The PCO2 is determined by the ventilatory rate. Increasing ventilation decreases PCO2, while decreasing ventilation increases it (Fig. 37.8). The ventilatory rate is regulated by the blood PCO2 and pH. Chemoreceptors in the brainstem (ventral surface of the medulla) and periphery (carotid and aortic bodies) sense changes in PCO2 and [H+] and adjust the ventilatory rate accordingly. Therefore, when metabolic acidosis occurs, an increase in [H+] (decrease in pH) stimulates the ventilatory rate. Conversely, during metabolic alkalosis, a decrease in [H+] (increase in pH) reduces the ventilatory rate. Maximal hyperventilation can lower the PCO2 to approximately 10 mm Hg. However, hypoxia, which develops with hypoventilation, limits the extent to which the PCO2 can be increased. In a healthy individual, hypoventilation cannot raise the PCO2 above 60 mm Hg. The respiratory response to metabolic acid-base disturbances may start within minutes but may take several hours to complete.

The kidneys play a crucial role as the third line of defense against acid-base disorders. In response to changes in plasma pH and PCO2, the kidneys adjust the excretion of renal net acid excretion (RNAE). The renal response may take several days to complete because it takes hours to days to increase the synthesis and activity of the proximal tubule enzymes involved in NH4+ production. In cases of acidosis (increased [H+] or PCO2), the nephron stimulates the secretion of H+ and reabsorbs the entire filtered load of HCO3-. Titratable acid excretion and the production and excretion of NH4+ are also increased, leading to an increase in RNAE (Fig. 37.9). The newly generated HCO3- during net acid excretion is added to the body, resulting in an increase in plasma [HCO3-].

In the presence of metabolic alkalosis (decreased [H+]), the filtered load of HCO3- is increased (elevated plasma [HCO3-]). With respiratory alkalosis (decreased PCO2), plasma [HCO3-] is decreased, leading to a decrease in the filtered load. In both conditions, the secretion of H+ by the nephron is inhibited. Consequently, HCO3- excretion is increased. Simultaneously, the excretion of both titratable acid and NH4+ is decreased, resulting in a decrease in RNAE. HCO3- is also secreted into urine by the HCO3--secreting intercalated cells of the distal tubule and collecting duct. Increased excretion of HCO3- leads to a decrease in plasma [HCO3-].
The ventilatory rate determines the PCO2. Increased ventilation decreases PCO2, whereas decreased ventilation increases it (Fig. 37.8 ). The blood PCO2 and pH are important regulators of the ventilatory rate. Chemoreceptors located in the brainstem (ventral surface of the medulla) and periphery (carotid and aortic bodies) sense changes in PCO2 and [H+] and alter the ventilatory rate appropriately. Thus when metabolic acidosis occurs, a rise in the [H+] (decrease in pH) stimulates the ventilatory rate. Conversely, during metabolic alkalosis, a decreased [H+] (increase in pH) reduces the ventilatory rate. With maximal hyperventilation, the PCO2 can be reduced to approximately •Fig. 37.8 EffectofventilatoryrateonalveolarPCO2andthusarterialbloodPCO2.
10 mm Hg. Because hypoxia, a potent stimulator of ventilation, also develops with hypoventilation, the degree to which the PCO2 can be increased is limited. In an otherwise normal individual, hypoventilation cannot raise the PCO2 above 60 mm Hg. The respiratory response to metabolic acid-base disturbances may be initiated within minutes but may require several hours to complete.
The third and final line of defense against acid-base disorders involves the kidneys. In response to an alteration in plasma pH and PCO2, the kidneys make appropriate adjustments in the excretion of RNAE. The renal response may require several days to reach completion because it takes hours to days to increase the synthesis and activity of the proximal tubule enzymes involved in NH4 + production. In the case of acidosis (increased [H+] or PCO2), the secretion of H+ by the nephron is stimulated and the entire filtered load of HCO3 − is reabsorbed. Titratable acid excretion is increased and production and excretion of NH4 + is also stimulated, and thus RNAE is increased (
Fig. 37.9). The new HCO3 − generated during the process of net acid excretion is added to the body, and the plasma [HCO3 −] increases.
When metabolic alkalosis exists (decreased [H+]), the filtered load of HCO3 − is increased (plasma [HCO3 −] is elevated). With respiratory alkalosis (decreased PCO2), plasma [HCO3 −] is decreased and thus the filtered load is decreased. In both conditions, secretion of H+ by the nephron is inhibited. As a result, HCO3 − excretion is increased. At the same time, excretion of both titratable acid and NH4 + is decreased. Thus RNAE is decreased and HCO3 − appears in urine. Also, some HCO3 − is secreted into urine by the HCO3 −-secreting intercalated cells of the distal tubule and collecting duct. With enhanced excretion of HCO3 − , plasma [HCO3 −] decreases.
•Fig. 37.9 Responseofthenephrontoacidosis.Pi,phosphate;PTH,parathyroidhormone;Rhbg&Rhcg,rhesusglycoproteins;RNAE,renalnetacidexcretion;TA,titratableacid;V,urineflowrate.