So much pathology is reflected in the acid-base status of a patient.

I’ve always found acid-base analysis challenging. I probably look at a couple of ABGs on most of my shifts in the ED, and up until now have scarcely ventured beyond the basics.

I used to be able to say whether a patient was acidotic/alkalotic (or is it acidaemic/alkalaemic??), and I could usually indicate whether the primary aetiology was respiratory or metabolic. On a good day, I may have been able to stumble my way through saying if there was any degree of ‘compensation’ (I think). But beyond that I got lost in a haze of confusion and numbers.

I’ve gotten sick of feeling stupid, and so I’ve decided to blog about acid-base physiology in an effort to teach myself. I hope this post is helpful for others who have found themselves equally frustrated with blood gases in the past.

No longer will I feel clueless when grilled by a boss, and I’ll be able to offer something to a curious medical student when armed with an interesting ABG.

And of course, I’ll understand better why my patient is so sick, and do something about it!

This will be the first of two posts tackling acid-base physiology. Here, I’ll be discussing the traditional Henderson-Hasselbalch method (or a very abbreviated version of it!) – I’ll explain the bread-and-butter basics, and go through some examples at the end.

The second post will take a dive into the more modern ‘Fencl-Stewart Approach’. I hope you are excited…

What is pH?

pH is defined as the negative log of the hydrogen ion activity:

pH = -log [H+]

All this means is that when the concentration of H+ goes up, the pH goes down… And when the concentration of H+ goes down, the pH goes up.

The normal or ‘neutral pH’ of the body = 7.4

Normal pH on a blood gas is between 7.35-7.45

Acidaemia/Alkalaemia or Acidosis/Alkalosis??

An -aemia is a state of being.

If the pH is <7.35 the patient is acidaemic. If the pH is > 7.45 the patient is alkalaemic. A patient cannot be both at the same time, they can be one or the other (or completely neutral – 7.4)

An -osis is a physiological process (e.g. metabolic acidosis, or respiratory alkalosis). Multiple processes can be going on at the same time. The balance of these processes determines a patient’s pH.

Why is pH important?

At a normal (neutral) pH, most compounds involved in important metabolic pathways are in their ionised state. This ionisation at neutral pH keeps these compounds ‘trapped’ in the cell and its organelles. (This is ‘Davis Hypothesis’).

Also, neutral pH provides the optimal environment for protein function. At very acidic pHs proteins become ‘denatured’ and cease to function properly.

The Henderson-Hasselback Equation (gulp!)

As already discussed – normal pH is 7.35-7.45

pH is determined by this scary chemical equation:

… It’s not as complicated as it looks!

All that Professor Henderson and Professor Hasselback are illustrating here is that pH is determined by 2 key components – pCO2 and [HCO3−].

 

The pCO2 is controlled by ventilation in the lungs (respiratory system).

The [HCO3−] is controlled by excretion in the kidneys (metabolic system).

When a process occurs which alters a patient’s pH, the body ‘compensates’ by adjusting the other component, in an effort to restore a normal pH.

The respiratory system provides compensation for metabolic processes immediately. It achieves this by hyper/hypoventilating, and subsequently adjusting the pCO2.

The metabolic compensation for respiratory processes is delayed. The kidneys adjust HCO3− reabsorption in the proximal tubules. It can take up to 24-48 hours to reach a steady state.

As illustrated in the diagram to the right, whenever the pH and the pCO2 are moving in the same direction (i.e. up or down), a metabolic process is occurring.

Whenever the pH and pCO2 are moving in opposite directions, a respiratory process is occurring.

 

 

What are the Differential Diagnoses of the Primary Acid-Base Disturbances?

Primary Metabolic Acidosis

A primary metabolic acidosis is the most important acid-base disturbance to recognise.

It is common in the ED. We cannot miss an ongoing metabolic acidosis – it harms patients.

It occurs when [HCO3−] drops. This can happen in two ways:

1.  HCO3− is lost (normal anion gap)
2.  or it combines with an acid to produce CO2 and H2O (increased anion gap)

There is respiratory compensation by hyperventilation – this reduces pCO2 in an effort to restore a normal pH.

The Anion Gap

‘The anion gap is a clue to the presence of many potentially fatal diseases.’ (2)

It should be calculated on every set of electrolytes. There may be subtle disturbances that are not obvious on first glance.

The serum is electrically neutral. Cations (90% Na+) must equal anions (85% HCO3−/Cl-).

Anion gap = Na+ – (HCO3− + Cl−)

Normal anion gap = between 8 and 14 (usually quoted as 10)

The anion gap consists of unmeasured anions. The majority of a normal anion gap is albumin.

