Acid-Base Disorders

Chapter: Acid-Base Disorders
McMaster Section Editor(s): Christine M. Ribic, Karen C.Y. To
Section Editor(s) in Interna Szczeklika: Franciszek Kokot, Robert Drabczyk
McMaster Author(s): Karen C.Y. To
Author(s) in Interna Szczeklika: Franciszek Kokot, Edward Franek
Additional Information

Overview of Acid-Base HomeostasisTop

Under physiologic conditions, blood concentration of hydrogen ions [H+] ranges from 35 to 45 nmol/L. The constant [H+] in the body fluids is the basis for normal enzymatic reactions, particularly those associated with the formation of high-energy compounds. It is largely maintained by the lungs (elimination of CO2) and kidneys (excretion of H+ in the form of ammonium and titratable acids). This is described by the Henderson-Hasselbalch equation:

Blood pH = 6.1 + log [HCO3]
0.03 × PaCO2

Where: [HCO3], bicarbonate level in mmol/L; PaCO2, blood level of CO2 in mm Hg.

The equation can be rearranged in the following way:

[H+] (in nmol/L) = 24 × PaCO2 (in mm Hg)
[HCO3] (in mmol/L)

Blood pH depends on the respiratory component (partial pressure of carbon dioxide in arterial blood [PaCO2]) and on the metabolic (renal) component. Consequently, blood pH may be normal despite considerable changes in PaCO2 and bicarbonate concentration [HCO3].

Under physiologic conditions, blood pH is 7.35 to 7.45 and PaCO2 is 35 to 45 mm Hg (4.65-6.00 kPa).

Key factors involved in the maintenance of a constant pH of blood and body fluids:

1) Blood and tissue buffers, which consist of bicarbonate, phosphate, proteinate, and hemoglobin buffers. They are characterized by the following: (a) addition of an acid or a base to the buffer results in only minor changes in buffer pH; (b) the buffer binds or releases hydrogen ions, depending on the conditions.

2) Lungs: Blood pH depends on PaCO2, which in turn depends mostly on alveolar ventilation. Respiratory disturbances of acid-base homeostasis are mainly caused by abnormal alveolar ventilation, with hypoventilation leading to respiratory acidosis and hyperventilation leading to respiratory alkalosis.

3) Kidneys: The main role of kidneys in pH regulation involves the reabsorption of filtered HCO3, excretion of H+ in the form of titratable acid (mainly phosphoric acid) and ammonium, and formation of HCO3. Impaired renal function with respect to these processes results in metabolic acidosis. Kidneys are the most important organ involved in compensatory responses to primary respiratory acid-base disturbances.

Parameters of Acid-Base HomeostasisTop

The following 3 parameters are required to accurately describe the acid-base equilibrium. Values of these parameters are obtained from blood gas analysis (blood sampling: see Blood Sample Collection for Blood Gas Analysis; parameters: Table 1; interpretation: Table 2).

1) pH­­ is measured in arterial or arterialized capillary blood. A normal blood pH does not exclude very serious metabolic or respiratory (nonmetabolic) disturbances. Venous blood pH is usually 0.01 to 0.03 lower than arterial blood pH.

2) [HCO3], expressed in mmol/L, is a parameter of the metabolic component. It reflects the current plasma [HCO3] measured in blood drawn without contact with air. Venous blood [HCO3] is usually 1 to 3 mmol higher than arterial blood [HCO3].

3) Partial pressure of carbon dioxide is a parameter of the respiratory component. Partial pressure of CO2 in venous blood is usually 1 to 3 mm Hg higher than partial pressure of CO­2 in arterial blood (PaCO2).

If 2 of the above 3 parameters are measured, the remaining one can be calculated using the Henderson-Hasselbalch equation (see above).

Other useful parameters:

1) Buffer base (BB) is the sum of levels of bicarbonate, plasma proteins, phosphate, and hemoglobin (in mEq/L). It is rarely used clinically.

