Editing Carpal tunnel syndrome (section)

== Pathophysiology ==
[[File:Carpal-Tunnel.svg|thumb|right|Transverse section at the wrist. The [[median nerve]] is colored yellow. The carpal tunnel consists of the bones and [[Flexor retinaculum of the hand|transverse carpal ligament]].]]{{See also|Pathophysiology of nerve entrapment}}
The carpal tunnel is formed by the carpal bones and the transverse carpal ligament. The median nerve passes through this space along with the flexor [[tendon]]s. Increased compartmental pressure for any reason can squeeze the median nerve.<ref name=":8">{{cite journal |vauthors=Joshi A, Patel K, Mohamed A, Oak S, Zhang MH, Hsiung H, Zhang A, Patel UK |date=July 2022 |title=Carpal Tunnel Syndrome: Pathophysiology and Comprehensive Guidelines for Clinical Evaluation and Treatment |url= |journal=Cureus |volume=14 |issue=7 |pages=e27053 |doi=10.7759/cureus.27053 |doi-access=free |pmc=9389835 |pmid=36000134}}</ref> Theoretically, increased pressure can interfere with normal intraneural blood flow, eventually causing a cascade of physiological changes in the nerve itself.<ref name=":10">{{cite journal |vauthors=Mackinnon SE |date=May 2002 |title=Pathophysiology of nerve compression |url= |journal=Hand Clin |volume=18 |issue=2 |pages=231–41 |doi=10.1016/s0749-0712(01)00012-9 |pmid=12371026}}</ref> There is a dose-respondent curve such that greater and longer periods of pressure are associated with greater nerve dysfunction.<ref name=":10" /> The symptoms and signs of carpal tunnel syndrome causes are hypertrophy of the [[Synovial membrane|synovial tissue]] surrounding the flexor tendons such as with rheumatoid arthritis.<ref name=":8" /><ref name=":11">{{cite journal |vauthors=Aboonq MS |date=January 2015 |title=Pathophysiology of carpal tunnel syndrome |url= |journal=Neurosciences (Riyadh) |volume=20 |issue=1 |pages=4–9 |doi= |pmc=4727604 |pmid=25630774}}</ref>

Prolonged pressure can lead to a cascade of physiological changes in neural tissue. First, the blood-nerve barrier breaks down (increased permeability of [[Perineurium|perineureum]] and endothelial cells of [[Endoneurium|endoneural]] blood vessels).<ref name=":10" /> If the pressure continues, the nerves will start the process of [[Demyelinating disease|demyelination]] under the area of [[Pathophysiology of nerve entrapment#Compression|compression]].<ref name=":10" /> This will result in abnormal [[Action potential|nerve conduction]] even when the pressure is relieved leading to persistent sensory symptoms until [[remyelination]] can occur. If the compression continues and is severe enough, [[axon]]s may be injured and [[Wallerian degeneration]] will occur.<ref name=":12">{{cite journal |vauthors=Lundborg G, Dahlin LB |date=May 1996 |title=Anatomy, function, and pathophysiology of peripheral nerves and nerve compression |url= |journal=Hand Clin |volume=12 |issue=2 |pages=185–93 |doi=10.1016/S0749-0712(21)00303-6 |pmid=8724572}}</ref> At this point there may be weakness and [[muscle atrophy]], depending on the extent of axon damage.<ref>{{cite journal |vauthors=Menorca RM, Fussell TS, Elfar JC |date=August 2013 |title=Nerve physiology: mechanisms of injury and recovery |url= |journal=Hand Clin |volume=29 |issue=3 |pages=317–30 |doi=10.1016/j.hcl.2013.04.002 |pmc=4408553 |pmid=23895713}}</ref>

