pH-stat and alpha-stat

What do you do if the patient is really cold and you want to do a blood gas analysis of their acid base balance?

Alpha-Stat Method:

You accept that pH and PaCO₂ will naturally change with changes in body temperature.

• As body temperature drops, pH naturally rises and PaCO₂ decreases
• You are not trying to "correct" these changes because they are a normal part of how the body adapts to cooling
• The blood gas sample is warmed to 37°C by the machine
• You interpret the results as if the patient were at 37°C, even if they are actually colder

pH-Stat Method:

You aim to keep pH at 7.4 and PaCO₂ at 5.3 kPa, even when the patient’s temperature changes.

• You actively intervene to normalise these values as if the patient were at 37°C, regardless of their actual body temperature
• The blood gas is measured at the patient’s actual temperature, and not warmed to 37°C
• The results are interpreted in the context of what the reference values would be at 37°C, but adjustments (like adding CO₂) are made to bring the patient's pH back to 7.40

Most people agree to just use Alpha stat and be done with the whole argument.

• Water (H2O) splits into (OH-) and (H+) as a natural and reversible equation
• At 25°C for pure water this ends up giving a pH of 7.0, which we call neutral and use as our reference range

As temperature drops

• Dissociation or ionisation is an endothermic process
• At lower temperatures, molecules move more slowly, and there's less splitting (ionisation) into H+ and OH-, meaning the pH is higher and the water is measured as more alkalotic
• It is still neutral, however, as there are equal numbers of H+ and OH-
• The reverse happens with an increase in temperature
• For each 1 degree change in temperature, the pH changes by 0.017

This change with temperature is called the ionisation constant of water (Kw)

• At body temperature, water has a pH of 6.8
• At 0°C, the pH is around 7.5
• At -35°C the pH is 8.5

Thus the 'neutral', normal operating pH inside each of a healthy human's cells is 6.8.

• Cold fluid will dissolve more gas, because the dissolving process is exothermic
• This is why rising sea temperatures is bad news, as it releases yet more dissolved CO2 into the atmosphere
• If the solubility is higher then there is less partial pressure exerted by that gas (Henry's law)
• If you take blood from a cold patient, and warm it up, more CO2 will be released, the partial pressure will increase, and the reading you get on the machine will be higher.

The PaCO2 reading on a blood gas will be higher than the actual PaCO2 in a cold patient.

• We've already shown how pH increases with temperature
• Cold blood samples will therefore appear alkalotic and hypocarbic

"Let the pH change naturally with temperature because the body adjusts to it, and that's what is supposed to happen."

• You take any sample that enters the machine and warm it to 37°C
• You measure the newly-warmed sample and use your normal (37°C) reference ranges when interpreting the results
• You accept that the measured numbers will be slightly different to the actual values in the cold patient's blood, because they will have changed during the warming process
• You accept that nature's pretty slick at figuring this stuff out and just treat them like normal

Keep it simple - heat the sample to normal body temperature, and then interpret the numbers as if the patient has a normal temperature.

Scroll to the bottom of the post if you want to know why it's called 'alpha'.

"Force the pH to stay the same, even if the temperature changes."

• Analyse the sample at the temperature at which it happens to be
• Take the numbers and compare them to your normal reference ranges
• Make deliberate changes to make the numbers look normal, because you don't trust nature and its devious schemes

A pHstat is a piece of chemistry laboratory equipment that ensures a solution stays at a set pH throughout the course of an experiment.

Kind of like your kidneys and lungs.

A cold sample will appear alkalotic and have a low CO2 (if you haven't warmed it up) compared to a warmed sample.

This will then tempt you to increase the CO2 by hypoventilating the patient.

• This will increase the PaCO2
• This will help push the oxyhaemoglobin curve to the right (remember the curve shifts to the left in hypothermia)
• It will also cause vasodilatation of cerebral blood vessels
• Together these two processes give better oxygen delivery to the brain

At least that's the theory.

Welcome, friend, we're so proud of you for joining us.

These are two slightly different definitions of what an acid actually is.

Arrhenius theory

• An acid is anything that increases the number of H+ ions
• A base is something that increases the number of OH- ions

The Arrhenius theory only applies to water-based solutions, and doesn't explain why ammonia acts like a base, because it doesn't actually increase the number of OH- ions.

Brønsted-Lowry theory

• An acid donates a proton
• A base accepts a proton

This theory can apply to all sorts of fluids, and also explains why ammonia acts like a base.

BUT the Brønsted-Lowry theory has no convenient definition of neutral.

We mentioned earlier that the protein imidazole residues change their operating pKa depending on temperature.

The alpha of the imidazole residues is the ratio of residues that are currently holding onto a proton

• It is the ratio of how many imidazole residues are protonated
• Because the pKa changes with temperature, the alpha remains stable even as temperature changes
• At any body temperature, around half of the residues are protonated (alpha = 0.55)

You do not need to know any of this, except that this is why it's called the 'alpha-stat' method.

Frogs are cool because they don't really control their own body temperature, but somehow still function in a variety of climates.

• At 5°C, their measured pH is above 8 and their PaCO2 is around 0.6 kPa

The cells don't care what the measured pH is, they just care about being neutral.

While they are cold-blooded and not exactly the perfect model for human physiology, it does demonstrate that pH and CO2 in living tissue can quite happily alter with temperature without compromising the wellbeing of the organism, and thus lends credence to the alpha stat approach of - just trust nature.