How exactly do urinary tract infections (UTIs) cause delirium in my elderly patients?

 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.

 

References

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

How exactly do urinary tract infections (UTIs) cause delirium in my elderly patients?

What is the association between sepsis and jaundice in patients without biliary obstruction?

Sepsis and bacterial infection account for up to 20% of cases of jaundice in community hospitals, and may occur within a few days of onset of bacteremia or even before other clinical features of the underlying infection become apparent1.  

Although biliary obstruction is usually considered, many such patients lack extrahepatic cause for their jaundice. Gram-negative bacteria (eg, E. coli) are often the culprit with intraabdominal or urinary tract infection, pneumonia, endocarditis, and meningitis sources often cited. Hyperbilirubinemia (often 2-10 mg/dl) is commonly associated with elevated alkaline phosphatase and mild aminotransferases elevations, and usually resolves with treatment of infection1.

Although factors such as increased bilirubin load from hemolysis, hepatocellular injury, and drugs (eg, penicillins and cephalosporins) may play a role, cholestasis—likely due to cytokines such as tumor necrosis factor (TNF)α— is the predominant cause1.  Interestingly, anti-TNF-α antibodies block reduction in bile flow and bile salt excretion in laboratory animals2

 

References

  1. Chand N, Sanyal AJ. Sepsis-induced cholestasis. HEPATOLOGY 2007;45: 230-240.
  2. Whiting J, Green R, Rosenbluth A, Gollan J. Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. HEPATOLOGY 1995;22:1273-1278.
What is the association between sepsis and jaundice in patients without biliary obstruction?

Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?

Although cachexia , a loss of >5% body weight over 12 months,  has been reported in about 30% of patients with cancer, many other chronic conditions  commonly encountered in our hospitalized patients may also be a culprit.  In fact, cachexia is not infrequent in CHF (20%), COPD (20%), kidney failure (40%), or rheumatoid arthritis (10%) (1,2).  We also shouldn’t overlook HIV and tuberculosis as a cause.

Cachexia is a multifactorial disease which does not fully reverse with nutritional support.  Numerous mediators have been implicated, including cytokines such as tumor-necrosis factor-α, and interleukin [IL]-1 and -6, as well as transforming growth factors such as myostatin and activin A.  In patients with CHF, angiotensin II appears to be a key mediator, associated with insulin resistance, depletion of  ATP in skeletal muscles, poor appetite, reduction in insulin-like growth factor-1 (IGF-1), and an increase in glucocorticoid and IL-6 levels, all contributing to “cardiac cachexia” through muscle wasting, reduced food intake and lower muscle regeneration. 

Morely JE, Thomas DR, Wilson M-M G. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 2006;83:735-43.

Yoshida T, Delafontaine P. Mechanisms of cachexia in chronic disease states. Am J Med Sci 2015;35:250-256.

Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?