CIROZE

CIROZA

TERMEN GENERIC PENTRU TOATE FORMELE DE

BOALA CRONICA DIFUZA CARACTERIZATA PRIN :

1. PIERDEREA CELULARA
2. COLAPS SI FIBROZA RETELEI RETICULINICE
3. DISTORSIONAREA PATULUI VASCULAR
4. REGENERARE NODULARA
CIROZA - este un proces difuz cu fibroza si formare de noduli ce succed
necrozei hepato – celulare.

CLASIFICARE
ANATOMICA ETIOLOGICA

MACRONODULARA 1. VIRALA ( B, C, D)

MICRONODULARA 2. ALCOOLICA
3. METABOLICA Fe
Cu
1AT
glicogenoza IV
galactozemie
4. COLESTATICA
5. BLOC VENOS S. BUDD – CHIARI
I. CARDIACA
6. TOXICE – MEDICAMENTOASE
7. IMUNOLOGICE
8. CRIPTOGENETICE
 DIAGNOSTIC

1. ANAMNEZA
2. EXAMEN FIZIC FOETOR, ICTER, PURPURA, DEGETE
HIPOCRATICE, STELUTE VASCULARE
ERITROZA PALMARA, GINECOMASTIE
ATROFIE TESTICULARA, EDEME

3. HEPATOMEGALIE / FICAT MIC

4. SPLENOMEGALIE
5. CIRCULATIE COLATERALA
 ANATOMIA PATOLOGICA

1. INFLAMATIA PORTALA / INTRALOBULARA

2. STAZA BILIARA
3. PROLIFERARE DUCTULARA / DUCTOPENIE
4. GRANULOAME
5. ANOMALII SPECIFICE - CORPII MALLORY
- INCARCARE CU - Fe
- Cu
- PAS +
PIERDEREA DE HEPATOCITE

1. ICTER
2. ASCITA
3. EDEME
4. TULBURARI NEUROLOGICE
5. CASEXIE
6. DECES
 FIBROZA

1. DISTORSIONAREA CAPILARELOR

2. HIPERTENSIUNE PORTALA

VARICE ESO - GASTRICE SPLENOMEGALIE

 REGENERAREA

1. MODIFICARI ALE FORMEI

2. TULBURARI LIMFATICE

ASCITA
DIAGNOSTICUL CLINIC

1. SEMNE GENERALE

a) HABITUS CHVOSTEK
b) BUZE CARMINATE
c) PALME HEPATICE
d) GINECOMASTIE
e) PILOZITATE GINOIDA
f) ATROFIA TESTICULARA
2. SEMNE LOCALE

a) ANOMALII ALE DIMENSIUNILOR

b) MODIFICARE DE CONSISTENTA
c) SPLENOMEGALIE
d) ASCITA – OMFALOCEL
e) CIRCULATIE COLATERALA – CAPUT MEDUSAE
Clinical Features of
Chronic Liver Disease
 Fatigue
 Vascular spiders
 Liver - may be enlarged or shrunken
 Enlarged spleen
 Finger clubbing
 Advanced disease
– Ascites
– Bruising
– Oesophageal varices
A 47-year-old man with a seven-year history of compensated hepatic cirrhosis due to chronic
hepatitis B infection presented for routine evaluation

Yang P and Chen D. N Engl J Med 2005;353:e19

DIAGNOSTIC ANATOMIC

1. MACROSCOPIC - LAPAROSCOPIE
- SCINTIGRAFIE
- ECHOGRAFIE
- TOMOGRAFIE

2. MICROSCOPIC - COLORATII RETICULINA

- COLORATII COLAGEN
DIAGNOSTIC BIOLOGIC

1. EXPLORARI ETIOLOGICE ( VIRUSOLOGICE, IMUNOLOGICE )

2. EXPLORARI FUNCTIONALE
a ) SINDROM INFLAMATOR
b ) SINDROM CITOCITIC
c ) SINDROM COLESTATIC
d ) SINDROM INSUFICIENTA CELULARA
3. HEMATOLOGIE
4. IMPUSE DE COMPLICATII ( Electroliti, amoniac, uree )
 SCORUL CHILD - PUGH

PUNCTE 1 2 3

ENCEFALOPATIE ABSENTA MINIMA COMA

ASCITA ABSENTA MINIMA ABUNDENTA

BILIRUBINA < 3.5 mg % 3.5 – 5 >5

ALBUMINEMIE >3.5 g % 2.8 – 3.5 <2.8

T.P ( % ) >54 45 – 54 < 45

CLASA A <6 CLASA B 7 – 9 CLASA C > 9

TESTE CANTITATIVE

EVALUAREA GRAVITATII BOLII / PROGNOSTIC

• ALEGEREA TERAPIEI
• SORTAREA GRUPELOR OMOGENE
• EVALUAREA TERAPIEI
• ADAPTAREA POSOLOGIEI pentru droguri metabolizate
 NORMAL CIROZA PROGNOSTIC PROST

VERDE INDOCIANIN 1200 400 < 900

( ml / min )

GALACTOZA 400 200 < 100

CAFEINA 140 50 < 17

AMINOPIRINA ( CO2 ) >0.04 > 0.018 <0.01

INTERES - CHIRURGIA HEPATICA

1. Mortalitate
2. Complicatii
3. Evaluarea functiei postoperator
4. Prognosticul posttransplant
 1 / 3 COMA HEPATICA

EVOLUTIE INEXORABIL
1 / 3 H.D.S.
FATALA

1 / 3 HEPATOCARCINOM

CIROZE INACTIVE 1 / 3 DESCOPERITE

NECROPTIC
TRATAMENT :

