C H A P T E R
14  
Respiratory Acidosis, Respiratory Alkalosis,
and Mixed Disorders
Horacio J. Adrogué, Nicolaos E. Madias
Deviations of systemic acidity in either direction can have adverse
consequences and, when severe, can be life-threatening. There-
fore, it is essential for the clinician to recognize and properly
diagnose acid-base disorders, to understand their impact on
organ function, and to be familiar with their treatment and the
potential complications of treatment.1,2
RESPIRATORY ACIDOSIS
(PRIMARY HYPERCAPNIA)
Definition
Respiratory acidosis is the acid-base disturbance initiated by an
increase in CO2 tension of body fluids and in whole-body CO2
stores. The secondary increment in plasma bicarbonate [HCO3−]
observed in acute and chronic hypercapnia is an integral part
of the respiratory acidosis.3 The level of arterial CO2 tension
(Paco2) is above 45 mm Hg (to convert values from mm Hg to
kP, multiply by 0.1333) in patients with simple respiratory aci-
dosis (measured at rest and at sea level). An element of respira-
tory acidosis may still occur with lower Paco2 in patients residing
at high altitude (e.g., 4000 m or 13,000 ft) or with metabolic
acidosis, in whom a normal Paco2 is inappropriately high for this
condition.4 Another special case of respiratory acidosis is the
presence of arterial eucapnia, or even hypocapnia, occurring
together with severe venous hypercapnia, in patients having
an acute, profound decrease in cardiac output but relative pre­
servation of respiratory function.5,6 This disorder is known as
pseudorespiratory alkalosis and is discussed under respiratory
alkalosis.
Etiology and Pathogenesis
The ventilatory system is responsible for eucapnia by adjustment
of alveolar minute ventilation ( V A ) to match the rate of CO
2
production. Its main elements are the respiratory pump, which
generates a pressure gradient responsible for airflow, and the
loads that oppose such action.
Carbon dioxide retention can occur from an imbalance
between the strength of the respiratory pump and the extent of
respiratory load (Fig. 14.1). When the respiratory pump is unable
to balance the opposing load, respiratory acidosis develops.
Respiratory acidosis may be acute or chronic (Figs. 14.2 and
14.3). Life-threatening acidemia of respiratory origin can occur
during severe, acute respiratory acidosis or during respiratory
decompensation in patients with chronic hypercapnia.
A simplified form of the alveolar gas equation at sea level and
on breathing of room air (Fio2, 21%) is as follows:
176
PAO 2 = 150 − 1.25 PaCO 2
where Pao2 is alveolar O2 tension (mm Hg). This equation dem-
onstrates that patients breathing room air cannot reach Paco2
levels much greater than 80 mm Hg (10.6 kP) because the
hypoxemia that would occur at greater values is incompatible
with life. Therefore, extreme hypercapnia occurs only during O2
therapy, and severe CO2 retention is often the result of uncon-
trolled O2 administration.
Secondary Physiologic Response
Adaptation to acute hypercapnia elicits an immediate increment
in plasma HCO3− concentration due to titration of non-HCO3−
body buffers; such buffers generate HCO3− by combining with
H+ derived from the dissociation of carbonic acid:
CO2 + H 2O ↔ H 2CO3 ↔ HCO3− + H + and H + + B− ↔ HB
where B− refers to the base component and HB refers to the acid
component of non-HCO3− buffers. This adaptation is completed
within 5 to 10 minutes from the increase in Paco2, and assuming
a stable level of hypercapnia, no further change in acid-base
equilibrium is detectable for a few hours.7 Moderate hypoxemia
does not alter the adaptive response to acute respiratory acidosis.
However, preexisting hypobicarbonatemia (whether it is caused
by metabolic acidosis or chronic respiratory alkalosis) enhances
the magnitude of the HCO3− response to acute hypercapnia; this
response is diminished in hyperbicarbonatemic states (whether
they are caused by metabolic alkalosis or chronic respiratory
acidosis).8,9
The adaptive increase in plasma HCO3− concentration observed
in acute hypercapnia is amplified greatly during chronic hypercap-
nia as a result of HCO3− generation by the kidney. In addition, the
renal response to chronic hypercapnia includes a reduction in the
rate of Cl− reabsorption, resulting in depletion of body Cl− stores.
Complete adaptation to chronic hypercapnia requires 3 to 5 days.7
Quantitative aspects of the secondary physiologic responses to
acute and chronic hypercapnia are depicted in Figure 14.4. The
renal response to chronic hypercapnia is not altered appreciably
by dietary Na+ or Cl− restriction, moderate K+ depletion, alkali
loading, or moderate hypoxemia. However, recovery from chronic
hypercapnia is crippled by a diet deficient in Cl−; in this circum-
stance, despite correction of the level of Paco2, plasma [HCO3−]
remains elevated so long as the state of Cl− deprivation persists,
leading to posthypercapnic metabolic alkalosis.