Syllabus, which expects the exam candidates to be able to "explain the effect of ventilation-perfusion mismatch on oxygen transfer and carbon dioxide elimination". One could have easily titled this chapter "How does V/Q mismatch affect gas exchange, and why should I care". This topic appears to be a favourite among the Part One examiners, and is represented in several past paper questions:
- V/Q ratios throughout the lung:
- The upright lung has a V/Q gradient from top to bottom:
- The lung bases have a low V/Q ratio (~ 0.6)
- V/Q ratio reaches 1.0 at around the 3rd rib
- Lung apices have a high V/Q ratio (~ 3.0)
- The effect of changing V/Q ratio on gas exchange:
- The lower the V/Q ratio, the closer the effluent blood composition gets to mixed venous blood, i.e. to "true" shunt.
- The higher the V/Q ratio, the closer the effluent blood composition gets to alveolar gas.
- The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q.
- The effect of low V/Q ratio on oxygenation:
- Low V/Q values (V/Q ratios between 0 and 1) result in hypoxia
- The hypoxia due to low V/Q ratio is reversible with increased FiO2
- "True" shunt where V/Q = 0 does not improve with increased FiO2
- The effect of low V/Q ratio on CO2 removal:
- The same change in V/Q (from 1.0 to 0.1) has a significant effect on oxygenation, but a minimal effect on CO2 removal
- This is because the relationship of CO2 clearance to V/Q ratio is more flat and linear than the relationship of O2 uptake
- High V/Q ratio units have excellent gas exchange but minimal blood flow
- Only about 15% of the cardiac output circulates through lung units with a V/Q ratio of 5 and above
- Therefore, these units cannot contribute enough oxygenated blood to compensate for the poor gas exchange occuring in low V/Q units
The best article to discuss these matters is probably the review paper written by J.B.West in 1977, mainly because the diagrams presented therein have been reproduced in various textbooks and are therefore potentially examinable. This excellent paper is, unfortunately, paywalled by the AJRCCM. All of the material from this paper is present in one form or another in Nunn's, but is distributed throughout the chapters, and is not presented in a clear "what-this-means" format. The next best resource would have to be Petersson & Glenny (2014). Virtually all the data discussed here comes from the research of a single group headed by Peter D. Wagner, which included J.B. West and which cranked out numerous papers on V/Q matching between 1975 and 1977.
Judging by the three-line examiners' comment to Question 6 from the second paper of 2017, an essential part of being able to "describe the effects of Ventilation/Perfusion (V/Q) inequality on the partial pressure of oxygen (PaO2) in arterial blood" was a discussion of V/Q ratio distribution throughout the lungs. Without recapitulating whole sections from major chapters such as Global and regional ventilation and perfusion, West's zones of the lung and Ventilation-perfusion matching and mismatching, one may summarise such a discussion with this graph:
Thus, both the largest volume of blood flow and the most substantial volume of gas ends up passing through the bases of the lung.
The diagram discussed here originates from West (1977). It describes the changes in the gas content (partial pressure and total oxygen carriage) of what West called "effluent" blood, i.e. blood emerging from the alveolus into the pulmonary venous circulation. The graph makes various assumptions about the mixed venous oxygen content and haemoglobin concentration (i.e. that they are normal), but is otherwise sound.
What is the point of this graph? Well. It serves to demonstrate three essential features:
The latter point is most important in the coming paragraphs, which explore the effects of high and low V/Q ratios on gas exchange:
The difference between V/Q scatter and shunt is somewhat blurred, and resources which bother to describe the distinction typically do so by describing one of them as "true shunt". Observe the diagram below:
Consider: shunt is where the lung unit has zero ventilation. One of the depicted lung units is affected by shunt. Observe, the neighbouring lung unit has the same blood flow (1000ml/min) and some sort of minimal but non-zero ventilation (say, 100ml/min), giving a V/Q ratio of 0.1. Those 100ml/min will deliver an extra 21 ml of oxygen to the bloodstream, which will increase the oxygen content of the effluent blood. That increase will not be spectacular when compared to raw shunt blood (say, from 65% to 80% saturation, as in the diagram above), but the bottom line is that it will be different and not the same as shunt.
Now, consider what might happen if one increases the FiO2.
