Curs gastroenterologie 3

Maldigestie/malabsorbie
Sdr malabsorbie-consecina maldig sau
malalabs
Malabsorbie-deficit preluare a nutrientelor
Maldigestie-deficit de degradare

Absorbia
Duoden, jejun, ileon
Glucide, lipide, proteine-abs n D, J-100cm
de lig Treitz
Ca, Fe, Zn, ac folic, vit A,D, E, K-I prox
B12, ac biliari- ileon
Ileonul poate prelua f D, J


Glucide
Ingerate poli, di, monozaharide-absorbie mono
Amilaze salivare i pancreatice
Enzimele periei enterocitare->monozaharide
Abs glucozei, galactozei-mec activ-transport Na
dep-apical
Glucoz-difuziune facilitat-prot transport
bazolateral
Fructoz-bazo+apical
HC neabs-colon-sub act florei-ac grai

Proteine
Pepsina
CCK-endopeptidaze-tripsina,
chimiotripsina, elastaza i exopeptidaze-
carboxipeptidaza A i B-inactivi
Enzimele periei-activeaz
AA, peptide scurte dezintegrate de perie
Absorbie activ, facilitat, pasiv
Lipide
Stadiul lipolitic
Lipaza salivar, gastric, pancreatic-din tg lungi-
AG,monogliceride, digliceride, glicerol-stimulat de
bicarbonat,sruri biliare
Stadiu micelar
sruri biliare conj+AG+mono, di gliceride
Std celular
in citoplasm :RE-glicerofosfai, monogliceride, fosfolipide;ap
Golgi-chilomicroni
Eliberare
Depinde de apolipoproteina B
Exocitoz n limfaticele intra- i extraintest

B12
Proteina R salivar-vit B12
FI-vit B12 n duoden
Cx FI-vit B12 se fixeaz de R specific n
ileon
Intracitoplasmatic cx se destram-B12 se
fixeaz de transcobalamina II i circul n
c enterohepatic

Abordarea sdr malabs
Suspiciune clinic
Confirmarea malabs
Definirea etiologiei
suspiciunea
Consecine malabs-diaree
Consecina lipsei subst. neabs-anemie
feripriv-b celiac
Boala cauzal-durere-pancreatit cr

Simptome
GI
Diaree, steatoree, flatulen, dusitensie,
durere, glosit, cheilit, stomatit, ascit
Musculo-scheletale
Fracturi, drr os, slbiciune, tetanie,
hipocratism
Neurologce
Parestezii, neuropatie perif, demen,
cecitate nocturn
Dermato
Edem, acroderamtit, hiperpigmentri,
foliculara

Hematologice
Echimoze, sg facile
Endocrine
Amenoree, infertilitate, <libido
Constituionale
Slbire, oboseal, caexie


Laborator

Anemie microcitar
Anemie macrocitar
Limfocitopenie
Eozinofilie
Hipoprotrombinemie

hipoK
hipoCA
HipoMg
Hipofosfatemia
Hipoalb
Hipocol
HpoTg
>FA
Cauze

B luminale
Insuf pancreatic
Insuf saruri biliare
Zollinger-Elisson
Suprapop bact IS
B inf
Sprue tropical,
WhippleParazitozeGiardia
zmicobact avium
Postoperatorii
Gastric, intestinal, bariatric
B sist
Endocrine, DZ,
colagenoze,amiloidoz




B MUCOASE
B celiac/colagenic
Insuf lactaz
Crohn
Limfom
Gastroenterit eozinofilic
Mastocitoz sist
Limfangiectazia
B imunoprolif IS
Enterit radic
B mezenteric vasc
abetalipoproteinemia

Anamnez
Antecedente pers, heredo, chirurgicale
Efectul unor alimente-lapte, cereale
Boli hepatice

Confirmarea malabs
Grsimi-steatoreea
Glucide-intolerana, osmotic gap (>50-
100), pH scaun, test resp cu H, D-xiloza
B12-det B12, test Schilling


Etiologia
Ex radiologice
Rx simpl-calcificri
IS-Crohn, limfom
CT
Endoscopie+histo
EDS-B crohn, celiac, gastroenterit eozinofilic
Colono+ileo-Crohn,limfom
Videocapsula-Crohn, limfangiectazia, B celiac,
amiloidoza

