Download - ICTERUL
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ICTERULICTERUL
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DIAGNOSTICUL DIAGNOSTICUL ICTERELORICTERELOR
ICTER:ICTER: Simptom caracterizat prin apari\ Simptom caracterizat prin apari\
ia ia unei colora\ii g`lbui la nivelul unei colora\ii g`lbui la nivelul
tegumentelor ]i sclerelor.tegumentelor ]i sclerelor.
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ICTERUL DEVINE ICTERUL DEVINE SINDROMSINDROM C^ND SE C^ND SE
ASOCIAZ~ CU:ASOCIAZ~ CU:
ALTE SIMPTOME: PRURITALTE SIMPTOME: PRURIT
ALTE MANIFEST~RI:ALTE MANIFEST~RI:
- URINARE- URINARE
- COPROLOGICE- COPROLOGICE
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CULOAREA ICTERIC~ DEPINDE DE:CULOAREA ICTERIC~ DEPINDE DE:
NIVELUL BILIRUBINEMIEINIVELUL BILIRUBINEMIEI
TIPUL EITIPUL EI
INTENSITATEA CIRCULA|IEI INTENSITATEA CIRCULA|IEI
LOCALELOCALE
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SURSE BILIRUBIN~SURSE BILIRUBIN~
• 70% DIN CATABOLISMUL Hb70% DIN CATABOLISMUL Hb
• 30% "EARLY LABELED":30% "EARLY LABELED":
- NON ERITROPOIETIC P- NON ERITROPOIETIC P450450
- ERITROPOIEZ~ INEFICIENT~- ERITROPOIEZ~ INEFICIENT~
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METABOLISMUL BILIRUBINEIMETABOLISMUL BILIRUBINEI
1. 1. Hb Hb Hematin` + globin` Hematin` + globin`
2. Hematin` 2. Hematin` HemoxigenazaHemoxigenaza Biliverdin` Biliverdin`
3. Biliverdin` 3. Biliverdin` ReductazaReductaza Bilirubin` I Bilirubin` I
4. Transport [n plasm`4. Transport [n plasm`
5. Captare hepatic` GTransferaz` B5. Captare hepatic` GTransferaz` B
6. Glicuronidare 6. Glicuronidare Bilirubin` D Bilirubin` D
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CLASIFICAREA DUCCICLASIFICAREA DUCCI
1. PREHEPATIC:1. PREHEPATIC:
a) reten\iea) reten\ie
b) produc\ieb) produc\ie
2. HEPATIC:2. HEPATIC:
a) hepatocelulara) hepatocelular
b) hepatocanalicularb) hepatocanalicular
3. POSTHEPATIC3. POSTHEPATIC
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ICTER PREHEPATICICTER PREHEPATIC DE PRODUC|IEDE PRODUC|IE
• INCAPACITATEA DE A {NDEP~RTA BDINCAPACITATEA DE A {NDEP~RTA BD
• BI BI
• UROBILINOGEN N sau UROBILINOGEN N sau
• EXPLORARE FUNC|IONAL~ NEXPLORARE FUNC|IONAL~ N
• ANEMIE, RETICULOCITE N sau ANEMIE, RETICULOCITE N sau
• SIDEREMIE SIDEREMIE
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SOARTA BILIRUBINEISOARTA BILIRUBINEI
1.1. Exportat` [n c`i biliareExportat` [n c`i biliare
2.2. Eliminat` [n duodenEliminat` [n duoden
3.3. Transformare urobilinogenTransformare urobilinogen
4.4. ReabsorbitReabsorbit
5.5. Eliminat Eliminat
1gHb = 35 mgB = 280 mg/zi1gHb = 35 mgB = 280 mg/zi
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CAUZE ICTER BICAUZE ICTER BI
I. HIPERPRODUC|IE:I. HIPERPRODUC|IE:
a) eritropoiez` ineficient` : - primar`a) eritropoiez` ineficient` : - primar`
- secundar`- secundar`
b) hiperhemoliz` : - compensat`b) hiperhemoliz` : - compensat`
- decompensat`- decompensat`
c) reducerea capt`rii - GILBERTc) reducerea capt`rii - GILBERT
d) reducerea conjug`rii - CRIGLER NAJJARd) reducerea conjug`rii - CRIGLER NAJJAR
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b) ICTERUL HEMOLITIC b) ICTERUL HEMOLITIC = = ANEMIE ANEMIE HEMOLITIC~HEMOLITIC~