Let's say that the FiO2 is now 100%. The low V/Q lung unit now ventilates with 100ml of fresh O2 per minute. If the mixed venous oxygenation stays the same, this extra oxygen can actually maximise the saturation of the effluent blood up to 100%. If the Hb is 100, the total oxygen content increases from 89ml/L to 137ml/L, i.e. not all of the 100ml of oxygen is utilised and theoretically one could even increase the FiO2 to only 50% and still achieve the same effect. In contrast, because the shunt remains completely unventilated, the change in FiO2 will not affect it in any way. This is the cardinal difference between low V/Q ("V/Q scatter") and shunt:
Increasing the FiO2 will reverse the hypoxia when it is due to a low V/Q ratio (V/Q scatter),
but not when it is due to shunt.
So, in summary, one can say that:
- "V/Q scatter" ( for V/Q ratios between 0 and 1) results in hypoxia
- The hypoxia due to low V/Q ratio is reversible with increased FiO2
- "True" shunt where V/Q = 0 does not improve with increased FiO2
Consider the shape of the relationship between effluent blood PaO2, PaCO2 and V/Q from the graph displayed earlier. Observe what happens in the 0.1-1.0 range of V/Q ratios to the exchange of these two gases: the relationship of CO2 clearance to V/Q ratio is more flat and linear than the relationship of O2 uptake, and when the V/Q ratio of a lung unit drops from 1.0 to 0.1, the CO2 clearance is relatively unaffected (whereas the oxygen content of effluent blood drops dramatically).
So: the greatest change in the V/Q range of 0.1-1.0 occurs to oxygenation. Here, a small decrease in V/Q significantly degrades the oxygen content of effluent blood. At the same time, the CO2 clearance decreases trivially. Thus, decreasing the V/Q ratio does not significantly affect CO2 clearance, until a massive amount of "true" shunt has developed. In fact, because CO2 and the control of ventilation are so closely linked, it is quite difficult to develop hypercapnia purely as the consequence of shunt and V/Q mismatch.
The easy availability of fresh gas in regions with a high V/Q ratio makes plenty of gas available for exchange. Assuming that the gas exchange surface is highly permeable, gas exchange will occur according to the laws of diffusion, which means arterial oxygen and CO2 will trend to equilibrate with alveolar. Alveolar oxygen being very high and alveolar CO2 being very low, this could cause the arterial gas content to trend towards bizarre nonphysiological values:
Indeed, hypothetically, in this scenario effluent blood could end up with an arterial CO2 tension close to 0 mmHg, provided there was an infinitely small amount of blood slowly crawling its way across the surface of an alveolus which is being ventilated by an infinitely large amount of gas. Even though this is absurd and doesn't happen in a real lung, it illustrates the main points. Increasing the V/Q ratio of a lung unit from 10 to 100 will not produce much of a change (i.e. the CO2 might drop from 10 to 1 mmHg).
That can be summarised by simply saying that they don't contribute much of anything. Though the gas exchange in these high V/Q ratio segments is excellent, their total contribution to the gas exchange of the whole respiratory system is minimal, because blood flow to these segments is also minimal. A rabbit study by Lamm et al (1995) demonstrated that overall, only about 15% of the cardiac output goes to the "Zone 1" segments of the lung, with most of the ventilation there being in lung units with a V/Q ratio around 5.
The most important implication of this is that the high V/Q units cannot compensate for the failure of low V/Q units. Low V/Q units are responsible for most (85%) of the blood flow returning to the left atrium. Therefore, when they fail to oxygenate the blood (or clear CO2 out of it), this 85% of the cardiac output ends up looking a lot like mixed venous blood. In this scenario, "good" V/Q units will not be able to contribute enough arterial-looking blood to compensate.
Recall this graph demonstrating the distribution of blood flow and ventilation according to V/Q ratio in the healthy lung of a 44-year-old non-smoker:
Note that the V and Q curve do not cross at 1.0, as one might expect them to. This is probably an error on the part of the publisher, who failed to correct the diagram (I am sure the fact that West submitted the paper had nothing to do with the porosity of the editorial process). All of the other curves presented in that paper tend to have the correct curve crossover at V/Q=1.0, and in any case it defies logic to have it otherwise (i.e. when ventilation and perfusion are the same, the V/Q ratio should definitely be 1.0).
Anyway. The mild maldistribution of V/Q in the graph here is the effect of age on a healthy lung. Obviously different lung pathologies produce markedly mismatched V/Q distributions. Nunn's reproduces some representative maldistribution patterns from an out-of-print 1977 textbook by J.B. West, which appears impossible to obtain by electronic means. Fortunately, in the same year West had also published a review in the American Review of Respiratory Disease which appears to contain the same information.
The original scanned images were too grainy to reproduce even by the low standards of Deranged Physiology. Moreover, all the graphs were with different scales and too reliant on the text for explanations. As a result, the author has taken it upon himself to reproduce these images with vector graphics, as faithfully as possible (using the shapes of the original curves) but significantly modified.