RX
IS<-sdr intestin scurt
Diverticul IS-suprapopulare bact
Fistul-Crohn, enteropatie radic
Hipomotilitate-DZ, scleroderma, amiloid
Dilatatie-scleroderma, celiac. Amiloid
Stenoze-Crohn, radic
Tumor-limfom
Ulcer-Crohn, AINS
Pliuri groase-Whipple, enterit eozinofilic
Histologie
Boala Histo
Modif generalizate
Abetalipoproteinemia


B celiac colagenic

Mycobacteria avium intracelular
Whipple
Modificri parcelare
Amiloidoza
Crohn
Gastroent eozinofilic
Limfagiectazia
Limfom
Mastocitoz
parazii


Acumularea lipidelor, vacuolizarea
enterocitelor
Benzi colagenice sub mucoasa
atrofic

Macrofage spumoase PAS+ cu bacili
acid
PAS+macrofage fr bacili
Depozite rou Congo+
Granuloame non cazeificare
Infiltrare eozinofilic
Dilataie limfatice
Expansiune clonal a limfocitelor
Infiltrare cu mastocite
identif
Std Organul defect Boli patofizie
Lipolitic pancreas lipaza Panc cr
Ca panc
ZE
Op S

Prod lipaz
Eliberare L
Inhib L
amestecare
micelar Ficat, cai Saruri B


Circ
Enterohep
B hep cr
Obstrucie bil
Suprapop b
Crohn, rezecie
ileal, bypass
Sintez deficit
Eliberare deficit
Deconj
Deficit circ
Celular





Eliberare
Duoden,
jejun




Circ
limfatic
Enterocite



Apo B

limfatice
Sprue celiac
Giardiaz
Insuf
mezenteric
Abetalipoprot

Whipple,
limfangiectazie,
fibroz
Infl/atrofie
Interferen abs
Atrofie enterocit

Sintez
chilomicronip
Obstrucie
et confirmare
Panc cr
Calcif, anomalii duct p,intoleran HC, enzime
fecale, ef+enzime p
B celiac
Istoric fam, Ac antigliadin, antiendomisium,
transglutaminaz, biopsie IS, +restricie gliadin
suprapop
Parez, diverticul jejunal, fistul enterocolonic,
obstr IS, abs B12 deficitar, supresie secr acid,
cretere folai, +AB
Crohn
Rezecie ileal, boal extensiv IS, fistule, pop
Giardiaz
Parazii, ag in scaun, parazii n aspirat duodenal
B cr hep
Enzime, CT, US, bio hep
Def.lactaz
pH acid, osmotic gap, cond predispozante, + fr
lactoz
D acid biliar
Laxative
Rezecie ileal, b ileal, colestiramin

Osmotic gap
Interpretarea testelor pt
steatoree
Stadiul
asimilrii
D-xiloz Schilling Biopsie IS
lipolitic N N N
micelar N sau nu
(suprapop)
N sau nu N
celular anormal N anormal
eliberare N N Limfatice
anormale
Boli inflamatorii intestinale
Grup de boli inflamatorii cronice ale
tractului digestiv
Rectocolita ulcero-hemoragic
B Crohn (ileita terminal, enterita regional,
colita granulomatoas)
Rectocolita ulcero-hemoragic
B inflamatorie localizat strict la nivelul
mucoasei colonice cu evoluie ondulant
cu remisiuni i recurene numeroase.
evrei, status ec inalt
ri dezvoltate
Truelove-medicin bazat pe dovezi
Epidemiologie
Problem mondial
I=6-8- 10-20/100000; P= 70-150-250/100000
-metode de dg
Cretere a RCUH urmat la 1-2 decade de
Crohn (Crohn a crescut de 5x mai repede)
Gradient N-S ?, urban- rural
F=<B
Fumat protectiv RCUH, risc Crohn
Clasificare
Severitate: forme uoare, moderate,
severe
Extensie : proctit, rectosigmoidit, colit
stng, pancolit
Clinico-evolutiv: f acut fulminant, f
cronic recurent, f cronic continu
Fct care au determinat creterea
riscului pt RCUH
Igiena
Refrigerare
Scadere consum alim fermentate
Declin Hp
Declin parazitoze
Reducere expunere microbi pmnt
Creterea utilizrii antibioticelor
Vaccinare
Familii mici
Reducerea infeciilor copilriei
Cauze

Interacie factori genetici-mediu-
modificatori endogeni
->activarea sistemului imun intestinal->
-> ciclu inflamaie-vindecare
Etiologia RCUH

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? ?
? ?
5
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Introduction: Inflammatory bowel diseases (IBD)
Aetiology
Infectious factors
Viruses, bacteria, fungi
Genetic factors

