Pathophysiology
Clinical meaning
Delirium is an acute, fluctuating disturbance in attention and cognition caused by an underlying medical condition. The pathophysiology involves a complex interplay of neurotransmitter dysfunction: acetylcholine deficiency (the primary neurotransmitter implicated, explaining why anticholinergic medications are a major risk factor), dopamine excess (explaining the efficacy of low-dose antipsychotics), serotonin and GABA imbalance, and neuroinflammation (elevated IL-6, IL-8, TNF-alpha). The cholinergic deficit theory explains why elderly patients (who have age-related cholinergic decline) are most susceptible. Precipitating factors such as infection, metabolic disturbance, medications, or surgery act on a vulnerable brain (reduced cognitive reserve from aging, dementia, or neurodegeneration). Delirium is classified as hyperactive (agitation, hallucinations), hypoactive (lethargy, withdrawal, reduced responsiveness - often missed), or mixed (fluctuating between both). Hypoactive delirium has the worst prognosis because it is frequently unrecognized.