2) Base excess (BE) is the amount of titratable acid or alkali obtained when titrating a solution to a pH of 7.40 at a PaCO2 of 40 mm Hg and a temperature of 37 degrees Celsius. If BE is negative, the solution contains an excess of nonvolatile acids or a deficit of bases.

3) Anion gap (AG) is the difference between [Na+] and the sum of [Cl] and [HCO3]. Under physiologic conditions, AG is from 8 to 12 mEq/L. On the basis of AG, acidosis can be subdivided into non-AG acidosis (~12 mEq/L), also termed hyperchloremic acidosis and caused mainly by loss of bases, and high-AG acidosis with normal serum chloride levels, caused by exogenous or endogenous nonvolatile acids (eg, lactic acidosis or ketoacidosis), decreased bicarbonate regeneration, toxins (eg, methanol, ethylene glycol, acetylsalicylic acid) or decreased H+ excretion.

Classification of Acid-Base DisordersTop

Classification of acid-base disorders: Table 2.

1. Changes in [H+] due to primary changes in PaCO2 levels:

1) Respiratory acidosis caused by an increase in PaCO2 and [H+] and a decrease in blood pH.

2) Respiratory alkalosis caused by a decrease in PaCO2 and [H+] and an increase in blood pH.

2. Changes in [H+] due to primary changes in [HCO3]:

1) Metabolic acidosis caused by an increase in [H+] and a decrease in blood pH and [HCO3].

2) Metabolic alkalosis caused by a decrease in [H+] and an increase in [HCO3] and blood pH.

3. Changes in [H+] due to changes in both PaCO2 and [HCO3] cause mixed acid-base disorders.


Table 1. Parameters of arterial blood gas analysisa

Symbol and definition

Normal range


Negative logarithm of hydrogen ion concentration

7.35 to 7.45


Arterial level of carbon dioxide

32 to 45 mm Hg (4.27-6.00 kPa)


Current plasma bicarbonate level

21 to 27 mmol/L


Standard plasma bicarbonate level

24 (21-25) mmol/L


Base excess in blood

−2.3 to +2.3 mEq/L


Arterial oxygen level

75 to 100 mm Hgb (10.00-13.33 kPa)


Total plasma content of carbon dioxide

22 to 28 mmol/L

47.0% to 60.5% (volume)


Oxygen saturation of hemoglobin in arterial blood

95% to 98%b

a Blood drawn without contact with air.

b When interpreting PaO2 and SaO2, always record the fraction of inspired oxygen (FiO­2). The normal ranges given here are for respiration with atmospheric air at sea level (an oxygen concentration of 20.9%, which corresponds to an FiO­2 of 0.209). When a healthy individual is breathing 100% oxygen (FiO­2 = 1.0), PaO2 may be as high as ~600 mm Hg and SaO2 may reach 100%.

Table 2. Diagnosis of acid-base disorders based on blood gas analysis





Simple acid-base disorders

Respiratory acidosis — Uncompensateda


Partially compensateda

Completely compensated respiratory acidosis or completely compensated metabolic alkalosisb


Metabolic acidosis — Uncompensated


Partially compensated

Completely compensated metabolic acidosis or completely compensated respiratory alkalosisb


Respiratory alkalosis — Uncompensateda


Partially compensateda

Metabolic alkalosis — Uncompensated


Partially compensated

Mixed acid-base disordersc

Metabolic and respiratory acidosis

Metabolic and respiratory alkalosis

a In patients with respiratory disturbances, changes in pH and in PaCO2 develop in opposite directions.

b These entities may be differentiated only on the basis of a complete clinical presentation.

c In mixed acid-base disorders, changes in PaCO2 and in [HCO3] develop in opposite directions.

↑, increased; ↓, decreased; N, normal; PaCO2, partial pressure of carbon dioxide in arterial blood.

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