Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultrastructural studies with the transmission (TEM) and scanning (SEM) electron microscopes have added greatly to our knowledge of cellular structure and function in the liver. The normal polyhedral hepatocyte has numerous subcellular organelles, such as mitochondria, peroxisomes, lysosomes and complex rough (rer) and smooth (ser) endoplasmic reticulum. The normal hepatocyte stores glycogen, and sometimes lipid droplets, and secretes bile through the bile canaliculi between adjacent liver cells. It receives nutrients from the sinusoidal lumen across a fenestrated endothelium which is separated by the Space of Disse' from the plasma membrane. The Space of Disse' contains a scant network of reticulin fibers but no basal lamina. Two types of parasinusoidal cells are found in Disse's space: the fat storing cells of Ito, and the Pit cells which may have an endocrine function. The diseased liver has yielded much information in studies with TEM and SEM. The studies with TEM have been most helpful in studying the etiology of infectious diseases such as hepatitis B; have revealed organelle changes such as megamitochondria in cirrhosis and the fibrillar nature of alcoholic hyaline; have led to the identification of specific deposits in metabolic and storage diseases such as hemochromatosis (iron). Wilson's disease (copper), and alpha-1-antitrypsin deficiency (glycoprotein) have proven useful in identifying drug induced liver cell changes such as proliferation of SER and cholestasis, and are useful for identifying specific cell types in inflammatory and neoplastic diseases. In the future, both TEM and SEM coupled with histochemical, cytochemical, immunohistochemical and other analytic techniques will continue to add greatly to our understanding of the liver in health and disease.
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PMID:Ultrastructure of the liver and biliary tract in health and disease. 637 90

Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal). At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.
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PMID:Laboratory and histological similarities between Wilson's disease and rats with copper toxicity. 645 May 19

Serum parameters of calcium metabolism were measured in 32 consecutive patients with biopsy-proven cirrhosis due to either hepatitis (n = 13), alcohol abuse (n = 11), Wilson's disease (n = 3), or primary or secondary biliary cirrhosis (n = 5). All measurements were normal in the small group of patients with Wilson's disease. The serum concentrations of albumin, vitamin D-binding protein, total calcium, phosphorus, and 1,25-dihydroxyvitamin D3 (1,25-(OH2)D3) were decreased in the other patients with cirrhosis, but their mean serum concentrations of ionized calcium, 25-hydroxyvitamin D3 (25-OHD3) and free 1,25-(OH2)D3 index were normal. A slight but significant increase in the serum PTH measured using a carboxyl-terminal antiserum was found. A significant correlation was found between the serum concentration of either albumin or vitamin D-binding protein and the serum concentrations of total calcium, 25-OHD3, 1,25-(OH2)D3, and PTH but not with ionized calcium or free 1,25-(OH2)D3 index. The observed abnormalities of calcium metabolism in unselected patients with cirrhosis were mainly due to decreased protein synthesis. Only the patients with severe cirrhosis had decreased concentrations of 25-OHD3 but they were nevertheless able to maintain a normal ionized serum calcium and free 1,25-(OH2)D3 level, possibly by means of compensatory hyperparathyroidism.
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PMID:Serum vitamin D metabolites and their binding protein in patients with liver cirrhosis. 654 47

Although Wilson's Disease is a treatable disorder, 9 of 15 cases referred with undiagnosed liver disease in the present series died in 3 to 53 days of admission. We have reviewed these cases to identify features that would allow earlier diagnosis and improvement in management. The presenting symptoms were lethargy and malaise (11 cases), jaundice (11), abdominal pain (9), and deteriorating school performance (4). At diagnosis, all fatal cases had jaundice and ascites, while only one of the 6 survivors had ascites and two had jaundice. Evidence of hemolysis was found in 3 fatal cases and 5 survivors. Serum bilirubin concentrations, aspartate transaminase, and prolongation of prothrombin time were significantly more abnormal in the fatal cases (p less than 0.01) as compared with the survivors. Cirrhosis was present in all fatal cases and in 2 of the 6 survivors. Wilson's Disease must be excluded in children presenting with frank liver disease as well as those with hemolytic anemia, persisting lethargy, abdominal pain, or deteriorating school performance.
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PMID:Wilson's disease in childhood. Variability of clinical presentation. 661 55

Acute hemolytic anemia and the development of liver cirrhosis with ascites 3 month thereafter suggested Wilson's disease in a 12 years old child, which was confirmed by inappropriate copper metabolism. In addition, neurological symptoms and renal tubular insufficiency characterized the early stage of the disease.
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PMID:[Acute hemolysis and liver cirrhosis as leading symptoms of Wilson's disease in childhood]. 663 16

