# Lactic acidosis due to severe anaemia

Severe anaemia can result in decreased oxygen delivery to the tissues even in the context of normal intravascular volume.

The issue of oxygen delivery is central to the concept of lactate as a surrogate marker of tissue perfusion. Certainly, regional ischaemia (like a segment of gut) will produce large amounts of lactate shortly after the onset of ischaemia. But what of whole body oxygen debt?

Here are several examples of such a state. Unlike shock, the flow of blood is never impaired; it is the quality of blood which suffers.

## Anaemia, and the loss of oxygen-carrying capacity

The oxygen carrying capacity of blood is well explored in another page, from the grossly bloated chapter on arterial and venous blood gas analysis. In brief, it is strongly influenced by the haemoglobin content. In every litre of maximally oxygen-saturated blood (i.e. at an alveolar O2 of around 100ml) there is only 3ml of dissolved oxygen. However, there is about 1.34-1.39ml of oxygen per every gram of haemoglobin.

This would suggest that at a Hb of 150 g/L you have about  200ml of O2 in every litre of whole blood.

Thus, at a Hb of 150g/L, in a well-oxygenated 70kg patient with a PaO2 of 100 and an SaO2 of 100%, with a normal cardiac output of 5L/min, the equation looks like this:

DO2 = 5 x (1.39 x 150 x 1 + (0.03 x 100)

=  5 x (208.5 + 0.3)

= 1044 ml/min

Thus, the total rate of O2 delivery (DO2) is around 15ml/kg/min.

We know from empirical data that the overall oxygen consumption of the human body at rest is around 3.5ml/kg/minute, or around 250ml for the aforementioned healthy 70kg specimen. Thus, venous blood should contain roughly 750ml of O2 (actually closer to 730, accounting for the loss of 2% saturation to some normal shunt).

Imagine, then, that the concentration of haemoglobin should halve.

The total amount of oxygen per litre of blood would halve proportionally.

The DO2 would be ~ 500ml/min, or around 7ml/kg/min

However, given that the oxygen extraction would remain the same, the mixed venous oxygen content would drop to about 250ml/L.

The natural extension of this is to halve the hemoglobin concentration again. Or rather, ask of oneself: how far would the haemoglobin concentration need to drop to in order to reach the limits of oxygen extraction? How anaemic does one need to be?

Well, going from a previously stated number, one’s oxygen delivery would need to be below 3.5ml/kg/min.

A straightforward calculation leads one to conclude that a Hb of 37.5 is that limit - IF your cardiac output remains the same. But of course it will not.

However, there are numerous ways in which one can adjust to severe anaemia, provided the haemoglobin is lost gradually. Conversely, a rapid drop in haemoglobin to some value above 37.5g/L can still result in an oxygen delivery deficit with lactic acidosis, because the organism has not had time to adjust to it.

## But is there any experimental evidence for this?

Again, we turn to AJP legacy content; this time from 1965. Unfortunately I do not have access to the full version of this paper. Which is a pity, because it sounds very interesting. Anaesthetised dogs were haemodiluted with dextran and ventilated with perversely oxygen-poor gas mixtures. Whatever happened, it stays behind the paywall – but from the abstract we can infer that the investigators have found  a VO2 threshold beyond which anaerobic metabolism begins. A later group had confirmed that in this model it did not matter by which method the VO2 was decreased, only that it was decreased. Contrary to the human model the dogs began to produce lactate en masse when the VO2 reached 10-12ml/kg/min.

…But is there any evidence that this happens to real people?

Yes. There is at least one case report of lactic acidosis in an insanely anaemic young man. The Hb was 12 (Twelve!!) g/L, and the admission pH was 6.9, with a lactate of 28mmol/L. The lactic acidosis resolved quite rapidly as blood transfusions were given-  in fact  in the first 12 hours a normal pH was restored with only a single unit of PRBCs, up to a Hb of 22.

## References

Cain, Stephen M. "Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia." American Journal of Physiology--Legacy Content209.3 (1965): 604-610.

Chapter 14 in Ohs Manual, by Thomas John Morgan and Balasubramanian Venkatesh, titled  “Monitoring oxygenation “

Law, Rob, and H. Bukwirwa. "The physiology of oxygen delivery." Update Anaesthesia 10.1-2 (1999): 39.

Harris J, Benedict F (1918). "A Biometric Study of Human Basal Metabolism". PNAS 4 (12): 370–3

Essex, David W., David K. Jin, and Thomas P. Bradley. "Lactic acidosis secondary to severe anemia in a patient with paroxysmal nocturnal hemoglobinuria." American journal of hematology 55.2 (1997): 110-111

Cilley, Robert E., et al. "Low oxygen delivery produced by anemia, hypoxia, and low cardiac output." Journal of Surgical Research 51.5 (1991): 425-433.