Pathophysiology & Complications of Snake Bite

Prepared by: Arma

Neurotoxin
Neurotoxins play a key role in immobilizing prey through paralysis, disorientation and depressed respiration.
Venoms often contain different neurotoxins that work synergistically to cripple the nervous system. Neurotoxins can be classified according to their site of action: pre-synaptic neurotoxins block neurotransmission by affecting acetylcholine transmitter release; post-synaptic neurotoxins are antagonists of the acetylcholine receptor. Together these neurotoxins effectively block skeletal neuromuscular transmission by crippling receptors, while at the same time acting to destroy any neurotransmitter that might compete with the toxin for receptor binding. Venoms often contain several post-synaptic neurotoxins, each with a high affinity for a nicotinic receptor subtype - in this way the venom can cripple as many receptors as possible. The post-synaptic neurotoxins are found only in elapids and sea snakes (Hydrophiidae). In the many-banded krait, a pre-synaptic toxin is -bungarotoxin, while post-synaptic toxins are  and -bungarotoxins.

There are two types of acetylcholine receptors (AchR): muscarinic-type, which are primarily neuronal, and nicotinic-type, which are either neuronal or muscle-type. The venom from the many-banded krait (Bungarus multicinctus) contains toxins that can bind to each type of receptor: the -bungarotoxins act primarily on nicotinic AchRs at the neuromuscular junction, the -bungarotoxins act primarily on nicotinic AchRs in neuronal tissue, and there are also muscarinic AchR-binding toxins. These toxins show almost irreversible binding to the receptors, competitively inhibiting acetylcholine binding and, consequently, inhibiting the acetylcholine-induced electrical response.

b-Bungarotoxin is much more lethal than either a- or k-bungarotoxin. b-Bungarotoxin is a pre-synaptic toxin that acts on the (pre-synaptic) motor nerve terminals to block the release of acetylcholine. The action of b-bungarotoxin is complex. It has phospholipase A2 activity, which functions to hydrolyse phosphatidylcholine, in this case the phospholipids in the nerve membrane. Yet b-bungarotoxin displays both phospholipase-dependent and –independent activities. b-Bungarotoxin is thought to bind to and block Shaker-type potassium channels; the subsequent block of transmitter release is probably due to phospholipase A2-mediated destruction of the nerve terminal. Animals die as a consequence of respiratory failure.

Acetylcolinesterase (AchE) plays a key role in cholinergic nerve transmission, acting to breakdown acetylcholine to choline and acetate, which is important in controlling a receptor’s response. Snake venom makes use of AChE to breakdown any neurotransmitter that might compete with a- or k-bungarotoxin for binding to AchRs. Venom AChE contains an additional exon over endogenous AChE, which generates a soluble form of the enzyme that is suitable for its venomous use.

Neurotixin can cause:
- Neurotoxic paralysis may also begin within the first hour of snake bites and is seen first as ptosis, then blurred vision and diplopia, followed by facial weakness and dysarthria. In severe cases, weakness of the limbs, paralysis of respiration, and fixed and dilated pupils may be observed.
- Ptosis which is also called "drooping eyelid." It is caused by the damage of nerves that control the muscle responsible for raising the eyelid.
- Circumoral parethesia- An abnormal touch sensation, such as burning or prickling, often in the absence of an external stimulus. A sagging or prolapse of an organ or part, paralysis of the oculomotor nerve.
- Muscle paralysis by blocking the nicotinic acetylcholine receptors at the post-synaptic motor endplates, or they affect the mode of neurotransmitter release at the presynaptic motor nerve endings.
- The most common eye symptom - ophthalmoplegia, paresis of the right medial rectus muscle; incomplete motion of each eye on upward, downward and inwardgaze, due to dysfunctions of oblique muscles, which is considered as a rare complication.
-Restriction in mouth opening- indicate trismus (sea snake envenoming) or more often paralysis of pterygoid muscles
-Respiratory paralysis occurs when the muscles associated with breathing become do weak to function properly. Breathing becomes difficult and severe cases can result in death if breathing assistance is not delivered

Myolisis
It is generally systemic rather than local. Systemic myolisis may take several hours, occasionally more than 24 hours, to become clinically apparent. Features include muscle pain, tenderness and weakness, elevated plasma creatine kinase, which may be grossly elevated and myoglobinuria.

Cardiac toxicity
Viper’s venom can cause cardiac dysrhythmias or arrest in envenomed patient. This effect is not common. It is more commonly as a secondary effect of other processes such as hyperkalemia secondary effect to severe myolisis.

Local tissue injury
It is variable in extent and presentation. Local pain may be severe, and often is associated with moderate to marked swelling that may ultimately involve in the entire bitten limb. Local oozing, bleeding, blistering and discolouration may occur. The extent of necrosis varies from none, to superficial skin loss in the bite area, to widespread skin loss. The development of necrosis often occurs over days. One of the biggest hazards from the tissue injury is hypovolemic shock secondary to massive fluid shifts, particularly apparent in younger children in whom this complication can prove rapid lethal.

References:
http://www.ebi.ac.uk/interpro/potm/2004_6/Page1.htm
http://www.nlm.nih.gov/medlineplus/ency/article/001018.htm
http://www2.merriam-webster.com/cgi-bin/mwmednlm
http://www.health-glossary.com/1001-circumoral-paresthesia.html
http://jkms.org/Synapse/Data/PDFData/0063JKMS/jkms-19-631.pdf

http://books.google.com.my/books?id=BfdighlyGiwC&pg=PA1579&lpg=PA1579&dq=respiratory+paralysis+and+snake+venom&source=bl&ots=Krc8xQp5_d&sig=w5r4uONEpuMFHIXbVM8nVbZP7pc&hl=en&ei=5A9vSpqmB9K9kAWA_8HBBQ&sa=X&oi=book_result&ct=result&resnum=6
http://priory.com/med/ophitoxaemia.htm#LOCAL%20MANIFESTATIONS
http://www.wrongdiagnosis.com/r/respiratory_paralysis/intro.htm