The Henderson-Hasselbalch (H-H) equation, known to virtually everyone who has studied basic physiology, tells us that pH in extracellular fluids is regulated by the relationship between the presence of carbon dioxide, PCO₂, regulated by breathing, and bicarbonate concentration, [HCO₃^‾], regulated by the kidneys:

pH = [HCO₃^‾] ÷ PCO₂, (or pH = bicarbonates ÷ carbon dioxide)

Changes in the numerator of the equation, bicarbonate levels, are generally slow (8 hours to 5 days), whereas changes in the denominator, carbon dioxide, are immediate. This places breathing center stage in moment-to-moment acid-base regulation.   In the case of blood plasma, a PaCO₂ of about 40 mmHg results in a pH of about 7.4. The normal range of plasma pH is 7.35 to 7.45.   Ventilating off too much CO₂ by breathing too deeply, or rapidly, or both, constitutes overbreathing behavior, which lowers PCO₂ below 40 mmHg and raises the pH above 7.4, making plasma (and other extracellular fluids) too alkaline. PCO₂ levels below 35 mmHg constitute hypocapnia, which may lead to pH levels above 7.45 (alkalemia). PCO₂ levels above 45 mmHg as a result of underbreathing behavior constitute hypercapnia, and may lead to pH levels below 7.35 (acidemia). Click here to learn about measurement of gases.

Acid-base balance is about the regulation of hydrogen ion concentration, written [H⁺], in body fluids (50% of body weight). These fluids are both intracellular (fluids within cells, 32% body weight) and extracellular (fluids outside cells, 18% body weight).   Extracellular fluids include blood plasma, cerebrospinal fluid, lymph fluid, and interstitial fluid (fluid immediately surrounding cells). Maintaining correct levels of [H⁺], also known as pH, is absolutely critical to healthy physiology, healthy psychology, and optimal performance.   Because pH, mathematically speaking, is the negative logarithm of [H⁺], as pH rises [H⁺] decreases, and as pH drops [H⁺] increases. Click here to learn about the definition of pH.

Hydrogen ions are generated by the body as a result of metabolism. Most of these ions are “utilized,” which means that once they are produced, they are “used up” in either the synthesis of other body substances, like glucose, or they are oxidized, converted into CO₂ and H₂O. Before hydrogen ions are utilized, or before they are excreted as in the case of protein metabolism, they are “buffered” (neutralized) by bicarbonates (HCO₃^‾). Thus, pH level is maintained and metabolic acidosis (lower pH) is prevented. Examples of metabolic acids include lactic acid, generated in its largest quantities during anaerobic metabolism, and ketoacids, generated as a result of fat metabolism. The hydrogen ions of these acids are continuously utilized, and thus the bicarbonates used to buffer them, are also continuously restored.

Click here to learn about basic chemistry.

Click here to learn about bicarbonate regulation (numerator of H-H equation).

Click here to learn about compensatory breathing (denominator of H-H equation).