Aspirin (acetylsalicylic acid) is a common over-the-counter medication, but an overdose, known as salicylate toxicity, is a significant medical emergency. The effect of salicylate poisoning on the body’s pH balance is complex. It does not cause a simple shift to one side; instead, it triggers a mixed acid-base disorder. This disorder begins with one state and progresses into a life-threatening combination of both acidosis and alkalosis. This toxic effect involves simultaneous interference with both the respiratory and metabolic systems, making it challenging to diagnose and manage.
Understanding Acid-Base Imbalance
The body maintains a tightly regulated internal environment, particularly its acidity level, measured by pH. The normal human blood pH range is very narrow, typically between 7.35 and 7.45. A pH below 7.35 indicates acidosis (too much acid), while a pH above 7.45 indicates alkalosis (too much base).
The lungs and the kidneys are the two primary organ systems that buffer and correct pH imbalance. The lungs regulate carbon dioxide (\(\text{CO}_2\)), which acts as an acid, and can quickly change the pH by altering the breathing rate. The kidneys act more slowly, regulating bicarbonate (\(\text{HCO}_3^-\)), the body’s main base buffer. Disorders are classified as respiratory if caused by \(\text{CO}_2\) or breathing, and metabolic if related to bicarbonate or other organic acids.
The Initial Effect: Respiratory Alkalosis
The initial acid-base disturbance seen in an acute salicylate overdose is typically respiratory alkalosis. Salicylates directly stimulate the respiratory center in the brainstem, causing an increase in the rate and depth of breathing (hyperventilation). This rapid breathing results in the body “blowing off” excessive amounts of carbon dioxide (\(\text{CO}_2\)).
Since \(\text{CO}_2\) acts as an acid in the bloodstream, its rapid removal causes the blood pH to rise, leading to alkalosis. This early phase is often more pronounced in adults. The body attempts to compensate by excreting bicarbonate and electrolytes in the urine. However, this compensation is quickly overwhelmed as the salicylate level in the blood continues to rise.
Progression to Severe Metabolic Acidosis
Following the initial phase, a severe metabolic acidosis develops. This is the most serious acid-base disorder caused by salicylate toxicity and occurs due to profound cellular interference. Salicylates disrupt cellular energy production by uncoupling oxidative phosphorylation in the mitochondria.
This uncoupling prevents the normal synthesis of adenosine triphosphate (ATP). The energy normally used to create ATP is instead released as heat, contributing to the fever often seen in severe toxicity. To compensate for the lack of ATP, cells switch to less efficient, anaerobic metabolic pathways.
This shift leads to a rapid accumulation of organic acids, primarily lactic acid. Salicylates also interfere with the Krebs cycle and increase fatty acid metabolism, generating ketoacids. The combination of lactic acid, ketoacids, and the salicylate anion creates a massive acid load, resulting in a high anion gap metabolic acidosis.
This influx of acid overwhelms the body’s ability to buffer it. As acidosis worsens, salicylic acid shifts into its non-ionized, lipid-soluble form. This form easily crosses cell membranes, including the blood-brain barrier, significantly increasing toxicity to the central nervous system and vital organs.
Clinical Consequences of the Mixed Disorder
The simultaneous presence of respiratory alkalosis and metabolic acidosis creates a complex mixed disorder that complicates diagnosis and treatment. The respiratory alkalosis, with its elevated pH, can initially mask the severity of the underlying metabolic acidosis. This is deceptive because the patient may appear to have a near-normal blood pH while high levels of organic acids accumulate.
Severe metabolic acidosis signals impending end-organ damage and is associated with a poor prognosis. The low pH causes toxic salicylate to move readily into the brain, leading to neurotoxicity (confusion, seizures, cerebral edema, and coma). Compensatory hyperventilation eventually fatigues the respiratory muscles, leading to respiratory failure and a fatal drop in pH.
A primary goal of treatment is correcting the acid-base imbalance by maintaining a high blood pH, typically using intravenous sodium bicarbonate. Alkalinizing the blood and urine transforms the lipid-soluble salicylic acid into its ionized, water-soluble form. This process traps the salicylate, preventing it from entering sensitive tissues like the brain and enhancing its elimination via the kidneys.