Causes of acidosis in hyperlactataemia

Though the term "lactic acidosis" is imbibed together with mother's milk in one's medical training, the very concept of lactate causing acidosis is mired in sordid controversy. The question of whether or not lactate actually causes acidosis is itself debated; highly respected members of the intensive care community disagree on this rather important point. Less respected members are even more conflicted. Capture a senior intensivist, and corner them with the question: can infusion of Hartmanns cause lactic acidosis in an anhepatic patient? Why or why not? How can there be severe hyperlactataemia with a normal base excess? One may be disappointed with the results of this experiment.

Myocardial infarction with acute pulmonary oedema

A 59 year old gentleman in the cardiology ward, enjoying a new LAD stent, suddenly complains of shortness of breath. On her arrival, the medical registrar finds him with a respiratory rate of 30 and coarse creps in both bases. A solid 80mg of IV frusemide is given; CPAP is commenced. Some hours (and litres of urine) pass before somebody compares the trend in ECGs and realises that the left bundle branch block is new.

This gas is aspirated from the femoral sheath once the patient is back to the cath lab:

The spectrum of inherited defects of lactate metabolism

Sigh. These are numerous, exquisitely rare, and one cannot help but wonder whether one is wasting one’s time reading about them, given that it is highly unlikely that such a situation will present itself. However, an excellent article is available to the public, and I present it as a reference here so as to be able to revisit this at some later stage.

Salicylates interfere with oxidative phosphorylation enzymes

Salicylates cause lactic acidosis by interfering with the enzymes of Krebs cycle. Specifically, alpha-ketoglutarate dehydrogenase and succinic acid dehydrogenase appear to be targets. Obviously this sort of uncoupling would lead to increased anaerobic metabolism, and therefore lactate levels would rise. However, it seems clinically that the lactate levels in these people rise only infrequently, which makes salicylates an unusual cause of lactic acidosis.

Toxic alcohols as metabolic substrates favour lactate production

Lactate production due to ethanol intoxication is another incidence of lactate metabolism being derailed by the poor availability of NAD, or rather the excess of NADH NADH produces an imbalance in the equilibrium equation which governs the proportion of lactate and pyruvate.; and of course by the Law of Mass Action the NADH/NAD ratio determines the lactate/pyruvate ratio. Too much NADH, and lactate cannot be converted into pyruvate; the reverse takes place instead. Hence, when ethanol is metabolised into acetaldehyde, it creates a vast excess of NADH which drives the conversion of pyruvate into lactate (and prevents the conversion of pyruvate into glucose).

Propofol infusion syndrome

This is an uncommon side-effect of having a massive amount of propofol over a short period of time. The timeframe seems to be around 48 hours, and one requires quite a good amount of propofol for this to happen – about 4mg/kg/hr, or 28ml per hr of straight propofol for a 70kg adult male.  Seems like a lot – but considering that this male might be struggling vigorously against the ventilator, irritating the nurses, propofol rate keeps going up, boluses happen for pressure area care et cetera… One can see how such a thing could happen.

Unregulated xylitol, sorbitol or fructose metabolism

The monosaccharides are all ultimately metabolised into pyruvate. The addition of lots of monosaccharide results in the delivery of a lot of glycolysis pathway intermediates. The outcome is an increase in gluconeogenesis, glycogenesis and lipogenesis.   What else are you going to do with all this fuel, if not store it? The result of increased substrate delivery for the glycolysis-like “fructolysis” pathway is the arrival of huge amounts of pyruvate into the process, because it is the end result for all these pathways.