The concepts of venous admixture and 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", and to Section V(ii), which asks them to "explain venous admixture, its relationship to shunt and ventilation-perfusion                           
(V/Q) mismatch". This specific matter has appeared in Question 6 from the second paper of 2009. The fact that it has only appeared once should not discourage exam candidates from becoming familiar with the topic, as it is fairly fundamental. If one's eyes glaze over from the discussion of the difference between venous admixture and shunt, then at the very least the Berggren equation should be firmly understood and committed to memory, because it is fair game for future questions and viva stations.

In summary:

The most detailed explanation of these concepts can be found in "Understanding the meaning of the shunt fraction calculation" by Cruz & Metting (1987), but this article is not freely available, and by virtue of being comprehensive may be unreasonable for last-minute revision. A better reference is probably Bigeleisen (2001), which is not only a free article, but also one which was written with the express intention of explaining these concepts to people who are then expected to teach others.

The relationship of venous admixture to shunt

What is "shunt"? An authoritative-sounding document from the 1970s ("Glossary on respiration and gas exchange", Hughes et al, 1973) defines it as :

"Vascular connection between circulatory pathways so that venous blood is diverted into vessels containing arterialized blood"

So, that's clearly not the sort of shunt we are talking about here. For respiratory physiology,Wests' (p.68 of the 10th edition) defines shunt as:

"blood that enters the arterial system without going through ventilated areas of the lung"

West does not try to make a distinction between venous admixture and shunt, but in other textbooks (Nunn's and Levitzky included) the two terms are made distinct. In the 8th edition of Nunn's (p. 123), venous admixture is defined as:

"the degree of admixture of mixed venous blood with pulmonary endcapillary blood that would be required to produce the observed difference between the arterial and the pulmonary end-capillary PO₂ (usually taken to equal ideal alveolar PO₂)"

Thus, "venous admixture" is the calculated estimate of how much hypoxic blood would be required to produce the measured arterial oxygen results, for a given cardiac output. It is a volume of deoxygenated blood from the venous circulation which appears to have bypassed the lungs, not participating in any gas exchange. 

So... How is this different to shunt? Well. The two terms are often used interchangeably. For the editors of Nunn's, the confusion in students must have been viewed as having such magnitude as to warrant a brief subsection on the nomenclature, at the end of which the authors admitted that, even though the two concepts are distinct, "venous admixture is ...often loosely termed shunt".

However, venous admixture is not shunt. It is a calculated volume which appears to have bypassed the pulmonary gas exchange surface.  It is the product of the shunt equation, which assumes that there are only two kinds of alveoli (perfectly ventilated and perfectly collapsed).  "True" intrapulmonary shunt, in contrast, is the volume of venous blood which actually bypassed the aerated alveoli, and returned deoxygenated blood to the left heart via the pulmonary circulation. "True" shunt does not integrate the contribution of Thebesian veins and alveolar regions with V/Q ratios between 0 and 1.0, or any other added sources of extra venous blood contributing to the systemic circulation (like intracardiac right-to-left shunts) and therefore the calculated venous admixture volume will usually be larger. 

Thus, venous admixture does not accurately estimate the volume of true intrapulmonary shunt, nor does it help to determine exactly where that extra venous blood is coming from. The very term "venous admixture" implies that there is some known amount of hypoxic venous blood which gets mixed with the arterial circulation, but in actual fact, there is no such thing; you never quite know how much shunt blood volume there is, or how hypoxic that blood is. Instead, one calculates a certain fraction of the cardiac output which consists of that blood. This is a completely reasonable shortcut, because it is actually impossible to measure "true" shunt, as practically one can never separate the fraction of blood coming from truly unventilated lung units (V/Q =0) from blood which comes from merely incompletely ventilated units (V/Q < 1.0). For this reason, we resort to using venous admixture as a surrogate for shunt, and report it as "shunt fraction", or Fshunt. 

