Clinical meaning
Acid-base homeostasis maintains arterial pH within a narrow range (7.35-7.45) through three integrated systems: chemical buffers (immediate, seconds), respiratory compensation (minutes to hours), and renal compensation (hours to days). The bicarbonate buffer system (H2CO3 ↔ H+ + HCO3-) is the most clinically important, described by the Henderson-Hasselbalch equation: pH = 6.1 + log([HCO3-] / [0.03 x PaCO2]). Normal values: pH 7.35-7.45, PaCO2 35-45 mmHg, HCO3- 22-26 mEq/L, PaO2 80-100 mmHg, SaO2 >95%, base excess -2 to +2. Primary metabolic acidosis (HCO3- <22) triggers respiratory compensation through peripheral chemoreceptor stimulation of the medullary respiratory center, increasing minute ventilation (Kussmaul breathing) to lower PaCO2. Winter's formula predicts expected PaCO2: PaCO2 = (1.5 x HCO3-) + 8 ± 2. If measured PaCO2 differs from predicted, a concurrent respiratory disorder exists. Primary respiratory acidosis (PaCO2 >45) triggers renal compensation: proximal tubular cells increase H+ secretion and HCO3- reabsorption; type A intercalated cells in collecting duct increase H+ secretion via H+-ATPase. Acute compensation: HCO3- rises 1 mEq/L per 10 mmHg PaCO2 increase. Chronic compensation (3-5 days): HCO3- rises 3.5 mEq/L per 10 mmHg PaCO2 increase. The anion gap (AG = Na+ - [Cl- + HCO3-]; normal 8-12 mEq/L, or 10-14 if K+ included) identifies the etiology of metabolic acidosis. Elevated AG (>12) indicates accumulation of unmeasured anions: MUDPILES mnemonic (Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates). Normal AG (hyperchloremic) metabolic acidosis: diarrhea, RTA, normal saline infusion, acetazolamide. The delta-delta ratio (ΔAG/ΔHCO3-) identifies concurrent metabolic disorders: ratio <1 suggests coexisting non-AG metabolic acidosis; ratio >2 suggests coexisting metabolic alkalosis. The A-a gradient (PAO2 - PaO2; normal = [Age/4] + 4) differentiates hypoxemia causes: normal A-a gradient (hypoventilation, high altitude, low FiO2) vs elevated A-a gradient (V/Q mismatch, shunt, diffusion impairment).