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Inervaia ficatului structur i funcie

Inervaia ficatului
Costin Teodor Streba, Cristin Constantin Vere Introducere Ficatul are o inervaie vegetativ, simpatic i parasimpatic, realizat prin intermediul nervilor splahnici i vagi, care conin att fibre eferente ct i aferente. (1) Fibrele nervoase vegetative, care provin din ganglionii toracici inferiori, plexul celiac, nervul vag i din nervul frenic drept, ajung la ficat prin intermediul hilului i formeaz plexuri nervoase n jurul arterei hepatice, venei porte i canalului biliar. Se descriu un plex anterior, situate n micul epiplon, naintea venei porte, i un plex posterior, napoia venei porte. (2, 3) Din plexurile nervoase pornesc fibre vegetative care se ramific n interiorul parenchimului hepatic. Ramurile arterei hepatice sunt inervate predominant de fibre simpatice, n timp ce ductele biliare sunt inervate att de fibre simpatice ct i parasimpatice (2) Inervaia intrahepatic este asigurat de fibre aminergice, colinergice, peptidergice i nitrergice. (4, 5). La nivelul hepatocitelor ajung fibre amielinice simpatice. (2, 6) Inervaia hepatic are un rol esenial n reglarea proceselor metabolice, a circulaiei hepatice i n transmiterea semnalelor aferente de la nivel hepatic ctre creier. (4, 79) De-a lungul timpului s-au realizat numeroase studii de fiziologie i farmacologie n urma crora s-a stabilit c nervii hepatici ndeplinesc numeroase funcii. Astfel, inervaia motorie, eferent, intervine n controlul metabolismului hidrailor de carbon i lipidelor (1016), n reglarea microcirculaiei hepatice i a fluxului biliar (10, 11, 17, 18), precum i n regenerarea celulelor parenchimatoase hepatice (1922), n timp ce inervaia senzitiv, aferent, este implicat n osmorecepie, ionorecepie, barorecepie i n controlul receptorilor metabolici hepatici. (2333) Inervaia eferent Fibrele nervoase simpatice care realizeaz inervaia hepatic au originea n coarnele laterale ale mduvei spinrii, n regiunea T3-T11. Prsesc mduva prin rdcina anterioar a nervilor spinali, trec prin lanul ganglionar paravertebral i se grupeaz n nervii splahnici, care fac sinaps cu neuronii vegetativi din ganglionul celiac. Fibrele postganglionare formeaz mpreun cu cele parasimpatice plexuri hepatice, din care se desprind fibre vasomotorii ce ajung la nivelul vaselor hepatice care posed perei cu musculatur neted (venule portale intrahepatice i arteriole hepatice), precum i la nivelul hepatocitelor i ductelor biliare. (3, 34) Fibrele parasimpatice au originea n bulbul rahidian, n nucleul dorsal al vagului. Prsesc bulbul pe calea nervului vag i ajung la nivelul ficatului, unde fac sinaps cu neuronii postganglionari, a cror localizare la nivel hepatic nu este bine precizat. (3, 34, 35) Nervii vegetativi, simpatici i parasimpatici, ptrund n ficat la nivelul hilului, mpreun cu vena port, artera hepatic i canalul coledoc, i formeaz plexuri nervoase. Se descriu un plex anterior, n jurul arterei hepatice, i altul posterior, localizat n jurul venei porte i cii biliare principale. De asemenea, un numr redus de fibre nervoase pot ajunge la nivelul ficatului pe calea venei hepatice. (4, 36) Inervaia aferent Ficatul comunic cu restul organismului att pe cale umoral ct i nervoas. Creierul este informat cu privire la funciile ficatului (metabolic, imun etc), (34, 3739) pe care le poate modula prin intermediul hormonilor i nervilor. (40, 41) Comunicarea nervoas a ficatului cu sistemul nervos central este bidirecional, realizndu-se prin intermediul fibrelor