Family predisposition,
twins (more probable
in Crohns disease)
Dietary
factors

Sugars, proteins
Ulcerative colitis

Viruses: Herpes
Bacteria: E. coli species
Immune system

Dysregulation of
autoimmune process
Psychosocial
factors
Ulcerative
colitis
Crohns
disease
?
? ?
? ?
Crohns disease

Measles
M. para-TB.
Fct genetici
Agregare fam; gemeni monozigoi 6-14%
Cromozom 6-DRB1*0103 (forma severa,
extensiva), DRB1*1502, DRB10401
Haplotip promotor TNF
Fenotip, susceptibilitate la trat
Fct mediu
AINS
expunerea n copilrie la microbi-educarea
SI; subexpunere, inadecvat stimulare-
>disfuncie, erori de percepie imun
Flor indigen comensal-trigger,
promotor al infl
Pierdere a toleranei fa de flor
comensal
Modificatori endogeni
axul creier-intestin -fct emoionali
Capacitatea de adaptare
Stress psihologic
Asocieri cu alte boli
5-10% manif extradigestive
General: scdere ponderal, anemie, retard
cretere
articulare: artrite (pauci I, poliarticulare II),
spondilartrite -nonerozive
teg:pyoderma gangrenosum, eritem nodos, afte
orale
Ficat:colangit sclerozant (+CCR,
colangicarcinom)
Oculare:uveit, irit,conjunctivit, episclerit
pulmonare

Patogeneza
Mucoasa colonic=barier ntre o mas
vie de antigene i mediul intern
Mec imun?
Ac umorali
Complexe imune
Imunitate celular
Patogenez
1. b autoimun organ-specific, contra
mucoasei colonice. Flora bacterian este
necesar cu rol permisiv, iniiator
2. reactivitate imun anormal contra florei
colonice, mucoasa fiind doar o victim
colateral inocent
3. sindrom heterogen rezultatul fiind
comun
Fct ce influeneaz
Societatea industrializat
Fumat: protecie RCUH, risc Crohn
Infecii enterice: precipitare
Apendicectomie-protecie
Stress
Medicamente:AINS
Anatomie patologic-
macroscopic
Rect afectat imediat dup inel anal, proximal
limit precis, afectarea simetric, continu
Mucoas colonic hiperemic, granular,
friabil, sngernd spontan i la atingere
Ulceraii punctiforme, confluente cu insule de
inflamat
Polipi inflamatori, puni de mucoas
Scurtarea i reducerea diametrului colonic-
hipertrofie ms
Fibroza nu e caracter important
A-P-microscopie
Congestie, edem,depleie mucus n c
caliciforme, abcese criptale (PMN), infiltrat
inflamator n lamina propria (L,P, E, M)
B cronic-modificarea arhitecturii glandulare:
scurtare, pierderea paralelismului, ramificare
Ulceraii rare, superficiale; ptrund la nivelul
musc propria in megacolon toxic sau form
fulminant
Metaplazia c Paneth la baza criptelor-b cronic
veche


CLINIC
Debut cvasiacut -spt, luni
Diaree cu snge, mucus sau pasaj snge
D nocturn, tenesme rectale
Durere medie sau absent/+++ dg dif,
complicaii
Proctit-tenesme, eliminare sg, mucus,
constipaie, urgen
Astenie, artralgie, febr, scdere n G (mic)
Manif extradig-rar naintea celor colonice



Ex fizic
Normal
Sensib sigmoid
Absena lez perianale sau necaract-
escoriaii, prolaps, hemoroizi, fisuri superf,
abces perianal
Prezena fistulelor-Crohn!!
extradigestive
LAb
Inflamaie sever:
VSH
PCR
Leucocitoz, trombocitoz, anemie
hipoK, hipoalbuminemia, uree>-depleie

Dg
Dg:
1) tb clinic compatibil cu colita (diaree cu
sg mucus);
2) excludere colit acut;
3) demonstrarea cronicitii
Dd RCUH-Colita infecioas
>3 spt
Modificarea arhitecturii glandulare
Plasmocitoz in lamina proprie
Evoluia pacientului
DD b Crohn
Parcelar
asimetric, cruare
rect, granulom
Colit nedeterminat-
5-10%

DD
Inflamator:Crohn, Bechet
Inf:Salmonella, Shigella, Cl difficilae, E.
Coli
B cu transmitere sexual:
cytomegalovirus, herpes, chlamidia
Neoplazii:cancer colo-rectal, polipi
Vascular-ischemie
iatrogenic: radic, AINS


