Mechanisms of poisoning by venomous snake bites and their treatment

There are more than 2,700 kinds of snakes in the world, and there are more than 200 kinds of snakes distributed in our country, belonging to 9 families and 62 genera, among which there are nearly 57 kinds of venomous snakes, and there are more than 10 kinds of harmful snakes, such as gold ring snakes, silver ring snakes, sea snakes, bamboo leaf green, branded iron head, vipers, five-step snakes, cobras, king cobras, pit vipers, etc. Every year, more than 300,000 people are bitten by venomous snakes. The number of people bitten by venomous snakes is more than 300,000 per year worldwide, with a mortality rate of about 10%. People who have more chances of being bitten by venomous snakes are farmers, field workers and staff engaged in venomous snake breeding. Understanding the poisoning mechanism and clinical characteristics of snakebite is of great clinical significance to improve the level of treatment of snakebite and reduce the mortality rate of snakebite. The venom secreted by the venomous glands in the head of viper is called venom. The toxic components of snake venom are mainly peptides and proteins with enzymatic activity. Snake venom can have a wide range of effects on the body’s nervous system, blood system, muscle tissue, circulatory system, urinary system, endocrine system, digestive system and other organs. After absorption, snake venom is distributed to all tissues of the body, with the kidneys being the most abundant and the brain the least. Snake venom is mainly decomposed in the liver and excreted by the kidneys, and the amount of snake venom in the body after 72 hours has been minimal. According to the different toxicological effects of snake venom, our country for decades is still generally divided into neurotoxicity, blood circulation venom, mixed venom three categories are not conducive to clinical diagnosis and treatment. According to the initiative of the International Society of Toxins and the research results of scholars from various countries, the toxins that are more certain, can be separated, know the molecular weight and structure, the poisoning mechanism is clear and closely related to the clinical toxins are neurotoxins (neurotoxin), blood toxins (blood toxin) and cytotoxins (cytotoxin) and so on several categories. 1, neurotoxin mechanism of action neurotoxin is mainly β neurotoxin (β-neurotoxin, β-NT) and α neurotoxin (α-neurotoxin, α-NT), respectively, the role of synapses and end plates, β-NT inhibits the release of acetylcholine, α-NT competition for cholinergic receptors, can be blocked by the normal conduction of the nerve caused by the neuromuscular bradyarrhythmia. Early clinical manifestations are drooping eyelids, dysphagia, followed by respiratory muscle paralysis causing respiratory failure and even respiratory arrest. Silver ring snake toxin is the most typical neurotoxin. 2, blood toxin mechanism of action There are many types of blood toxins, respectively, in various parts of the blood system. Snake venom protease acts directly and indirectly on the blood vessel wall, destroying the relevant structure of the wall, inducing the release of bradykinin, histamine, 5-hydroxytryptamine, damaging the capillary endothelial cells, inhibiting platelet aggregation, which can cause bleeding. Snake venom direct hemolytic factor acts on the blood cell membrane to increase its permeability and fragility. Phospholipase A can hydrolyze lecithin in blood and become hemolytic lecithin, producing hemolytic effect. Snake venom procoagulant factors (e.g., factor X and V activators of viper subfamily venom) cause blood clots and microcirculatory thrombosis, resulting in disseminated intravascular coagulation (DIC). The thrombin-like enzyme in the venom of viper subfamily can promote the generation of fibrin monomers as well as activate the fibrinolytic system, so it has a dual role (low-dose procoagulant and high-dose anticoagulant); under the joint action of the venom’s fibrinolytic enzyme to cause defibrinogeny, also called DIC-like, some domestic scholars disagree with this call, that is DIC, in fact, it is in the molecular hematology of the two are very big difference. the difference between the two is very large. the DIC or DIC-like The common clinical manifestation of DIC is hemorrhage, light subcutaneous hemorrhage, epistaxis, gingival hemorrhage, and in severe cases, it can cause blood loss, wound bleeding, hematuria, gastrointestinal bleeding, and even cerebral hemorrhage, etc. DIC is often accompanied by shock, microcirculatory disorders, circulatory failure and acute renal failure, etc. The mechanism of cytotoxic action of cytotoxicity is as follows: DIC is a kind of cytotoxic disease. 3, cytotoxic mechanism of action of snake venom hyaluronidase to make the wound local tissue hyaluronic acid depolymerization, intercellular plasmolysis and tissue permeability increase, in addition to causing local swelling, pain and other symptoms, snake venom toxin can be more easily absorbed by the lymphatic vessels and capillaries into the blood circulation, resulting in systemic symptoms of poisoning. Snake venom protein hydrolase can damage blood vessels and tissues, while releasing histamine, 5-hydroxytryptamine, adrenaline and other vasoactive substances. Cardiac toxins (or membrane toxins, muscle toxins, cobra amines, etc.) cause cell destruction, tissue necrosis, mildly can cause local swelling skin necrosis, severe local necrosis of a large area, deep into the musculoskeletal membrane, limb crippled, but also directly cause myocardial damage, and even myocardial cell degeneration and necrosis. 