1. ETIOLOGIC
2. DIETA 1 g proteine / Kcorp / zi
3. DROGURI ANTIFIBROTICE
4. AL COMPLICATIILOR
 MECANISMUL FIBROZEI

I. NECROZA

a) HEPATOCITELE LIBEREAZA MEDIATORI

ACTIVAREA STIMULAREA
KUPFERIANA CELULELOR ITO

b) CELULELE MONONUCLEARE ELIBEREAZA CITOKINE

II. CITOKINELE AMPLIFICA ACTIVITATEA
CELULELOR ITO

PDGF
TNF
TGF,
III. CELULELE ITO -Prolifereaza

-Produc componenti ai fibrozei

 MEDICATIA ANTIFIBROTICA

I. CITOPROTECTIE

1. PGE 1 , 2
2. SILIMARINA
3. FOSFATIDIL COLINA
4. AUDC
5. VITAMINA E
6. Zn
II. REDUCEREA ACTIVITATII ITO.

1. Glicocorticoizii
2. IFN
3. Retinoizii
4. Estrogenii
III. ACTIUNE PE CITOKINE

1. Pentoxfilina  inhiba PDGF

2. Anticorpi anti TGF
3. ENDOTELINA, REDUC PROLIFERAREA
CELULELOR ITO
 IV. INHIBATORII SINTEZEI

1. Prolyl 4 hidroxilaza  efecte nedorite oculare

2. Colchicina

V. CRESTEREA DEGRADARII

1. CORTICOIZII
2. IFN
3. PGE
4. COLCHICINA
HEMOCROMATOZA
PROCES REGLATOR DEFICITAR

ABSORB|IE CRESCUT~

• C. STELATE  COLAGEN

• HEPATOCITE  COLAGEN
 BOLI CU FIER CRESCUT
• HEMOCROMATOZA EREDITAR~: CY282M
• SECUNDARE:
- talasemie
- sideroblastic`
- hemolitic` cronic`
- aport
- boli cronice: BC, PCT
 Hemocromatoza – Anomalie
mostenita a metabolismului Fe
1. Ducand la :

- Absorbtie
- Acumulare > anormale
- Distributie
 2. Afecteaza

Ficatul

Pancreasul

Inima

Rinichii

Articulatiile
 Istoria
• Sheldon 1935 descrie 311 cazuri

• Simon 1974 asociaza boala cu HLA-A3 si A7

• Feder 1996 izoleaza gena HFE

 Boala
… se transmite autosomal recesiv
Gena HFE mutanta C 282 Y
Dar !
25% homozigoti
50% heterozigoti
25% sanatosi
 Patogenie

Gena mutanta (cisteina-tirozina) creste

absorbtia intestinala a fierului prin
incapacitatea acestuia de a patrunde in
enterocit.
 Normal Iron Homeostasis in Humans

Pietrangelo, A. N Engl J Med 2004;350:2383-2397

 Istoria naturala
1. Acumulare asimptomatica
2. Anomalii biologice
- Cresterea sideremiei
- Cresterea coeficientului de saturare a transferinei
- Cresterea feritinei
3. Manifesta clinic
- Astenie fizica
- Dureri articulare
 Criterii de diagnostic
1. Fe hepatic crescut
2. Fe hepatic> 80 mmoli/g
3. Cresterea indexului Fe hepatic
(concentratie/varsta>1.9)
4. Spolierea a 5 g Fe fara anemie
5. Genetic
- Homozigotie C 282 Y
- Heterozigotie C 282 Y + H 63 D
 Dg Diferential in HC

 Suprasarcina Fe din mutatia genei SLC11A3

 - “ – receptorului transferinei
 Aceruloplasminemia
 Atransferinemia congenitala
 Hemocromatoza neonatala
 Hemocromatoza juvenila
 Secundare
• Aport alimentar
• Aport parenteral
• Anemii hemolitice
• Hemodializa
• Boli hepatice (hepatita C,ciroza
alcoolica,SHNA)
• Porfiria cutanata
• Sunturi porto-cave
 Sindromul cataracta
-hiperferitinemie
- Descris 1995 in Italia si Franta
- Boala transmisa autosomal dominant
- Caracterizata prin
- Fe seric normal
- Saturare normala a transferinei
- Feritinemie crescuta
 BAZA GENETIC~

• HFE - HHC gen` MHC I

• TfR - C7922
 DIAGNOSTIC
• ASTENIE
• ARTRALGII
• HEPATOMEGALIE 95%
• DIABET 60%
• ARTROPATII 25%
• HIPERPIGMENTARE
 HISTOPATOLOGIE
• FIER COLORABIL 3,4
• FIER HEPATIC > 80M/g
• INDEX HEPATIC > 2
• SCOATEREA A 5g DE FIER F~R~ ANEMIE
• CY282M
 TRATAMENT

• FLEBOTOMIE  TRANSFERIN~ 50%

SATURAT~

• DESFERIOXAMIN~ 2g/zi
 Boala Polichistica
Variante

1. Hepato-renala

2. Exclusiv hepatica
A 44-year-old woman presented with a 10-month history of intermittent discomfort in the right upper
abdomen

Halkic N and Gillet M. N Engl J Med 2004;351:e3