Bites by venomous snakes are not always accompanied by venom injection and symptoms of envenomation (so-called "dry bites"). The interval between bite and possible death can vary greatly. In general it can be said that death comes most quickly after cobra bites and most slowly after viper bites. The prognosis depends on many factors and can be strongly influenced by treatment. Inappropriate pre-hospital treatment, such as prolonged arterial tourniquet, incisions at the bite site and sustained aspiration by suction pumps, can cause major complications. Clinical effects of venomous snake bites include vomiting, pain at the bite site and anxiety. This anxiety can lead to dizziness, sweating, shortness of breath or hyperventilation (not to be confused with neurotoxicity). Further, there are a number of specific problems:

Local cytotoxicity is characterised by local swelling and blister formation. Later, necrosis can develop, which can be promoted by arterial thrombosis, inappropriate tourniquet use and local excess pressure in the tissues. A compartment syndrome is probable if the tissue pressure amounts to >30 to 40 mm Hg. This is rare. Prophylactic fasciotomy is not recommended. Local necrosis is primarily encountered with vipers, pit vipers and some elapids. Wound infections are not unusual and can aggravate local necrosis. It is possible that sucking out the wound can promote wound infections. Sometimes fangs or teeth break off and remain in the wound. The venom spreads via the lymphatics and lymphadenopathy can occur. Most tissue destruction develops in the first 3 days. Chronic ulceration, osteomyelitis or arthritis can follow a snakebite. The cytotoxic components in snake venom are responsible for most of the chronic physical handicaps which occur as sequelae.

Cardiovascular toxicity can occur with viper bites. Hypotension can result from vasodilatation, extravasation, haemorrhages and direct myocardial toxicity. Venom-induced shock leads to a combination of hypotension, lactate acidosis, haemoconcentration and hypoproteinemia. The venom of mole vipers includes so-called "sarafotoxins", peptides which strongly resemble endothelins and provoke profound vasoconstriction (including coronary arteries). On the other hand, vasodilatation can occur due to ACE inhibition. Historically, the first angiotensin-converting enzyme inhibitor was discovered in the venom of a South American venomous snake, Bothrops jararaca. The venom caused hypotension through inhibition of ACE. The responsible oligopeptide teprotide was isolated from the venom. This formed the basis for developing captopril, the prototype of a very important class of drugs (Lasker Award 1999). Since then ACE inhibitors have been discovered in the venom of numerous snake species. The effect of some components of certain snake venom is comparable to an overdose of captopril, with serious hypotension as a consequence. Taicatoxin is a component of the venom of Oxyuranus scutellatus scutellatus. It blocks calcium channels in myocytes, resulting in bradycardia and AV-block.

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Reminder: Renin is an enzyme secreted by the juxtaglomerular cells located around the afferent arterioles of the renal glomeruli. These cells are specialised myoepithelial cells which function as mini-sphygmomanometers. The lower the blood pressure, the more renin is released. Do not confuse renin with rennin (syn. chymosin, used in making cheese). Renin has a half-life of 15ī. This enzyme works on angiotensinogen, an a ₂-globulin which is produced by the liver. Renin splits angiotensinogen leaving the inactive decapeptide angiotensin I. This in turn is converted in the lung circulation by ACE into the active octapeptide angiotensin II, a very strong vasoconstrictor with a half-life of 1 minute. Angiotensin II is also locally produced in a number of tissues. Along with the vasoconstriction, angiotensin II also stimulates production of aldosterone in the zona glomerulosa of the adrenal gland. This mineralocorticosteroid promotes sodium and water retention, increasing the blood pressure. If this entire system is blocked by venom, the blood pressure falls and the patient can go into shock.

Haemostasis disturbances are primarily seen with vipers, pit vipers, Australian elepids and colubrids. The most notorious are the Russellīs viper, the Malayan pit viper and the saw-scaled viper (Echis carinatus). The haemorrhagic tendency manifests itself as minor subcutaneous haemorrhages, bleeding gums, epistaxis, haematemesis, melena and/or bleeding from venipuncture sites. Retroperitoneal bleeding can occur. Haemorrhages in the adrenal gland and pituitary gland are found with bites by the Russellīs viper. This last symptom can be compared with Sheehanīs syndrome (post-partum pituitary necrosis). An acute Addison crisis can follow, which has to be treated with steroids. Panhypopituitarism, secondary hypogonadism and diabetes insipidus can be late consequences.