4, other mechanisms snake venom as a heterogeneous heterogeneous protein into the human body can cause allergic reactions. Viruses, bacteria and other pathogenic microorganisms can enter the body through fangs and wounds causing infection, aggravating local swelling and systemic symptoms. Under the action of many kinds of snake toxins, immune cells release inflammatory mediators to cause systemic inflammatory response syndrome (SIRS), or even multiple organ dysfunction syndrome (MODS). Clinical manifestations of venomous snake bite Clinical manifestations include local manifestations of wound and systemic poisoning symptoms, the severity of poisoning symptoms is closely related to the species of venomous snake, the amount of venom discharge, virulence, venom absorption, the location of the bite, the pathway of poisoning, and the time of consultation. 1.Localized manifestations Viper bites can be seen locally in the form of two large “…” Shaped fang bite marks (larger than the general non-venomous fang marks); there are also “::” shaped, in addition to the fang marks, there are also traces of paratoxic fangs, the latter shows that the snake bite is deeper. The larger the snake, the wider the distance between the fangs. And there are two rows of neat depth consistent fang marks are mostly non-venomous snake bites. Neurotoxic local symptoms are not obvious, no redness, swelling and pain or at first there is a slight pain and swelling, numbness occurs soon, tooth marks are small and do not ooze. Blood venom local swelling and pain, mild blood from the teeth marks or wounds out of difficult to coagulate, serious cases can cause wounds bleed more than. Cytotoxic effect of local manifestations of severe pain, redness, swelling, blisters, necrosis and ulceration. 2, the performance of neurotoxin poisoning limb weakness, dysphagia, slurred speech, diplopia, eyelid ptosis, shallow and slow respiration, sense of suffocation, pupil light reflex and set reflex disappeared, coma, respiratory paralysis, spontaneous respiratory arrest, cardiac arrest. It is seen in venomous snake bites such as silver-ringed snake, golden-ringed snake and so on. Hematotoxic poisoning performance Subcutaneous hemorrhagic purpura, epistaxis, bleeding gums, and even large subcutaneous hemorrhagic bruises. Hematuria, tarry stools, even cerebral hemorrhage. When combined with DIC, in addition to systemic bleeding, cold skin, thirst, rapid pulse, decreased blood pressure, shock, jaundice in intravascular hemolysis, soy sauce-like urine, and acute renal failure in severe cases. Coagulation function test is a reliable index of hematotoxic poisoning, DIC-like syndrome may appear prolonged coagulation time, prolonged APTT, PTT, TT, reduced Fg, positive “3 P” test and FDP, reduced α2-PI activity, but AT-III activity and platelet decline is not obvious, the decline is obvious and D-dimer is positive when DIC. The DIC-like syndrome can be seen in bites of bamboo leaf green, branded iron head, five-step snake, and red-necked swimming snake. Viper and pit viper bites are often combined with DIC, or even MODS. 4, cytotoxic poisoning manifestations Localized swelling can extend to the affected limbs and even trunk, necrosis and ulceration can make the affected limbs crippled; generalized pain and SIRS, myocardial damage and cardiac insufficiency, such as cobra bites. Rhabdomyolysis can be combined with myoglobinuria and renal insufficiency, such as sea snake bite. 5.Mixed toxin poisoning manifestations such as king cobra bites with neurotoxin poisoning manifestations, accompanied by cytotoxic poisoning manifestations; five-step snake bites with blood toxin and cytotoxin poisoning manifestations; pit viper, sea snake bites that are neurotoxin and blood toxin poisoning manifestations. Third, the diagnosis of venomous snake bite has been recognized as a snake bite or has captured the bite of the snake, snake bite diagnosis is not difficult. However, most of the snakebite victims can not see the appearance of the snake, it is difficult to accurately determine what kind of snakebite. Immunological methods such as enzyme-linked immunosorbent assay (ELISA) can be used to determine specific snake venom antigens in wound exudate, serum, cerebrospinal fluid, and other body fluids to assist in the diagnosis, but they are not commonly used in clinical practice. Clinically, identification of venomous and non-venomous snake bites is mainly based on tooth marks, wound condition, and systemic symptoms. In addition, venomous snake bites need to be differentiated from centipede bites and bee stings. In order to assess the condition of venomous snake bites and guide treatment, venomous snake bites should be correctly diagnosed according to the clinical characteristics triggered by the toxins contained in various venomous snakes, such as the local condition of the wounds, neurotoxic symptoms, hematotoxic symptoms, and cytotoxic symptoms, and to determine the mild, severe (dysfunctional stage), and critical (functional failure stage) types. IV. Treatment of venomous snake bites Snake bites, such as those who cannot definitively exclude venomous snake bites, should be observed and treated as venomous snake bites. After being bitten by a venomous snake, on-site first aid is very important. Various measures should be taken to rapidly discharge the snake venom and prevent the absorption and spread of the venom. After arriving at the hospital, comprehensive measures should continue to be taken for treatment. V. Treatment principles Immediately exclude and destroy the local venom in the wound, discharge the absorbed toxin, use antivenom as soon as possible after clarifying the species of poisonous snake, and treat various comorbidities.