This graph represents the distribution of flow across the lungs of a patient with severe bullous emphysema. It comes from a study by Wagner et al (1977), where the MIGET technique was used to study "23 male patients with severe and advanced but stable COPD".
One can immediately notice the difference between this plot and the plot of the normal young patient. For one, it extends well beyond the young man's maximum V/Q ratio, past a V/Q of 10. At that range, there is an obvious excess of ventilation for a region where perfusion is poor. These are the people who present to hospital with hypercapnia in spite of their having a minute volume of 12L/min or more. All that ventilation is wasted on lung regions with a high V/Q.
In the course of investigating their COPD patients, Wagner et al (1977) identified a distinct phenotype which represented the people with chronic bronchitis and sputum plugging.
This is the group in whom hypoxic respiratory failure is the dominant feature. Notable is the distribution of blood flow to poorly ventilated regions with V/Q ratios around 0.1.
Wagner et al also explored the VQ distribution in asthmatic patients, and though that article is not available online, their findings are reproduced in West (1977) perhaps because West was one of the et al.
As one can see, about 25% of the total blood flow going to poorly ventilated lung units with V/Q in the region of 0.1, similar to the V/Q distribution of a patient with chronic bronchitis. These are thought to be "lung units situated behind airways that are completely closed by mucous plugs or extreme bronchoconstriction." The reason for the low shunt value, West theorised, was that these units probably still enjoy a reasonable amount of collateral Pendelluft and therefore get enough oxygen.
Again from Wagner (this time from 1976), this graph represents the V/Q distribution of an acute heart failure patient "in whom there were clinical signs of mild pulmonary edema, including rales at the lung base":
West and Wagner attributed the increased shunt fraction and "tail" of extra blood flow in unventilated regions to the presence of pulmonary oedema. Of course the investigators Swan-Ganzed the patient and were able to report that the cardiac output was only 3.0L/min and the mixed venous PO2 was 29 mmHg, corresponding to a SvO2 of around 55%.
The origin of this graph is also a paper by Wagner and West (1978), except for some reason this time they let David R. Dantzker be the first author. The investigators anaesthetised a bunch of dogs and then sent large (30ml) tantalum-doped emboli into their pulmonary circulation.
As one can see, this scenario produced a similar effect to emphysema; i.e. as the result of taking out a large segment of the pulmonary circulation, the patient developed a significant amount of dead space, poorly perfused but normally ventilated lung.
Also in 1977 (it was a big year for the V/Q ratio), Dueck Wagner and West explored the effects of positive pressure ventilation on the V/Q distribution in the pulmonarily oedematous dog:
As one can see, with PEEP the shunt disappeared, but the ventilation was now distributed into lung regions with a high V/Q ratio. In short, PEEP increased the size of West's Zone 1.
West, John B. "Ventilation-perfusion relationships." American review of respiratory disease 116.5 (1977): 919-943.
Petersson, Johan, and Robb W. Glenny. "Gas exchange and ventilation–perfusion relationships in the lung." (2014): 1023-1041.
Wagner, P. D., et al. "Ventilation-perfusion inequality in chronic obstructive pulmonary disease." The Journal of clinical investigation 59.2 (1977): 203-216.
Wagner, P. D., et al. "Distributions of ventilation-perfusion ratios in asthma." AMERICAN REVIEW OF RESPIRATORY DISEASE. Vol. 111. No. 6. 1740 BROADWAY, NEW YORK, NY 10019: AMER LUNG ASSOC, 1975.
Wagner, P. D., et al. "EFFECTS OF VENTILATION-PERFUSION INEQUALITY ON ARTERIAL PO-2 FOLLOWING ACUTE MYOCARDIAL-INFARCTION." CLINICAL RESEARCH. Vol. 24. No. 2. 6900 GROVE RD, THOROFARE, NJ 08086: SLACK INC, 1976.
Dantzker, DAVID R., et al. "Gas exchange after pulmonary thromboemoblization in dogs." Circulation research 42.1 (1978): 92-103.
Dueck, Ronald, Peter D. Wagner, and John B. West. "Effects of positive end-expiratory pressure on gas exchange in dogs with normal and edematous lungs." Anesthesiology 47.4 (1977): 359-366.
Lamm, W. J., et al. "Perfusion through vessels open in zone 1 contributes to gas exchange in rabbit lungs in situ." Journal of Applied Physiology 79.6 (1995): 1895-1899.