Sepsis pathophysiology

Gelfand, J.A., Shapiro, L. Cytokines and sepsis pathophysiology and therapy. New Horizons 1... 

Discuss the pathophysiology of sepsis as it relates to endotoxin, peptidoglycan, and pro-and anti-inflammatory mediators. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

Fong, Y., and Lowry, S. F. (1990). Tumor necrosis factor in the pathophysiology of infection and sepsis. Clin. Immunol. Immunopathol. 55, 157-170. 

Loppnow, H., Flad, H.-D., Rietschel, E.Th., Brade, H. The active principle of bacterial lipopolysac-charides (endotoxins) for cytokine induction. In Schlag, G., Redl, H.(eds), Pathophysiology of Shock, Sepsis, and Organ. Springer-Verlag, Heidelberg (1993), pp. 405-416. 

Furthermore, tolerance to the vasodilatory effects of dopamine after 24 to 48 hours is evident in nonohguric patients with sepsis syndrome and has been reported in others. The lack of response to dopamine in septic shock patients on vasopressors and the tolerance that develops in responders to low-dose dopamine may be explained in part by time- and disease-dependent desensitization of the dopamine receptors this may not occur in those with sepsis syndrome or normal volunteers. Furthermore, differences in the extent of preexisting vasodilation and the pathophysiology of renal dysfunction in oliguric and septic shock patients also may contribute to the inconsistent responses seen to the administration of low doses of dopamine. 

Sepsis represents a complex pathophysiology characterized by the activation of multiple overlapping and interacting cascades leading to systemic inflammation, a procoagulant state, and decreased fibrinolysis. 

Sepsis represents a significant burden to the national health care system. In 2000, sepsis affected approximately 660,000 people, an increase of 8.7% per year since 1979. Over half the patients were admitted to the intensive care unit (ICU) with a mean length of stay of 15.7 days. The total number of deaths increased from 21.9 per 100,000 population in 1979 to 43.9 per 100,000 populations in 2000. With the annual cost of approximately 16.7 billion, there remains a vital need for clinicians to comprehend the pathophysiology and to appreciate the management options available for acutely ill patients with sepsis or septic shock. ... 

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