Biology of Disease

hypoglycemia and the catabolism of lipids producing ketone bodies

(Chapter 7). Salicylate also inhibits enzymes of the TCA cycle, leading to an

accumulation of oxoglutarate and oxaloacetate, and of amino acid metabolism,

causing an increase in amino acids that accentuates the metabolic acidosis.

Fluid and electrolyte losses are increased by the nausea and vomiting.

Toxic dose

Common therapeutic levels of salicylate are 50 mg dm–3 although they can

be as high as 250 mg dm–3 in the serum of patients with rheumatoid arthritis

(Chapter 5). The potentially lethal dose of aspirin in adults is 24 to 30 g but

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Figure 12.10 An overview of the toxic effects of

aspirin.See text for details.

Dehydration

Increased

water loss

Overdose of aspirin

Overdose of aspirin

[Salicylate]

increases in the brain

Stimulates the

respiratory center

Hyperventilation

IncreasedPCO 2

Renal compensation, that

is the excretion of HCO 3 -

and retention of H+

Inhibition of amino

acid metabolism

Inhibition of TCA

cycle enzymes

Increased

peripheral

glucose demand

Uncoupling of oxidative

phosphorylation

Decreased ATP

Respiratory alkalosis

Stimulation of

lipid metabolism

Increased glycolysis

Increased lactate

Increased pyruvate

Increased

ketone

bodies

Increased

amino acids

Metabolic acidosis

Increased

A oxoglutarate

oxaloacetate

Vomiting

and fever

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