Aspirin (acetylsalicylic acid) is rapidly hydrolyzed to salicylic acid, which at toxic doses (> 150 mg/kg acute ingestion or levels > 30 mg/dL) produces a characteristic biphasic acid-base disturbance. Initially, salicylate directly stimulates the medullary respiratory center, causing central hyperventilation and primary respiratory alkalosis. As toxicity progresses, salicylate uncouples oxidative phosphorylation in mitochondria, disrupting ATP production and shifting cellular metabolism to anaerobic glycolysis. This generates lactic acid, ketoacids, and organic acids, producing a superimposed anion-gap metabolic acidosis (mixed respiratory alkalosis + metabolic acidosis). Critically, salicylic acid exists in equilibrium between ionized (charged, cannot cross membranes) and non-ionized (uncharged, freely crosses blood-brain barrier and cell membranes) forms. Acidemia shifts the equilibrium toward the non-ionized form, dramatically increasing CNS penetration and cellular toxicity — this is why even small decreases in blood pH markedly worsen salicylate poisoning. Salicylate also directly inhibits Krebs cycle enzymes, stimulates lipid metabolism (ketogenesis), causes pulmonary capillary leak (noncardiogenic pulmonary edema), depletes hepatic glycogen, and disrupts platelet function. Chronic salicylism is more dangerous than acute overdose because steady-state tissue saturation occurs at lower serum levels.