UTIs are often considered in the differential diagnosis of causes of delirium in the elderly. Though largely speculative, 2 possible pathophysiologic basis for this association are suggested: 1. Direct brain insult (eg, in the setting of sepsis/hypotension); and 2. Indirect aberrant stress response, involving the hypothalamic-pituitary-adrenal [HPA] axis, sympathetic nervous system (SNS) and/or inflammatory pathways1-3.
One or both pathways can interact with the neurotransmitter and intracellular signal transduction systems underlying delirium in the brain, which may already be impaired in the elderly due to age-related or other pathologic changes. The indirect aberrant stress pathway suggests that not only can UTI-associated circulating cytokines cause delirium but pain and discomfort (eg, from dysuria) may also contribute via the HPA axis and SNS. If true, this explanation makes it unlikely for bacteriuria or pyuria to be associated with delirium in the absence of significant systemic inflammatory response or pain and discomfort.
1.Trzepacz P, van der Mast R. The neuropathophysiology of delirium. In Lindesay J, Rockwood K, Macdonald A (Eds.). Delirium in old age, pp. 51–90. Oxford University Press, Oxford , 2002.
2.Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999; 54: B239–B246
3. Maclullich AM, Ferguson KJ, Miller T, de Rooij SE, Cunningham C. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008;65:229–38.
Contributed by Henrietta Afari MD, Mass General Hospital, Boston, MA