amino acid metabolism Inhibition of Krebs cycle enzymes and uncoupling of oxidative phosphorylation in conjunction with lipid disturbances create the combined lactic and ketoacidosis responsible for metabolic acidosis (which leads to the mixed respiratory alkalosis and metabolic acidosis found on the arterial blood gas) Volume losses caused by vomiting, tachypnea, and diaphoresis can lead to significant volume depletion In addition to inhibiting platelet function, aspirin intoxication is associated with disturbances in vitamin K–dependent and vitamin K–independent clotting factors, resulting in a significant coagulopathy Mild elevations in liver enzymes are also common Other features of aspirin intoxication include leukocytosis and electrolyte disturbances, particularly hypokalemia Clinical Considerations Physical manifestations of salicylism include fever, tachypnea, nausea, vomiting, lethargy, slurred speech, and seizures Children with chronic salicylism are more likely to present with severe metabolic acidosis and seizures than those with acute intoxication The combination of respiratory alkalosis with metabolic acidosis produces an arterial blood gas that is almost pathognomonic for salicylism Serum pH typically ranges from 7.41 to 7.55, except in severe cases in which metabolic acidosis combined with respiratory acidosis from severe CNS depression leads to pH less than 7.35, and PCO is generally less than 30 mm Hg Serum bicarbonate is mildly depressed, often ranging from 15 to 20 mEq/L Although adults may continue to hyperventilate for extended periods when poisoned with salicylates, children with mild to moderate poisoning quickly lose this respiratory drive and are more likely to present with metabolic and respiratory acidosis Glucose homeostasis is seriously altered in acute aspirin poisoning Early in the course, hyperglycemia usually occurs because of glycogenolysis and decreased peripheral use Later, hypoglycemia may supervene as glucose stores are depleted High rates of oxidative metabolism in the CNS may lead to low CNS glucose concentration even in the presence of peripheral hyperglycemia Fluid and electrolyte disturbances are multifactorial, resulting in dehydration, hyponatremia or hypernatremia, and hypokalemia Among contributing factors are increased insensible water losses through both skin and lungs, emesis, and increased renal water and potassium loss The patient with severe salicylate poisoning may lose to L of water per square meter The initial clinical signs and symptoms, the estimate of dose ingested, and the measurement of salicylate levels all serve to gauge the severity of a given acute