scurtarea duratei de via\`scurtarea duratei de via\`
ICTERUL SE CARACTERIZEAZ~ PRIN:ICTERUL SE CARACTERIZEAZ~ PRIN:
- galben - icter- galben - icter
paloare - anemiepaloare - anemie
- intensificare brusc` dup` transfuzii- intensificare brusc` dup` transfuzii
- scaune normale/pleiocrome- scaune normale/pleiocrome
- urobilinogen crescut- urobilinogen crescut
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ALTE CARACTEREALTE CARACTERE
1. anemie 1. anemie ++ modific`ri eritrocitare modific`ri eritrocitare
2. hipersideremie2. hipersideremie
3. reticulocitemie3. reticulocitemie
4. test Coombs +4. test Coombs +
5. deficite enzimatice [n eritrocit5. deficite enzimatice [n eritrocit
6. cre]terea stercobilinogenului > 280 6. cre]terea stercobilinogenului > 280
mg/zimg/zi
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c) ICTER GILBERT - ICTER DE RETEN|IEc) ICTER GILBERT - ICTER DE RETEN|IE
• Boal` genetic` autosomal predominantBoal` genetic` autosomal predominant
• bolnav icteric > suferindbolnav icteric > suferind
• icter izolaticter izolat
• accentuat de ajunare, infec\ii, alcoolaccentuat de ajunare, infec\ii, alcool
• generat de deficitul de GTgenerat de deficitul de GT
• defect comun cudefect comun cu
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d) ICTER CRIGLER NAJJARd) ICTER CRIGLER NAJJAR
• ICTER NEONATAL GRAVICTER NEONATAL GRAV
• COMPLICA|II NEUROLOGICE:COMPLICA|II NEUROLOGICE:
- NUCLEII CENTRALI- NUCLEII CENTRALI
- C. AUDITIVI- C. AUDITIVI
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FORME CLINICEFORME CLINICE
I. NU R~SPUNDE LA TRATAMENT: I. NU R~SPUNDE LA TRATAMENT: FOTOTERAPIEFOTOTERAPIE
II.R~SPUNDE LA TRATAMENT: II.R~SPUNDE LA TRATAMENT: FENOBARBITALFENOBARBITAL
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AMBELE BOLI AU DEFICIT DE AMBELE BOLI AU DEFICIT DE GLUCURONILTRANSFERAZ~GLUCURONILTRANSFERAZ~
30% - GILBERT30% - GILBERT
10100%- CRIGLER NAJJAR0%- CRIGLER NAJJAR
ENZIM~ CODAT~ C2 DISTALENZIM~ CODAT~ C2 DISTAL
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FORMA MIXT~ FORMA MIXT~ CAPTARE/CONJUGARECAPTARE/CONJUGARE
• LAPTE DE MAM~: pregnan 3LAPTE DE MAM~: pregnan 32020 diol diol
• LUCEY DRISCOLL: alt steroid inhibitor LUCEY DRISCOLL: alt steroid inhibitor
al al BGTBGT
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ICTERE CU BILIRUBIN~ ICTERE CU BILIRUBIN~ DIRECT~DIRECT~
• ICTERE HEPATICE:ICTERE HEPATICE: a) hepatocelularea) hepatocelulareb) hepatocanaliculareb) hepatocanaliculare
• ICTERE POSTHEPATICE:ICTERE POSTHEPATICE:a) malforma\iia) malforma\iib) muraleb) muralec) intraluminalec) intraluminaled) extrinsecid) extrinseci
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ICTERE POSTHEPATICEICTERE POSTHEPATICE
SE {NSO|ESC DE:SE {NSO|ESC DE:1. durere1. durere2. febr`2. febr`3. prurit3. prurit4. sl`bire4. sl`bire5. diabet5. diabet6. urini hipercrome6. urini hipercrome7. scaune acholice7. scaune acholice
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BIOLOGICBIOLOGIC
1. 1. BD 60%BD 60%
2. 2. Ac BILIARI Ac BILIARI
3. 3. FA FA > ALAT> ALAT
4. 4. T. PROTROMBIN~ T. PROTROMBIN~
5. 5. COLESTEROL COLESTEROL
6. 6. BILIRUBINURIEBILIRUBINURIE
