Blood pH is maintained between 7.35–7.45 by three mechanisms: buffering by bicarbonate and phosphate, respiratory regulation of CO₂ elimination, and renal regulation of HCO₃⁻ reabsorption and H⁺ excretion. Respiratory compensation occurs within minutes; renal compensation takes hours to days. Primary acid-base disorders are metabolic (altered HCO₃⁻) or respiratory (altered pCO₂), with compensatory responses that are predictable and measurable.
Use the Henderson-Hasselbalch equation to relate pH, pCO₂, and HCO₃⁻. Analyze primary disorders by identifying which variable changed first, then determine if appropriate compensation has occurred.
From your acid-base chemistry prerequisites, you know that pH reflects proton concentration and that buffer systems resist pH change. The body runs on enzymes and ion channels with very narrow pH tolerances — a shift of just 0.1 units outside the 7.35–7.45 window alters protein shape and impairs function. The challenge is that metabolism constantly produces acid: CO₂ from aerobic respiration and various organic acids from intermediary metabolism. Your body's response is a three-layer defense that operates at different timescales.
The first layer is buffering, which acts within seconds. The bicarbonate buffer system (H₂CO₃ ⇌ H⁺ + HCO₃⁻) is the dominant extracellular buffer. The Henderson-Hasselbalch equation — pH = 6.1 + log([HCO₃⁻] / [0.03 × pCO₂]) — shows that pH is governed by the ratio of bicarbonate to dissolved CO₂. This equation reveals something powerful: the body doesn't need to hold either value constant, only their ratio. This sets up the second and third defense layers.
The respiratory system controls pCO₂ within minutes. If blood becomes too acidic (low pH), the respiratory centers in the brainstem drive faster and deeper breathing, exhaling more CO₂ and shifting the equation to raise pH. If blood becomes too alkalotic, breathing slows, CO₂ accumulates, and pH falls back toward normal. The kidneys control HCO₃⁻ over hours to days, reabsorbing bicarbonate or excreting H⁺ (as ammonium or titratable acid) to restore the ratio from the other direction.
Primary acid-base disorders arise when one of these variables goes wrong first. Metabolic acidosis (low HCO₃⁻) drives compensatory hyperventilation — the lungs blow off CO₂ to restore the ratio. Respiratory acidosis (high pCO₂ from hypoventilation) drives the kidneys to retain more HCO₃⁻. The compensations are predictable and calculable, so when you see an ABG with pH, pCO₂, and HCO₃⁻, you can determine whether the compensation is appropriate (suggesting a simple disorder) or insufficient (suggesting a mixed disorder with two simultaneous primary problems). This diagnostic logic — identify the primary disturbance, predict the expected compensation, compare to the measured value — is the clinical skill this topic builds toward.