Experimental pathophysiology of systemic alterations induced by Bothrops asper snake venom
Section snippets
Envenomations by Bothrops asper may involve drastic systemic alterations
Envenomations induced by bites of B. asper present a spectrum of clinical severity that ranges from mild cases, with local edema and pain as predominant manifestations, to moderate and severe cases, in which a more drastic picture of local pathological alterations is accompanied by a series of systemic deleterious effects (Bolaños, 1982, Gutiérrez, 1995, Arroyo et al., 1999, Otero et al., 2002, Warrell, 2004). The subject of local pathological effects is covered in detail in another
Systemic hemorrhage
Systemic bleeding is one of the most serious manifestations in severe envenomations by B. asper in humans (Otero et al., 2002, Warrell, 2004). Hemorrhage occurs in various organs, and is responsible for hypovolemia, hypotension, tissue hypoperfusion, cardiovascular shock and severe cerebrovascular accidents in these patients. A series of experimental studies have succeeded in the isolation of hemorrhagic components from this venom and in the elucidation of some aspects of the mechanism of
Defibrin(ogen)ation
Defribrin(ogen)ation, with the consequent alteration in laboratory assays such as whole blood clotting time, prothrombin time, and activated partial thromboplastin time, is commonly described in patients suffering an envenomation by B. asper (Peña-Chavarría et al., 1970, Barrantes et al., 1985, Arroyo et al., 1999, Otero et al., 2006). At the same time, the fibrinogen concentration is drastically reduced and fibrin(ogen)-degradation products increase, as a consequence of the activation of the
Cardiovascular alterations
Hemodynamic alterations associated with hypovolemia constitute a serious consequence of severe envenomations by B. asper, cardiovascular shock being one of the leading causes of fatality in these accidents (Gutiérrez, 1995, Otero et al., 2002, Warrell, 2004). It is likely that one of the main mechanisms that promote such cardiovascular collapse is the massive loss of blood secondary to local and systemic hemorrhage. Therefore, the toxins responsible for local and systemic vascular damage, i.e.
Renal alterations
Acute renal failure is one of the most critical complications in envenomations following B. asper bites (Gutiérrez, 1995, Otero et al., 2002, Warrell, 2004). Pathological investigations of human fatal cases revealed renal cortical necrosis, distal nephron nephrosis, thrombotic microangiopathy, and acute tubular necrosis (Mekbel and Céspedes, 1963, Vargas-Baldares, 1978). Experimental studies in mice injected with B. asper venom from adult specimens show glomerular congestion, vacuolar
Intravascular hemolysis
Intravascular hemolysis is not a common observation in human envenomations by B. asper (Gutiérrez, 1995). However, mice injected i.m. with venoms of newborn specimens of B. asper developed intravascular hemolysis associated with a significant increment of serum hemoglobin concentration and a drop in hematocrit (Chaves et al., 1992). B. asper venom does not have a direct hemolytic effect; therefore, it was proposed that such intravascular hemolysis is the consequence of the mechanical effect of
Lethality
In severe cases, the combined action of several toxins, and of endogenous deleterious mechanisms elicited by the action of venom components, may result in death. Despite lethality being the most serious consequence of snakebite envenomation, the mechanisms of lethality and the identification of toxins responsible for the death of experimental animals have not been properly identified for many snake venoms. A number of experimental studies have approached the issue of B. asper venom-induced
Concluding remarks
In contrast with the pathogenesis of local tissue damage induced by B. asper venom, which has been extensively investigated at the experimental level (see Gutiérrez et al., in this issue), many unanswered issues persist regarding the pathogenesis of systemic alterations provoked by this venom. It is clear that systemic hemorrhage and coagulopathy constitute the two most conspicuous systemic effects of these envenomations, both clinically and experimentally. P-III SVMPs, serine proteinases and a
Acknowledgements
Many of the studies reviewed in this work have been supported by Vicerrectoría de Investigación (Universidad de Costa Rica), the Wellcome Trust, NeTropica, and the International Foundation for Science (IFS).
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