When there is an increased anion gap, that means that there are extra anions unaccounted for in the serum. This means that there is extra acid (H+) that was originally bound to those anions, and has now attached to HCO3− to produce CO2 and H2O.

An increased anion gap means that there is extra acid in the serum.

The presence of an increased anion gap always indicates that there is a primary metabolic acidosis. If the pH is >7.35, there must be an additional primary process occurring at the same time.

The presence of an anion gap/non-anion gap acidosis allows us to narrow down our list of differential diagnoses, as there are lists of specific, well-defined causes for both. When combined with the clinical picture, a robust diagnosis can be made, and we can get on with managing the patient appropriately.

Causes of an Increased Anion Gap Metabolic Acidosis 

The ‘MUDPILES’ mnemonic is not always easy to remember. Perhaps a simpler way to arrange your mind when tackling an increased anion gap metabolic acidosis is:

• Lactic acidosis (shock, toxins)
• Ketoacidosis (DKA, AKA, starvation)
• Uraemia (renal failure)
• Ingestions

Causes of a Normal Anion Gap Metabolic Acidosis

This occurs when HCO3− is lost.

The kidneys retain Cl− to replace the lost HCO3− (remember, the body must always maintain electroneutrality). Therefore, it is also known as a hyperchloraemic metabolic acidosis.

The most common cause by far is diarrhoea.

Other causes to be aware of:

• Renal Tubular Acidosis (especially Type 1)
• Carbonic Anhydrase Inhibitor drugs (e.g. acetazolamide)
• Addison’s Disease

 Mixed acid-base disturbances

There are rules we can apply in order to work out if the degree of compensation that has occurred is ‘appropriate’ in response to the primary process. This will help us work out if there is another process occurring at the same time – a ‘mixed’ acid-base disorder.

You should suspect a mixed disturbance if the compensation does not correlate as predicted by the ratios in the following diagram.

In a metabolic acidosis, for every 1 (mmol/L) the HCO3− goes down, the pCO2 should also go down by 1 (mmHg).

Perhaps this is the most important clinical situation that we should be aware of – whether a metabolic acidosis has appropriate respiratory compensation.

We can also work out if there is appropriate respiratory compensation for a metabolic acidosis using Winter’s Formula.

pCO2 = 1.5 x [HCO3−] + 8 ± 2

e.g. if the [HCO3−] = 10

1.5 x 10 + 8 = 23 ± 2

Therefore, when the [HCO3−] = 10, if there is appropriate respiratory compensation for the metabolic acidosis, the pCO2 should be approximately 23 (similar figure to above).

If the pCO2 is greater than 23, there is an additional primary respiratory acidosis.

If the pCO2 is less than 23, there is an additional primary respiratory alkalosis.

What is the Delta Gap?

Calculating the delta gap allows us to know the patient’s HCO3− equivalent.

By subtracting 10 (a normal anion gap) from the patient’s actual anion gap, you get a figure that represents how many extra unaccounted anions (conjugate base) are in the serum – and therefore how much HCO3− combined with H+ (acid) that was originally attached to those anions.

Another way to look at it – the delta gap is the amount of excess acid in the serum.

Delta Gap = Anion Gap – 10

By adding the delta gap to the patient’s actual HCO3− level, you have a hypothetical HCO3− if there was magically no metabolic acidosis.

If that level is above 26, there is a concurrent primary metabolic alkalosis. 

If that level is below 22, there is a concurrent normal anion gap metabolic acidosis.

… The concept of the delta gap will make much more sense when working through some examples – which is up next!

A Good Method for approaching VBGs in practice

Step 1: Calculate the Anion Gap

Step 2: Calculate the Delta Gap

Step 3: Look at pH and pCO2

Step 4: Is there appropriate compensation?

Example 1

A 14 year old male presents with abdominal pain, vomiting, polyruria and polydipsia.

• pH 7.25
• pCO2 27
• HCO3- 12
• Na 140
• K 3.9
• Cl- 96
• HCO3- 12
• Glucose 31.7
• Urea 14

Step 1: Calculate the anion gap

140 – (96+12) = 32

There is, therefore, an increased anion gap metabolic acidosis

Step 2: Calculate the Delta Gap

32-10 = 22

What does this mean? It means that there are 22 units of extra anions (unaccounted for) floating around in the serum. These anions have had to be balanced out by missing HCO3− – that will have bound to the H+ originally attached to the extra anions.

Now add the delta gap to the patient’s actual HCO3− (to get an HCO3− equivalent – the figure represents what the HCO3− would be if the metabolic acidosis was taken away).

