Guía de práctica clínica en atresia de las vías biliares / Clinical practice guidelines in biliary atresia

Basada en la mejor evidencia científica disponible, se presenta la guía de práctica clínica en atresia de vías biliares, la cual se define como una obstrucción progresiva de las vías biliares intra- o extrahepáticas en recién nacidos y lactantes pequeños y causa ictericia colestásica grave y cirrosis hepática. Es una enfermedad poco frecuente, de etiología desconocida, con mayor incidencia en países asiáticos. Clínicamente se expresa por ictericia obstructiva, acolia, coluria y hepatoesplenomegalia. Los complementarios expresan una hiperbilirrubinemia directa con aumento de las enzimas hepáticas, y el diagnóstico se confirma en nuestro hospital con la colangiografía, generalmente en el curso de una laparoscopía. El tratamiento es quirúrgico y consiste en la portoenterostomía de Kasai, con mejores resultados en cuanto al drenaje biliar si se realiza antes de los 60 días de vida, así como el trasplante hepático. La enfermedad tiene un curso progresivo hacia la cirrosis hepática en etapas tempranas de la vida, sobre todo si no se realiza el diagnóstico y tratamiento quirúrgico precozmente, con implicaciones en la supervivencia y calidad de vida de estos pacientes. Por tanto, referir precozmente al paciente con sospecha de atresia de vías biliares a un centro especializado es la piedra angular de la actitud médica. La presente guía de práctica clínica pretende ofrecer las herramientas técnicas estandarizadas para mejorar los resultados a los pacientes con esta enfermedad, así como contribuir con la docencia y las investigaciones(AU)

Based on the best scientific evidence available, it is presented the clinical practice guidelines on biliary atresia. This disease is defined as a progressive obstruction of the intra and/or extrahepatic bile ducts in newborns and young infants, causing severe cholestatic jaundice and cirrhosis of the liver. It is a rare disease of unknown etiology, with a higher incidence in Asian countries. It is clinically expressed by obstructive jaundice, acholia, choluria and hepatosplenomegaly. Laboratory tests show a direct hyperbilirubin and elevated liver enzymes, and in our hospital, the diagnosis is confirmed by a cholangiography, usually during a laparoscopy procedure. It has surgical treatment and it involves a Kasai portoenterostomy, with better results regarding biliary drainage if it is performed before 60 days of life, as well as liver transplant. This condition has a progressive course towards liver cirrhosis in early stages of life, mainly if the diagnosis and surgical treatment are not made timely, with implications for the survival and quality of life of these patients. Therefore, early referral of the patient with suspected biliary atresia to a specialized center is the cornerstone of the medical attitude. This clinical practice guidelines aims to offer standardized technical tools to improve the outcome for patients with this disease, as well as to contribute to teaching and research(AU)

Effect of silymarin on oxidative stress and liver histopathology in experimental obstructive jaundice model

ABSTRACT PURPOSE: To investigate the effect of silymarin on oxidative stress and hepatic injury induced by obstructive jaundice in an experimental model. METHODS: Thirty Wistar-Albino type female rats were divided into 3 groups each including 10 rats. Only laparotomy was performed in group 1. Bile duct ligation was performed in group 2. In group 3, bile duct ligation was performed and orogastic silymarin 300 mg/kg/day dose was given for seven days. At the end of seven days, rats were sacrificed. The blood and liver tissue samples were taken to be examined biochemically and histopathologically. RESULTS: The plasma and liver levels of malondialdehyde were significantly lower in silymarin group than in the bile duct ligated group. Although liver levels of GSH were significantly higher in silymarin group than in the bile duct ligated group, there was no significant difference between the plasma GSH levels of these groups. In silymarin group; the enlargement of hepatocytes, dilatation of canaliculi and the edema were regressed. CONCLUSION: Silymarin diminished the harmful effects of obstructive jaundice on liver.

Effect of silymarin on oxidative stress and liver histopathology in experimental obstructive jaundice model.