3 nervoase aferente (sensitive) i eferente (motorii) cu origine att n nervul vag (parasimpatic), ct i n nervii spinali (simpatici). (34) Au fost identificate dou ci nervoase aferente: calea aferent vagal i nervii afereni spinali. Fibrele nervoase aferente vagale ajung la nivelul stromei ce nconjoar vasele hepatice i ductele biliare intrahepatice i n poriunea extrahepatic a venei porte i a cilor biliare. Ele nu ptrund n lobulii hepatici, (4, 4244) considerndu-se c au funcie senzitiv, de transmitere la creier a informaiilor despre citokinele circulante i despre unii metabolii, cum sunt glucoza, (45) interleukina-1, (46) aminoacizii (47) i nicotina (48) Nervii afereni spinali par a avea funcie senzitiv, transmind la creier informaii nociceptive prin intermediul ganglionilor rdcinii dorsale cu origine la nivel toracal inferior (T7 T12). (42, 43) Se consider c nervii afereni senzitivi reprezint peste 90% din fibrele nervului vag abdominal i aproximativ 50% din fibrele nervului splahnic. (11, 49) Distribuia fibrelor nervoase aferente a fost analizat prin utilizarea de metode imunohistochimice de nalt specificitate. Astfel, calretinina poate fi un marker relativ specific pentru evidenierea inervaiei aferente vagale din spaiul port, n timp ce CGRP este specific pentru aferenele rdcinii dorsale. Fibrele nervoase CGRP-imunoreactive sunt prezente mai ales n jurul ramurilor vasculare intrahepatice, dar i la nivelul aferenelor vagale extrahepatice. (34) Inervaia intrinsec Pn n prezent s-au efectuat puine studii cu privire la inervaia ficatului uman. (36) Distribuia fibrelor nervoase este relativ asemntoare la nivelul tractului portal la diverse mamifere, ns exist o mare diferen n distribuia inervaiei intralobulare n funcie de specie. Aceast diversitate a inervaiei intrahepatice ar putea explica efectele hemodinamice i metabolice diferite, dependente de specie, obinute prin stimularea nervilor hepatici. (34) Inervaia hepatic intrinsec este incomplet cunoscut, ca i efectele fibrelor nervoase intrahepatice asupra microcirculaiei hepatice, funciilor hepatocitelor, activitii celulelor Kuppfer, contractilitii celulelor stelate i permeabilitii capilarelor sinusoide. (4, 5) De la nivelul plexurilor nervoase hepatice pornesc fibre vegetative care se ramific progresiv pn la contactul cu celulele efectoare. Fibrele nervoase sunt identificate n interiorul spaiilor Disse, fiind n strns legatur cu celulele perisinusoidale, endoteliale i Kupffer. Fibrele simpatice din cadrul plexurilor nervoase ale ficatului ajung la nivelul vaselor hepatice cu musculatur neted n perete, la nivelul hepatocitelor i al ductelor biliare, n timp ce fibrele parasimpatice nu inerveaz direct hepatocitele, ajungnd pn la nivelul stromei ce nconjoar vasele hepatice i ductele biliare intrahepatice i n poriunea extrahepatic a venei porte i a ductelor biliare. (8) Studii de microscopie electronic au artat c inervaia intrahepatic este reprezentat de fibre nervoase amielinice nconjurate de citoplasma celulelor Schwan. Majoritatea fibrelor nervoase conin n poriunea terminal elemente sinaptice sub forma unor varicoziti n care sunt incluse mai multe vezicule mici, cteva vezicule de dimensiuni mari, mici mitocondrii i alte elemente sinaptice. Prin intermediul sinapselor se poate realiza comunicarea nervilor terminali cu celulele efectoare. S-au descris tipuri distincte de sinapse, n funcie de celulele efectoare. Astfel, legtura dintre filetele nervoase i hepatocite sau celulele Ito se realizeaz prin intermediul sinapselor cu spaiu intersinaptic mic, n timp ce contactul cu elementele vasculare din tecile glissoniene i cu celulele sinusoidale ale canaliculelor biliare se realizeaz prin sinapse cu spaiu intersinaptic mare.(9) Influena inervaiei intrahepatice se poate exercita direct, prin reglarea microcirculaiei hepatice sau prin stimularea funciilor hepatocitelor, i indirect, influennd eliberarea de metabolii de ctre hepatocite sau de mediatori de ctre celulele canaliculelor sinusoidale. (4, 11, 50, 51)