The critical pressure above which the microcirculatory environment of a nerve becomes compromised depends on diastolic/systolic [[blood pressure]]. Higher blood pressure will require higher external pressure on the nerve to disrupt its microvascular environment.<ref name=":9">{{cite journal |vauthors=Szabo RM, Gelberman RH, Williamson RV, Hargens AR |date=1983 |title=Effects of increased systemic blood pressure on the tissue fluid pressure threshold of peripheral nerve |url= |journal=J Orthop Res |volume=1 |issue=2 |pages=172–8 |doi=10.1002/jor.1100010208 |pmid=6679859|s2cid=367271 }}</ref> The critical pressure necessary to disrupt the blood supply of a nerve is approximately 30[[mm Hg]] below diastolic blood pressure or 45mm Hg below [[mean arterial pressure]].<ref name=":9" /> For normohypertensive (normal blood pressure) adults, the average values for systolic blood pressure is 116mm Hg diastolic blood pressure is 69mm Hg.<ref>{{cite journal |vauthors=Wright JD, Hughes JP, Ostchega Y, Yoon SS, Nwankwo T |date=March 2011 |title=Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001-2008 |url= |journal=Natl Health Stat Report |volume= |issue=35 |pages=1–22, 24 |doi= |pmid=21485611}}</ref> Using this data, the average person would become symptomatic with approximately 39mm Hg of pressure in the wrist (69 - 30 = 39 and 69 + (116 - 69)/3 - 45 ~ 40). Carpal tunnel syndrome patients tend to have elevated carpal tunnel pressures (12-31mm Hg) compared to controls (2.5 - 13mm Hg).<ref>{{cite journal |vauthors=Gelberman RH, Hergenroeder PT, Hargens AR, Lundborg GN, Akeson WH |date=March 1981 |title=The carpal tunnel syndrome. A study of carpal canal pressures |url= |journal=J Bone Joint Surg Am |volume=63 |issue=3 |pages=380–3 |doi= 10.2106/00004623-198163030-00009|pmid=7204435}}</ref><ref name=":7">{{cite journal |vauthors=Rojviroj S, Sirichativapee W, Kowsuwon W, Wongwiwattananon J, Tamnanthong N, Jeeravipoolvarn P |date=May 1990 |title=Pressures in the carpal tunnel. A comparison between patients with carpal tunnel syndrome and normal subjects |url= |journal=J Bone Joint Surg Br |volume=72 |issue=3 |pages=516–8 |doi=10.1302/0301-620X.72B3.2187880 |pmid=2187880|doi-access=free }}</ref><ref>{{cite journal |vauthors=Luchetti R, Schoenhuber R, De Cicco G, Alfarano M, Deluca S, Landi A |date=August 1989 |title=Carpal-tunnel pressure |url= |journal=Acta Orthop Scand |volume=60 |issue=4 |pages=397–9 |doi=10.3109/17453678909149305 |pmid=2816314}}</ref> Applying pressure to the carpal tunnel of normal subjects in a lab can produce mild neurophysiological changes at 30mm Hg with a rapid, complete sensory block at 60mm Hg.<ref>{{cite journal |vauthors=Lundborg G, Gelberman RH, Minteer-Convery M, Lee YF, Hargens AR |date=May 1982 |title=Median nerve compression in the carpal tunnel--functional response to experimentally induced controlled pressure |url= |journal=J Hand Surg Am |volume=7 |issue=3 |pages=252–9 |doi=10.1016/s0363-5023(82)80175-5 |pmid=7086092}}</ref> Carpal tunnel pressure may be affected by wrist movement/position, with flexion and extension capable of raising the tunnel pressure as high as 111mm Hg.<ref name=":7" /> Many of the activities associated with carpal tunnel symptoms such as driving, holding a phone, etc. involve flexing the wrist and it is likely due to an increase in carpal tunnel pressure during these activities.<ref name=":8" />

Nerve compression can result in various stages of nerve injury. The majority of carpal tunnel syndrome patients have a degree I [[Peripheral nerve injury classification|nerve injury]] (Sunderland classification), also called [[Neurapraxia|neuropraxia]].<ref name=":10" /> This is characterized by a conduction block, segmental demyelination, and intact axons. With no further compression, the nerves will remyelinate and fully recover. Severe carpal tunnel syndrome patients may have degree II/III injuries (Sunderland classification), or [[axonotmesis]], where the axon is injured partially or fully.<ref name=":10" /> With axon injury there would be muscle weakness or atrophy, and with no further compression the nerves may only partially recover.

While there is evidence that chronic compression is a major cause of carpal tunnel syndrome, it may not be the only cause. Several alternative, potentially speculative, theories exist which describe alternative forms of nerve entrapment.<ref name=":11" /> One is the theory of nerve scarring (specifically adherence between the mesoneurium and [[Epineurium|epineureum]]) preventing the nerve from gliding during wrist/finger movements, causing repetitive traction injuries.<ref>{{cite journal |vauthors=Armstrong TJ, Chaffin DB |date=July 1979 |title=Carpal tunnel syndrome and selected personal attributes |url= |journal=J Occup Med |volume=21 |issue=7 |pages=481–6 |doi= |pmid=469613}}</ref> Another is the double crush syndrome, where compression may interfere with axonal transport, and two separate points of compression (e.g. neck and wrist), neither enough to cause local demyelination, may together impair normal nerve function.<ref name=":0" />