PURPOSE:: To investigate the effect of silymarin on oxidative stress and hepatic injury induced by obstructive jaundice in an experimental model. METHODS:: Thirty Wistar-Albino type female rats were divided into 3 groups each including 10 rats. Only laparotomy was performed in group 1. Bile duct ligation was performed in group 2. In group 3, bile duct ligation was performed and orogastic silymarin 300 mg/kg/day dose was given for seven days. At the end of seven days, rats were sacrificed. The blood and liver tissue samples were taken to be examined biochemically and histopathologically. RESULTS:: The plasma and liver levels of malondialdehyde were significantly lower in silymarin group than in the bile duct ligated group. Although liver levels of GSH were significantly higher in silymarin group than in the bile duct ligated group, there was no significant difference between the plasma GSH levels of these groups. In silymarin group; the enlargement of hepatocytes, dilatation of canaliculi and the edema were regressed. CONCLUSION:: Silymarin diminished the harmful effects of obstructive jaundice on liver.

[Endoscopic ultrasound-guided choledocho-duodenostomy in advanced pancreatic cancer with duodenal obstruction]. / Colédoco-duodenostomía guiada por ecoendoscopía en cáncer de páncreas avanzado con obstrucción duodenal.

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the first-approach for biliary drainage. In cases of ERCP failure, patients are usually referred for percutaneous transhepatic biliary drainage or surgical biliary bypass. In the last decade, the indications of endoscopic ultrasound (EUS) in the management of patients with pancreatic cancer have increased, and numerous cases of EUS-guided biliary drainage have been reported in patients with failures during the ERCP. Our goal is to report a patient with locally advanced pancreatic cancer who presented with painless jaundice and cholestasis with biliary and duodenal obstruction. A EUS-guided choledochoduodenostomy was performed by placement of a self-expanding metal stent.

Colédoco-duodenostomía guiada por ecoendoscopia en cáncer de páncreas avanzado con obstrucción duodenal / Endoscopic ultrasound-guided choledocho-duodenostomy in advanced pancreatic cancer with duodenal obstruction

La colangiopancreatografía retrógrada endoscópica (CPRE) se considera el tratamiento de primera línea para el drenaje biliar en pacientes con cáncer de páncreas. En los casos de fracaso por CPRE, generalmente se realiza un drenaje biliar transparietohepático o una derivación biliar quirúrgica. En la última década, las indicaciones y la utilidad de la ecoendoscopia en pacientes con cáncer de páncreas han ido creciendo, y se han informado numerosos casos de drenajes biliares guiados por ecoendoscopia como una alternativa al drenaje biliar percutáneo o quirúrgico en fracasos en la CPRE. Nuestro objetivo es comunicar un caso con cáncer de páncreas localmente avanzado que se presentó con ictericia indolora y síndrome coledociano con obstrucción biliar y duodenal, en el que se realizó una colédoco-duodenostomía guiada por ecoendoscopia mediante la colocación de una prótesis metálica autoexpandible.

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the first-approach for biliary drainage. In cases of ERCP failure, patients are usually referred for percutaneous transhepatic biliary drainage or surgical biliary bypass. In the last decade, the indications of endoscopic ultrasound (EUS) in the management of patients with pancreatic cancer have increased, and numerous cases of EUS-guided biliary drainage have been reported in patients with failures during the ERCP. Our goal is to report a patient with locally advanced pancreatic cancer who presented with painless jaundice and cholestasis with biliary and duodenal obstruction. A EUS-guided choledochoduodenostomy was performed by placement of a self-expanding metal stent.

Primeras experiencias con drenaje biliar percutáneo de urgencia en la colangitis aguda / First experiences in performing urgent percutaneous biliary drainage for acute cholangitis

Introducción: la obstrucción biliar es motivo frecuente de morbilidad en los pacientes con metástasis hepáticas, adenopatías periportales y cáncer hepatobiliopancreático. La colangitis aguda es la complicación más temida, debido a su mortalidad. En este trabajo se presentan los primeros abordajes percutáneos realizados por cirujanos del Hospital Clínicoquirúrgico Hermanos Ameijeiras como herramienta para el tratamiento urgente de esta entidad. Objetivo: caracterizar el drenaje percutáneo transparietohepático de urgencia en pacientes con colangitis aguda e ictericia obstructiva. Métodos: se realizó un estudio descriptivo, prospectivo y aplicado con 30 pacientes atendidos de esta forma en dicha institución entre enero de 2008 y diciembre de 2010. Resultados: el diagnóstico etiológico preponderante fue el de tumor maligno de la cabeza del páncreas. La localización baja de la lesión duplicó a la localización alta. La mejoría clínica de la ictericia se evidenció en la mayoría de los pacientes después de una semana tras el procedimiento: el drenaje percutáneo constituyó el método definitivo en el 73,3 por ciento de los pacientes. Las edades medias para los distintos diagnósticos etiológicos exhibieron diferencias estadísticamente significativas. No hubo complicaciones ni mortalidad relacionadas con el procedimiento. Conclusiones: el drenaje biliar percutáneo guiado por ultrasonido es una herramienta útil y segura para el tratamiento de urgencia de la colangitis aguda. Es un método que pueden realizar los cirujanos generales con entrenamiento adecuado y específico, y tiene asociadas pocas complicaciones(AU)

