1 Zpalov ochorenia riev Inflammatory bowel disease (IBD)

1 Zpalov ochorenia riev Inflammatory bowel disease (IBD)

1 Zpalov ochorenia riev Inflammatory bowel disease (IBD) PREDNKY Z PATOLOGICKEJ FYZIOLGIE OLIVER RCZ 2017 git17b 30.4.17 2 Defincia IBD IBD irok skupina rznych ochoren Dve ast a dobre charakterizovan m. Crohn a ulcerzna kolitda (s aj in a niekedy nieo medzi CD a UC) revn sliznica je neustle drden stav fyziologickho zpalu (iastone autonmny

obrann systm) Neadekvtna reakcia sliznice na rzne podnety (exogenn, endogenn) Genetick pozadie a autoimunita Nezabudli sme na nieo? Glutnov enteropatia git17b 30.4.17 3 IR ZBER Neustly slab (subklinick) zpal aj u zdravch Ditne chyby*, fast food, convenience food (?) pokazen jedl a infekcie (nevinn a po choleru) Znma prina, jasn patogenza Enterocolitis necrotisans u malch det, Clostridium difficile Mikrobim! A aj parazitm (?)

INFLAMMATORY BOWEL DISEASE M. Crohn Colitis ulcerosa git17b *Koljtis Ms. Idy 30.4.17 4 2 ROZDIELNE CHOROBY, CDCU CROHN* COLITIS ULCEROSA Cel GIT ale nie Sigmoid a rektum kontinulne Kontinulne Najviac colon, Len sliznica

doln as tenkho Krvav hnaky, reva kre a bolesti Transmurlne (aj perforcia, fistuly) Kaovit hnaky, kre a bolesti, ale *Burrill Crohn, USA, 1932 aj zpcha git17b 30.4.17 2 ROZDIELNE CHOROBY 5 CROHN Cel GIT ale nie kontinulne

Najviac colon, doln as tenkho reva Transmurlne (aj perforcia, fistuly) Kaovit hnaky, kre a bolesti, ale aj zpcha COLITIS ULCEROSA Sigmoid a rektum Kontinulne Len sliznica Krvav hnaky, kre a bolesti PRZNAKY MIMO GIT Svisiace s poruchami GIT chudnutie, horka, anmia Nesvisace (CD) artritda, uveitda, peeov, kon... git17b

30.4.17 6 git17b 30.4.17 7 Types of Crohns disease; A, stenosing; B, inflammatory; C, fistulizing; D, radiographic image of fistula. git17b 30.4.17 Extraintestinal features

joints: arthritis (25%) eye: uveitis (10%) 8 skin: erythema nodosum, pyoderma gangrenosum (10%) liver: pericholangitis, fatty liver (3%) blood: thromboembolic disease (rare) Extraintestinal findings Investigations

FBC: iron deficiency anaemia. Stool culture: exclude infective colitis Plain abdominal radiograph: colonic dilatation or air under diaphragm indicating perforation in fulminant colitis Barium enema: loss of haustrations, shortened lead pipe colon Sigmoidoscopy: inflammed friable mucosa,

bleeds to touch Colonoscopy: extent of disease at presentation, screening of longstanding disease for dysplasia Biopsy: typical histological features git17b 30.4.17 9 SPOLON ALEBO ROZDIELNE? Relatvne nov ochorenia (150 r) Zaiatok vinou 20 40, ale aj 60 Extrmny nrast prevalencie v

poslednch dvoch troch desaroiach EU: UC 505 CD 322 USA: UC 249 CD 319 na 100 000 obyvateov VIAC U IMIGRANTOV Obrovsk rast v zii Hong Kong 30-nsobn nrast 1985 2014 git17b 30.4.17 10 SPOLON ALEBO ROZDIELNE OBROVSK RAST V ZII Hong Kong 30-nsobn nrast 1985 2014, viac CROHN AKO UC (ale je ich stle menej, ako v EU a USA)

Zmeny stravovacch nvykov Podobne Jun Krea, Brazlia ALE Viac na severe ako na juhu (eny) Ovea viac v mestch, ako na vidieku Extrmne ast vskyt u idov pvodu Akenzy ijcich v EU a USA kosher? trefli? git17b 30.4.17 11 SPOLON ALEBO ROZDIELNE Pomerne ast familrny vskyt gny Antibiotick lieba - mikrobim Orlna kontraceptva a apendektmia: CD

Vy socioekonomick stav Stres, depresia (a vice versa) Nezdrav viva a deficit vitamnu D Fajenie zvyuje riziko CD a zniuje UC? git17b 30.4.17 12 GNY ? Viac ako 200 mutci, polymorfizmov... Pozor na etnick zloenie probandov Tie ist aj u inch autoimunitnch ochoren Niektor tie ist ako citlivos na mykobaktria (TBC, lepra) Lene o to m spolon s nrastom incidencie??? Gny sa nemenia! ATG16L1, NOD2, CARD 15 git17b

