Respiratory Acid–Base Disturbances

The bicarbonate/carbonic acid buffer system

Major changes in the H ⁺ ion concentration in the body are prevented by buffering. Buffers are primarily weak acids with their conjugate bases, which are able to take up or release H ⁺ ions so that changes in free H ⁺ ion concentration are minimized. The major buffer system in the body is the bicarbonate ( ${{\text{HCO}}_3}^{-}$ ; H ⁺ ion acceptor)/carbonic acid (H ₂ CO ₃ ; H ⁺ ion donor) buffer system ( Eqn 1 ).

H ⁺ ion concentration in the extracellular fluid (ECF) compartment is determined by the ratio of the concentrations of H ₂ CO ₃ to ${{\text{HCO}}_3}^{-}$ ions as described by the Henderson equation ( Eqn 2 ).

where K _a includes the dissociation constant for H ₂ CO ₃ and the solubility coefficient of the gas CO ₂ .

The content of ${{\text{HCO}}_3}^{-}$ ions in the body is large, and hence the bicarbonate buffer system (BBS) is able to titrate a large H ⁺ ion load. Furthermore, in response to a chronic acid load, the kidneys can generate an excess of 200 mmol of new ${{\text{HCO}}_3}^{-}$ ions per day via excretion of ammonium (NH ₄ ⁺ ) ions in the urine.

Because CO ₂ partially dissolves in water, H ₂ CO ₃ acid is formed from the hydration of CO ₂ ( Eqn 3 ).

H ₂ CO ₃ is a weak acid; it will only partially dissociate into H ⁺ + ${{\text{HCO}}_3}^{-}$ ions. Because the concentration of H ⁺ ions in plasma is in nanomol/L terms, while the concentration of ${{\text{HCO}}_3}^{-}$ ions in plasma is in mmol/L terms, and H ⁺ and ${{\text{HCO}}_3}^{-}$ ions are produced from dissociation of H ₂ CO ₃ in a 1:1 ratio, the relative increase in H ⁺ ion concentration will be substantially higher than the relative increase in ${{\text{HCO}}_3}^{-}$ ion concentration ( Eqn 4 ).

CO ₂ is the major carbon end product of oxidative metabolism. In an adult human subject, about 15,000 mmol of CO ₂ are produced each day. This CO ₂ is transported to the lungs (see the following section on transport of CO ₂ ), where the rate of its elimination via alveolar ventilation matches the rate of its production. The amount of CO ₂ that dissolves in a solution is proportional to the partial pressure of CO ₂ (PCO ₂ ) in mm Hg in that solution. Hence, the amount of H ₂ CO ₃ in a solution is proportional to the PCO ₂ . In humans, the PCO ₂ in arterial blood is in equilibrium with the PCO ₂ in alveolar air, which is normally 40 mm Hg. In arterial blood, when the PCO ₂ is 40 mm Hg and the solubility coefficient of CO ₂ in plasma is 0.03, the concentration of H ₂ CO ₃ is 1.2 mmol/L. If alveolar ventilation is decreased, the PCO ₂ in alveolar air will be higher and the PCO ₂ in arterial blood will rise, as will the concentration of H ₂ CO ₃ , a process called respiratory acidosis . If alveolar ventilation is increased, the PCO ₂ in alveolar air will be lower and the PCO ₂ in arterial blood will decrease, as will the concentration of H ₂ CO ₃ , a process called respiratory alkalosis .

Although respiratory acid-base disorders are detected by measurement of PCO ₂ and pH in arterial blood and reveal the presence of disease processes that lead to altered alveolar ventilation, it is important to recognize the effect of changes of PCO ₂ in capillary blood in the individual organs on binding of H ⁺ ions to intracellular proteins, which may change their charge, shape, and possibly affect their functions (as enzymes, contractile proteins, ion transporters). In more detail, in a patient with respiratory acidosis, because the arterial PCO ₂ sets the lower limit on the capillary blood PCO ₂ , the capillary blood PCO ₂ will be higher. This may limit the ability of the BBS in that organ to titrate an H ⁺ ion load. Thererfore, in the steady state, intracellular H ⁺ ion concentration will be higher and intracellular proteins will be in a more protonated form. In a patient with respiratory alkalosis, the capillary blood PCO ₂ may be lower. More of an H ⁺ ion load will be removed by the BBS. Therefore, in the steady state, intracellular H ⁺ ion concentration may be lower, and as a result, intracellular proteins will be in a less protonated form ( Figure 8-1 ).

Production of CO ₂

CO ₂ is the major carbon end product of oxidative metabolism. When carbohydrates are oxidized, 1 mmol of CO ₂ is produced for every mmol of O ₂ that is consumed (the respiratory quotient [RQ] is 1.0; see margin note). In contrast, less CO ₂ is formed per unit of O ₂ consumed when fatty acids are oxidized (RQ ∼ 0.7). In a typical Western diet, the usual RQ is close to 0.8, which reflects the oxidation of the mixture of fat and carbohydrate in the diet. The type of fuel that is being oxidized influences the rate of production of CO ₂ ; this can be illustrated by considering the ratio of the rate of production of CO ₂ and the rate of regeneration of adenosine triphosphate (ATP) from the oxidation of the different fuels ( Table 8-1 ).

When more work is being performed, the rate of consumption of O ₂ rises and more CO ₂ is produced. For example, during vigorous aerobic exercise, the rate of consumption of O ₂ can increase close to 20-fold and there is a large increase in the rate of CO ₂ production in skeletal muscles. The rate of production of CO ₂ decreases during hypothermia and in patients with severe hypothyroidism, conditions that result in a correspondingly lower rate of oxidative metabolism because of a lower rate of turnover of ATP. A list of clinical settings in which there is an altered rate of CO ₂ production in individual organs is provided in Table 8-2 .

Arterial blood contains approximately 8 mmol/L of O ₂ . Therefore, if all the content of O ₂ in 1 L of blood is extracted, 8 mmol of CO ₂ will be added to the venous blood, and the venous PCO ₂ will be considerably higher than the arterial PCO ₂ . There are two conditions during which most of the O ₂ that is delivered in a liter of blood may be consumed. First, when there is a large rise in the rate of work in an organ without a change in the rate of its O ₂ delivery. Second, when there is delivery of a fewer liters of blood per minute with no change in the rate of work. Of clinical relevance, when the effective arterial blood volume (EABV) is contracted and the blood flow rate falls, more O ₂ is extracted from each liter of blood delivered, and hence each liter of capillary blood must carry more CO ₂ to the lungs. This requires a high PCO ₂ in cells and capillary blood.

CO ₂ is also produced during buffering of an H ⁺ load by the BBS; this is called “acid–base” CO ₂ (e.g., buffering of L -lactic acid produced in glycolysis during a sprint). CO ₂ is produced in the liver when acetoacetic acid is converted to acetone.