Diagnostic
Complex de semne i simptome i nu pe
un singur marker

Colonoscopia piatra de cpati a dg, dar
nu patognomonic
DIAGNOSTIC
Teste indicatoare ale inflamaiei: VSH, PCR, Tr, L, Hb, alb, enzime
hep
Ex scaun:microscopie (ou, parazii) culturi, Cl difficile- toxin
Serologie (selectiv): pANCA(perinuclear antineutrophilic cytoplasmic
antibody), ASCA(anti Saccharomyces cerevisiae), HIV, Amoeba
RADIOLOGIE. Rx-pe gol dilatare colonic
Rx tracic-TBC, imunosupresie
Clism baritat (nu e necesar i nici de dorit n gen)
Tranzit IS-obs Crohn
ENDOSCOPIE-afectare difuz, simetric, imediat dup inel anal:
edem, granularitate, friabilitate, exudat, ulceraii, pseudopolipi
Post-trat-aspect de afectare parcelar


Aspect radiologic RCUH
Precauie n indicarea clismei cu dublu
contrast
Reducerea distensibilitii, scurtarea
colonului, aspect tubular
Aspect neregulat, fin granular, ngroarea
mucoasei, spiculi marginali, pete baritate,
ulceraii n buton de cma, defecte de
umplere (pseudopolipi),
17
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Radiological diagnosis
Ulcerative colitis: Chronic disease
Ulcers
Pseudo-
polyps
Mild inflammation Moderate inflammation
13
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Endoscopic diagnosis
Ulcerative colitis:
Acute mild to moderate clinical course
Complicaii
intestinale:
Megacolon toxic
Perforaia colonic-
Hemoragia digestiv sever
Stenozele colonice-rare
Cancerul colorectal ;>10 ani, f pancolice
28
Clinical course
Ulcerative colitis: Long-term complications
Contents


Information


Farmer et al.
(1993)
0
10
20
30
40
50
60
Surgery Severe bleeding Toxic megacolon Severe flare
Complications [%]
Pancolitis Left sided
Colitis
Proctitis Total
MEGACOLON TOXIC
Dilataia acut toxic a colonului.ex RX pe gol colon
transvers>6cm
Toxicitate sistemic-min 3 din febr>38, tahic>120,
L>10500; min 1 din deshidratare, diselectrolitemie,
hipoT, tulburri mentale
Pp-opiacee, anticolinergice, hipoK, clisma baritat sau
colonoscopia
Durere, oprire diaree, distensie abdominal, absena zg
intestinale, timpanism
Trat medical-post, aspiraie, AB, corecie H-E, corticoT
parenteral
Mortalitate-30%
Left colonic
flexure
> 8 cm
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Radiological diagnosis
Ulcerative colitis: Toxic megacolon
Tratament
Nu exist trat specific sau curativ
Msuri individualizate, utilizare judicioas a
medicamentelor posibil toxice
Obiective:
Creterea calitii vieii
Scderea riscului de complicaii
Evitarea chirurgiei
Medic interesat de boal, dotat cu compasiune
i capabil de angajament pe termen lung
Msuri generale
Educaia pacientului-
Diet echilibrat, restricii minime
Suplimentare cu Fe, Ca, acid folic
Sport
Spitalizai-prevenia tromboemboliilor-
ciorapi, heparin G molec joas
Evitarea anticolinergicelor, AINS, AB
Preparate -Acid 5-aminosalicilic
Sulfatate-salazopirina (sulfapiridin-5ASA)
Non-sulfatate:mesalazina, olsalazina, balsalazina
Ef: inhib ciclooxigenaza, 5-lipooxigenaza, leucotrieneiB4,
tromboxanA2, PG, efect pe Ri, inhib chemotactismul PMN,
macrofage, ndeprteaz radicalii liberi
Ef adverse: doza dep-grea, vrsturi, anorexie, cefalee, malabs
folai; orice doz: rash, anemie hemolitic, leucopenie, infertilitate
masc
Doza 3-6g atac salazopirin;3,2-4,8 mesalazin