Neurotoxic effects are a characteristic of elapids and sea snakes. Some Central and South American Crotalus species can also be neurotoxic. The venom of the rare "berg adder" (Bitis atropos in South Africa and Zimbabwe) is also neurotoxic, which is highly exceptional for a viper. After berg adder bites, there is initially often headache and abdominal pain, sometimes with vomiting. Paresthesiae and fasciculations can develop. Gradually ptosis develops, with vision impairment and eye muscle paralysis (ophthalmoplegia). Afterwards hoarseness, dysphagia and pharyngeal paralysis develop, producing drooling of saliva. The patient can sometimes have difficulty sticking out his or her tongue. Weakening of the neck muscles means the patient can appear to have a "broken-neck symptom". When the patient is drawn up by the hands from a supine position to 45°, the head hangs backwards if there is neck muscle paralysis. Paradoxical respiration (upon inhalation the belly expands instead of the thorax) shows that the diaphragm is still contracting although the intercostal and auxiliary respiratory muscles are paralysed. Ultimately the patient develops respiratory paralysis. Typical neurological symptoms for "berg adder" bites are ptosis, coupled with ophthalmoplegia, mydriasis as well as swallowing, taste and smell disturbances (dysphagia, ageusia and anosmia). Bitis atropos sometimes also causes an abundant secretion of antidiuretic hormone (SIADH), characterised by hyponatraemia, oliguria and concentrated urine.

Neurotoxicity must be distinguished from the symptoms caused by anxiety. Some people who believe that they have been bitten by a snake (even if this is not the case), will hyperventilate, resulting in perioral or diffuse paresthesiae or rigidity and tetany of the hands (decrease of the free plasma Ca⁺⁺-concentration due to respiratory alkalosis). Others experience dizziness or syncopal tendencies, even vasovagal syncope. A few people will become agitated, possibly with a series of bizarre complaints.

Muscle toxicity is most pronounced with sea snake bites, although it also occurs with bites by rattlesnakes, Russellīs viper and Australian snakes (primarily tiger snakes). Severe muscle pains and myoglobinuria develop. Cardiac arrhythmia can occur as a result of hyperkalaemia. This last symptom is promoted by the release of intracellular potassium with rhabdomyolysis, as well as by kidney failure. An electrocardiogram is a relatively insensitive (ą50%) method for identifying hyperkalaemia. With this condition, the T waves begin to increase when kalaemia is more than 5.5 mmol/L. The QRS complex begins to broaden from 6.5 mmol/L. The P wave flattens from a kalaemia of 7 mmol/L. The PR interval also grows longer. The P wave can disappear when the kalaemia reaches 8 mmol/L or more. Evolution to AV block, atrial arrest and ventricular fibrillation can follow.

Kidney toxicity is often multifactorial. Hypotension/shock, diffuse intravascular coagulation with intrarenal micro-thrombi, myoglobinuria and haemoglobinuria are major causes of kidney damage. Myoglobinuria as a result of rhabdomyolysis can cause acute tubular necrosis. Myoglobin is filtered through the glomeruli and is reabsorbed through the tubules, where direct damage is caused. Distal tubular obstruction can also occur. The urine is dark and will test positive for blood. Massive haemolysis causes a similar picture. Another form of kidney problem is immune complex nephritis following administration of antiserum. Russellīs vipers can provoke bilateral cortex necrosis in the kidney, with chronic renal failure as a result. Pain at the level of the costovertebral angle suggests renal damage.

Eye lesions can occur when a snake spits venom in the eyes (spitting cobras). The snake can spit its venom over distances of up to 3 metres. Burning pain, itching, oedema and eyelid spasms develop. In more than 50 % of cases there are corneal erosions, sometimes leading to blindness. After rinsing copiously with a non-irritating liquid, a local anaesthetic can be given to stop the pain and the blepharospasms. Afterwards an eye ointment containing antibiotics and steroids is applied. In case of bites by Burmese Russellīs vipers, chemosis can develop (conjunctival oedema), sometimes combined with subconjunctival haemorrhages. Due to the increased capillary permeability, periorbital oedema, facial oedema and serous effusions can also develop.

However, there are exceptions to this rule of thumb:

• e.g. Naja nigricollis (black-necked cobra):® only haemotoxic
• e.g. Crotalus durissus terrificus: ® primarily neurotoxic
• e.g. Bitis atropos ("berg adder"): à primarily neurotoxic

Note carefully: Variability within one species, e.g. Mojave rattlesnake (Crotalus scutellatus)

• Crotalus scutellatus type A venom: presynaptic neurotoxic, virtually without pain or local tissue destruction.
• Crotalus scutellatus type B venom: haemotoxic.