Introduction: bile duct obstruction is a frequent source of morbidity among patients with liver metastasis, periportal lymph nodes and hepatobilopancreatic cancer. Acute cholangitis is the most feared complication because of its mortality. The present paper showed the first percutaneous approaches performed by surgeons in Hermanos Ameijeiras clinical and surgical hospital as a tool for treatment of this urgent complication. Objective: to characterize the urgent transparietohepatic bile drainage performed on patients with acute cholangitis and obstructive jaundice. Methods: this is a prospective, descriptive and applied study with 30 patients cared for in this institution from January 2008 through December 2010. Results: the most frequent etiology was malignancy of the pancreas head; the lower location of the lesion doubled the upper location. Most of the patients clinically improved their jaundice problems after one week of procedure. The percutaneous drainage was the definitive procedure in 73.3 percent of patients. Average ages for the various etiologic diagnoses showed statistically significant differences. There were no complications or death related with the procedure. Conclusions: US-guided percutaneous biliary drainage is a safe useful tool for the urgent treatment of acute cholangitis, it can be performed by general surgeons with specific adequate training and has few associated complications(AU)

Biliary tract schwannoma: a rare cause of obstructive jaundice in a young patient.

Schwannoma is a tumor derived from Schwann cells which usually arises in the upper extremities, trunk, head and neck, retroperitoneum, mediastinum, pelvis, and peritoneum. However, it can arise in the gastrointestinal tract, including biliary tract. We present a 24-year-old male patient with obstructive jaundice, whose investigation with computed tomography abdomen showed focal wall thickening in the common hepatic duct, difficult to differentiate with hilar adenocarcinoma. He was diagnosed intraoperatively schwannoma of common bile duct and treated with local resection. The patient recovered well without signs of recurrence of the lesion after 12 mo. We also reviewed the common bile duct schwannoma related in the literature and evaluated the difficulty in pre and intraoperative differential diagnosis with adenocarcinoma hilar. Resection is the treatment of choice for such cases and the tumor did not recur in any of the resected cases.

Pseudoaneurisma de la arteria hepática propia: reporte de un caso / Traumatic pseudoaneurysm of hepatic artery: case report

Los aneurismas de la arteria hepática son relativamente poco frecuentes y representan del 16 al 20 % de los aneurismas de las arterias viscerales. Las manifestaciones clínicas no son específicas y pueden incluir dolor abdominal, hemorragia digestiva alta o ictericia obstructiva, como el caso que se presenta. Caso clínico: presenta el caso de un hombre de 17 años remitido por ictericia obstructiva; se determinó que la patología causante era un pseudoaneurisma de más de 30 mm. de diámetro en la arteria hepática propia, de origen traumático. La evolución fue tórpida por las lesiones asociadas, pese a la colaboración intensiva de distintas especialidades y al tratamiento electivo. Conclusiones: este tipo de aneurisma ocurre con muy poca frecuencia y tiene un pronóstico muy incierto. El tratamiento debe ser necesariamente individual para cada caso. La ictericia constituyó el signo de debut e indicó la gravedad del pseudoaneurisma de la arteria hepática, cuyo pronóstico es incierto, precisando tratamiento individualizado. Debe seleccionarse cuidadosamente el abordaje que requiere cada paciente, y aunque la vía endovascular es una opción, a veces es imposible recurrir a ella por la complejidad de la localización de la lesión, de ahí la necesidad de que el cirujano posea experiencia en el eje hepatobiliar y su vascularización.