Indicaii: inducie f medii, uoare, meninere RCUH



Antibiotice
Metronidazol 10-20mg/kg/zi

Ciprofloxacin 500mgx2/zi
Corticosteroizii
Inhib activitate L: marginaia L, chemotactism,
fagocitoza, metb ac arahidonic, blocheaz elib
ac arahidonic, fosfolipide, scade PG, leucotriene
Diminu sinteza citokinelor proinflamatorii
Doze 0,5-0,75mg/kgcorp/zi;doza 40-60mg/zi cu
scdere treptat de 5-10mg/spt apoi 2,5-
5mg/spt
Trat de inducie a formelor moderate, severe
RCUH, B Crohn; nu se indic pt meninere
Forme corticodependente
Budesonid-9mg/zi
Ag imunomodulatori
Blocheaz proliferarea, activarea i mec efectorii
ale L
Azatioprina-2-2,5mg/kg/zi
6-mercaptopurina 1,5mg/kgcorp/zi
Toxicitate:leucopenie, pancreatit, depresie medular, r alergice, infecii
Metotrexat 15-25mg/sapt
Grea, supresie medular, toxicitate hep,CI sarcin
Ciclosporina-inhib ciclofilina celular, inhib producerea fct
infl IL-2, IL-4, IFN, TNFalfa, ef antiprolif L
4mg/kgcorp/zi n perfuzie continu
Ef renale, HTA, tremor, cefalee, parestezii

Modificatori ai rspunsului
biologic
Nu inc in RCUH
Infliximab!?
Proctita, proctosigmoidita
Local-microclisme, spume, supozitoare
Corticosteroizi:Cortenema, Colofoam,
Cortifoam
5-ASA-Salofalk
Trat oral 5 ASA-3.4g/zi, 2,4-4,8
mesalazin
Corticosteroizi 30-40mg/zi
RCUH extins uoar/moderat
5ASA doz maximal-3-4 spt
Lips r corticosteroizi 20-40 mg/zi redus
progresiv , odat cu reintroducerea 5 ASA
pt meninere
+Adm local
Form sever
Excludere megacolon toxic, perforaie
Consult chirurg, internare, reechilibrareHE
Exclus colono, clism, pregtire pt ele
Oprire opiacee, anticolinergice
Profilaxie tromboembolism
5ASA nu au efect; corticoterapie iv
Ciclosporin 2-4mg/kg/zi
Colectomie



T meninere
Control i evaluare pe baze clinice i nu
radiologice, colono (s vezi cum e!)
5 ASA
6 mercaptopurin- 50mg/zi i se poate
crete pn la 1,5mg/kg/zi cu cte 25mg/zi
Azatioprina-doz dubl ca 6MP
Nu este T de meninere metotrexatul sau
ciclosporina i nici corticosteroizii
Terapii care ncearc
Micofenolate mofetil
Heparin, nicotin,inhib leucotriene, ulei
pete, infliximab, epidermal growth factor,
anticorpi monoclonali, antagoniti alfa-4-
integrine
probiotice
Chirurgia
I.Colit fulminant;Megacolon toxic
II. Electiv la pacient care t medical
ineficace, efecte adverse importante,
inacceptabile, calitatea vieii joas, cortico
dependen
III. Identificarea displaziei sau a CCR
Colectomie cu ileostomie
Colectomie cu ileal pouch-anal
anastomoz

Prognostic
Risc recdere la 1 an-50%
Supravieuire similar cu pop general
Boala Crohn (ileita terminala,
enterita segmentara)
B inflamatorie cronic de etiologie
necunoscut, frecvent la tineri
caracterizat clinic
prin diaree,
crampe abdominale,
scdere n greutate
febra
Epidemiologie
1931-prima descriere
Inciden n cretere
5-6/100000loc
Gradient N-S, V-E
Evrei, americani, N europeni
Agregare fam, concordan de 33% la
gemeni monozigoi
F risc
Fumat
Standard inalt
Igien bun
Alptat protectiv
Diet rafinat
Ag infecioi
Asociere cu alte boli AI: spondilit,
psoriazis
Patogenie
Flora intestinal mpreun cu un factor
neidentificat iniiaz un rspuns imun
inadecvat aberant la o gazd cu
susceptibilitate genetic
flor
Raspuns imun
mediu
gene
Anatomie patologic
Inflamaie discontinu,
parcelar asimetric,
transmural care afecteaz i
org vecine i gngl limfatici
Localizare+oriunde; frecvent
ileon terminal; nu rectul
Ulceraie aftoid cu halou
eritematos.ulcere profunde,
ine de tren, piatr de pavaj,
fistulizri, afectarea seroasei i
a org vecine, ngroarea
peretelui, stenoza
Histo-infiltrat inflamator,
granulom tip sarcoid,
colagenizare

Clinic
Diaree-colonic, malabs sruri bil-IS
Scadere in G-inflamaie, anorexie
Durere-FID-ileon
Af perianal-20-80%:abces, fistule, fisuri
Astenie, anemie, febr
Scdere ponderal
Leziuni perianale

