Editing Snakebite (section)

== Pathophysiology ==
Since [[envenomation]] is completely voluntary, all venomous snakes are capable of biting without injecting venom into a person. Snakes may deliver such a "[[dry bite]]" rather than waste their venom on a creature too large for them to eat, a behaviour called [[venom metering]].<ref name="Young2002">{{cite journal | vauthors = Young BA, Lee CE, Daley KM |year=2002 |title=Do Snakes Meter Venom? |journal=BioScience |volume=52 |issue=12 |pages=1121–26 |doi=10.1641/0006-3568(2002)052[1121:DSMV]2.0.CO;2 |quote=The second major assumption that underlies venom metering is the snake's ability to accurately assess the target |doi-access=free}}</ref> However, the percentage of dry bites varies among species: 80 percent of bites inflicted by [[sea snakes]], which are normally timid, do not result in envenomation,<ref name="Phillips2002" /> whereas for [[pit viper]] bites the number is closer to 25 percent.<ref name="Gold2002" /> Furthermore, some snake [[genera]], such as [[rattlesnake]]s, can internally regulate the amount of venom they inject.<ref name="Young2001">{{cite journal | vauthors = Young BA, Zahn K | title = Venom flow in rattlesnakes: mechanics and metering | journal = The Journal of Experimental Biology | volume = 204 | issue = Pt 24 | pages = 4345–4351 | date = December 2001 | pmid = 11815658 | doi = 10.1242/jeb.204.24.4345 | bibcode = 2001JExpB.204.4345Y | url = http://jeb.biologists.org/cgi/reprint/204/24/4345.pdf | url-status = live | quote = With the species and size of target held constant, the duration of venom flow, maximum venom flow rate and total venom volume were all significantly lower in predatory than in defensive strikes | archive-url = https://web.archive.org/web/20090109013518/http://jeb.biologists.org/cgi/reprint/204/24/4345.pdf | archive-date = 9 January 2009}}</ref> There is a wide variance in the composition of venoms from one species of venomous snake to another. Some venoms may have their greatest effect on a victim's respiration or circulatory system. Others may damage or destroy tissues. This variance has imparted to the venom of each species a distinct chemistry. Sometimes antivenins have to be developed for individual species. For this reason, standard therapeutic measures will not work in all cases.

Some dry bites may also be the result of imprecise timing on the snake's part, as venom may be prematurely released before the fangs have penetrated the person.<ref name="Young2002" /> Even without venom, some snakes, particularly large constrictors such as those belonging to the [[Boidae]] and [[Pythonidae]] families, can deliver damaging bites; large specimens often cause severe [[laceration]]s, or the snake itself pulls away, causing the flesh to be torn by the needle-sharp recurved teeth embedded in the person. While not as life-threatening as a bite from a venomous species, the bite can be at least temporarily debilitating and could lead to dangerous infections if improperly dealt with.{{citation needed|date=May 2021}}

While most snakes must open their mouths before biting, African and Middle Eastern snakes belonging to the family [[Atractaspididae]] can fold their fangs to the side of their head without opening their mouth and jab a person.<ref name="Deufel2003">{{cite journal | vauthors = Deufel A, Cundall D | title = Feeding in Atractaspis (Serpentes: Atractaspididae): a study in conflicting functional constraints | journal = Zoology | volume = 106 | issue = 1 | pages = 43–61 | year = 2003 | pmid = 16351890 | doi = 10.1078/0944-2006-00088 | bibcode = 2003Zool..106...43D | url = https://www.academia.edu/7083466 | access-date = 19 May 2014 | url-status = live | archive-url = https://web.archive.org/web/20160107214703/http://www.academia.edu/7083466/Feeding_in_Atractaspis_-_for_analysis | archive-date = 7 January 2016}}</ref>

