Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease that occurs over wide areas of Europe and Asia. Hantaviruses are the cause of this syndrome. The hallmark of HFRS is the triad of fever, hemorrhage, and renal failure. In its severe form it is associated with significant mortality. The syndrome evolves through five phases: febrile, hypotensive, oliguric, diuretic, and convalescent. The central physiologic derangement in HFRS is vascular dysfunction, manifested by impaired vascular tone and increased vascular permeability. The systemic effects of this dysfunction account for the occurrence of hypotension and shock, while local effects are probably important in the development of renal failure. Shock in HFRS has distributive and oligemic features, while renal failure has features of acute tubular necrosis. Hemorrhage is a consequence of vascular injury and a deficit of functional platelets. Vascular and platelet dysfunction are both compounded by uremia. Disseminated intravascular coagulation contributes to hemorrhage in some patients. Although hantaviruses are infectious for endothelial cells and may cause direct injury, a large body of evidence suggests that immune mechanisms play an important role in the pathogenesis of HFRS.