4 Pentru evidenierea inervaiei intrahepatice s-au utilizat iniial coloraii pe baz de aur, argint i osmiu, (4, 5, 52, 53) ns aceste metode nu permiteau diferenierea dintre nervii aminergici i cei colinergici i nici diferenierea fibrelor nervoase de elementele conjunctive ale ficatului. n prezent se utilizeaz metode neurohistochimice, de nalt specificitate i mult mai precise, pentru analiza distribuiei intrahepatice a fibrelor nervoase aminergice, colinergice, peptidergice i nitrergice. (4, 5) Inervaia aminergic Majoritatea nervilor aminergici urmeaz calea tractului portal, cele mai multe fibre nervoase fiind asociate cu ramurile arterei hepatice i mai puin cu ramificaiile venei porte sau cu ductele biliare. (5, 54) n general, venele hepatice centrale i sublobulare au o inervaie srac, ns n pereii venelor hepatice mari au fost evideniate fibre nervoase aminergice. (5, 5458) Distribuia intralobular a nervilor aminergici variaz n funcie de specie. (5, 54, 56, 58, 59) La majoritatea mamiferelor, inclusiv la om, nervii aminergici urmeaz traiectul spaiilor porte pn la nivelul spaiului Disse, fiind n relaie strns cu celulele stelate, cu hepatocitele, ca i cu celulele endoteliale sinusoidale i celulele Kupffer. Ulterior, fibrele nervoase aminergice se extind n lobulul hepatic, predominnd n regiunea periportal. (5, 60) Nu exist o distribuie uniform a fibrelor aminergice n lobulii hepatici. (5, 57, 61) Rolul principal al nervilor aminergici intrahepatici pare s fie reglarea tonusului vaselor extrasinusoidale. Se consider c efectele asupra metabolismului hepatocitelor s-ar datora difuziunii neurotransmitorilor eliberai la nivelul terminaiilor fibrelor nervoase aminergice sau ar putea fi rezultatul alterrii fluxului sanguin i oxigenrii tisulare n teritoriul inervat de aceste fibre. (4, 5, 11, 13, 24, 49, 6265) Influena fibrelor nervoase aminergice se poate propaga la toate hepatocitele din cadrul lobulului hepatic prin intermediul numeroaselor jonciuni de tip gap dintre hepatocitele nvecinate. (5, 66) Prezena fibrelor aminergice n spaiile perisinusoidale, n imediata apropiere a hepatocitelor i a celulelor sinusoidale, la primate i alte specii, sugereaz c nervii aminergici pot influena direct nu numai metabolismul hepatocitelor, ci i tonusul pereilor sinusoidali i permeabilitatea acestora prin modificarea diametrelor endoteliului fenestrat al capilarelor sinusoide. (4, 5, 55) Inervaia colinergic Nervii colinergici formeaz plexuri care nsoesc vasele din spaiile porte. Fibrele nervoase colinergice sunt complet separate de fibrele aminergice. (4, 67, 68) n timp ce unii autori au sugerat c nervii colinergici ptrund n lobul i inerveaz hepatocitele (69, 70), mai recent, ali cercettori utiliznd tehnici mai performante, (7173) infirm acest fapt, artnd c fibrele colinergice nu inerveaz direct hepatocitele, ajungnd pn la nivelul stromei ce nconjoar vasele hepatice i ductele biliare intrahepatice i n poriunea extrahepatic a venei porte i a cilor biliare. Totui, se pare c unele fibre intr n contact cu hepatocitele care mrginesc tractul portal, terminaiile lor prezentndu-se sub forma unor vezicule. Prezena celulelor ganglionare acetilcolinesterazo-pozitive la nivelul tractului portal din apropierea hilului hepatic sugereaz c majoritatea nervilor colinergici care asigur inervaia ficatului ar fi efereni, dar exist posibilitatea ca unii dintre acetia s fie senzitivi. Inervaia colinergic, ca i cea aminergic, nu este egal distribuit n interiorul diverilor lobuli hepatici. (4, 5) Acetilcolina eliberat de la nivelul terminaiilor fibrelor nervoase colinergice influeneaz metabolismul hepatocitelor, inclusiv sinteza glucozei, prin intermediul receptorilor muscarinici de tip 3. (74, 75) Receptorii muscarinici de tip 1,2 i 3 se gsesc la nivelul celulelor epiteliului biliar, venei porte i colangitelor. (7678) Receptorii muscarinici de tip 3 se evideniaz i n