Types of shunt and venous admixture

A classification system seems to exist for shunt, which tends to vary across textbooks (whereas some, eg. West's, abandon the whole idea of classifying things). Not only are the categories different, but the same nominal category may have different meanings to different authors. For example, here is a comparison of Nunn's and Levitzky:

 Different Classification Systems
for Venous Admixture and Shunt

From Nunn's, 8th edition	From Levitzky, 7th edition
Anatomical shunt: Physiological shunt Bronchial veins Thebesian veins "True" shunt Intracardiac shunt "Virtual" shunt Pathological anatomical shunt  V/Q scatter  Physiological shunt	Physiological shunts Physiological anatomical shunt  Bronchial veins Thebesian veins Pathological anatomical shunt Intracardiac shunt Intrapulmonary shunt Absolute intrapulmonary shunt ("true" shunt) "Shunt-like states": V/Q scatter, i.e. V/Q < 0
From Basic Physiology for Anaesthetists by Chambers et al (2015) Physiological shunt: Anatomical shunt Bronchial veins Thebesian veins Functional shunt V/Q scatter Pathological shunt: Intracardiac shunt Pulmonary AVM Intrapulmonary shunt (true shunt)

These are only a few of the possible taxonomies. Judging by the lack of literature references, these were not composed by the work of some sort of scientific body, but rather concocted by each textbook author independently. As such, it is impossible to say which of them is "better". The exam candidates are invited to choose a system and stick with it. 

Without trying to justify any of the existing classification systems or trying to invent a new one, the following list of shunts and shuntish admixtures is offered in an unordered state.

Different sources of venous admixture

• "True" shunt through useless lung: blood passing through a diseased pneumonic lung (or one which has collapsed), with V/Q ratio of 0 (i.e. no V, all Q). This blood will exchange no gas. 
• "V/Q scatter": Lung regions which have a V/Q ratio less than 1 will have inefficient gas exchange, and will return pulmonary venous blood which is incompletely oxygenated. As the name suggests, the oxygen content of such blood will be available in a wide range, from blood which closely resembles mixed venous, to blood which is only slightly deoxygenated. The category of anatomical shunt for some reason excludes this form of venous admixture.
• Thebesian veins, otherwise known as venae cordis minimae, are tiny valveless veins in the walls of the four cardiac chambers. Their contribution to blood flow is piddling - examination of anaesthetised subjects has suggested that thebesian vein flow contributes 0.12% to 0.43% of the total aortic flow. However, the oxygen content within these veins is probably very low, and the impact on the A-a difference is not trivial.
• Bronchial veins contribute probably no more than 1% of total cardiac output. This is blood which leaves the aorta, nourishes the bronchial wall, and then rejoins the central circulation by draining into the pulmonary veins. According to Nunn's , in patients with bronchiectasis or COPD this contribution could be considerable - as much as 10% of the cardiac output.
• Congenital heart disease with right-to-left shunting is a possibility that should be mentioned, as it allows the right heart to eject into the left circulation, bypassing the lungs.
• Intrapulmonary arteriovenous connection, such as an AVM or fistula, would do exactly the same thing as the intracardiac shunt
• Intrapulmonary sources of poorly oxygenated blood, such as blood draining from the anoxic depths of a lung tumour, or portopulmonary shunts in liver disease, can deliver very oxygen-poor blood to the pulmonary venous circulation
• Virtual shunt is virtual in the sense that it may not actually exist. When one's measurement of shunt is performed without a mixed venous blood sample, the resulting shunt is referred to as virtual. As far as one can tell, this terminology is unique to works published by, or about, Nunn (see Lawler & Nunn, 1984). According to the original authors, this is  "the shunt which would explain the relationship between arterial PO2 and inspired oxygen concentration if the arterial-to-mixed venous oxygen concentration difference was 5 vol %".

The magnitude of a normal shunt fraction

In Question 6 from the second paper of 2009, CICM examiners seem to have expected some statement of a "normal" shunt fraction or venous admixture value. In summary, this is far from clear.

For shunt proper, different sources quote very different fractions. For example, Smeenck et al (1997) explored this in a group of patients undergoing a 100% oxygen text prior to cardiac surgery, and calculated a shunt fraction of 10%. This group, of course, cannot be considered normal or healthy, as they were all awaiting cardiac surgery.  Ming et al (2014) used a shunt fraction of 5% as the normal range cut-off for their study evaluating the 100% oxygen test. Sarkar et al (2017) report 2-3% in their review, but do not quote a source. Probably the most authoritative reference on this subject is Wagner et al (1974), who used MIGET to evaluate healthy volunteers. These subjects had essentially no shunt with normal room air, and a mean shunt of around 3.2% while breathing 100% FiO₂ (or up to 10.7% in the case of one subject), which the investigators attributed to denitrogenation atelectasis. 

Venous admixture, as measured in normal subjects breathing room air, is usually about 3%. This value comes from Said & Banerjee (1963).