Hemobilia: diagnóstico por imágenes a propósito de dos casos / Hemobilia: imaging report of two cases

El diagnóstico de hemobilia resulta difícil en la práctica diaria; el tratamiento está destinado a detener el sangrado y resolver la causa del mismo. Los aneurismas de la arteria hepática constituyen una patología poco frecuente y una de las causas raras de hemobilia, la presentación clínica es inespecífica e incluye dolor abdominal, ictericia obstructiva y sangrado digestivo alto. Recientemente con el desarrollo de la radiología intervencionista se ha logrado reducir el número de cirugías, mediante la embolización transarterial, obteniendo tasas de éxito entre 80-100%.2 Se presentaran 2 casos de hemobilia, todos fueron estudiados con ecografía, colangiografía por resonancia magnética y angiotomografía. Se describen las características de esta patología con los distintos métodos por imágenes; se destaca la indicación de la arteriografía no sólo para el diagnóstico sino también como tratamiento (embolización). En un caso, la hemobilia fue identificada por duodenoscopia y en el otro por gastroscopia. A ambos pacientes se le realizó ultrasonido abdominal el cual mostró hepatomegalia, vesícula distendida con barro biliar, dilatación de vías biliares e imagen hipoecogénica en segmento V hepático. El doppler revela flujo activo en la vía biliar. Angiotomografía y colangiografía por resonancia magnetica revelaron aneurisma en la arteria hepática derecha en íntimo contacto con la vía biliar, correlacionado con la imágen hipoecogénica observada por ultrasonido. Ambos casos fueron resueltos por la liberación de coils intra-arteriales sin complicaciones.

The diagnosis of hemobilia is difficult in daily practice; treatment is designed to stop the bleeding and resolve its cause. Hepatic artery aneurysms are an uncommon condition and one of the rare causes of hemobilia; clinical presentation is nonspecific and includes abdominal pain, obstructive jaundice and upper gastrointestinal bleeding. Recently, due to the development of interventional radiology, the number of surgeries has successfully been reduced through transarterial embolization, achieving success rates between 80-100%.2 We present 2 cases of hemobilia that were evaluated by ultrasound, MRI cholangiography and angiotomography. We describe the characteristics of this disease with the use of different imaging methods; with emphasis on the use of arteriography not only for diagnosis but also for treatment (embolization). In one case, the hemobilia was identified by duodenoscopy, and in the other by gastroscopy. Both patients underwent abdominal ultrasound that showed hepatomegaly, distended gallbladder with biliary sludge, distended bile ducts and a hypoechoic image in liver segment V. Doppler revealed active flow into the bile duct. Angiotomography and MRI reported an aneurysm in the right hepatic artery in close contact to the bile duct, correlated to the hypoechoic image seen by ultrasound. Both cases were treated with transarterial coil placements without any complications.

Icterícia colestática por lesões de natureza maligna: ensaio iconográfico / Cholestatic jaundice by malignant lesions: pictorial essay

A icterícia colestática de natureza tumoral maligna tem como causas mais frequentes o tumor da cabeça do pâncreas, o tumor da papila, o colangiocarcinoma e os quadros obstrutivos biliares determinadospor lesão secundária hepática parenquimatosa ou linfonodal. Os pacientes geralmente se apresentam com perda ponderal, dor abdominal, icterícia progressiva e aumento de bilirrubina direta, sendo fundamental a avaliação pelos métodos de imagem para o adequado diagnóstico, estadiamento e planejamento terapêutico. O presente ensaio ilustra, com correlação anatomocirúrgica, os aspectos de imagem da ultrassonografia, tomografia computadorizada e, em situaçõesespecíficas, colangiorressonância, das principais neoplasias malignas que cursam com icterícia colestática.

Malignant obstructive jaundice is most commonly caused by cancerof pancreatic head, papilla tumor, cholangiocarcinoma and biliary obstruction induced by secondary lesions of the liver or lymph nodes. Patients usually present with weight loss, abdominal pain, jaundice and progressive increase of direct bilirubin, being essential the evaluation by imaging methods for the proper diagnosis, staging and therapeutic planning. This essay illustrates the imaging aspects of ultrasound and computed tomography – and in specific situations magnetic resonance cholangiography – of the major malignancies that lead to cholestatic jaundice.

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction.

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5% (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction / Avaliação da respiração mitocondrial de miócitos cardíacos em ratos ictéricos sumetidos à obstrução do ducto biliar

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5 percent (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.

