Monday, August 6, 2007
Pathophysiology of Snake Venom
Snake venoms are complex substances, chiefly proteins, with enzymatic activity. Although enzymes play an important role, lethal properties of venom can be due to certain smaller polypeptides. Most venom components appear to bind to multiple physiologic receptors, and attempts to classify venom as toxic to a specific system (eg, neurotoxin, hemotoxin, cardiotoxin, myotoxin) are misleading and can lead to errors in clinical judgment.
The venom of most North American pit vipers produces local effects and coagulopathy and other systemic effects. Results may include local tissue damage; vascular defects; hemolysis; a disseminated intravascular coagulation (DIC)–like (defibrination) syndrome; and pulmonary, cardiac, renal, and neurologic defects. Venom alters capillary membrane permeability, causing extravasation of electrolytes, albumin, and RBCs through vessel walls into the envenomated site. This process may occur in the lungs, myocardium, kidneys, peritoneum, and, rarely, the CNS. Initially, edema, hypoalbuminemia, and hemoconcentration occur. Later, blood and fluids pool in the microcirculation, causing hypotension, lactic acidemia, shock, and, in severe cases, multisystem organ failure. Effective circulating blood volume falls and may contribute to cardiac and renal failure. Clinically significant thrombocytopenia (platelet count < 20,000/μL) is common in severe rattlesnake bites and may occur alone or in combination with other coagulopathies. Venom-induced intravascular clotting may trigger defibrination syndrome, resulting in epistaxis, gingival bleeding, hematemesis, hematuria, internal hemorrhage, as well as spontaneous bleeding at the bite site and venipuncture sites. Renal failure may result from severe hypotension, hemolysis, rhabdomyolysis, nephrotoxic venom effects, or a DIC-like syndrome. Proteinuria, hemoglobinuria, and myoglobinuria may occur in severe rattlesnake bites. The venom of most North American pit vipers produces very minor changes in neuromuscular conduction, except for Mojave and Eastern diamondback rattlesnake venom, which may cause serious neurologic deficits.
Coral snake venom contains primarily neurotoxic components, which result in a presynaptic neuromuscular blockade, potentially causing respiratory paralysis. The lack of significant proteolytic enzyme activity accounts for the paucity of symptoms and signs at the bite site.