CHAPTER 53
Acid–Base Disorders

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:
  - PCO₂ = VCO₂ (CO₂ production) × 0.863/alveolar ventilation.
- Regulation in H⁺ ion concentration: renal excretion of H⁺ and reabsorption of HCO₃ ^– regulates the normal HCO₃ ^– concentration at 24 mEq/L.
- Intrinsic buffering: mediated by serum phosphates and serum anionic proteins.

Etiology

Acid–base disorder	Etiology
Respiratory acidosis	Decreased minute ventilation: ↑ Airway resistance (asthma, COPD, upper airway obstruction) ↓ 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
Respiratory alkalosis	Chronic	Pregnancy Liver disease
Metabolic acidosis	↑ Anion gap	MUDPILES (see later)
Metabolic acidosis	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 53.1 Relationship 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.

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

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 53.2 Expected 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