5 celulele hepatice progenitoare. (79) Prin aciunea asupra acestor receptori, acetilcolina influeneaz secreia biliar, fluxul sanguin portal i regenerarea hepatic. (74, 80) Inervaia peptidergic Studiile imunohistochimice efectuate de diveri cercettori au permis identificarea la nivelul ficatului a numeroase fibre nervoase, aminergice sau colinergice, care conin neuropeptide, cum sunt: neuropeptidul Y (NPY), substana P (SP), peptidul vasoactiv intestinal (VIP), peptidul calcitonin gene-related (CGRP), peptidul glucagons-like (GLP), somatostatina (SOM), neurotensina (NT), galanina (GAL) i serotonina. (5, 74 8183) Fibrele nervoase pozitive pentru CGRP, NPY i SP sunt distribuite n zona periportal att la om, ct i la pisic, cine i porcuorul de guineea. Fibrele nervoase imunoreactive pentru NPY, SOM i SP, dar nu i pentru CGRP i VIP, au fost evideniate la nivel intralobular. Aceste fibre sunt n strns legtur cu celulele sinusoidelor hepatice. (74) NPY a fost identificat n nervii aminergici de la nivelul tuturor segmentelor hepatice ce conin ramificaii ale venei porte, arterei hepatice i sistemului biliar. SP i SOM au o distribuie similar, dar nu este clar dac sunt asociate fibrelor nervoase aminergice. Distribuia intralobular a fibrelor nervoase NPY-, SP- i SOMpozitive variaz n funcie de specie. (5, 54, 56, 57, 8187) Spre deosebire de fibrele nervoase aminergice i colinergice, care au o distribuie neuniform n ficatul uman, fibrele NPYpozitive sunt distribuite mult mai uniform. (5, 56) Fibrele SP-pozitive sunt mai puin numeroase i sunt localizate predominant n regiunea periportal a lobulului hepatic. (5, 82) CGRP i VIP se gsesc mai ales la nivelul nervilor colinergici i senzitivi dect la nivelul nervilor vegetativi care inerveaz venele porte, arterele hepatice i ramificaiile lor, dar nu sunt prezeni n alte segmente vasculare sau la nivelul ductelor biliare. (5, 84, 8993) nc mai exist controverse cu privire la distribuia intralobular a fibrelor nervoase VIP- i CRGPpozitive. (5, 8183, 91) Prezena nervilor GAL-pozitivi este controversat. Astfel, unii autori raporteaz prezena GAL la nivelul nervilor aminergici n cazul unor specii cum sunt cinele i omul, (5, 81, 94) ns ali cercettori contest acest fapt. (4) Fibrele nervoase care conin SP sunt distribuite n special n regiunile periportale i intralobulare ale ficatului att la om, ct i la porcuorul de guineea, cine i pisic, (74, 82, 87) iar terminaiile lor sunt n strns legtur cu celulele stelate hepatice.(95, 96) SP, neurotransmitor din clasa tahikininelor, se gsete n concentraii mari n stratul superficial al coarnelor posterioare ale mduvei spinrii. (9799) De asemenea, SP a fost evideniat n fibrele nervoase aferente amielinice care mediaz durerea. (100) Barja i Mathison au artat c nervii derivai din ganglionii dorsali toracici conin SP. (43) n plus, denervarea sau tratamentul cu capsaicin, care produce degenerarea nervilor senzitivi, determin reducerea numrului terminaiilor nervoase SP-pozitive de la nivel hepatic. (43, 54, 101) Toate aceste studii duc la concluzia c nervii hepatici Sp-pozitivi provin din ganglionii rdcinii nervoase dorsale. (74) Se consider c SP are rol n transmiterea informaiei nociceptive, precum i n apariia durerii, inflamaiei i leziunilor nervoase. (74) Fibrele nervoase hepatice CGRP-pozitive sunt distribuite n zona periportal, ns la mamifere nu se ntlnesc n interiorul lobulului hepatic. (74, 8284) Fibrele CGRP-pozitive au fost identificate n special la nivelul ductelor biliare i mai puin ramurilor arterei hepatices au venei porte. (82, 83, 102) CGRP are rol de transmitere a informaiei nociceptive la nivelul nervilor afereni senzitivi amielinici. (103) Frecvent, nervii afereni SP-pozitivi conin i CGRP. (103, 104) Similar SP, CGRP este localizat n neuronii ganglionilor spinali, iar denervarea sau tratamentul cu capsaicin determin scderea fibrelor nervoase hepatice CGRPpozitive. (74, 82, 84) Cercetrile efectuate au artat, ca i pentru SP, c nervii hepatici CGRPpozitivi provin din ganglionii rdcinii nervoase dorsale. (44, 74) Se consider c nervii CGRP-pozitivi au rol senzitiv. (74)

