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Diurētiskie līdzekļi mazina cirkulējošo asiņu masu, venozo asiņu satrēgumu un audu tūsku un ievērojami samazina sirds diastolisko slodzi (priekšslodzi), kā arī sirds muskuļa sistolisko slodzi (pēcslodzi).

Sirds sistoliskās un diastoliskās slodzes samazinājums, zināmā mērā ir sirds atpūta, veicina sirds mazspējas mazināšanos vai izzušanu.

Vairumam diurētisko līdzekļu ir arī hipotensīva iedarbība, kas saistīta ar šķidruma un nātrija jonu izvadi no organisma.

Sirds mazspējas ārstēšanai izmanto galvenokārt salurētiskos diurētiskos līdzekļus.

Urīndzenošie līdzekļi (diurētiķi) ir līdzekļi kuri aizstur elektrolītu (galvenokārt Na un Cl) kā arī ūdens reabsorbciju nieru kanāliņu aparātā līdz ar to tiek palielināts urīna izdales ātrums un tilpums, likvidējas šķidruma uzskrāšanās audos, tūskas, samazinoties asins tilpumam novēršas hipertensija.

Tātad diurētiskās vielas jeb diurētiķi pastiprināti izdala sāļus un ūdeni.

Diurētisko līdzekļu izraisītā diurēzes palielināšanās ir saistīta ar šo līdzekļu ietekmi uz urīna veidošanos, kas notiek nieru funkcionāli strukturālā pamatvienībā - nefronā.

Cilvēkam abās nierēs ir aptuveni 2 miljoni nefronu, kuros notiek trīs galvenie procesi - ultrafiltracija, ultrafiltrāta reabsorbcija un organismam nederīgo vielu sekrēcija jeb izdale.

Urīna daudzums un sastāvs ir atkarīgs no šo procesu intensitātes.

Ekstracelulārā šķīduma daudzuma un sastāva uzturēšana,

Skābju - bāzu līdzsvara regulācija (proteīnu struktūras jutīgas uz pH izmaiņām),

Endogēno vielu metabolisma gala produktu un eksogēno vielu (medikamentu, toksīnu) izdalīšana.

Asinsspiediena uzturēšana

Sekretē renīnu (asinsspiediena regulācija), kinīnus (piedalās nieres asins plūsmas sadalē), prostaglandīnus (E2 - vazodilatācija), eritropoetīnus (piedalās eritropoēzē), pārvērš D vitamīnu aktīvā formā.

1.Filtrācija.

Ultrafiltrāts nonāk nefrona kanāliņos, no kurienes tā lielākā daļa uzsūcas atpakaļ jeb reabsorbējas, t. i., no kanāliņu lūmena caur kanāliņu sienu nonāk atpakaļ asinīs.

Diennaktī veidojas 150 - 170 I pirmurīna, bet 99 % no šī daudzuma uzsūcas atpakaļ, tādējādi tikai 1 % jeb 1,5 - 1,7 l tiek izvadīti īstā jeb definitīvā urīna veidā.

Filtrāts ir līdzīgs plazmai, bet satur maz proteīnu un ar proteīnu saistītu vielu.

Satur mazmolekulāras vielas elektrolītus (g.k. Na+ un Cl-), aminoskābes, glikozi.

Pirms tam gan tajā caur kanāliņu epitēliju tiek izvadīta urīnviela, kreatinīns, organiskās skābes (urīnskābe) un bāzes, kālija, ūdeņraža un citi joni.

2. Reabsorpcija.

Renālos tubuļos reabsorbējas 99% ūdens (kopā ar elektrolītiem), reabsorbējas pasīvi, pateicoties osmotiskā spiediena gradientam.

Aminoskābes, glikoze reabsorbējas caur aktīvā transporta mehānismiem.

DIURĒTIĶI IEDARBOJAS GALVENOKĀRT TIEŠI UZ REABSORPCIJAS PROCESIEM!!!

