REGULATION OF ACID-BASE BALANCE

Extracellular hydrogen ion concentration appears to be tightly controlled by the body. This should be viewed in terms of volatile and metabolic acids. A variety of intracellular and extracellular weak acid buffering systems have developed to prevent rapid changes in the electrochemical balance in the extracellular space from interfering with transcellular ion pumps. A buffer is a solution of two or more chemicals that minimizes changes in pH in response to the addition of an acid or base. Most buffers are weak acids. Ideally, a buffer has a pK_a that is equal to the pH, and an ideal body buffer has a pK_a between 6.8 and 7.2.

The major source of acid in the body is CO₂ , from which is produced 12,500 mEq of H⁺ each day. This is excreted by the lungs. In contrast, only 20 to 70 mEq of H⁺ -promoting anions are excreted through the kidney each day. Volatile acid is principally buffered by hemoglobin. Deoxygenated hemoglobin is a strong base, and there would be a huge rise in the pH of venous blood if hemoglobin did not bind hydrogen ions (derived from oxidative metabolism). Venous blood contains 1.68 mmol/L of extra CO₂ over arterial blood: 65% as HCO₃ ^- and H⁺ bound to hemoglobin, 27% as carbaminohemoglobin (i.e., CO₂ bound to hemoglobin), and 8% dissolved.

CO₂ easily passes through cell membranes. Within the erythrocyte, CO₂ combines with H₂ O under the influence of carbonic anhydrase to form H₂ CO₃ , which ionizes to hydrogen and bicarbonate. Hydrogen ions bind to histidine residues on deoxyhemoglobin, and bicarbonate is actively pumped out of the cell. Chloride moves inward to maintain electroneutrality (i.e., chloride shift). Large increases in PCO₂ (i.e., respiratory acidosis) overwhelm this system, leading to a rapid, dramatic drop in pH. The metabolic compensation³ for respiratory acidosis is increased SID by removal of chloride from the extracellular space, initially transcellularly and subsequently through urinary loss. There is a concomitant increase in [HCO₃ ^- ], often misrepresented as compensation for the increase in PaCO₂ . [HCO₃ ^- ] is a dependent variable, which increases or decreases with PCO₂ . The rate of conversion of CO₂ to HCO₃ ^- depends on carbonic anhydrase activity and occurs slowly. It is possible to mathematically determine whether a rise in PaCO₂ is acute or long-standing (see Table 4-2 ).

Metabolic acid is buffered principally by increased alveolar ventilation, producing respiratory alkalosis and extracellular weak acids. These weak acids include plasma proteins, phosphate, and bicarbonate. The bicarbonate buffering system (92% of plasma buffering and 13% overall) is probably the most important extracellular buffer. The pK_a of bicarbonate is relatively low (6.1), but the system derives its importance because of the enormous quantity of CO₂ in the body. The coupling of bicarbonate and H₂ O produces CO₂ , which is then excreted through the lungs. There is an increase in alveolar ventilation. Physicians must be aware of the importance of this compensatory mechanism. For example, anesthetized or critically ill patients on controlled mechanical ventilation lose the capacity to regulate their own PCO₂ . Consequently, the combination of acute metabolic and respiratory acidosis can cause a devastating reduction in pH.

The major effect of the kidney on acid-base balance is related to renal handling of sodium and chloride ions. Because dietary intake of sodium and chloride is roughly equal, the kidney excretes a net chloride load, using NH₄ ⁺ , a weak cation, to accompany chloride (electrochemically) in the urine.

In metabolic acidosis, chloride is preferentially excreted by the kidney. In metabolic alkalosis, chloride is retained, and sodium and potassium are excreted. The presence of bicarbonate in the urine reflects the needs to maintain electrical neutrality. In renal tubular acidosis, there is an inability to excrete Cl^- in proportion to Na⁺ . The diagnosis can be made by observing a hyperchloremic metabolic acidosis with inappropriately low levels of Cl^- in the urine; the urinary SID is positive. If the urinary SID is negative, the process is not renal. The other causes of hyperchloremic metabolic acidosis are gastrointestinal losses (e.g., diarrhea, small bowel or pancreatic drainage), parenteral nutrition, excessive administration of saline; and the use of carbonic anhydrase inhibitors.