22 + 12 = 34

This is more than 24 – therefore, the patient has a concurrent primary metabolic alkalosis

So far we have identified two different primary processes.

Step 3: Look at pH and pCO2

If going in the same direction – metabolic process

If going in different directions – respiratory process

In this case, they are going in the same direction – the pH is going down (7.25), and the pCO2 is going down (27).

This confirms that this is primarily a metabolic process. We were already aware of this from steps 1 and 2.

Step 4: Is there appropriate compensation?

As the patient is acidaemic, the stronger of the two primary processes going on must be the metabolic acidosis.

To check if there is appropriate respiratory compensation, we can use Winter’s Formula:

Predicted pCO2 = 1.5 x [HCO3−] + 8 ± 2

1.5 x [HCO3−] + 8 = 1.5 x 12 + 8 = 26

26 is a very similar figure to the patients real pCO2 (27)

Therefore Winter’s Formula holds – this is an appropriately compensated primary metabolic acidosis.

Conclusion: this is a mixed acid-base disturbance – there is an increased anion gap primary metabolic acidosis, with appropriate respiratory compensation, and a concurrent primary metabolic alkalosis.

Example 2

A 79 year old female presents with profuse diarrhoea

• pH 7.25
• pCO2 27
• HCO3- 12
• Na 140
• K 4.1
• Cl- 118
• HCO3- 12
• Glucose 5.1
• Urea 8

Step 1: Calculate the Anion Gap

140 – (118 + 12) = 10

Normal anion gap

Step 2: Calculate the Delta Gap

10 – 10 = 0

There are no extra unaccounted for anions in the serum. We already knew that as there was a normal anion gap.

Step 3: Look at the pH and pCO2

The pH (7.25) and the pCO2 (27) are both going down.

As they are going in the same direction, this is a primary metabolic process.

As the pH is low, this is a non-anion gap primary metabolic acidosis.

Step 4: Is there appropriate compensation?

Winter’s Formula:

Predicted pCO2 = 1.5 x [HCO3−] + 8 ± 2

1.5 x [HCO3−] + 8 = 1.5 x 12 + 8 = 26

patients real pCO2 = 27

Therefore Winter’s Formula holds, and this is an appropriately compensated metabolic acidosis.

Conclusion: This is a non-anion gap primary metabolic acidosis, with appropriate respiratory compensation.

Example 3

A patient with a small bowel obstruction has had an NG tube in situ for the last few days.

• pH 7.50
• pCO2 48
• HCO3- 38
• Na 135
• K 3.4
• Cl- 85
• HCO3- 38
• Glucose 5.1
• Urea 10

Step 1: Calculate the Anion Gap

135 – (85 + 38) = 12

Normal anion gap

Step 2: Calculate the Delta Gap

12 – 10 = 2

No significant delta gap

Step 3: Look at the pH and pCO2

The pH (7.50) and pCO2 (48) are both going up.

As they are going in the same direction, this is a primary metabolic process.

As the pH is high, this is a primary metabolic alkalosis.

Step 4: Is there appropriate compensation?

We know that in an appropriately compensated metabolic alkalosis, the pCO2 goes up by 1 for every 2 the HCO3- goes up.

Predicted… HCO3−: pCO2 = 2:1

Actual… HCO3−:pCO2 = 14:8

The ratios are similar. Therefore, this is an appropriately compensated metabolic alkalosis.

Conclusion: This is a primary metabolic alkalosis, with appropriate respiratory compensation.

Example 4

A frail 89 year old female from a nursing home presents profoundly unwell – febrile with a productive cough, and intermittently vomiting

• pH 7.15
• pCO2 40
• HCO3- 15
• Na 140
• K 4.0
• Cl- 98
• HCO3- 15
• Glucose 14
• Urea 19

Step 1: Calculate the anion gap

140 – (98 + 15) = 27

There is an increased anion gap metabolic acidosis

Step 2: Calculate the delta gap

27 – 10 = 17

Add the delta gap to the patients actual HCO3−:

17 + 15 = 32

32 is higher than 24. Therefore, there is a concomitant primary metabolic alkalosis.

Step 3: Look at the pH and the pCO2

The pH is low (7.15), and the pCO2 is normal (40). We know that there is an increased anion gap metabolic acidosis, and therefore would expect the pCO2 to be going down to compensate.

Therefore, despite the pCO2 being ‘normal’, we know it must be going up as it should be low in the setting of a metabolic acidosis.

As the pH and pCO2 are moving in opposite directions, there is also a primary respiratory process going on…

Step 4: Is there appropriate compensation?