6 Fibrele nervoase NPY-pozitive sunt distribuite predominant n regiunile periportal i intralobular n ficatul uman, dar i la porcuorul de guineea, cine i pisic. (57, 74, 82, 83) Fibrele nervoase imunoreactive sunt distribuite cu precdere n jurul ramurilor venei porte i arterei hepatice i mai puin la nivelul ductelor biliare. Se consider c ficatul reprezint principala surs de NPY circulante. (74, 105) Experimentele efectuate au artat c nervii NPYpozitivi coincid cu cei care conin tirozin-hidroxilaz. (106) Administrarea sistemic a unei neurotoxine sistemice, 6-hidroxidopamina, duce la dispariia aproape complet a neuronilor imunoreactivi att pentru NPY ct i pentru tirozin-hidroxilaz. (57) Experimente efectuate pe ficatul canin au evideniat eliberarea de NPY dup stimularea nervilor simpatici. (105) Din datele culese pn n prezent se poate concluziona c fibrele nervoase hepatice NPY-pozitive reprezint o subpopulaie de nervi simpatici. (74) Densitatea fibrelor nervoase NPY-pozitive de la nivel hepatic i din jurul arborelui biliar este mai mare dect a fibrelor imunoreactive pentru tirozin-hidroxilaz (107) astfel nct este posibil ca unele fibre NPY imunoreactive s nu fie de origine simpatic. (74) Exist puine date cu privire la funciile NPY la nivel hepatic. NPY poteneaz aciunea vasoconstrictiv a noradrenalinei asupra ramurilor venei porte la obolan (108, 109) i chiar poate produce singur o vasoconstricie mai puternic dect noradrenalina pe artera hepatic de cine. (110) Cu toate acestea, exist o serie de cercettori care nu au efectul vasoconstrictor al NPY asupra venei porte. (110, 111) Prin urmare, sunt necesare noi studii pentru a confirma sau aciunea vasoconstrictoare a NPY la nivelul vaselor hepatice. (74) Recent s-a constatat c NPY iniiaz proliferarea celulelor stelate hepatice, dar mecanismele de aciune ale NPY nu au fost nc elucidate. (112) Este posibil ca NPY s acioneze direct asupra celulelor stelate i s determine fibroz hepatic. (74) Fibrele nervoase VIP-pozitive sunt localizate n ficatul uman, la pisic i obolan n jurul ramurilor arterei hepatice i ductelor biliare din regiunea periportal, dar lipsesc n regiunea intralobular. (74, 81, 82) Numrul fibrelor nervoase VIP-pozitive este mult mai mic comparativ cu cel al fibrelor care conin SP i NPY. S-a constatat c hepatocitele exprim receptori pentru hepatocite, iar VIP au rol de cofactori mitogeni pentru hepatocite. (113) De asemenea, s-a observat c fibrele nervoase VIP-pozitive sunt situate n apropierea ductelor biliare i intervin n reglarea secreiei biliare de bicarbonat. (91) Infuzia de VIP crete semnificativ secreia biliar de bicarbonat la om, (114) experimentele pe culturi de colangite demonstrnd c VIP stimuleaz secreia de bicarbonat pe calea AMPc. (115) Fibrele nervoase SOM-pozitive din ficatul de om i pisic au o densitate crescut n jurul ramurilor venei porte i arterei hepatice din regiunea periportal, ca i n regiunea perisinusoidal. Terminaiile fibrelor nervoase imunoreactive pentru SOM sunt n relaie strns cu celulele sinusoidale hepatice. (83, 87) Stoyanova i Gulubova au artat c densitatea fibrelor nervoase SOM-pozitive este sczut la pacienii cu ciroz hepatic alcoolic. (83) Cercetri efectuate pe ficatul de pisic au artat c denervarea determin