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DIAGNOSTIC IMAGISTICDIAGNOSTIC IMAGISTIC
1. ECHOGRAFIE:1. ECHOGRAFIE:
- dilata\ii c`i biliare- dilata\ii c`i biliare
- colecist m`rit- colecist m`rit
- tumori de cap de pancreas- tumori de cap de pancreas
2. ERCP2. ERCP
3. COLANGIORMN3. COLANGIORMN
4. CT4. CT
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ICTER HEPATICICTER HEPATIC
PATOGENEZ~PATOGENEZ~
INSUFICIEN|~ SELECTIV~INSUFICIEN|~ SELECTIV~
INSUFICIEN|~ SECRETORIE INSUFICIEN|~ SECRETORIE
GLOBAL~GLOBAL~
OBSTRUC|IE CANALICULAR~OBSTRUC|IE CANALICULAR~
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I. HEPATOCELULAR:I. HEPATOCELULAR:
FAMILIALFAMILIAL
DOB^NDITDOB^NDIT
II. HEPATOCANALICULARII. HEPATOCANALICULAR
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I. a. S. DUBIN JOHNSONI. a. S. DUBIN JOHNSON
• AUTOSOMAL RECESIVAUTOSOMAL RECESIV
• ICTER - PRURITICTER - PRURIT
• TEST BSP SPECIFICTEST BSP SPECIFIC
• COLECISTOGRAFIA PER OSCOLECISTOGRAFIA PER OS
• FICAT NEGRU FICAT NEGRU == MELANIN~ MELANIN~
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I. b. S. ROTORI. b. S. ROTOR BSP ANORMAL LA 45 MINBSP ANORMAL LA 45 MIN
II. a. COLESTAZAII. a. COLESTAZA MORFOLOGIC - STAZ~MORFOLOGIC - STAZ~
ACUMULAREA ACUMULAREA COMPONEN|ILOR {N S^NGE COMPONEN|ILOR {N S^NGE
FUNC|IONAL - DEFECT FUNC|IONAL - DEFECT SECRETORSECRETOR
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BIOCHIMICBIOCHIMIC
1. AC. BILIARI 1. AC. BILIARI
2. ENZIME COLESTAZ~ 2. ENZIME COLESTAZ~
3. BILIRUBINA 3. BILIRUBINA ,, FACULTATIV FACULTATIV
4. COLESTEROL 4. COLESTEROL
5. ENZIME CITOLIZ~ 5. ENZIME CITOLIZ~
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ETIOLOGIEETIOLOGIE
1. CONGENITAL~1. CONGENITAL~
2. DOB^NDIT~:2. DOB^NDIT~:
a) SARCIN~a) SARCIN~
b) MEDICAMENTEb) MEDICAMENTE
c) CIROZ~ (HEPATITE)c) CIROZ~ (HEPATITE)
d) CSPd) CSP
e) CBPe) CBP
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PROCESUL DIAGNOSTICPROCESUL DIAGNOSTIC
I. ANAMNEZA:I. ANAMNEZA: V^RST~V^RST~ SEXSEX ISTORICUL BOLIIISTORICUL BOLII CIRCUMSTAN|ECIRCUMSTAN|E
II. EXAMEN FIZIC:II. EXAMEN FIZIC: FICATFICAT COLECISTCOLECIST ABDOMENABDOMEN
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III. EXPLOR~RI BIOCHIMICEIII. EXPLOR~RI BIOCHIMICE
1. BILIRUBIN~1. BILIRUBIN~
2. ALAT2. ALAT
3. FA3. FA
4. T. QUICK4. T. QUICK
5. UROBILINOGEN, 5. UROBILINOGEN,
BILIRUBINA URIN~BILIRUBINA URIN~
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IV BIOPSIEIV BIOPSIE
ERCPERCP
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DIAGNOSTIC DIFEREN|IALDIAGNOSTIC DIFEREN|IAL
INTRAHEPATIC EXTRAHEPATIC
DEBUT TINERI V R̂ST~ MEDIE
ANTECEDENTE DROGURIALCOOL
OPERA| II,LITIAZ~,SL~BIRE
DURERE + ++
SPLENOMEGALIE ++ +
SCAUNE ACOLICE + +
BD -
S. COURVOISIER - +
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COLESTAZACOLESTAZA
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Definitia colestazei:Definitia colestazei:
• Imposibilitatea sistemului Imposibilitatea sistemului
transportor de a conduce in duoden transportor de a conduce in duoden
cantitatile fiziologice de bila in cantitatile fiziologice de bila in
totalitatea ei, sau a oricarui totalitatea ei, sau a oricarui
component.component.