Simptome funcie localizare
Cavitatea oral-afte
Esofag-disfagie, durere
S,d-asimptomatic, stenoz piloric, ulcer
IS-malabs, enteropatie cu pierdere prot, diaree,
steatoree, durere, suprapop bact
Ileocecal-distensie abd, durere, borborisme,
mas palpabil
Colon-diaree, durere abd, rar snge
Perianal.fistule, abces

Fistulizare
Pneumaturia, scaun n urin, vagin, fistule
perete abd
Manifestri extraintestinale
Articulare: artrite
Spondilita ankilopoietic-nu e dep de activ
Ochi-irit, uveit, episclerit (dep)
Biliare-litiaz
Ficat-colangit sclerozant,
colangiocarcinom
Rinichi.amiloidoz, litiaz
SITUAII SPECIALE
Copii, tineri-cretere deficitar
Sarcin-remisie/recderi
Risc avorturi, nateri premature
Scade fertilitatea
Trat meninere similar cu cel premergtor
sarcinii
Clasificare-Viena 1998
Vrsta (Age)-A1-sub 40/A2 peste 40
Localizare: L1-ileon terminal; L2 colon; L3
ileocolon; L4-tract digestiv superior
Comportament (behaviour)-nonstenozant,
nonpenetrant-B1; stenozant-B2;
penetrant-B3
Diagnostic
Complex simptome, date Rx, endo, histo
Lab:VSH, PCR, Tr, anemie (deficit fe,
folai, B12), hipoalb, deficit minerale,
vitamine
Colonoscopia-leziuni colonice, ileale
Tranzit IS-cel puin o dat-fistule, extensie
videocapsul
Videocapsula endoscopica

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Pathology
Crohns disease:
Macroscopic and microscopic changes
Ulcerations
Edema
Cobblestone pattern
Fibrotic
thickening
Dilated
bowel segment
Viscero-
visceral
fistula
Fissure
Epitheloid-cell
granulomas
Aphthous
ulcerations
Transmural
inflammation Abscess
Fistula system
to surrounding tissue
Stenosis
27
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Disease localisation
Distributions in Crohns disease and Ulcerative colitis
Crohns disease Ulcerative colitis
Only small
bowel
25 30 %
Only
colon
20 25 %
Anorectal disease
(anal fistulae, anal fissures,
periproctitic abscesses
etc.) 30 40 %
Small
bowel
and colon
40 55 %
Esophagus
Stomach
Duodenum
3 5 %
Partial
colitis
30 50 %
(Sub-)total colitis
15 20 %
Proctosigmoiditis
30 50 %
back-
wash
ileitis
Involvement
of rectum
11 26 %
29
Clinical course
Crohns disease: Spontaneous remission
Contents


Information


Summers
et al. (1979)

Malchow
et al. (1984)
Remission rate [%]
Duration of therapy [weeks]
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
30
0
10
25
20
5
15
30
Clinical course
Crohns disease:
Relapse rate in the natural course
Contents


Information


Malchow
et al. (1984)
Duration of therapy [weeks]
40
0
20
60
80
100
0 100 200 300 400 500 600 700
Patients in remission [%]
31
Clinical course
Crohns disease:
Cumulative risk of fistula formation
Contents


Information


Schwartz
et al. (2002)
Cumulative risk of fistula formation [%]
Duration of therapy [weeks]
40
0
20
60
80
100
0 1 5 10 20
21 %
26 %
33 %
50 %
35
Contents


Information


Inflammatory bowel diseases (IBD)
Extraintestinal manifestations
Frequency

Joints Polyarthritis, monarthritis, sacroileitis 26 %

Skin Erythema nodosum, pyoderma gangraenosum 19 %

Liver Fatty liver, chronic active hepatitis,
primary sclerosing cholangitis (PSC) 7 %


Eyes Iridocyclitis, uveitis 4 %

Mouth Aphthous ulcerations 4 %

Lung Alveolitis, pulmonary fibrosis < 1 %


Diagnostic
Histo: arhitectur mucoas alterat,
infiltrat inflamator n lamina proprie,
granulom sarcoid fr cazeificare

Ac: ASCA- f ileal, ANCA-f colonic,
OmpC, I2-f ileal
Diagnostic diferenial
Manif sistemice-febr de origine?, retard
cretere, scdere ponderal, abces,
anemie, eritem nodos
Apendicit
Iritaie iliopsoas
Inf acute cu Yersinia
Dd Crohn/RCUH
caract Crohn RCUH
Localiz
are
Rect
Continue
Pe sarite
Simetrice
Afte
Fisuri
Piatr de pavaj
Perete gros
Fistule
stenoze

