Practical Acid-Base
Introduction
pH is vitally important as most metabolic processes are directly or indirectly affected by changes in pH.
Severe disorders of acid-base balance lead to organ dysfunction, especially when these derangements develop quickly.
Neurological - Cerebral oedema, seizures and coma.
Cardiovascular - Variable - altered sympathetic tone with arrhythmias, ↑ myocardial oxygen demand, ↓ myocardial contractility, pulmonary vasoconstriction and systemic vasodilatation or constriction.
Respiratory - ↑ RR → ↑ minute ventilation → respiratory muscle fatigue → respiratory failure or diversion of blood flow from vital organs to the respiratory muscles.
Immune system - Emerging evidence suggests that changes in acid-base variables influence immune function.
It is vitally important to understand that it is the underlying disorder rather than just the value of the pH that is important. For example, a patient with DKA with a pH of 6.8 will get better with fluid resuscitation and insulin, whereas someone with septic shock, and the same pH, will probably die.
It may also be beneficial to treat the acidosis directly but this should be of secondary importance.
Knowing how to interpret an ABG means being able to know the magnitude, the cause and what to do about an acid-base disturbance.
Magnitude
pH
The log 10 of the reciprocal of the hydrogen ion activity.
Thus it is simply a measure of the hydrogen ion concentration.
pH is logarithmic so it is therefore difficult to appreciate the magnitude of the change in H+. A fall in pH from 7.4 to 7.1 represents a doubling of H+ from 40 to 80 nmol/l, whereas a rise in pH from 7.4 to 7.7 represents a fall in H+ by only 20 nmol/l, from 40 nmol/l to 20nmol/l.
The normal pH of plasma is 7.35-7.45
<7.35 = acidaemia
>7.45 = alkalaemia
The terms acidosis and alkalosis describe the process leading to acidaemia or alkalaemia. Thus they can be present with a pH that is in the normal range due to respiratory or metabolic compensation.
Hydrogen ion concentration, and therefore pH, is temperature dependent. The pH of pure water (which is always acid-base neutral) ranges from 7.5 at 0 degrees to 6.1 at 100 degrees. It is noteworthy that its pH at 37 degrees is 6.8 which is close to the pH of intracellular fluid. It may well be that it is hydrogen and hydroxyl ions being present in equal numbers (neutrality) that is more important than pH itself (part of the alpha stat pH stat debate).
Actual and standard bicarbonate
These can be ignored as Base Excess is of more use.
Base Excess
It is independent of CO2 and therefore allows us to quantify the magnitude of the metabolic component.
It is defined as the amount of acid or base that must be added to a sample of whole blood in vitro to restore the pH of the sample to 7.40 while the PCO2 is held at 5.33 kPa at a given Hb concentration.
The BE of oxygenated blood with a Hb of 15 at a pH of 7.4 and PCO2 of 5.33 is zero.
BE is influenced by Hb concentration so accuracy is increased by using a Hb value of 5 which estimates the average content of Hb across the entire extracellular fluid space. This is called the standard BE (SBE) or BE(ecf).
BE does not tell us about the mechanisms of a metabolic acid–base disturbance.
Cause
Disturbances in acid-base balance are caused by 3 independent variables – CO2, Strong Ion Difference (SID) and the total concentration of weak acid (Atot).
CO2
CO2 is an independent determinant of plasma pH. Its level is normally maintained at 5.3kPa by a balance of cellular metabolic production and alveolar ventilation.
An increase in CO2 leads to an increase in the concentration of hydrogen ions (pH falls) while a decrease will reduce the hydrogen ion concentration (pH rises)
CO2 + H2O → H2CO3 → H + HCO3
Intracellular, as well as extracellular, acidosis will result as CO2 freely diffuses through cell membranes.
Thus a raised CO2 causes a respiratory acidosis while a low CO2 causes a respiratory alkalosis. These may or may not result in acidaemia or alkalaemia depending on metabolic compensation.
SID
The human body is 60% water which provides an inexhaustible source of hydrogen ions.
Strong ions are ions that completely dissociate in water.
In plasma strong cations outnumber strong anions – the difference between them is termed SID
SID = (Na + K + Ca + Mg) – (Cl + lactate)
It is mathematically provable that the SID causes water to dissociate or associate, thus determining the hydrogen ion concentration.
A reduced SID causes an acidosis; an increased SID causes an alkalosis.
The normal SID in plasma is 42mEq/L.
Because the concentrations of the ions other than Na and Cl is so small and varies little, the SID is basically the difference between Na and Cl.
SID = Na – Cl
The normal difference between these 2 ions is 38mEq/L
As these ions and the BE are measured in mEq/L it makes it easy to calculate the effect on the BE of any change in SID.
Increasing SID by 1 will increase the BE by 1.
Decreasing the SID by 1 will decrease the BE by 1.
It can therefore be seen that an acidosis will be caused by a reduced gap between Na and Cl concentration.
This can be caused by:
- Water overload (eg TURP syndrome) diluting plasma will reduce SID.
- Failure of chloride excretion – renal failure.
- Administration of chloride in excess of sodium – giving 0.9% saline which has 154mmol/l of Na and Cl will proportionally increase Cl more than Na.
- Diarrhoea and pancreatic drainage (large bowel and pancreatic fluid has a high SID so more cations than anions will be lost).
- Vomiting with loss of chloride.
- Administration of Na without Cl eg sodium bicarbonate.
Atot
It can again be proved mathematically that the total concentration of weak acids (Atot) determines pH.
In plasma Atot is predominantly albumin.
Hypoalbuminaemia has an alkalinizing effect while hyperalbuminaemia would cause an acidosis.