modificri semnificative ale numrului i distribuiei fibrelor nervoase SP-pozitive, dar nu i a numrului fibrelor SOM-pozitive. (87) Majoritatea fibrelor nervoase imunoreactive pentru SOM par a avea rol senzitiv. (74) SOM este un peptid care conine 14 aminoacizi, larg rspndit n organism. Concentraii crescute ale SOM se ntlnesc n intestin, creier i pancreas. SOM ndeplinete numeroase funcii, cum sunt: modularea neurotransmisiei, secreia proteic, contractilitatea fibrelor musculaturii netede, motilitatea intestinal i reglarea funciei celulelor imune. Funciile SOM se exercit prin intermediul a cinci tipuri de receptori. Receptorii SOM hepatici sunt localizai n colangite (receptorii 1, 2, 3 i 4) (116118) i n celulele stelate hepatice activate (receptorii 1, 2 i 3). (119) La nivelul colangitelor, SOM inhib att exocitoza bazal ct i secretinindus, precum i creterea AMPc. (117) Experimente efectuate in vivo au artat c SOM inhib secreia biliar ductal bazal i secretin-indus, (116118) precum i proliferarea

7 colangitelor indus de ligatura ductului biliar. Cercetri efectuate pe oareci au artat c receptorul 2 pentru SOM exprimat la nivelul colangitelor are un rol important n secreia biliar. (118) De asemenea, SOM influeneaz direct microcirculaia la nivelul capilarelor sinusoide prin activarea receptorului 1 pentru SOM, determinnd inhibiia endotelinei 1 care produce contracia celulelor stelate hepatice. (119) Inervaia nitrergic n ultimii ani au fost descoperii, la o serie de mamifere, nervi intrahepatici care conin oxid nitric (NO), cu rol de neuroefector. (5, 120123) Fibrele nervoase imunoreactive pentru sintetaza oxidului nitric (nNOS) formeaz plexuri dense n jurul ramificaiilor venelor porte, arterelor hepatice i ductelor biliare. Numrul fibrelor nervoase nNOS-pozitive diminu n poriunea terminal a structurilor pe care le nconjoar. Asocierea nNOS cu NPY i CGRP la porcuorul de guineea sugereaz c aceste fibre au att funcie aferent, ct i eferent. (5, 121123) Nu au fost identificate fibre nervoase nNOS-pozitive n interiorul lobulilor hepatici. (5) Studiile efectuate pn n prezent sugereaz c inervaia nitrergic a ficatului intervine n reglarea fluxului sanguin hepatic, a funciilor hepatobiliare i a metabolismului hepatocitelor. (123) Astfel, nervii nitrergici contribuie la reglarea tonusului vaselor mici din ficat prin diferite mecanisme, inclusiv prin eliberarea de oxid nitric. (124, 125) De asemenea, fibrele nervoase nitrergice par a fi implicate n activitatea contractil a veziculei biliare (126, 127), precum i n stimularea secreiei canaliculelor biliare. (120, 121, 128, ) n plus, McCuskey i colab. au demonstrat implicarea nervilor nitrergici n reglarea metabolismului hepatocitelor. (4) Distribuia intralobular a fibrelor nervoase aferente nu este pe deplin elucidat i se pare c difer n funcie de specie. (4) Astfel, la porcuorul de guineea terminaiile nervilor senzitivi sunt n contact cu hepatocitele i cu celulele Ito, n timp ce la om nu s-au identificat terminaii ale nervilor afereni la acest nivel. (4, 129) n ficatul uman, terminaiile nervilor senzitivi sunt localizate n capsula hepatic, la nivelul venelor centrale i n ductele biliare. (130) Tsai a descris trei tipuri de posibile terminaii nervoase senzitive hepatice la cine i la om. (34, 80 ) Receptori non-metabolici nc din anul 1965 Haberich i colab. au sugerat existena osmoreceptorilor hepatici, localizai la nivelul venei porte. (131) n urma experimentelor efectuate de Andews i Orbach, care au stimulat nervii hepatici de iepure cu soluii de diverse osmolariti i au nregistrat activitatea nervilor afereni, s-a observat c activitatea nervoas difer n funcie de osmolaritatea soluiei utilizate. (131) Niijima a efectuat cercetri pe ficat izolat de porcuor de