OBJETIVO: A proposta deste trabalho é avaliar a capacidade de produção energética do miocárdio mediante análise da respiração mitocondrial em ratos ictéricos submetidos à ligadura do ducto biliar. MÉTODOS: Foram utilizados 16 ratos Wistar machos divididos em 2 Grupos: Grupo SO , os quais foram submetidos à Laparotomia branca e Grupo IC, os quais sofreram ligadura do ducto biliar para o desenvolvimento de icterícia obstrutiva. Todos os animais após 7 dias de cirurgia foram submetidos à nova laparotomia para extração e análise do músculo cardíaco. O consumo de oxigênio pelas mitocôndrias foi determinado pela velocidade do estado 3 e velocidade do estado 4. A razão do controle respiratório (RCR) foi obtida pela relação entre as velocidades dos estados 3 e 4. A análise estatística foi feita pelo teste de Mann-Whitney com nível de significância de 5 por cento (p<0.05). RESULTADOS: Observou-se queda estatisticamente significante nos valores do consumo de oxigênio do estado 3 da respiração mitocondrial no grupo IC em relação ao SO, no entanto os valores para estado 4 permaneceram basicamente inalterados entre os grupos. Os valores de RCR entre os grupos também apresentaram diminuição significativa. CONCLUSÃO: A respiração celular do 'coração ictérico' está deprimida em decorrência da redução da capacidade da mitocôndria cardíaca em consumir oxigênio e sintetizar ATP, o que pode contribuir para a disfunção cardiovascular na vigência da colestase.

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction / Avaliação da respiração mitocondrial de miócitos cardíacos em ratos ictéricos sumetidos à obstrução do ducto biliar

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5 percent (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.(AU)

OBJETIVO: A proposta deste trabalho é avaliar a capacidade de produção energética do miocárdio mediante análise da respiração mitocondrial em ratos ictéricos submetidos à ligadura do ducto biliar. MÉTODOS: Foram utilizados 16 ratos Wistar machos divididos em 2 Grupos: Grupo SO , os quais foram submetidos à Laparotomia branca e Grupo IC, os quais sofreram ligadura do ducto biliar para o desenvolvimento de icterícia obstrutiva. Todos os animais após 7 dias de cirurgia foram submetidos à nova laparotomia para extração e análise do músculo cardíaco. O consumo de oxigênio pelas mitocôndrias foi determinado pela velocidade do estado 3 e velocidade do estado 4. A razão do controle respiratório (RCR) foi obtida pela relação entre as velocidades dos estados 3 e 4. A análise estatística foi feita pelo teste de Mann-Whitney com nível de significância de 5 por cento (p<0.05). RESULTADOS: Observou-se queda estatisticamente significante nos valores do consumo de oxigênio do estado 3 da respiração mitocondrial no grupo IC em relação ao SO, no entanto os valores para estado 4 permaneceram basicamente inalterados entre os grupos. Os valores de RCR entre os grupos também apresentaram diminuição significativa. CONCLUSÃO: A respiração celular do 'coração ictérico' está deprimida em decorrência da redução da capacidade da mitocôndria cardíaca em consumir oxigênio e sintetizar ATP, o que pode contribuir para a disfunção cardiovascular na vigência da colestase.(AU)

Hepatocolangitis por drogas simulando un hepatocarcinoma / Drug-induced hepatocholangitis with characteristics of hepatocarcinoma

La hepatotoxicidad por drogas es una entidad frecuente, con un amplio espectro de manifestaciones y muchas veces subestimada por los médicos. Existen escasos reportes acerca de los hallazgos anatomopatológicos en pacientes con toxicidad hepática aguda causada por drogas...El hallazgo de atipias celulares que simulan neoplasias en tejidos agredidos por drogas es una situación en la cual la experiencia del patólogo y una historia clínica completa son decisivos para orientar el diagnóstico.

Obstructive jaundice induces early depression of mitochondrial respiration in rat hepatocytes

