In addition to patient history and their clinical manifestations, we clinically diagnose acid base imbalance with a venous or arterial blood gas. A blood gas is a direct measurement of pH and PaCO₂, the Henderson-Hasselbalch equation is used to infer bicarbonate. ^[3] Thus, diagnosis of acid base disturbances rely on blood levels of pO₂, pH, pCO₂, and HCO₃^–.  The pO₂ level first determine is hypoxemia is present which sheds a lot of information as to why there is a pH disturbance.  A change in pH will have a value associated with the cause and, if the body compensates, a value to indicate the extent of compensation. Because pCO₂ is an indicator of carbonic acid, its level determines how much acid is present in the blood.  Similarly HCO₃^– is a marker of how much base is circulating in the blood.

In metabolic acidosis, we will see a decrease in pH <7.35 (i.e. acidosis), which the cause is either a either a gain of acid (that is NOT from CO₂) or loss of base (i.e. abnormally low HCO₃^–).  If the body compensates, it will do so by trying to get rid of acid in the form of CO₂, making it abnormally low in blood.  However, if the body does not compensate, the blood CO₂ level will not change from normal range.

In respiratory acidosis, we will see a decrease in pH <7.35 (i.e. acidosis), which the cause is respiratory, thus an increased blood pCO₂ level will be seen.  If the body compensates, the kidneys will try to reabsorb base leading to an increase in blood HCO₃^– , above the normal range.  However, if the body does not compensate, the HCO₃^– levels will not change from its normal range.

In metabolic alkalosis, we will see an increase in pH >7.45 (i.e. alkalosis), which the cause is either a gain of base (HCO₃^– will be increased) or loss of H⁺ (which is NOT in CO₂ form). If the body compensates, the lungs are quick to change respiratory rate to retain CO₂ (i.e. acid) such that pCO₂ levels will increase to above normal range.  However, if the body does not compensate, the pCO₂ levels will not change from its normal range.

In respiratory alkalosis, we will see an increase in pH >7.45 (i.e. alkalosis), which the cause is loss of pCO₂ to abnormally low levels.  If the body compensates, the kidneys will try to retain acid and lose HCO₃^–, as such HCO₃^– will increase to above normal range.  However, if the body does not compensate, the HCO₃^– levels will not change from its normal range.

There are many methods to interpret blood gases to determine the type of acid base disturbance.  We highlight 3 different methods.

Method 1:  Tic-Tac-Toe

The aforementioned summary is written out in a chart which can be used as a form of Tic-Tac-Toe (or Connect Four!!)  Thus, when presented with blood gases, you use this chart to make the match.

Method 2: ROME = Respiratory Opposite; Metabolic Equal

The acronym R means that in respiratory disorders and O means opposite. This means that the pH will be in the opposite direction of the cause.  For  example, respiratory acidosis will have a pH going down with a pCO₂ going up. The M means metabolic disorder and E means equal.  This means the direction the pH goes will be the same direction as the cause.

Once you figure out the cause, signs of compensation will be the other blood gas value.  So, if it’s a respiratory cause (ie pCO₂ is moving out of range in the opposite direction as pH), then you’ll see the HCO₃^– move out of normal range IF there is compensation.  Similarly, if it’s a metabolic cause (i.e. HCO₃^– is out of range in the same direction as pH), they you’ll see pCO₂ move out of normal range IF there is compensation.

Method 3: Matching pH with Cause

Because we know high pCO₂ means a lot of acid, we use pCO₂ as an indicator for acidosis in respiratory situations.  Because we know high HCO₃^– means a lot of base and that it’s reabsorbed & generated in the kidneys (ie not the lungs), we use this high HCO₃^– as an indicator for alkalosis in metabolic situations (ie not the lungs). Once we know which indicator matches the abnormal pH, the other indicator will be moving if there is compensation.  So, in respiratory causes, the HCO₃^– will go up (in the case of respiratory acidosis) or down (respiratory alkalosis) when the body can compensate.  For metabolic pH disturbances, the lungs will quickly change respiratory rate to either tachypnea for pCO₂ to go down (in situations of metabolic acidosis) and bradypnea for pCO₂ to go up (during metabolic alkalosis)

Diagnosis of Mixed Acid-Base Disorders:  What If I Have Both a Respiratory AND Metabolic Cause to pH Disturbance?

So far, we’ve introduced pH disturbances which are due to one cause – either a respiratory (i.e. lungs) or metabolic (i.e. any tissue other than lungs).  However, it is possible for one to have two causes for the pH disturbance. This is definitely evident with patients under medical care. For example, a patient who has sustained hypoxemia from obstruction in the airway (say, for example, pulmonary edema) would be the cause of respiratory acidosis.  However, the prolonged hypoxemia means that all of the tissues are getting insufficient oxygen for aerobic metabolism. As a result, the tissues switch to anaerobic metabolism which lactic acid is generated as a byproduct. This accumulation of lactic acid would be a cause of metabolic acidosis.   Thus, you have both respiratory (carbonic acid from the impaired ventilation) and metabolic acidosis (lactic acid as a result of hypoxemia).  This is what we call a mixed condition or mixed disorder.

