NORMAL ACID-BASE HOMEOSTASIS

Systemic arterial pH is maintained between 7.35 and 7.45 by extracellular and intracellular chemical buffering together with respiratory and renal regulatory mechanisms. The control of arterial CO₂ tension (Pa_CO2 ) by the central nervous system and respiratory systems and the control of the plasma bicarbonate by the kidneys stabilize the arterial pH by excretion or retention of acid or alkali. The metabolic and respiratory components that regulate systemic pH are described by the Henderson-Hasselbalch equation:



Under most circumstances, CO₂ production and excretion are matched, and the usual steady-state Pa_CO2 is maintained at 40 mmHg. Underexcretion of CO₂ produces hypercapnia, and overexcretion causes hypocapnia. Nevertheless, production and excretion are again matched at a new steady-state Pa_CO2 . Therefore, the Pa_CO2 is regulated primarily by neural respiratory factors (Chap. 258) and is not subject to regulation by the rate of CO₂ production. Hypercapnia is usually the result of hypoventilation rather than of increased CO₂ production. Increases or decreases in Pa_CO2 represent derangements of neural respiratory control or are due to compensatory changes in response to a primary alteration in the plasma [HCO₃ ^–].

The kidneys regulate plasma [HCO₃ ^–] through three main processes: (1) “reabsorption” of filtered HCO₃ ^–, (2) formation of titratable acid, and (3) excretion of NH₄ ⁺ in the urine. The kidney filters ~4000 mmol of HCO₃ ^– per day. To reabsorb the filtered load of HCO₃ ^–, the renal tubules must therefore secrete 4000 mmol of hydrogen ions. Between 80 and 90% of HCO₃ ^– is reabsorbed in the proximal tubule. The distal nephron reabsorbs the remainder and secretes protons, as generated from metabolism, to defend systemic pH. While this quantity of protons, 40–60 mmol/d, is small, it must be secreted to prevent chronic positive H⁺ balance and metabolic acidosis. This quantity of secreted protons is represented in the urine as titratable acid and NH₄ ⁺. Metabolic acidosis in the face of normal renal function increases NH₄ ⁺ production and excretion. NH₄ ⁺ production and excretion are impaired in chronic renal failure, hyperkalemia, and renal tubular acidosis.

In sum, these regulatory responses, including chemical buffering, the regulation of Pa_CO2 by the respiratory system, and the regulation of [HCO₃ ^–] by the kidneys, act in concert to maintain a systemic arterial pH between 7.35 and 7.45.