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Remember:Remember:
• Bila – rezultatul functiei exocrineBila – rezultatul functiei exocrine
- contine – apa- contine – apa
- electroliti- electroliti
- acizi biliari- acizi biliari
- colesterol- colesterol
- fosfolipide- fosfolipide
- pigmenti biliari- pigmenti biliari
- proteine: mucus, - proteine: mucus, enzime.enzime.
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Fluxul biliar este dependent de:Fluxul biliar este dependent de:
• Sinteza de “novo”Sinteza de “novo”
• Ciclul Ciclul
enterohepaticenterohepatic
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Sinteza de novo:Sinteza de novo:
Reprezentarea schematica a metabolismului colesterolului la mamifere
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Sinteza de novo:Sinteza de novo:
Reprezentarea schematica a metabolismului colesterolului la mamifere
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In intestinul subtire:In intestinul subtire:
Ac.Chenocolic Ac.Chenocolic
Ac.ColicAc.Colic
7 7 dehidroxilare dehidroxilare
SECUNDARISECUNDARI Ac.LithocolicAc.Lithocolic
Ac.DezoxiocolicAc.Dezoxiocolic
TERTIARI TERTIARI Ac.UrsodeoxicolicAc.Ursodeoxicolic
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Ciclul enterohepatic:Ciclul enterohepatic:
• 98% din acizii biliari 98% din acizii biliari
sunt extrasi la prima sunt extrasi la prima
trecere interesand 2 trecere interesand 2
proteine:proteine: Na taurocolat Na taurocolat
cotransport proteincotransport protein sisi
organic anion transport organic anion transport
polipeptid.polipeptid.
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Pasul urmator – traversarea celulei:Pasul urmator – traversarea celulei:
• Proteina “Proteina “YY” – glutation transferaza” – glutation transferaza
• Proteina “Proteina “YY’” – ENZIMA?’” – ENZIMA?
• Proteina legand acizii grasi (Proteina legand acizii grasi (FABPFABP))
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Secretia canaliculara recunoaste:Secretia canaliculara recunoaste:
Mecanism – Mecanism – electrogenelectrogen
- ATP-- ATP-azicazic
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Colestaza se caracterizeaza prin:Colestaza se caracterizeaza prin:
1.1. CrestereaCresterea dihidroxiacizilordihidroxiacizilor
2.2. Reducerea raportuluiReducerea raportului 3OH3OH / / 2OH2OH
3.3. Creste : Creste : SulfatareaSulfatarea si si
GlicuronoconjugareaGlicuronoconjugarea
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Nocivitatea acizilor biliari este Nocivitatea acizilor biliari este generata de:generata de:
1.1. Cresterea influxului de Cresterea influxului de CaCa2+2+
2.2. Alterarea respiratiei celulareAlterarea respiratiei celulare
3.3. Modificari metaboliceModificari metabolice
4.4. Solubilizarea membranelorSolubilizarea membranelor
5.5. Ac.litocolic Ac.litocolic ColestazaColestaza
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Clasificarea colestazei:Clasificarea colestazei:
I.I. Extrahepatica – bloc mecanicExtrahepatica – bloc mecanic
II.II. Intrahepatica – a) cu dilatare de Intrahepatica – a) cu dilatare de
cai biliarecai biliare
b) fara dilatare b) fara dilatare
de cai biliarede cai biliare
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Cai biliare nedilatate se intalnesc in:Cai biliare nedilatate se intalnesc in:
hepatitehepatite
cirozeciroze
colestaze congenitalecolestaze congenitale
colestaza de sarcinacolestaza de sarcina
colestaze medicamentoasecolestaze medicamentoase
atrezie de cai biliareatrezie de cai biliare
ductopenieductopenie
C.B.PC.B.P
P.S.C.P.S.C.
