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14 - Familial Hepatocellular Cholestasis
- from SECTION II - CHOLESTATIC LIVER DISEASES
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- By Frederick J. Suchy, M.D., Professor and Chair, Department of Pediatrics, Mount Sinai School of Medicine of New York University, New York, New York; Pediatrician-in-Chief, Department of Pediatrics, Mount Sinai Hospital, New York, New York, Benjamin L. Shneider, M.D., Visiting Professor, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania; Director of Pediatric Hepatology, Department of Pediatrics/Gastroenterology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
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- Book:
- Liver Disease in Children
- Published online:
- 18 December 2009
- Print publication:
- 07 May 2007, pp 310-325
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Summary
Inherited cholestasis of hepatocellular origin has long been described in the neonate or during the first year of life [1]. Many of these infants were categorized as having idiopathic neonatal hepatitis after biliary atresia, metabolic diseases, and congenital infections were excluded [2, 3]. The prognosis in familial cases was poor compared with sporadic cases that sometimes had an identifiable etiology. As the clinical and genotypic heterogeneity of these inherited disorders has become apparent, it is now recognized that patients may present initially and progress to end-stage liver disease at ages ranging from infancy to adulthood [4]. There may be significant overlap in clinical features such as intense pruritus and a low serum concentration of γ-glutamyl transpeptidase (γGT). The histopathology, immunohistochemical staining, and hepatic ultrastructure may provide additional diagnostic clues as to the underlying defect. However, the identification of the genes responsible for several of these disorders now allows a specific diagnosis in many cases, may suggest therapy with varying success based on the genotype of the patient, and has advanced our understanding of molecular mechanisms of bile secretion and acquired cholestasis. It is not surprising that, so far, mutations in three genes encoding adenosine triphosphate (ATP)-dependent transport proteins localized to the canalicular membrane that result in progressive cholestasis and liver injury have been discovered. The features of these disorders are compared in Table 14.1. Other genes encoding proteins involved in membrane transport, vesicular trafficking, and integrity of the cell junction may also be mutated in some patients.
7 - Portal Hypertension
- from SECTION I - PATHOPHYSIOLOGY OF PEDIATRIC LIVER DISEASE
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- By Benjamin L. Shneider, M.D., Visiting Professor, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania; Director of Pediatric Hepatology, Department of Pediatrics/Gastroenterology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
-
- Book:
- Liver Disease in Children
- Published online:
- 18 December 2009
- Print publication:
- 07 May 2007, pp 138-162
-
- Chapter
- Export citation
-
Summary
A portal system is one, which by definition, begins and ends with capillaries. The major portal system in humans is one in which the capillaries originate in the mesentery of the intestines and spleen and end in the hepatic sinusoids. Capillaries of the superior mesenteric and splenic veins supply the portal vein with a nutrient- and hormone-rich blood supply (Figure 7.1). The partially oxygenated portal venous blood supplements the oxygenated hepatic arterial flow to give the liver unique protection against hypoxia. Blood flow from the hepatic artery and portal vein is well coordinated to maintain consistent flow and explains the ability of the liver to withstand thrombosis of either of these major vascular structures. This well-regulated blood flow in conjunction with the very low resistance found in the portal system results in a low baseline portal pressure in healthy individuals.
Portal hypertension, defined as an elevation of portal blood pressure above 5 mm Hg, is one of the major causes of morbidity and mortality in children with liver disease (Table 7.1). The high prevalence of biliary tract disease in pediatric liver disorders (e.g., biliary atresia), as compared with adult liver disorders, predisposes to the expression of portal hypertension earlier in the clinical course of liver disease relative to the manifestation of the sequelae of hepatic insufficiency. Portal hypertension is a complication of a wide variety of pediatric liver disorders (Table 7.1). Its complications are some of the leading indications for liver transplantation.