Download Daño hepático es secundario a la respuesta inmune HAV se replica

FISIOLOGIA DIGESTIVA (BCM II)
Hepatitis viral y alcohólica,
esteatohepatitis, cirrosis
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Hepatitis viral
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Human hepatitis viruses
The human hepatitis viruses
Feature
HAV
HBV
Family
Picornavirus
Genome
RNA
HCV
HDV
HEV
Hepadnavirus Flavivirus
Satellite
Caliciviridae
DNA
RNA
RNA
RNA
Virion size, nm 27
42
55
35
32
Enveloped
No
HBsAg
Yes
HBsAg
No
Enteric
transmission
Yes
No
No
No
Yes
Carrier state
No
Yes
Yes
Yes
No
Chronic
hepatitis
No
Yes
Yes
Yes
No
© 2005 Current Medicine Group Ltd
Otros virus pueden producir
hepatitis:
•
•
•
•
Citomegalovirus
Virus Ebstein Barr
Virus herpes
etc
© 2005 Current Medicine Group Ltd
Acute and chronic viral hepatitis
© 2005 Current Medicine Group Ltd
Hepatitis aguda viral A
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Hepatitis A Virus
1 serotipo
4 genotipos
© 2005 Current Medicine Group Ltd
Transmisión de la infección por Hepatitis A
Vía fecal-oral, usualmente contacto de otros enfermos
Se asocia a falta de saneamiento ambiental
Falta de buenas prácticas de higiene
Áreas de bajo nivel socio-económico
Virus vive
hasta 4 horas en los dedos
hasta 6 meses en pozos contaminados
Brotes descritos por consumo de
cebollas verdes (México, USA)
almejas Shanghai
© 2005 Current Medicine Group Ltd
Patogenia de la Hepatitis A
Daño hepático es secundario a la respuesta inmune
HAV se replica en el citoplasma (infección no citopática)
Daño hepatocelular mediado por
Linfocitos T (CD8+)
Natural killers
Interviene el interferón gamma
Respuesta excesiva causa hepatitis severa
© 2005 Current Medicine Group Ltd
Incubation period of hepatitis A virus, Shanghai, 1988, 290.000 cases
Rango: 15 to 49 días
© 2005 Current Medicine Group Ltd
Hepatitis A virus serologic events
© 2005 Current Medicine Group Ltd
Hepatitis fulminante
Definición:
Encefalopatía dentro de las 8 semanas del inicio de
los síntomas en un paciente con hígado previamente sano
Encefalopatía dentro de las 2 semanas del inicio de la
ictericia, incluso en paciente con daño hepático previo
© 2005 Current Medicine Group Ltd
Hepatitis aguda viral B
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Hepatitis B virus particles
© 2005 Current Medicine Group Ltd
The hepatitis B virus life cycle
© 2005 Current Medicine Group Ltd
Risk factors for infection with HBV
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
Hepatitis aguda viral D
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Hepatitis D virus genome
© 2005 Current Medicine Group Ltd
Sequelae of hepatitis D virus
© 2005 Current Medicine Group Ltd
Hepatitis aguda viral C
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Hepatitis C virus particles and genome
© 2005 Current Medicine Group Ltd
Phylogenetic analysis of hepatitis C virus
© 2005 Current Medicine Group Ltd
Sequence of serological events in acute HCV infection
© 2005 Current Medicine Group Ltd
Sequence of serologic events in chronic HCV
© 2005 Current Medicine Group Ltd
HCV risk factors
© 2005 Current Medicine Group Ltd
Frecuency of HCC in Cirrhosis caused by HBV or HCV infection
© 2005 Current Medicine Group Ltd
Typical biopsy findings in viral hepatitis
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
Hepatitis aguda alcohólica
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd
Natural history of alcoholic liver disease
Consumo OH > 60 g/día = Esteatosis
© 2005 Current Medicine Group Ltd
Dose effect and gender differences
Table 9-3. Dose Effect and Gender Differences
Alcohol Intake, units/w Women
Men
ALD Cirrhosis ALD Cirrhosis
<7
1.0
1.0
7-13
2.9
*
4.1
*
14-27
2.9
*
3.1
*
28-41
7.3
*
42-69
70+
1.0
1.0
0.9
1.1
1.4
1.6
3.8
*
N/A N/A
5.9
*
13.0
N/A N/A
9.1
*
18.1
16.8
*
7.0 *
*
*
Statistically significant.