7
Contents


Information



Introduction: Inflammatory bowel diseases (IBD)
Symptoms
Ulcerative colitis
80 %
90 %
47 %
0 %
5 %
1 %
40 %
38 %
11 %
Crohns disease
22 %
73 %
77 %
16 %
54 %
35 %
27 %
29 %
10 %

Bleeding
Diarrhea
Abdominal pain
Fistulae
Weight loss
Fever
Anemia
Arthralgia
Iridocyclitis, uveitis
27
Contents


Information


Disease localisation
Distributions in Crohns disease and Ulcerative colitis
Crohns disease Ulcerative colitis
Only small
bowel
25 30 %
Only
colon
20 25 %
Anorectal disease
(anal fistulae, anal fissures,
periproctitic abscesses
etc.) 30 40 %
Small
bowel
and colon
40 55 %
Esophagus
Stomach
Duodenum
3 5 %
Partial
colitis
30 50 %
(Sub-)total colitis
15 20 %
Proctosigmoiditis
30 50 %
back-
wash
ileitis
Involvement
of rectum
11 26 %
Ulcerative colitis Crohns disease

First diagnosis Colonoscopy Colonoscopy
and flare Small bowel radiology Gastroscopy
Small bowel radiology

ESR, WBC, CRP, K
+
, Ca
++
, Mg
++
, AP, -GT, AST, ALT, platelets,
vitamin A, vitamin B
12
and stool: pathogenic microbes

Follow-up Sigmoidoscopy Ultrasound
(Colonoscopy) (CT)
(Ultrasound, CT)

ESR, WBC, CRP
8
Introduction: Inflammatory bowel diseases (IBD)
Diagnosis
Contents


Information



Dd histo Crohn/RCUH
caracter RCUH Crohn
Inflamaie transmural
Infiltrat infl cr
Infiltrat acut
Granulom sarcoid
Abces criptal
Atrofie glandular
Distorsiune cripte
Depleie mucus
fisuri
-
++
++
-
+++
+++
+++
+++
-
+++
+++
+
++
+
+/-
+/-
+
+++
Tratament
T inducie: sulfasalazin, antibiotice,
budesonide, corticosteroizi po, infliximab

T meninere: ag imunosupresori
(azatioprin, mercaptopurin, metotrexat)
sau infliximab
T
5 ASA?
Corticosteroizi-prednison 40mg/zi,
budesonide 9mg/zi
PDN-intoleran dig, fa n lun, acnee,
hiperglicemie, depresie, psihoz,
osteoporoz, cataract, retard cretere
Azatioprin, 6-mercaptopurin
Metotrexat-25mg/spt
Ciprofloxacin, metronidazol
T BIOLOGIC
Ac anti TNFalfa
Blocarea selectiv a cascadei inflamatorii
Infliximab-5mg/kgcorp
Rezistent sau fistulizant
RA: reactivare tbc, agravare IC, inf,
anafilaxie
Ac anti-infliximab-61%
Alte trat biologice
Adalimumab-imunogenicitate sczut
Molecule de adeziune-alfa4 integrine AC
Natalizumab

Trat chirurgical
Refractar la trat!
1. stenoze persistente
2.fistule simpt n vezica urinar, vagin,
piele
3. fistule perianale, abcese
4.abcese intraabdominale, dilataii toxice,
perforaii
Rezecii minime

Endoscopia (colonoscopia, EDS)
Acces direct la organul afectat
Examinarea suprafeei mucoasei
Posibiliti de a ntrezri straturile
subdiacente:
Ecoendoscopie
Tehnici optice noi care utilizeaz interaciunea
luminii cu esutul:nivel microscopic, celular,
biochimic
Endoscopia-dezavantaje
Pregtirea colonului-neplcut, uneori
dificil, riscant
Complicaii legate de procedur
Cost real relativ ridicat
Diagnostic corect
Dg corect (Crohn,
RCUH)-strategie
terapeutic
Ileonocolonoscopie
total-colon perfect
pregtit

Elemente de diagnostic
RCUH
Afectare continu,
difuz,simetric
eroziuni, desen
vascular ters, VIC
normal, inflamaie
periapendicular



Crohn
Leziuni aftoide, ulcere
longitudinale, pietre
de pavaj, leziuni
anale





Diagnostic endoscopic
Acurateea dg 89%
Erori 4%
Cazuri severe-9%
Cazuri uoare-2,5%