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Clinica colestazeiClinica colestazei
1.1. pruritprurit
2.2. icter cu bilirubina directa icter cu bilirubina directa
3.3. semne de malabsorbtiesemne de malabsorbtie
4.4. cresteri enzimatice: FA, cresteri enzimatice: FA, GT, ALATGT, ALAT
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Colestaza ereditara:Colestaza ereditara:
1.1. Recurenta benignaRecurenta benigna
2.2. Familiara progresiva (1, 2, 3)Familiara progresiva (1, 2, 3)
3.3. Deficit de sintezaDeficit de sinteza
4.4. Sindromul AlagilleSindromul Alagille
5.5. Deficit de Deficit de 1 1 ATAT
6.6. Mucoviscidoza.Mucoviscidoza.
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Baza genetica a colestazei ereditare:Baza genetica a colestazei ereditare:
LOCUSLOCUS BOALABOALA TRANSPORTORTRANSPORTOR
18q18q C.R.B.C.R.B. ATP azaATP aza
18q18q CP.1CP.1 ATP azaATP aza
2q2q CP.2CP.2 SPGPSPGP
7q7q CP.3CP.3 MDR3MDR3
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Baza genetica a colestazei ereditare:Baza genetica a colestazei ereditare:
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CARACTERE GENERALECARACTERE GENERALE
C.R.B.C.R.B. C.I.H.F.P.C.I.H.F.P.
11 22 33
TRANSMISITRANSMISIEE A.R.A.R. A.R.A.R. A.R.A.R. A.R.A.R.
PRURITPRURIT 3+3+ 3+3+ 3+3+ ++
GTGT NN NN NN
Proliferare Proliferare DuctalaDuctala -- -- -- ++
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Colestaza gravidica:Colestaza gravidica:
• Apare in al IIIApare in al IIIlealea trimestru de sarcina trimestru de sarcina
• Icterul este prezent in 10-20% din Icterul este prezent in 10-20% din
cazuricazuri
• Prurit nocturnPrurit nocturn
• ALAT x 10 > NormalALAT x 10 > Normal
• GT este normalGT este normal
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Prognosticul colestazei gravidice:Prognosticul colestazei gravidice:
1.1. MATERN - favorabil, pot sa apara MATERN - favorabil, pot sa apara
hemoragiihemoragii
2.2. FETAL - frecvent prematuritate, FETAL - frecvent prematuritate,
deces intrauterindeces intrauterin
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Colangita sclerozanta primitiva:Colangita sclerozanta primitiva:
• Reprezinta a IIReprezinta a IIaa
afectiune afectiune
colestatica avand colestatica avand
in general o in general o
evolutie spre evolutie spre
ciroza.ciroza.
• Poate afecta caile Poate afecta caile
intra- si intra- si
extrahepatice.extrahepatice.
