Pathophysiology

Sepsis is a clinical syndrome defined by bacteremia with clinical evidence of invasive, systemic infection that can progress with variable rapidity to circulatory failure. Sepsis can occur in isolation or with focal bacterial disease such as meningitis. The pathophysiology of sepsis is related to (1) colonization with a bacterial pathogen, usually nasopharyngeal, (2) invasion of the blood by encapsulated organisms and release of inflammatory mediators, and (3) host defense-response failure. This process results in systemic manifestations that are clinically detectable. Circulatory consequences may include alteration in systemic vascular tone and decreased myocardial contractility. Neurologic effects include decreased cerebral perfusion pressure and abnormal temperature homeostasis. Sepsis may also result in a microvascular angiopathy and disseminated intravascular coagulopathy involving the kidneys, lungs, skin, and central nervous system.

Host defense risk factors for sepsis include impaired splenic function (e.g., congenital absence, surgical removal, or functional impairment in sickle hemoglobinopathy) and congenital metabolic disease (e.g., galactosemia), as well as the more rare primary or acquired humoral and cellular immunodeficiency states. The presence of an indwelling foreign body or obstruction to drainage of a body cavity represents additional risk factors.

The likely pathogens for sepsis demonstrate an age-related distribution. In the first month of life, group B Streptococcus and E. coli dominate and are capable of causing an explosive sepsis syndrome that may increasingly be recognized in the ED with the trend to early newborn discharge. The risk presented by these organisms falls dramatically by the third month of life. In infancy and early childhood, HIB and N. meningitidis predominate as pathogens for sepsis, although the incidence of HIB disease has fallen markedly since the introduction of the HIB vaccine. Streptococcus pneumoniae is more likely to cause focal disease but may also result in sepsis syndrome, particularly with sickle cell disease and other causes of asplenia. In school-age children, N. meningitidis predominates as the cause of sepsis, but group A b-hemolytic Streptococcus has increasingly been implicated. Rocky Mountain spotted fever, caused by Rickettsia rickettsi. and acquired following tick bite in endemic areas of the United States, must not be overlooked as possible cause of sepsis in the summer and fall seasons.

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