Reabsorbcija notiek galvenokārt aktīva transporta veidā, patērējot enerģiju un piedaloties speciālām enzīmsistēmām, piemēram, karboanhidrāzei un sukcīndehidrogenāzei. Proksimālajos kanāliņos reabsorbējas lielākā daļa kālija jonu, distālajos kanāliņos un

savācējkanāliņā reabsorbējas ap 10% nātrija jonu.

Šajā daļā to reabsorbciju stimulē virsnieru garozas hormons aldosterons.

Savācējkanāliņos hipofīzes antidiurētiskā hormona (vazopresīna) hialuronidāzi aktivējošās darbības rezultāta palielinās kanāliņu caurlaidība un tā rezultāta pastiprināti reabsorbējas ūdens.

Tādējādi, mineralokortikoīds aldosterons veicina nātrija jonu reabsorbciju (t. i., aizturi organismā) un kālija jonu izvadīšanu no organisma, bet hipofīzes mugurejās daivas hormons vazopresīns (antidiurētiskais hormons) nodrošina ūdens reabsorbciju.

Urīnizdales traucējumi rodas ne tikai šīs hormonālās regulācijas izmaiņu gadījumā (piemēram, pie Adisona slimības un bezcukura diabēta), bet arī nieru slimību - nefrīta (glomerulonefrīta) un nefrozes gadījumā.

DISTĀLĀ DAĻĀ un SAVĀCĒJKANĀLIŅOS:

Šajās daļās nieres epitēlija aktivitāti atbilstoši homeostāzes prasībām regulē hormoni:

ja organismā ir pārāk daudz ūdens, tad pazeminās asiņu osmotiskais spiediens un samazinās centrālo (hipotalāmā) un perifēro (nierēs, aknās u.c. orgānos) osmoreceptoru aktivitāte, samazinās antidiurētiskā hormona (ADH) izdalīšanās un ūdens tiek izvadīts.

Ja organisms zaudē ūdeni vai asinīs ir paaugstināts Na+ līmenis, osmoreceptori aktivējas un pakāpeniski izdalās ADH (vazopresīns), kura ietekmē palielinās ūdens kanālu skaits un pastiprinās ūdens uzsūkšanās atpakaļ asinīs.

Ja distālajā nefrona daļā paaugstinās Na+ jonu koncentrācija vai pazeminās arteriālais asinsspiediens, tad jukstaglomerulārais komplekss izdala renīnu.

Aktivējas renīna-angiotenzīna sistēma un virsnieru garoza sekretē aldosteronu.

Aldosterona ietekmē veidojas Na+ kanāli, aktivizējas bazolaterālais Na+/K+ATP sūknis, kas sūknē ārā Na+, tiek veicināta Na+ reabsorbcija un K+ sekrēcija.

ADH ietekmē izdalās glikuronidāzes un citi fermenti, kas var ietekmēt kanāliņu caurlaidību

ADH stimulē prostaglandīnu sekrēciju, kas samazina kanāliņu sienu jutību pret ADH.

ADH regulē ūdens izdalīšanos nefrona distālajā daļā un savācējkanāliņos, taču proksimālajā daļā ūdens reabsorbciju stimulē parathormons, mainot šūnstarpu kanālu caurlaidību.

Minerālvielu uzsūkšanās humorālā regulācija norit nefrona distālajā daļā.

Na+ un K+ homeostāzes uzturēšana ir sarežģīts process.

Na+ reabsorbcija ir atkarīga no tā koncentrācijas asinīs.

Ja asinīs ir pazemināts Na+ līmenis, pastiprināti izdalās minerālkortikoīdi.

Aldosteronu aktivē asinsspiediena samazināšanās nierēs.

Tad, kad renīns ir izdalīts tas aknās sintezēto angiotenzinogēnu pārveido par angiotenzīnu I.