guineea i a gsit o relaie direct ntre osmolaritatea soluiei n care a fost introdus ficatul i activitatea aferenelor vagale, demonstrnd, cel puin parial, c ramura hepatic a nervului vag transmite la nivel central informaii de la receptorii hepatici. (131) O serie de autori au ridicat problema existenei receptorilor ionici hepatici, diferii de osmoreceptori. (80) Daly i colab. au artat c infuzia portal de soluie salin hiperton determin la cine o excreie crescut de sodiu comparativ cu administrarea soluiei saline n circulaia general. (132) nregistrrile electrofiziologice au evideniat modificri ale activitii nervilor afereni hepatici stimulai cu soluii saline, nefiind sesizate modificri n cazul soluiilor normoosmolare de glucoz i manitol. (132) Ali cercettori au raportat creterea excreiei de potasiu dup infuzia unei soluii de clorur de potasiu n vena port, fenomen care este abolit dup vagotomie. (132) Alte experimente au urmrit demonstrarea existenei baroreceptorilor n vena port i n ficat. (80) Astfel, Ohm i Haberich au raportat modificarea diurezei n funcie de variaiile presiunii portale, fenomen care nu dispare dup vagotomie, dar este abolit dup blocarea

8 nervilor renali. (130) De asemenea, Lautt a evideniat influena congestiei hepatice asupra funciei renale manifestat, printre altele, prin reducerea diurezei i a excreiei de sodiu. (130) Receptori metabolici Unii cercettori au sugerat prezena receptorilor metabolici la nivelul ficatului. (80) Russek a fost primul care a sugerat rolul receptorilor senzitivi ai ficatului n controlul ingestiei de alimente, precum i aciunea glucozei de la nivel hepatic de inducere a saietii. (Russek, M. (1963). Nature 197.79-80.) Nu s-a stabilit nc dac receptorii senzitivi hepatici sunt stimulai numai de glucoz sau i de ali metabolii. (80) Studiile electrofiziologice efectuate de Niijima pe ficat izolat de porcuor de guinea au demonstrat sensibilitatea ficatului la glucoz. Autorul a nregistrat activitatea electric a ramurii hepatice a nervului vag, observnd c infuzia de glucoz reduce activitatea nervoas, spre deosebire de alte hexoze care nu au nici un efect. (130) Acelai cercettor a evideniat creterea activitii fibrelor nervoase aferente hepatice n timpul terapiei cu insulin, n timp ce activitatea nervoas este deprimat de colecistokinin i glucagon. (130) Ali autori au artat c ficatul detecteaz nu numai modificrile metabolismului glucozei, dar i ale altor metabolii. (80) Astfel, Langhans i colab. au observat c o serie de metabolii, cum sunt glicerolul, 3-hidroxibutiratul, maleatul, lactatul i piruvatul, determin scderea apetitului, efect dependent de integritatea ramurii hepatice a nervului vag. (130) Infuzia portal de lizin la pui deprim apetitul, n timp ce vagotomia local, hepatic i pancreatic, inhib aciunea lizinei. (131) Studiile histochimice efectuate au indicat c informaiile culese de la nivelul ficatului de ctre receptorii senzitivi sunt transmise la nivelul sistemului nervos central pe calea aferenelor vagale hepatice ajungnd la nucleul tractului solitar. (132) Ali receptori Ficatul conine i ali receptori, cum sunt cei pentru temperatur i durere. (80) Sawchencko i Friedman au constatat c o cretere a temperaturii ficatului determin reducerea ingestiei de hran, efect care se obine i prin secionarea nervilor splahnici. (132) Lewis susine ipoteza existenei algoreceptorilor artnd c durerea resimit de majoritatea bolnavilor cu hepatopatii, n absena inflamaiei hepatice, nu se datoreaz distensiei capsulei hepatice, fiind deci posibil prezena acestor receptori. (133) n plus, Sawchencko i Friedman au afirmat c vagul i nervii splahnici ar putea fi implicai n transmiterea la nivel central a senzaiei de durere. (133)

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