INTRODUCTION: Oxidative phosphorylation dysfunction of hepatocyte mitochondria is involved in the pathophysiology of organ dysfunction following obstructive jaundice (OJ). However the time period from biliary occlusion to the occurrence of the dysfunction has not been determined decisively. PURPOSE: To evaluate the early effects (1 d and 7 d) of OJ on liver mitochondria respiratory function in rats. METHODS: Male Wistar rats (200-250 g) were randomly divided into the following 3 groups: laparotomy plus OJ for 24 h (1d group) (n = 10); laparotomy plus OJ for 7 d (7d group) (n = 10); sham control procedure (CTR group) (n = 12). At the end of OJ periods, total serum bilirubin level, hepatic enzyme activity levels (GOT, GTP, Gama-GT, ALP), mitochondrial respiration phases S3 and S4, as well as the respiratory control ratio (RC = S3/S4), and ADP consumption/oxygen consumption (ADP/O) ratio, were determined. RESULTS: Total serum bilirubin, activity of most hepatic enzymes, and O2 consumption during basal (S4) respiration were increased in the 1d and 7d groups (ANOVA, p = 0.05 vs. CTR). After ADP addition, the O2 consumption rate (S3) in the 1d group remained similar to the CTR rate (ANOVA p > .05), while the RC rate was reduced (ANOVA, p = 0.001) vs. CTR. The effects observed on mitochondrial respiration in the 1d group were exacerbated in the 7d group. CONCLUSION: These results indicate that OJ induces early (24 h) depression of liver mitochondria respiration, and thus may lead to early reduction in the production of high energy bonds.

INTRODUÇÃO: A disfunção da fosforilação oxidativa das mitocôndrias do hepatócito está envolvida na fisiopatologia da disfunção orgânica subseqüente à icterícia obstrutiva (IO). Entretanto, a precocidade da ocorrência desta disfunção permanece obscura. OBJETIVO: Avaliar o efeito precoce da IO na função respiratória mitocondrial em ratos. MÉTODOS: Ratos Wistar machos (200 a 250g) foram randomizados em 3 grupos que foram submetidos a laparotomia mais: IO por 24hs (grupo 1d)(n=10); IO por 7 dias (grupo 7d)(n=10; procedimento simulado (grupo CTR)(n=12). Ao final dos períodos de IO, foram determinados: bilirrubina sérica total, atividade de enzimas hepáticas (TGO, TGP, Gama-GT, FA), e as fases S3 e S4 da respiração mitocondrial, bem como o razão do controle respiratório (RC = S3/S4), e a razão entre consumo de ADP/consumo de oxigênio (ADP/O). RESULTADOS: Observou-se significativo aumento de bilirrubina sérica total, enzimas hepáticas, e consumo de O2 durante a respiração basal (S4) no grupo de IO por 24hs (ANOVA, p=0.009). Após adição de ADP, a taxa de consumo de O2 (S3) não diminuiu significativamente no grupo de IO, comparado com o CTR (ANOVA, p>0.05); entretanto, a razão do controle respiratório (RC) foi significativamente mais baixa comparada com o CTR (ANOVA, p=0.001). Os efeitos observados na respiração mitocondrial no grupo do dia 1d estavam exacerbados no grupo 7d. CONCLUSÃO: Estes resultados indicam que a icterícia obstrutiva induz depressão precoce (24hs) da respiração mitocondrial, e pode assim levar à redução da produção de ligações de alta energia.

Obstructive jaundice induces early depression of mitochondrial respiration in rat hepatocytes.

INTRODUCTION: Oxidative phosphorylation dysfunction of hepatocyte mitochondria is involved in the pathophysiology of organ dysfunction following obstructive jaundice (OJ). However the time period from biliary occlusion to the occurrence of the dysfunction has not been determined decisively. PURPOSE: To evaluate the early effects (1 d and 7 d) of OJ on liver mitochondria respiratory function in rats. METHODS: Male Wistar rats (200-250 g) were randomly divided into the following 3 groups: laparotomy plus OJ for 24 h (1d group) (n = 10); laparotomy plus OJ for 7 d (7d group) (n = 10); sham control procedure (CTR group) (n = 12). At the end of OJ periods, total serum bilirubin level, hepatic enzyme activity levels (GOT, GTP, Gama-GT, ALP), mitochondrial respiration phases S3 and S4, as well as the respiratory control ratio (RC = S3/S4), and ADP consumption/oxygen consumption (ADP/O) ratio, were determined. RESULTS: Total serum bilirubin, activity of most hepatic enzymes, and O2 consumption during basal (S4) respiration were increased in the 1d and 7d groups (ANOVA, p = 0.05 vs. CTR). After ADP addition, the O2 consumption rate (S3) in the 1d group remained similar to the CTR rate (ANOVA p > .05), while the RC rate was reduced (ANOVA, p = 0.001) vs. CTR. The effects observed on mitochondrial respiration in the 1d group were exacerbated in the 7d group. CONCLUSION: These results indicate that OJ induces early (24 h) depression of liver mitochondria respiration, and thus may lead to early reduction in the production of high energy bonds.