Plaušu asinskapilāru endotēlija šūnas savukārt izdala fermentu - angiotenzinogēna konvertējošo enzīmu, kas angiotenzīnu I pārvērš par angiotenzīnu II

Angiotenzīns II sašaurina asinsvadus, paaugstinot arteriālo spiedienu, kā arī tālāk ietekmē virsnieru garozas kamoliņu zonu, kas izdala asinīs aldosteronu.

Aldosterons savukārt veicina Na+ jonu, kā arī H2O reabsorbciju asinīs un K+ jonu izdalīšanos nefrona distālajā daļā un taisnajos kanāliņos.

Līdz ar to Na+ jonu konc. asinīs atkal tiek paaugstināta un palielinās arī cirkulējošais apjoms, kas veicina asinsspiediena paaugstināšanos

Taču angiotenzīnu II pēc tam degradē angiotenzināze un rezultātā rodas angiotenzīns III.

Aldosterona antagonists (ar pretēju darbību) ir ANUP (atrium nātrija urētiskais peptīds), kas caur nierēm izvada Na+ jonus un līdz ar to arī H2O, bet aiztur K+ jonus ž pazeminās cirkulējošais apjoms un rezultātā arī asinsspiediens.

ANUP izdala sirds endokrīnās šūnas.

Nieru darbību ietekmē arī nucleus supraoticus izdalītais hormons vazopresīns un ADH - antidiurētiskais hormons, kas veicina ūdens reabsorbciju distālajos un taisnajos savācējkanāliņos.

3.Ekskrēcija:

Darbojas transporta sistēmas, kas aktīvi transportē dažādus organisko savienojumus.

Pirmie diurētiķi - metilksantīni (kofeīns, teofilīns), vēlāk - osmotiskie diurētiķi (urīnviela) un karbonanhidrāzes inhibitori.

Zāļu vielu dizains sākas: ap 1950.gadu, kad atklāj sulfanilamīdus un sintezē to derivātus: acetazolamīdu (ir arī antidiabētiska darbība), tiazīdus (antihipertenzīva darbība).

1960.g. sintezē cilpas diurētiķus (furosemidu)

1962.g.- kāliju aizturošos diurētiķus (aldosterona antagonistus).

Diurētiķus lieto:

pie sastrēguma parādībām plaušās un aknās - sirds mazspēja dēļ

aknu ciroze - ascīts

hipertenzija

nieru saslimšanas

Lieto arī pie saindēšanās.

Bieži diurētiķus lieto arī bulīmijas slimnieki svara zaudēšanai

Kā aizliegtās vielas sportā (blakus efekti - hipotenzija, dehidratācija, elektrolītu disbalanss)

Ja tūsku cēlonis ir nieru bojājums, diurētiskie līdzekļi ir mazāk efektīvi, reizēm tos pat nedrīkst lietot.

Normāli urīna izdales stimulators ir ūdens. Pēc 1-1,5 litru ūdens izdzeršanas atbilstošs tā daudzums izdalās urīnā 3 - 6 stundu laikā. Tāpēc pie dažādām intoksikācijām ir ieteicama liela daudzuma ūdens vai tējas dzeršana, kas paātrina organisma atbrīvošanos no kaitīgām vielām.

Diurētiska darbība piemīt arī līdzekļiem, kas palielina filtrāciju. Tas var notikt, vai nu paplašinot nieru asinsvadus un pastiprinot asinsriti, vai arī ceļot asinsspiedienu glomerulos.

Tā darbojas sirds glikozīdi, ksantīna atvasinājumi kofeīns un eifilīns. Tomēr šo līdzekļu izraisītai diurēzes palielināšanai nav būtiskas nozīmes, jo tā kā tā no šīs palielinātās pirmurīna izdales 99% reabsorbējas.

Visizteiktāko diurētisko efektu var sasniegt, samazinot ūdens reabsorbciju, kas panākams, vai nu nomācot kanāliņu epitēlija funkcijas (tā darbojas vairums efektīvu diurētisko līdzekļu),


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