30.4.17 13 VEMI AK FORMA N. V. prv prznaky vo veku 2 rokov Extrmne ak priebeh, fistuly, opercie, ni nepomohlo XIAP mutcia imunodeficiencia, spen lieba kmeovmi bunkami z puponej nry Zatia len anekdoty git17b 30.4.17 PARAZITY 14

Choroby tejto skupiny v minulosti boli menej ast Nai predkovia sa o hyginu starali menej a nepouvali antibiotik V pokusoch na zvieratch schistostoma, trichuris, heligmosomoides prevencia IBD Blokuj SYK signalizan kaskdu, aktivciu T lymfocytov U loveka trichuris suis nie celkom jednoznan vsledky Zatia nie je odporan lieba git17b 30.4.17 PARAZITM A MIKROBIM 15 Choroby tejto skupiny v minulosti boli menej ast

Nai predkovia sa o hyginu starali menej a nepouvali antibiotik V pokusoch na zvieratch schistosoma, trichuris, heligmosomoides prevencia IBD Blokuj SYK signalizan kaskdu, aktivciu T lymfocytov Preo to Old friendsrobia? Ak a mikrb zabije, vymizne aj on (cholera) Radej sa dohodn s naim imunitnm systmom o prmer Tm chrnia aj nae zdravie Panensk prostredie predisponuje k omylom

git17b 30.4.17 16 GENETIKA, (AUTO)IMUNITA T1DM Deti IBD Neskr Vrazn svislos MHC Jasn obraz Menej Mikrobim nie u no

Nejasn Mikrobim, parazitm (2019) git17b 30.4.17 17 GENETIKA, IMUNITA A EXPOZM Najnov trend: Precision medicine Slogan ? Predpsanie okuliarov, inzulnu Vek peniaze USA, EU, UK (najviac na) Big data rozumn spojenie genomickch a lekrskych databz Nvrhy biomarkerov Genm nemenn informcia Epigenm, metabolm... Flexibiln realizcia

poda podmienok Prostredie (strava, alkohol, fajenie, stres) = EXPOZM git17b 30.4.17 18 NEZABUDLI SME NA NIEO? Je coeliakia (glutnov enteropatia, netropick sprue) nieo plne in? Vskyt okolo 1/100 170, viac u ien Detsk choroba: 6 m 2 r Hocikedy, ale asto nediagnostikovan Spolu s inmi autoimunitnmi chorobami Tenk revo Reakcia na glutn z obilnn (Triticiae) Je to alergia alebo autoimunita? git17b

30.4.17 19 NEZABUDLI SME NA NIEO? Vskyt okolo 1/100 170, viac u ien Tenk revo Reakcia na glutn z obilnn Steatorrhoea, veobecn dyspeptick akosti, malabsorbcia a jej nsledky Atrofia klkov (villous atrophy) Intolerancia laktzy (sekundrna) Vyie riziko rakoviny riev a lymfmu Neprehadn mnostvo inch prznakov a inch autoimunitnch pochodov git17b 30.4.17

GLUTNY 20 Geneticky modifikovan obilniny za 10000 rokov je v nich viac Zsobn bielkoviny s vysokm obsahom AK glutmov kyselina a proln (prolamny). Boli prtomn aj v pvodnch prrodnch formch ale ovea menej. Rezistentn na enzmy v udskom GIT Gliadn z penice, hordein z jamea, avenin z ovosa, secalin z rye git17b 30.4.17 21

AKO TO ROB GLIADN? Urit sek gliadnu (AK 56 68) vedie k poruche tight junctions medzi enterocytmi Dochdza k aktivcii nepecifickej aj adaptvnej imunity u nosiov DQ2 ast u Baskov a rov (a v niektorch oblastiach Afriky a Indie) Protiltky proti gliadnu, transglutaminze a in ale nie u kadho a opane, chor bez protiltok git17b 30.4.17 DOBR SPRVA 22 Paleodita ??? Obmedzenie vrobkov z penice

Ovos? Rya, kukurica, proso, sorghum, OK Quinoa, pohanka, zemiaky OK Pomhaj aj pri IBD??? git17b 30.4.17 GENETIKA, IMUNITA 23 T1DM Deti COELIAKIA Podobne Vrazn svislos MHC Jasn obraz

Podobne Tie (u det) Mikrobim Trigger? Mikrobim ? Znmy extern trigger git17b 30.4.17 ETE NIEO? 24 IBS irritable bowel syndrome Neviem, o to je Pome domov

git17b 30.4.17

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