Michael Bergman1, Lina Miyakawa2, and Young Im Lee2
1 University of Virginia Health System, Charlottesville, VA, USA
2 Icahn School of Medicine at Mount Sinai, New York, NY, USA
Background
The pH of plasma is tightly controlled at a pH of 7.40. The interaction of and effect of changes in CO2 and HCO3 on pH are defined by the Henderson–Hasselbalch equation:
Normal pH is maintained by three mechanisms:
Regulation of PCO2: normal PCO2 is 40 mmHg and is regulated by changes in alveolar ventilation:
↓ Central respiratory drive (CNS injury, sedating drugs)
↑ Dead space and V/Q mismatch (severe pulmonary embolism, parenchymal disease)
Neuromuscular weakness (neuromuscular disease, tiredness due to prolonged and increased work of breathing)
↑ CO2 production (fever, shivering, ↑ carbohydrate diet, hyperthyroidism)
Respiratory alkalosis
Acute
Pain, anxiety Hypoxia CNS stimulants Fever and sepsis ↑ Excessive ventilation on mechanical ventilator, post‐intubation
Chronic
Pregnancy Liver disease
Metabolic acidosis
↑ Anion gap
MUDPILES (see later)
Normal anion gap
GI HCO3– loss: diarrhea Renal HCO3– loss: type 1–4 renal tubular acidosis
Metabolic alkalosis
HCO3– gain (milk alkali syndrome, HCO3–‐rich fluids) H+ loss from GI (vomiting) or dehydration contraction alkalosis Excessive renal loss of chloride (diuretics) Post‐hypercapnia
Diagnosis
Five‐step approach
Systematically and accurately identifying one or multiple acid–base disturbances is vital to initiate or change management. Once the primary and secondary disturbances are identified, appropriate testing and treatment may be initiated.
Step 1: assess internal validity
Identifying acid–base disturbances can only be done if a blood gas is internally valid, thereby allowing its accurate interpretation. An ABG and serum chemistry taken simultaneously are assessed by the following two step approach:
Know the pH.
Calculate the expected H+ concentration.
There is a linear relationship between the expected [H+] ion concentration and pH between 7.25 and 7.5. Within that range, for every change in [H+] in one direction there is an expected change in pH of 0.01 in the opposite direction.
At pH below 7.25 there is a slightly greater change in [H+] for a given drop in pH; conversely at pH above 7.5 there is slightly less of a change in [H+] for a given change in pH (Table 53.1).
Next, calculate the measured H+ concentration on the blood gas using the modified Henderson–Hasselbalch equation:
Table 53.1Relationship between pH and [H+] ion concentration.
pH
[H+] (mmol/L)
pH
[H+] (mmol/L)
7.00
100
7.35
45
7.05
89
7.40
40
7.10
79
7.45
35
7.15
71
7.50
32
7.20
63
7.55
28
7.25
56
7.60
25
7.30
50
7.65
22
The expected and calculated H+ concentration should be similar. If discordant, the blood gas is not internally consistent and therefore should not be used for interpretation of acid–base abnormalities. The reasons for invalidity may be related to sample collection (venous versus arterial sample, samples not on ice, entrained ambient air into the sample, extremes of temperature).
An additional way to assess validity is to compare the serum HCO3– (which is directly measured) and the HCO3– on the blood gas (which is calculated automatically using the Henderson–Hasselbalch equation). If a blood gas is internally valid, the measured and calculated [HCO3–] should be similar.
Step 2: assess the primary acid–base disorder
Acidemia refers to a serum pH <7.40. Alkalemia refers to a serum pH >7.40. This is further classified by cause:
Respiratory acidosis: ↓ pH, ↑ PCO2.
Respiratory alkalosis: ↑ pH, ↓ PCO2.
Metabolic acidosis: ↓ pH, ↓ PCO2.
Metabolic alkalosis: ↑ pH, ↑ PCO2.
Note that there may be one or more acid–base abnormalities even when pH is at or near normal (7.35–7.45). This is due to the tight interaction and regulation of PaCO2 and HCO3–. Therefore look beyond the pH to assess for abnormalities in PaCO2 and HCO3–.
Step 3: assess for appropriate compensation
Changes in PaCO2 are offset by changes in HCO3– in the opposite direction (and vice versa) in an attempt to normalize the pH; however, most compensation is not complete and does not fully correct pH to normal.
When assessing compensation, if a response is not appropriate, then an additional acid–base disorder is present. Table 53.2 details the expected compensation for the given primary disturbance.
Table 53.2Expected compensation for acid–base disorders.
Primary disorder
HCO3– and PaCO2
Expected compensation
Metabolic acidosis
↓pH ↓PCO2
Winter’s formula: PaCO2 = (1.5 × HCO3–) + 8 ± 2
Metabolic alkalosis
↑pH ↑PCO2
ΔPCO2 = 0.6 × HCO3– ± 2
Respiratory acidosis
↓pH ↑PCO2
Acute Chronic
↑PCO2 by 10, ↑HCO3– by 1, ↓pH by 0.008 ↑PCO2 by 10, ↑HCO3– by 4–5, ↓pH by 0.003
Respiratory alkalosis
↑pH ↓PCO2
Acute Chronic
↓PCO2 by 10, ↓HCO3– by 2, ↑pH by 0.008 ↓PCO2 by 10, ↓HCO3– by 3.5‐4, ↑pH by 0.003
Step 4: calculate the anion and osmolal gaps
The anion gap (AG) is calculated as:
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