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Colangita Sclerozanta primitivaColangita Sclerozanta primitiva
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Manifestari generale C.S.P.:Manifestari generale C.S.P.:
• AstenieAstenie
• PruritPrurit
• SteatoreeSteatoree
• CirozaCiroza
• HTPHTP
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Manifestari specifice C.S.P.:Manifestari specifice C.S.P.:
• Domina stricturileDomina stricturile
• Litiaza biliara (+)Litiaza biliara (+)
• ColangiocarcinomulColangiocarcinomul
• Varice peristomaleVarice peristomale
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Diagnosticul C.S.P. are 4 criterii:Diagnosticul C.S.P. are 4 criterii:
1.1. Absenta unei cauzeAbsenta unei cauze
2.2. FA > x 2 fata de valorile normaleFA > x 2 fata de valorile normale
3.3. Aspectul histologic este specificAspectul histologic este specific
4.4. Apar anomalii radiologice Apar anomalii radiologice
colangiograficecolangiografice
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Histopatologia C.S.P.:Histopatologia C.S.P.:
Stadiul I (portal) – Edem, proliferare Stadiul I (portal) – Edem, proliferare
ductalaductala
II (periportal) – FibrozaII (periportal) – Fibroza
III (septal) – Fibroza P-P, III (septal) – Fibroza P-P,
ductopenieductopenie
IV (cirotic) – Noduli de IV (cirotic) – Noduli de
regenerareregenerare
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Histopatologia C.B.P.:Histopatologia C.B.P.:
Stadiul I – granuloame portale, Stadiul I – granuloame portale,
ductopenieductopenie
Stadiul II – proliferare ductotubularaStadiul II – proliferare ductotubulara
Stadiul III – fibroza portala, piece-Stadiul III – fibroza portala, piece-
meal necrosismeal necrosis
Stadiul IV - cirozaStadiul IV - ciroza
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Colestaza post administrare de Colestaza post administrare de medicamente:medicamente:
Colestaza Colestaza purapura
Hepatita Hepatita colestatica; colestatica; ALAT/FAL<2ALAT/FAL<2
Hepatite Hepatite mixte mixte
2<ALAT/FAL<2<ALAT/FAL<55
medicamentemedicamente putineputine numeroasenumeroase NumeroaseNumeroase
clinicaclinica Icter+/- pruritIcter+/- pruritDureri Dureri
abdominale, abdominale, icter, pruriticter, prurit
Icter frecventIcter frecvent
LeziuneLeziune Colestaza Colestaza centrolobularacentrolobulara
Colestaza+infiltColestaza+infiltrat inflamatorrat inflamator
Necroza + Necroza + inflamatie + inflamatie +
colestazacolestaza
evolutieevolutie Vindecare 4-6 Vindecare 4-6 saptamanisaptamani 1-12 saptamani1-12 saptamani
Idem, rar Idem, rar evolutie evolutie
fulminantafulminanta
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Diagnosticul colestazei prin Diagnosticul colestazei prin medicamente:medicamente:
- hipereozinofilie- hipereozinofilie
- anemie hemolitica- anemie hemolitica
- auto anticorpi serici- auto anticorpi serici
a) a) specificispecifici : : 1. Antimitocondriali1. Antimitocondriali
2. Aniti microsomi2. Aniti microsomi
3. Anti disulfid 3. Anti disulfid izomerazaizomeraza
b) b) nespecificinespecifici : 1. SMA : 1. SMA
2. ANA2. ANA
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Droguri care induc colestaza:Droguri care induc colestaza:
COLESTATICECOLESTATICE HEPATITAHEPATITA
1. Eritromicina 1. Azathriopina 1. Eritromicina 1. Azathriopina
2. Tetraciclina 2. Claritromicina2. Tetraciclina 2. Claritromicina
3. Co trimoxazolul 3. Amoxicilina + 3. Co trimoxazolul 3. Amoxicilina + ac.clavulanac.clavulan
4. Clorpromazina 4. Clorpromazina4. Clorpromazina 4. Clorpromazina
5. Captoprilul 5. AINS5. Captoprilul 5. AINS
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Hepatitele care apar in cursul TBC:Hepatitele care apar in cursul TBC:Printre altele sunt incriminate: Izoniazida, RifampicinaPrintre altele sunt incriminate: Izoniazida, Rifampicina
ALATALAT
< 3 N < 3 N
> 3 N > 3 N
Continua Continua
IntrerupeIntrerupe
ALAT N - icter ALAT N - icter
+ icter + icter
Continua urmarire Continua urmarire
spitalizarespitalizare
vindecare vindecare
HIN fara R, PirHIN fara R, Pir
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NASH ( non alchoolic steatotic NASH ( non alchoolic steatotic hepatitis):hepatitis):
Hepatopatie metabolica generata prin Hepatopatie metabolica generata prin
insulino-rezistentainsulino-rezistenta
-diabet 75%diabet 75%
- HTA 75%- HTA 75%
- hiperlipemie- hiperlipemie
- obezitate- obezitate
- medicamente- medicamente
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NASH - anatomopatologie:NASH - anatomopatologie:
- steatoza macroveziculara- steatoza macroveziculara
- inflamatie intralobulara- inflamatie intralobulara
- necroza intralobulara- necroza intralobulara
- fibroza variabila- fibroza variabila
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Diagnosticul NASH:Diagnosticul NASH:
• Trebuie avut in vedere, in primul rand Trebuie avut in vedere, in primul rand
cresterea ALAT, consecutiv P.B.Hcresterea ALAT, consecutiv P.B.H
• Prin anamneza trebuie exclus alcoolul.Prin anamneza trebuie exclus alcoolul.