Colita nedeterminat opiune de diagnostic




Pera A. et al. Gastroent. 1987;92:181-5.
Gastroent. 2005



Boli inflamatorii IGH: 2001-2004
RCUH
BC
Colit
nedeter
minat
280 cazuri
Neconcordan diagnostic
228
38
Diagnostice
concordante
Diagnostice
neconcordante
Colit nedeterminat
Boal
Crohn
RCUH
B.I.
idiopatic
Colit
nedeterm
inat
Boal
Crohn
RCUH B.I.
idiopatic
15 6 4 5
Colit nedeterminat
53%
47%
Forme severe
Forme uoare
Examenul anatomopatologic
Nu este diagnostic unic test

Granulom-diverticulit

Context clinic, endoscopic,
anatomopatologic, radiologic
Anatomie patologic-macroscopic
Rect afectat imediat dup inel anal, proximal
limit precis, afectarea simetric, continu
Mucoas colonic hiperemic, granular,
friabil, sngernd spontan i la atingere
Ulceraii punctiforme, confluente cu insule de
inflamat
Polipi inflamatori, puni de mucoas
Scurtarea i reducerea diametrului colonic-
hipertrofie ms
Fibroza nu e caracter important
A-P-microscopie
Congestie, edem,depleie mucus n c
caliciforme, abcese criptale (PMN), infiltrat
inflamator n lamina propria (L,P, E, M)
B cronic-modificarea arhitecturii glandulare:
scurtare, pierderea paralelismului, ramificare
Ulceraii rare, superficiale; ptrund la nivelul
musc propria in megacolon toxic sau form
fulminant
Metaplazia c Paneth la baza criptelor-b cronic
veche


Dg extindere i activitate

Dg stabilit
DOAR S ARUNCM O PRIVIRE?
Argumente pro i contra
Activitate?
Nesiguran
Lips de corelare ntre simptome i activitate
SII-BII:decizii eronate-corticoterapie, mrirea dozelor
etc.
Localizare-tip de medicaie
Modificarea extensiei pe parcursul bolii


DD
Inflamator:Crohn, Bechet
Inf:Salmonella, Shigella, Cl difficilae, E.
Coli
B cu transmitere sexual:
cytomegalovirus, herpes, chlamidia
Neoplazii:cancer colo-rectal, polipi
Vascular-ischemie
iatrogenic: radic, AINS


Diagnostic
Complex de semne i simptome i nu pe
un singur marker

Colonoscopia piatra de cpati a dg, dar
nu patognomonic
DIAGNOSTIC
Teste indicatoare ale inflamaiei: VSH, PCR, Tr, L, Hb, alb, enzime
hep
Ex scaun:microscopie (ou, parazii) culturi, Cl difficile- toxin
Serologie (selectiv): pANCA(perinuclear antineutrophilic cytoplasmic
antibody), ASCA(anti Saccharomyces cerevisiae), HIV, Amoeba
RADIOLOGIE. Rx-pe gol dilatare colonic
Rx tracic-TBC, imunosupresie
Clism baritat (nu e necesar i nici de dorit n gen)
Tranzit IS-obs Crohn
ENDOSCOPIE-afectare difuz, simetric, imediat dup inel anal:
edem, granularitate, friabilitate, exudat, ulceraii, pseudopolipi
Post-trat-aspect de afectare parcelar


RCUH - extindere
Rectite
Pancolite
Forme intermediare
0
26
28
15
43
Reevaluate
Evaluare unica
Aceeasi extindere
Extinse
RCUH form rectal
evaluare ulterioar
Pancolite
55%
45%
Forme severe
Alte forme
Evaluarea vindecrii
Clinic ameliorat-repetare?
Vindecarea mucoasei-standard de aur pt
rspunsul la tratament
Ulcere profunde-prognostic infaust
Studii clinice-vindecarea mucoasei-scop
evaluarea noilor medicamente
Dilatri stenoze
Balona
Rat mare de restenozare
Dilatri frecvente
complicaii
Supravegherea
Supraveghere prin colonoscopie cu 4
biopsii din 10 n 10cm+bio suplimentare
din orice leziune suspect
Displazie de grad nalt-colectomie
Displazie de grad mic???

Tehnici endoscopice noi

Cromoendoscopia i endoscopia cu
magnificare
NBI
Spectroscopia
Imunoscopia-imunofluorescen AC-ACE
Albastru de metilen-alterri ADN?
Indigo carmine