In addition to a thorough medical history and assessing clinical manifestations, blood tests again help the health care team to determine what the cause of the pH disturbance is so that an appropriate treatment plan can be proposed.

A Step-Wise Method For Diagnosing Disorders Mixed Acid-Base Disorders ^[2]

1: Obtain ABG/VBG and Blood Electrolyte Panel

2: Check Validity of pH using Henderson Hasselbalch

If there is discrepancy, consider faulty reading or HAGMA

3: Identify the primary disorder (metabolic/respiratory, acidosis/alkalosis) using the above chart

4: Calculate Anion gap

5: Consider the cause

6: Calculate expected compensation, use the Winter formula, or given values

7: Consider the presence of mixed acid-base disorder

8: Consider the Delta-Delta gap

Mixed Conditions, Winter Formula and Compensation

If we have established our patient has a metabolic acidosis should utilize the Winter formula to determine if the respiratory compensation is within normal ranges or if it is outside of what is expected. If it is outside what is expected, then we suspect a mixed acid base disorder in our patient, meaning the disorder is driven both by a Metabolic and a Respiratory pathology.

The Winter Formula

Expected PCO₂ = (1.5 * HCO₃^–)+8

Our expected PCO₂ should be within +/- 2 of our measured PCO₂ on our VBG to be considered normal compensation. ^[1]

Expected compensation. The Winter formula gives us the expected respiratory compensation in the case of a metabolic acidosis, however, you are probably wondering what the expected metabolic compensation is for a respiratory acidosis, and the respective compensations for alkalotic processes. The following chart will provide some reference figures.

Metabolic alkalosis ^[2]
For each mEq/L increase in HCO₃^–, pCO₂ increases by 0.7 mmHg

Respiratory acidosis: Acute
For each mmHg increase in pCO₂, HCO₃^– increases by 0.1 mEq/L

Respiratory acidosis: Chronic
For each mmHg increase in pCO₂, HCO₃^– increases by 0.4 mEq/L

Respiratory alkalosis: Acute
For each mmHg decrease in pCO₂, HCO₃^– decreases by 0.2 mEq/L

Respiratory alkalosis: Chronic
For each mmHg decrease in pCO₂, HCO₃^– decreases by 0.4 mEq/L

Mixed Conditions, Anion Gap, and The Delta Gap

If a patient is presenting with HAGMA, we must calculate the Delta Gap. If decrease in bicarbonate is greater than the increase in Anion Gap we know that in addition to all the bicarb lost due to an increase in organic acids in the serum, some is being lost by some other mechanism, so therefore we have a mixed HAGMA and NAGMA. When this is the case the Delta Gap will return as >-6. If the increase in Delta Gap is within normal ranges, [6 >x> -6], only a high anion gap acidosis exists. if Delta Gap > 6 that means that for every organic acid added, Bicarbonate levels are not dropping equally. This suggests an underlying metabolic alkalosis mixed with the HAGMA

Delta Gap = Delta AG – Delta HCO₃^–
Delta AG = Observed AG – upper normal AG (12 mmol/L)
Delta HCO₃^– = Lower normal HCO₃^– – observed HCO₃^– (22 mmol/L)^[3]

Case Studies

Below are 3 case studies with a small clinical picture and blood test results.  The goal of these case studies are for interpretation of blood gases, chemistry panel, clinical manifestations, and medical history. With this information, management and treatment options can be discussed to stabilize the patient while the health care team can address the underlying cause.

Reference Ranges

Case Study 1

42 year old man is brought into the emergency, found down by paramedics. He has a decreased level of consciousness and is rousable to pain.
The following vitals and labs are obtained.

Case Study 2

63 year old man walks himself into the emergency. He is experiencing nausea, fatigue, and shortness of breath. He has known Chronic Kidney Disease.
The following vitals and labs are obtained.

Case Study 3

22 year old woman brought into emergency by a friend. Experiencing a sudden onset of persistant vomiting for 36 hours, denies ingestion of toxins. Reports dizziness, weakness.
The following vitals and labs are obtained.

Video Solution: Case Study 1

Solution to Case Study 2

1. Obtain ABG/VBG and Blood Electrolyte Panel

pH 7.27
PaCO₂ 31mmHg
HCO₃^– 14 mEq/L
PaO₂ 86 mmHg

2: Check Validity of pH using Henderson Hasselbach

Henderson Hasselbach calculation of pH = 6.1 + log ([HCO₃^–]/ [CO₂]) where CO₂ is 31 mmHg  and HCO₃^– 14 mmol/L.

• Recall that we need to use the CO solubility coefficient  of 0.03 to convert mmHg to mmol/L (ie determine how much CO₂ is dissolved in blood)
  • [CO₂] = 31 mmHg * 0.03 = 0.93 mmol/L
• pH = 6.1 + log (14/0.93) = 7.27
•  The measured pH is equal to the calculated pH (via Henderson Hasselbalch).