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Mecanismul colestazei:Mecanismul colestazei:
1.1. HEPATITE ACUTE:HEPATITE ACUTE:
a) reducerea captarii de a) reducerea captarii de
acizi biliariacizi biliari
b) scaderea sintezei de b) scaderea sintezei de
acizi biliariacizi biliari
c) diluarea acizilor biliari c) diluarea acizilor biliari
in bilain bila
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Mecanismul colestazei:Mecanismul colestazei:
2. 2. CIROZE:CIROZE:
a) maldistributie prin HTPa) maldistributie prin HTP
b) pierderi urinareb) pierderi urinare
c) reducerea sintezeic) reducerea sintezei
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Colereza terapeutica:Colereza terapeutica:
Acidul Ursodeoxicolic (Acidul Ursodeoxicolic (UDCAUDCA):):
Actiune prin sunt cole-Actiune prin sunt cole-
hepatic:hepatic:
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Colereza terapeutica:Colereza terapeutica:
1975:1975:
utilizarea utilizarea UDCAUDCA in dizolvarea calculilor in dizolvarea calculilor
colesterolicicolesterolici
succes terapeutic succes terapeutic 70%70% fata de acidul fata de acidul
chenodeoxicoli (17%)chenodeoxicoli (17%)
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Mecanismul litogenezei:Mecanismul litogenezei:
Suprasaturare in Suprasaturare in colesterol:colesterol:
a) creste secretia de a) creste secretia de
colesterolcolesterol
b) scade concentratia b) scade concentratia
acizilor biliariacizilor biliari
c) scade sinteza de c) scade sinteza de
fosfolipidefosfolipide
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Factori de risc in Litogeneza:Factori de risc in Litogeneza:
a)a) demografici: I. geograficidemografici: I. geografici
II. familialiII. familiali
III. sexIII. sex
b)b) ObezitateaObezitatea
c)c) Droguri: hipocolesterolemiantele, Droguri: hipocolesterolemiantele,
estrogeniiestrogenii
d)d) Boli inflamatorii intestinaleBoli inflamatorii intestinale
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Indicatiile terapiei cu Indicatiile terapiei cu UDCAUDCA::
1. Vezicula biliara functionala1. Vezicula biliara functionala
2. Calculi biliari radiotransparenti2. Calculi biliari radiotransparenti
3. Dimensiuni < 15 mm3. Dimensiuni < 15 mm
4. Risc operator crescut4. Risc operator crescut
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Alte proprietati farmacologice ale Alte proprietati farmacologice ale UDCAUDCA::
1. Cito-protectie – stabilizarea 1. Cito-protectie – stabilizarea
membranelor;membranelor;
2. Imunomodulator : activeaza LT2. Imunomodulator : activeaza LTNK, NK,
scade MHC I, reduce TNFscade MHC I, reduce TNF, IL6;, IL6;
3. Rol antioxidativ;3. Rol antioxidativ;
4. Inhiba apoptoza hepatocitara.4. Inhiba apoptoza hepatocitara.
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Efectele biliare ale administrarii Efectele biliare ale administrarii UDCAUDCA::
1. Colereza;1. Colereza;
2. Inhibitia absorbtiei intestinale a 2. Inhibitia absorbtiei intestinale a
acizilor biliari;acizilor biliari;
3. Creste secretia acizilor biliari 3. Creste secretia acizilor biliari
primari.primari.