As critically ill patients all have an albumin of half normal (20) or less, this will disguise a significant presence of strong anions (ie they would be more acidotic than they actually are if they had a normal albumin).
The body does not compensate for a metabolic acidosis by albumin loss. Hypoalbuminaemia in the critically ill is the result of the switch of hepatic albumin production to the production of acute phase proteins, poor nutrition and the loss of albumin through leaky endothelium. It is therefore most likely just a lucky coincidence that hypoalbuminaemia is protective against an acidosis.
You will see that hypoalbuminaemic patients on ICU with a BE in the normal range have compensated by altering their chloride levels (and thus SID).
Bedside calculations
The cause of an acidosis can quickly be determined by the bedside.
Story et al (BJA 2004) described how the value of the BE can be accounted for by 3 simple calculations which take into account the above independent variables:
Sodium - chloride effect on BE = Na - Cl - 38 (normal Na-Cl gap is 38)
Albumin effect on BE = 0.25 x (42 - albumin)
Unmeasured ion effect on BE = BE - (Na - Cl effect) - (albumin effect)
(Remember to use SBE (BEecf) if alternatives are displayed on your ABG)
So you now know what effect the Na-Cl difference is having on the BE, what effect albumin is causing (albumin in ICU patients is usually around 20 which equates to a +ve BE of around 6) and what effect other ions are causing.
Possible unmeasured strong anions will be:
Ketones (hydroxybutyrate and acetate)
Lactate
Renal failure and hepatic failure anions (sulphate, phosphate, urate etc)
Methanol (formate)
Ethylene glycol (oxalate)
Aspirin (salicylate)
Lactate is of course measured on many ABG machines so can be factored into your calculation.
You are now a long way towards knowing the true cause. Methanol, ethylene glycol and aspirin poisoning are rare and will be suggested by the history. Ketones and lactate can be easily measured which leaves renal failure as the alternative cause (which you will know from the creatinine, urine output etc)
Eg
pH 7.2
BE -12
Na – Cl (135 - 105 – 38) = -8
0.25 x (42 - 20) = 5.5
– (-8) – 5.5 = -9.5
Here you can see that the Na-Cl effect on the BE is almost as great as the unmeasured ion effect (which in this example could come from acute renal failure). You can also see this patient would be more acidotic if not for the low albumin.
It can be seen from the above information that if each time you look at an ABG you look at the pH, BE, Na, Cl, albumin and lactate and do the above calculation you will know the cause and magnitude of any acid base disturbance. This will not just make you look clever but can pick up previously missed diagnoses such as ethylene glycol poisoning. It can also save a laparotomy in a patient with an acidosis caused by a narrowed Na-Cl gap which no one has realised (something I have unfortunately seen happen).
Anion gap
The traditional way of working out the cause of an acid-base disturbance is to calculate the anion gap.
There is in reality no ‘gap’ - as electrical neutrality has to exist in any solution:
measured anions + unmeasured anions = measured cations + unmeasured cations
Routinely measured anions are Cl– and HCO3–, and routinely measured cations are Na+ and K+.
AG = ([Na+] + [K+]) – ([CL-] + [HCO3-])
More recently, the reference range for AG has shifted downwards to 3–11 mmol litre–1 due to the improved accuracy of chloride measurement. (Kellum)
The unmeasured anions in a normal sample are mostly accounted for by albumin so the ‘gap’ is grossly underestimated in hypoalbuminaemia.
It is therefore essential to correct for albumin.
Assuming a normal albumin concentration of 40 g litre–1:
AG (albumin corrected) = AG + (0.25 x [40 – albumin])
You can work out that for every 10g/L of albumin rise or drop, you can correspondingly adjust the AG by about 3 mmol/l.
The unmeasured anions that will cause an increased anion gap are those strong anions listed above.
Changes in the concentrations of measured ions will leave the AG little affected (the effect of changes in Na and Cl will be countered by changes in HCO3). Only unmeasured ions will alter it.
A metabolic acidosis with a normal anion gap will be caused by a narrowed Na-Cl gap as above.
What to do about it
Treat the underlying cause first.
Only use 0.9% saline if there is a hypochloraemic alkalosis. 0.9% saline has a SID of zero and will increase Cl proportionally more than Na causing an acidosis.
Use Compound Sodium Lactate (Hartmanns) as your fluid of choice. This has an SID of 29 (assuming metabolism of the lactate which occurs very quickly). Although this SID is lower than normal for plasma it will cause haemodilution and a fall in albumin concentration, thus having a neutral effect on acid-base balance.
Remember that CSL will decrease plasma potassium if the plasma value is greater than 5 (imagine the ECF as a bucket) and that only a negligible amount of the lactate will be metabolised to glucose. This means it is safe (indeed desirable) to use it in renal failure and DKA.
Sodium Bicarbonate will reverse an acidosis by increasing the sodium concentration (the bicarb is irrelevant)
This will permanently treat an acidosis cased by a narrowed Na-Cl gap (the kidneys will do this themselves if working normally)
In an acidosis caused by other strong anions than chloride it should be seen as a temporising measure only to allow institution of renal replacement therapy.
The hypothesis that sodium bicarbonate worsens intracellular acidosis by generating extra CO2 is overstated. Its administration over 30-60mins will easily permit the removal of any additional CO2 load.
Eg
A BE of -10 can be corrected by increasing the SID of the ECF by 10 (accomplished by increasing the ECF Na by 10)
BE -10
ECF volume 15L
10mmol Na required for each litre of ECF
So 150mmol NaHCO3 will bring the BE to zero. This is theoretical and in practice it often requires more.
Give half the calculated dose of 8.4% sodium bicarb via a central line over 30-60mins and then reassess the patient.