Physiological consequences of increased shunt

This chapter is most relevant to Section F6(vi) from the 2017 CICM Primary Syllabus, which expects the exam candidates to be able to "explain the concept of shunt, its physiological effects and its measurement".  This chapter will focus on "its physiological effects", which could be easily summarised as "all gas-related things get worse". It is remarkable that this has never appeared in the past papers, and by this very fact one may be assured that one day it will.

In summary:

The best free peer-reviewed reference for this is Bigeleisen (2001), which is an excellent resource to "help students master these equations as well as their practical limitations". Original papers by J.F Nunn (1966) and later works by Petersson & Glenny (2014) are also useful. From the non-peer-reviewed FOAM world, the shunt post from the PFTforum blog is an excellent overview, though it may earn undeserved scowls of disapproval from the FOAM-weary CICM Illuminati.

Effect of shunt on oxygenation, and effect of oxygen on shunt

In short, venous admixture gives rise to systemic hypoxemia. The degree of hypoxemia is generally said to be roughly proportional to the shunt fraction. This relationship was discussed at great detail here at the PFTforum, and their graph is reproduced here with zero permission but in the spirit of Creative Commons camaraderie:

This is a demonstration of the range of arterial PO₂ values one may be expected to generate as one's shunt increases. At a shunt of 50%, the arterial oxygen tension at 21% FiO₂ is somewhere in the order of 53 mmHg. A shunt fraction of 25% is enough to drop one's oxygen saturation into the low 90s, prompting worried nursing staff to increase the oxygen flow rates. The latter manoeuvre, however, may have little effect.

Effect of oxygenation on shunt

As is mentioned in the end of the chapter on the measurement of shunt, lung regions with true shunt (V/Q = 0) are not expected to increase their endcapillary oxygen content in response to an increase in alveolar oxygen. From this, one might expect that, as the shunt fraction increases, so the increase of FiO₂ should yield smaller and smaller benefits, ultimately becoming pointless. This is indeed the scenario described by Nunn's iso-shunt lines, which one can find in virtually any physiology textbook (most of all in Nunn's).

In short, this is a graphical representation of the effect of increasing the FiO₂ on the arterial oxygenation, at different degrees of shunt. This thing appears to have its origin in a 1966 paper by J.F Nunn, where no experimental data or calculations are offered in support of it (so presumably it comes from another, earlier publication by the same author). The original 1966 image is used here, out of immense respect for the author. Later editions of his textbook justify the existence of this graph by saying that "it has been found useful to prepare a graph of the relationship at different levels of venous admixture", because one finds oneself constantly obsessing over the FiO₂ and PaO₂ in the course of clinical practice. It would indeed have been very useful in the distant past where oxygen saturation monitoring was unknown and one needed to adjust the FiO2 on the basis of infrequent PaO₂ measurements. In practice, "despite their simplicity, the isoshunt lines did not achieve popularity because pulmonary critical care involves treating more than a single parameter and because it was impractical to carry the nomogram around" (Bigeleisen, 2001). The main use of this graph in the modern era is to demonstrate for students of physiology that, with a true shunt of 50%, one's fiddling with the FiO₂ knob on the ventilator will yield little improvement in oxygenation.

Effects of shunt on CO₂ clearance

In short, shunt does not make much of a difference to CO₂ clearance, and in fact CO₂ clearance may increase in the presence of a massive shunt. 

True, the shunted blood has a high CO₂ content. Bypassing the gas exchange surfaces of the lungs, that CO₂ content ends up in the arterial circulation, and the arterial CO₂ should be expected to rise proportionally to the shunt fraction. However, in practice it does not. The main reason for this is that central control of ventilation maintains a very tight grip on the arterial CO₂ concentration, and any rise in arterial CO₂ is matched by an increase in alveolar ventilation.

Now, the blood which travels through non-shunt regions of the lung may already be maximally oxygenated by the available oxygen, and an increase in FiO₂ will not change the arterial oxygenation. However, that non-shunt blood is not maximally decarboxylated, and increasing the minute ventilation will still yield a reasonable improvement in CO₂ clearance even in the presence of a large shunt. This is enhanced by the hypoxic ventilatory drive which will increase the respiratory rate irrespective of the arterial CO₂ tension. In short, any patient with the capacity to increase their minute ventilation will be able to compensate for the hypercapnic effects of even a very large shunt.

But let's say the patient was unable to increase their minute volume, and the shunt fraction was substantial. how much would the PaCO₂ increase? Turns out, not very much.  Niklason et al (2008) determined that a shunt fraction of 50% would only increase the PaCO₂ by 15-30%, and that's in a patient whose minute volume was fixed. Their original images are reproduced below:

As one can see, the increase in PaCO₂ was greatest where cardiac output was low ("Qt = 3" on their graph means a cardiac output of 3L/min, or a cardiac index around 1.7). The main reason for this was thought to be an increase in mixed venous CO₂, and therefore more CO2 delivery through the shunt. Similarly, where there was a metabolic acidosis, the effect of the shunt on PaCO₂ was higher because metabolic acidosis suppresses the Haldane effect (Cavaliere et al, 2002), decreasing the affinity of deoxygenated haemoglobin for CO₂ and therefore increasing the concentration of free CO₂ in the venous blood.