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Utilizarea terapeutica a Utilizarea terapeutica a UDCAUDCA::
I. C.B.P.: BeneficiiI. C.B.P.: Beneficii
a) ameliorare biochimicaa) ameliorare biochimica
b) stagnare histologicab) stagnare histologica
c) reducerea mortalitatiic) reducerea mortalitatii
d) cresterea duratei pana d) cresterea duratei pana
la transplant (studiu dublu orb incluzand la transplant (studiu dublu orb incluzand
548 pacienti)548 pacienti)
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Utilizarea terapeutica a Utilizarea terapeutica a UDCAUDCA::
II. C.S.P.: Eficienta demonstrata prin:II. C.S.P.: Eficienta demonstrata prin:
a) ameliorare colestazei;a) ameliorare colestazei;
b) agaravarea CSP la oprirea b) agaravarea CSP la oprirea
terapiei;terapiei;
c) beneficii demonstrate c) beneficii demonstrate
histologic.histologic.
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Utilizarea Utilizarea UDCA UDCA in rejetul in rejetul transplantului hepatic:transplantului hepatic:
UTILIZARE bazata pe:UTILIZARE bazata pe:
a) similitudinea leziunilor cu CBPa) similitudinea leziunilor cu CBP
b) hiperexpresia HLA I, II b) hiperexpresia HLA I, II
(imunomodulare)(imunomodulare)
c) colestaza cu ductopeniec) colestaza cu ductopenie
REZULATAELE SUNT IN CURS DE REZULATAELE SUNT IN CURS DE
EVALUAREEVALUARE
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Utilizarea Utilizarea UDCA UDCA in boala grefei contra in boala grefei contra gazdei (GVHD):gazdei (GVHD):
1. Argumentele sunt similare;1. Argumentele sunt similare;
2. Eficienta probata dupa 2. Eficienta probata dupa
administrare 6 saptamani;administrare 6 saptamani;
3. Apar recidive la oprirea 3. Apar recidive la oprirea
tratamentului.tratamentului.
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Utilizarea Utilizarea UDCA UDCA in in transplantul transplantul medular:medular:
1. Morbiditate si mortalitate crescute 1. Morbiditate si mortalitate crescute
prin complicatii hepaticeprin complicatii hepatice
2. Scade incidenta boli veno- ocluzive2. Scade incidenta boli veno- ocluzive
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UDCA UDCA in transplant combate efectele in transplant combate efectele ciclosporineiciclosporinei::
UTILIZARE bazata pe:UTILIZARE bazata pe:
a) scaderea a) scaderea GT GT
b) scaderea FAb) scaderea FA
c) scaderea ALATc) scaderea ALAT
CICLOSPORINEMIA RAMANE CICLOSPORINEMIA RAMANE
NEMODIFICATA !!!NEMODIFICATA !!!
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Alte indicatii ale tratamentului cu Alte indicatii ale tratamentului cu UDCAUDCA::
• Colestaza gravidicaColestaza gravidica
• Colestaza recurenta benignaColestaza recurenta benigna
• Hepatita virala C cu colestazaHepatita virala C cu colestaza
• NASHNASH
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Utilizarea Utilizarea UDCA UDCA in rejetul in rejetul transplantului hepatic:transplantului hepatic:
UTILIZARE bazata pe:UTILIZARE bazata pe:
a) similitudinea leziunilor cu CBPa) similitudinea leziunilor cu CBP
b) hiperexpresia HLA I, II b) hiperexpresia HLA I, II
(imunomodulare)(imunomodulare)
c) colestaza cu ductopeniec) colestaza cu ductopenie
REZULATAELE SUNT IN CURS DE REZULATAELE SUNT IN CURS DE
EVALUAREEVALUARE