3: Identify the primary disorder (metabolic/respiratory, acidosis/alkalosis) using the Tic Tac Toe method

Tic Tac Toe method reveals Metabolic Acidosis

4: Calculate Anion gap

Na⁺ 128 mEq/L
Cl^– 104 mEq/L
HCO₃^– 14 mEq/L

128 – (104+14) = 10

Anion gap is less than 12, no HAGMA

5: Consider the cause

Metabolic acidosis with a low anion gap, or NAGMA. we use the following pneumonic.

HARDUP

H – Hyperchloremia
A – Acetazolamide, Addison’s disease
R – Renal Tubular Acidosis
D – Diarrhea, Ileostomies, Fistulae
U – Ureteroenterostomies
P – Pancreatoenterostomies

Our patient is mildly hyperchloremic but likely to maintain electroneutrality in the face of a dropping bicarbonate level. There is no way for us to know if bicarbonate is dropping due to retention of H+ or GI loss at this stage, so there is little to rule out at the moment. However given the history of CKD and the potential for dilutional hyponatremia (our sodium is a little low and our BP is a little high), we may want to obtain kidney labs

6: Calculate expected compensation, use Winters formula, or given values

The Winter Formula

Expected PCO₂ = (1.5 * HCO₃^–)+8

PaCO₂: 31mmHg
HCO₃^–: 14 mEq/L

Expected PCO2 = (1.5*14mmHg) +8
Expected PCO₂ = 29mmHg

Actual PCO₂ = 31mmHg

Our expected PCO₂ should be within +/- 2 of our measured PCO₂ on our VBG to be considered normal compensation ^[1]

Our expected PCO₂ is within +/-2 and is therefore normal compensation.

It is worth noting that our patient has a respiratory rate of 22 which is rapid (tachypnea). This extra ventilation is bringing down our CO₂ levels and causing this normal respiratory compensation

7: Consider the presence of mixed acid-base disorder

We do not suspect mixed respiratory disorder in this patient, compensation is as expected.

8: Consider the Delta-Delta gap

Patient is not presenting with HAGMA therefore the delta delta gap is not relevant

Final solution

Our patient is experiencing a NAGMA Metabolic Acidosis with partial respiratory compensation and no suspicion of mixed disorder

Solution to Case Study 3

1: Obtain ABG/VBG and Blood Electrolyte Panel

pH 7.50
PaCO₂ 44mmHg
HCO₃^– 32 mEq/L
PaO₂ 92 mmHg

2: Check Validity of pH using Henderson Hasselbalch

Henderson Hasselbalch calculation of pH = 6.1 + log ([HCO₃^–]/ [CO₂]) where CO₂ is 44 mmHg  and HCO₃^– 32 mmol/L.

• Recall that we need to use the CO solubility coefficient  of 0.03 to convert mmHg to mmol/L (ie determine how much CO₂ is dissolved in blood)
  • [CO₂] = 44 mmHg * 0.03 = 1.32 mmol/L
• pH = 6.1 + log (32/1.32) = 7.48
•  The measured pH is equal to the calculated pH (via Henderson Hasselbach). Within the acceptable margin of error.

3: Identify the primary disorder (metabolic/respiratory, acidosis/alkalosis) using the Tic Tac Toe

Tic Tac Toe method reveals Metabolic Alkalosis

4: Calculate Anion gap

This step may be somewhat unnecessary in our alkalotic patients, as we use it to detect the presence of underlying HAGMA, and differentiate between HAGMA and NAGMA. However it is a quick calculation, and easily done here.

134 – (95+32) = 6

Anion gap is less than 12, no HAGMA

5: Consider the cause

The cause of this metabolic alkalosis is likely secondary to GI loss of protons due to the vomiting

6: Calculate expected compensation, use Winters formula, or given values

Expected compensation for metabolic alkalosis:

For each mEq/L increase in HCO₃^–, pCO₂ increases by 0.7 mmHg

ΔpCO2 = Current – Original = 44 mmHg – 40 mmHg = 4 mmHg = ΔpCO₂

4 * 0.7 = expected compensation = 2.8

Actual compensation = ΔpCO₂ = 4

Within an acceptable margin of expected compensation.

7: Consider the presence of mixed acid-base disorder

No indication of mixed disorder, compensation is as expected.

8: Consider the Delta-Delta gap

Patient is not presenting with HAGMA therefore the delta delta gap is not relevant

Final solution:

So finally we can say we have a metabolic alkalosis with partial respiratory compensation which we suspect is secondary to the GI loss of H+ due to the persistent vomiting.

References

1. 1. Metabolic Acidosis – StatPearls
   2. Fluid, Electrolyte and Acid-Base Disorders: Clinical Evaluation and Management
   3. Physiology, Acid Base Balance – StatPearls 4