=== Snake venom ===
{{Main|Snake venom|Venom-induced consumption coagulopathy}}
It has been suggested that snakes evolved the mechanisms necessary for venom formation and delivery sometime during the [[Miocene]] epoch.<ref name="Jackson2003">{{cite journal | vauthors = Jackson K |year=2003 |title=The evolution of venom-delivery systems in snakes |journal=[[Zoological Journal of the Linnean Society]] |volume=137 |issue=3 |pages=337–354 |doi=10.1046/j.1096-3642.2003.00052.x |url=http://www.kingsnake.com/aho/pdf/menu2/jackson2002.pdf |access-date=25 July 2009 |url-status=live |archive-url=https://web.archive.org/web/20121010135351/http://www.kingsnake.com/aho/pdf/menu2/jackson2002.pdf |archive-date=10 October 2012 |doi-access=free}}</ref> During the mid-[[Tertiary]], most snakes were large [[ambush predator]]s belonging to the superfamily [[Henophidia]], which use constriction to kill their prey. As open grasslands replaced forested areas in parts of the world, some snake families evolved to become smaller and thus more agile. However, subduing and killing prey became more difficult for the smaller snakes, leading to the evolution of snake venom. The most likely hypothesis holds that venom glands evolved from specialized salivary glands. The venom itself evolved through the process of natural selection; it retained and emphasized the qualities that made it useful in killing or subduing prey. Today we can find various snake species in stages of this hypothesized development. There are the highly efficient envenoming machines - like the rattlesnakes - with large capacity venom storage, hollow fangs that swing into position immediately before the snake bites, and spare fangs ready to replace those damaged or lost.<ref>{{cite book|last1=Campbell|first1=Sheldon|last2=Shaw|first2=Charles E.|title=Snakes of The American West|year=1974|page=181|publisher=[[Alfred A. Knopf]]|location=New York|isbn=978-0-394-48882-0}}</ref><ref name="Jackson2003" /> Other research on [[Toxicofera]], a hypothetical [[clade]] thought to be ancestral to most living reptiles, suggests an earlier time frame for the evolution of snake venom, possibly to the order of tens of millions of years, during the [[Late Cretaceous]].<ref name="Fry2006">{{cite journal | vauthors = Fry BG, Vidal N, Norman JA, Vonk FJ, Scheib H, Ramjan SF, Kuruppu S, Fung K, Hedges SB, Richardson MK, Hodgson WC, Ignjatovic V, Summerhayes R, Kochva E | display-authors = 6 | title = Early evolution of the venom system in lizards and snakes | journal = Nature | volume = 439 | issue = 7076 | pages = 584–588 | date = February 2006 | pmid = 16292255 | doi = 10.1038/nature04328 | url = http://www.venomdoc.com/downloads/2005_BGF_Nature_squamate_venom.pdf | access-date = 18 September 2009 | s2cid = 4386245 | bibcode = 2006Natur.439..584F | archive-url = https://web.archive.org/web/20090530032125/http://www.venomdoc.com/downloads/2005_BGF_Nature_squamate_venom.pdf | archive-date = 30 May 2009}}</ref>

Snake venom is produced in modified [[parotid gland]]s normally responsible for secreting saliva. It is stored in structures called [[wikt:alveolus|alveoli]] behind the animal's eyes and ejected voluntarily through its hollow tubular [[fangs]].{{citation needed|date=March 2023}}