(One unit is equivalent to 10–12 g of alcohol, 12 oz of beer, 4 oz of wine, or 1 oz of spirits.)
© 2005 Current Medicine Group Ltd
Risk factors for alcoholic liver disease
© 2005 Current Medicine Group Ltd
Hepatitis C virus and alcoholic liver disease (A)
RR cirrosis HCV + OH vs. HCV = 8,7
© 2005 Current Medicine Group Ltd
Hepatitis C virus and alcoholic liver disease (B)
© 2005 Current Medicine Group Ltd
Hepatitis C virus and alcoholic liver disease (C): Hepatocarcinoma
RR
23,4
4,6
© 2005 Current Medicine Group Ltd
64,7
Major components of pathogenesis
Metionina
Mitochondrial dysfunction
© 2005 Current Medicine Group Ltd
Metabolism of alcohol: 3 vías de oxidación
Aldehido
deshidrogenasa
*
* MEOS
Catalasa
(peroxisomas)
1- alcohol deshidrogenasa
2- microsomal enzime oxidizing system
© 2005 Current Medicine Group Ltd
3- catalasa
Oxidative stress
NADH/NAD+
© 2005 Current Medicine Group Ltd
Altered methionine metabolism and mitochondrial function
MAT
cisteína
increased cellular sensitivity to oxidative stress, and decreased cellular ATP production
S-adenosylmethionine (SAM)
methionine adenosyltransferase (MAT).
© 2005 Current Medicine Group Ltd
Alcohol and drug metabolism
(MEOS)
sedatives,
oral hypoglycemic agents,
anticoagulants, and vitamins
MEOS—microsomal enzyme oxidizing system.
© 2005 Current Medicine Group Ltd
Alcohol and acetaminophen
N-acetyl-p-benzoquinoneimine
© 2005 Current Medicine Group Ltd
Clinical manifestations of alcohol abuse (Daño hepático crónico)
Table 9-12. Clinical Manifestations of Alc ohol Abuse
Hepatic
Synthetic function: ascites, coagulopathy, hepatomegaly, jaundice
Architecture: portal hypertension, ascites, regenerating nodules
Detoxification: encephalopathy, drug toxicity, feminization
Extrahepatic
Gastrointestinal: varices, diarrhea, mucosal inflammation, hemorrhage, malabsorption, peptic ulcers,
increased risk of malignancies
Neurologic: neuropathies, Wernicke's -Korsakoff's syndrome, depression
Hematologic: thrombocytopenia, leukopenia, hemolytic anemia
Pancreaticobiliary: pancreatitis, pancreatic insufficiency, cholelithiasis
Endocrine: gynecomastia, hypogonadism, infertility, loss of libido, spider nevi, palmar erythema, Dupuytren's
contractures
Cardiovascular: dilated cardiomyopathy, arrhythmias, hypertension
Dermatologic: spider nevi, palmar erythema, jaundice, caput medusae
© 2005 Current Medicine Group Ltd
Laboratory test abnormalities
Table 9-13. Laboratory Test Abnormalities
Liver enzymes
Hepatic function panel (with severe
disease)
AST > ALT; AST usually > 2 × ALT, both values usually < 300
Albumin decreased
IU/dL
GGT increased
Bilirubin usually increased
Alkaline phosphatase increased
Prothrombin time usually prolonged
Complete blood count
Metabolic panel
Leukocytosis
Hypertriglyceridemia
Mild anemia, raised MCV
Hyperuricemia
Thrombocytopenia
Hyperglycemia
Hypokalemia
Hypomagnesemia
Hypophosphatemia
© 2005 Current Medicine Group Ltd
Steatosis
© 2005 Current Medicine Group Ltd
Steatohepatitis (A)
© 2005 Current Medicine Group Ltd
Steatohepatitis (B)
© 2005 Current Medicine Group Ltd
Cirrhosis
© 2005 Current Medicine Group Ltd
Prognosis
Table 9-17. Prognosis
Maddrey Index (Modified Discriminant Function)
4.6 (Patient's prothrombin time - control time)
+ serum bilirubin (mg/dL)
Poor prognosis if >32
© 2005 Current Medicine Group Ltd
© 2005 Current Medicine Group Ltd
Patogenia de la cirrosis hepática
© 2005 Current Medicine Group Ltd
FIN
Dr. Michel Baró A.
© 2005 Current Medicine Group Ltd