As the patient is acidaemic, the prominent metabolic process (out of the two primary metabolic processes we have established are occurring) is the metabolic acidosis.

We must, therefore, apply Winter’s Formula:

1.5 x [HCO3−] + 8 ± 2

1.5 x [HCO3−] + 8 = 1.5 x 15 + 8 = 30.5

This figure is significantly lower than the patient’s actual pCO2 (40). Therefore, we have proved what we suspected from step 3 – that there is also a primary respiratory acidosis occurring.

Conclusion: This is a triple acid-base disturbance – there is an increased anion gap primary metabolic acidosis, a primary metabolic alkalosis, and a primary respiratory acidosis occurring all at the same time!

Example 5

A 60 year old male, who is a heavy smoker, presents with a 5-day history of shortness of breath

• pH 7.34
• pCO2 60
• HCO3- 30
• Na 140
• K 4.0
• Cl- 100
• HCO3- 30
• Glucose 4.5
• Urea 11

Step 1: Calculate the anion gap

140 – (100 + 30) = 10 (normal anion gap)

Step 2: Calculate the delta gap

10 – 10 = 0 (no delta gap)

Step 3: Look at pH and pCO2

The pH is going down (7.34) and the pCO2 is going up (60). They are moving in opposite directions. This is, therefore, primarily a respiratory process.

As the pH is low, this is a primary respiratory acidosis.

Step 4: Is there appropriate compensation?

In acute respiratory acidosis, the ratio for metabolic compensation is 1:10 (HCO3− increases by 1 for every pCO2 rise of 10).

In chronic respiratory acidosis, the ratio is 1:3

In this patient…

HCO3−:pCO2 = 6:20

This ratio fits more with a chronic respiratory acidosis.

Conclusion: This is a primary chronic respiratory acidosis.

Example 6

I recently saw an alcoholic come in looking very unwell, vomiting profusely. Here is his VBG (you can see my working out the steps at the bottom!)

Step 1: Calculate the anion gap

144 – (87 + 26.7) = 30.3

There is an increased anion gap metabolic acidosis

Step 2: Calculate the delta gap

30.3 – 10 = 20.3

Add the delta gap to the actual HCO3−:

20.3 + 26.7 = 47

there is a concurrent metabolic alkalosis

Step 3: Look at pH and pCO2

They are both going up – it is primarily a metabolic process

The pH is slightly low, therefore the strongest metabolic process is the metabolic acidosis.

Step 4: Is there appropriate compensation?

Winter’s Formula:

1.5 x [HCO3−] + 8 = 1.5 x 26.7 + 8 = 48.05 ± 2

Winter’s Formula holds as the patients real pCO2 is 45.6 (roughly the same)

Conclusion: There is an increased anion gap primary metabolic acidosis, with appropriate respiratory compensation, and a concurrent primary metabolic alkalosis.

Initially I thought it was alcoholic ketoacidosis causing the increased anion gap. But the lactate was 8.7 and the serum ketone level came back normal. The patient was clinically dehydrated and peripherally shutdown – the anion gap was secondary to a shock-induced lactic acidosis. The concurrent metabolic alkalosis was explained by his vomiting.

Take Home Learning Points

• The ability to interpret a blood gas, and describe the acid-base disturbance, allows the ED doc to generate a differential diagnosis.
• It gives clues as to how sick the patient is, and how well they are responding to treatment.
• All that the Henderson-Hasselback equation illustrates is that pH is governed by pCO2 and HCO3−.
• A metabolic acidosis is the most important acid-base disturbance to recognise – it can kill!
• There are specific compensation ratios for all of the primary acid-base disturbances. If the the compensation is inappropriate, there is another process occurring concurrently.
• Multiple primary processes can be occurring at the same time – they can easily be identified by following simple steps when tackling a ABG.

In Pondering Acid-Base Part 2, I will discuss the the ‘Fencl-Stewart Approach’ to acid-base physiology…

References

• This fantastic lecture by Dr. Michael Chansky over at The Maryland Critical Care Project – http://marylandccproject.org/core-content/dr-michael-chansky-acid-base-made-easy/
• 8 simple lectures on acid-base physiology by Dr. Roger Seheult for MEDCRAM – https://www.youtube.com/playlist?list=PLBD832B100067ECFF
• acidbase.org
• Patil, Ramesh S. Causal Representation of Patient Illness for Electrolyte and Acid-Base Diagnosis. MIT Lab for Comp. Sci. TR-267 (1981).
• Oxford Handbook of Clincial Medicine, Edition 8