Venom in many snakes, such as pit vipers, affects virtually every organ system in the human body and can be a combination of many toxins, including [[cytotoxins]], [[hemotoxins]], [[neurotoxins]], and [[myotoxin]]s, allowing for an enormous variety of symptoms.<ref name="Gold2002" /><ref name="Russell1980a">{{cite journal | vauthors = Russell FE | title = Snake venom poisoning in the United States | journal = Annual Review of Medicine | volume = 31 | pages = 247–259 | year = 1980 | pmid = 6994610 | doi = 10.1146/annurev.me.31.020180.001335 | s2cid = 1322336}}</ref> Snake venom may cause [[cytotoxicity]] as various enzymes including [[hyaluronidase]]s, [[collagenase]]s, [[proteinase]]s and [[phospholipase]]s lead to breakdown (dermonecrosis) and injury of local tissue and inflammation which leads to pain, edema and blister formation.<ref name="Seifert">{{cite journal |last1=Seifert |first1=Steven A. |last2=Armitage |first2=James O. |last3=Sanchez |first3=Elda E. |title=Snake Envenomation |journal=New England Journal of Medicine |date=6 January 2022 |volume=386 |issue=1 |pages=68–78 |doi=10.1056/NEJMra2105228|pmid=34986287 |pmc=9854269 |s2cid=245771267}}</ref> [[Metalloproteinase]]s further lead to breakdown of the extracellular matrix (releasing inflammatory mediators) and cause microvascular damage, leading to hemorrhage, skeletal muscle damage (necrosis), blistering and further dermonecrosis.<ref name="Seifert" /> The metalloproteinase release of the inflammatory mediators leads to pain, swelling, and white blood cell ([[leukocyte]]) infiltration. The lymphatic system may be damaged by the various enzymes contained in the venom leading to edema; or the lymphatic system may also allow the venom to be carried systemically.<ref name="Seifert" /> Snake venom may cause muscle damage or [[myotoxin|myotoxicity]] via the enzyme [[phospholipase A2]] which disrupts the plasma membrane of muscle cells. This damage to muscle cells may cause [[rhabdomyolysis]], respiratory muscle compromise, or both.<ref name="Seifert" /> Other enzymes such as bradykinin potentiating peptides, natriuretic peptides, [[vascular endothelial growth factor]]s, [[proteases]] can also cause [[hypotension]] or low blood pressure.<ref name="Seifert" /> Toxins in snake venom can also cause kidney damage (nephrotoxicity) via the same inflammatory cytokines. The toxins cause direct damage to the [[Glomerulus (kidney)|glomeruli]] in the kidneys as well as causing protein deposits in [[Bowman's capsule]]. Or the kidneys may be indirectly damaged by envenomation due to shock, clearance of toxic substances such as immune complexes, blood degradation products, or products of muscle breakdown (rhabdomyolysis).<ref name="Seifert" />

In [[venom-induced consumption coagulopathy]], toxins in snake venom promote hemorrhage via activation, consumption, and subsequent depletion of clotting factors in the blood.<ref name="Seifert" /> These clotting factors normally work as part of the [[coagulation cascade]] in the blood to form blood clots and prevent hemorrhage. Toxins in snake venom (especially the venom of New World pit vipers (the family [[crotalina]]))  may also cause low platelets ([[thrombocytopenia]]) or altered platelet function also leading to bleeding.<ref name="Seifert" />

Snake venom is known to cause neuromuscular paralysis, usually as a flaccid paralysis that is descending; starting at the facial muscles, causing [[Ptosis (eyelid)|ptosis]] or drooping eyelids and [[dysarthria]] or poor articulation of speech, and descending to the respiratory muscles causing respiratory compromise.<ref name="Seifert" /> The neurotoxins can either bind to and block membrane receptors at the post-synaptic neurons or they can be taken up into the pre-synaptic neuron cells and impair neurotransmitter release.<ref name="Seifert" /> Venom toxins that are taken up intra-cellularly, into the cells of the pre-synaptic neurons are much more difficult to reverse using anti-venom as they are inaccessible to the anti-venom when they are intracellular.<ref name="Seifert" />

The strength of venom differs markedly between species and even more so between families, as measured by [[median lethal dose]] (LD<sub>50</sub>) in mice. Subcutaneous LD<sub>50</sub> varies by over 140-fold within elapids and by more than 100-fold in vipers. The amount of venom produced also differs among species, with the [[Gaboon viper]] able to potentially deliver from 450 to 600 milligrams of venom in a single bite, the most of any snake.<ref name="Spawls">{{cite book |title=The Dangerous Snakes of Africa | vauthors = Spawls S, Branch B |year=1997 |publisher=Southern Book Publishers |location=Johannesburg |isbn=978-1-86812-575-3 |page=192}}</ref> [[Opisthoglyphous]] colubrids have venom ranging from life-threatening (in the case of the [[boomslang]]) to barely noticeable (as in ''[[Tantilla]]'').{{citation needed|date=May 2021}}