Idiopathic hemochromatosis (IHC) is a genetically determined impairment in control of iron absorption that results in excessive parenchymal iron deposition, particularly in the liver. Of patients with IHC, 50% have little or no chemical evidence of liver dysfunction. Cirrhosis may be clinically occult, but still cause a syndrome of chronic hepatocerebral degeneration. Two patients are reported with IHC and a syndrome of ataxia, rigidity, myoclonic jerks, and dementia. Other associated symptoms may include diminished libido, decreased hearing, peripheral neuropathy, and large joint disease. Because symptoms of IHC can be reversed by phlebotomy, appropriate laboratory studies should be considered to exclude IHC in any patient with unexplained dementia, encephalopathy, and gait ataxia.
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PMID:Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs. 668 41

The entity of chronic hepatitis has long been an enigma, and its treatment confusing. Recent studies have indicated the importance of excluding causes such as drugs, Wilson's disease and alpha 1-antitrypsin deficiency. After excluding such causes, there are 3 major groups--'autoimmune', hepatitis B, and non-A, non-B (NANB) in all of which an immunological basis for pathogenesis exists. The autoimmune group has been subdivided into a milder type (chronic persistent hepatitis) and a more severe type (chronic active hepatitis) on histological grounds. Corticosteroids are indicated in chronic active hepatitis if cirrhosis or bridging necrosis is present. However, corticosteroids are contraindicated in disease due to the hepatitis B virus where chronic active hepatitis correlates with the presence of replicating virus (serum positive for e antigen, DNA polymerase and HBV-DNA), and in such cases antiviral agents and immunomodulation are being studied. Very little is known about NANB hepatitis in the absence of an assay and there may be more than a single agent. In hepatitis B, the development of serological markers, molecular probes (HBV-DNA), natural animal hepatitis with near-identical viruses, and delta antigen (a virus requiring co-infection with hepatitis B) have all extended our knowledge so dramatically that it is hoped that the enigma of chronic hepatitis will be solved when an assay for NANB hepatitis becomes available.
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PMID:Chronic hepatitis. Aetiology and current management. 673 69

When hepatic excretion of copper into bile is impaired, the amount of copper in the liver increases. This happens in extrahepatic cholestasis, primary biliary cirrhosis and in two inherited diseases of copper disease. By six months of age the homozygously affected Bedlington terrier has already begun to accumulate copper in its liver. The trend continues, peaking at the age of five to eight years, when hepatic copper may exceed 10 000 microgram/g dry weight (normal 90--400 microgram/g in livers from mongrels). Despite these concentrations, which are several times higher than those found in any human disease, there is remarkable little evidence of hepatic inflammation or fibrosis in younger Bedlington terriers. The copper is condensed in lysosomes and is identified by X-ray emission spectroscopy. Hepatic cirrhosis eventually develops and death is often associated with ascites and jaundice. Despite characteristic histological differences between the livers in Wilson's disease and in the Bedlington disease, there is a striking general resemblance between the two conditions.
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PMID:Copper and hepatic function. 690 88

In Wilson's disease, redistribution of copper from the liver to extrahepatic tissue coincides with the development of liver disease and cirrhosis. We have considered the possibility that portasystemic shunting may be a factor determining the organ distribution of copper in patients with liver disease. Thirty-two Sprague-Dawley rats were randomized into a sham-operated group, and a group subjected to partial occlusion of the portal vein (PPVO). Half the rats in each group were fed on normal diet and the remainder had copper added to the drinking water. Rats subjected to PPVO developed large portasystemic shunts. Over a 3-month period, none of the groups showed an increase in serum copper concentrations, or copper oxidase levels. Liver and kidney copper concentrations were similarly increased in copper supplemented sham-operated and PPVO rats, but brain copper content in both groups was similar to the unsupplemented controls. In neither unsupplemented nor copper supplemented rats subjected to PPVO, was the organ distribution of copper different from sham-operated controls. This study suggests that portasystemic shunting does not alter the organ distribution, or tissue concentration of copper.
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PMID:The effect of oral copper loading and portasystemic shunting on the distribution of copper in the liver, brain, kidney, and cornea of the rat. 706 6

We studied the clinical histories of four white American siblings who died at 41/2 to six years of age of an unknown form of cirrhosis, in an effort to identify the etiologic factors in this familial syndrome. The family history disclosed no Indian heritage or parental consanguinity. The children were born and raised in New Jersey. Each had been well until progressive lethargy, abdominal swelling, jaundice, and fever developed four to seven months before death. The liver histopathology in each case closely resembled that of Indian childhood cirrhosis and included severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, "micro-micronodular" cirrhosis, and marked deposits of copper and copper-binding protein. Hepatic copper levels were as high as 2083 microgram per gram of tissue (normal, less than 50 microgram). A number of features distinguish this syndrome from Wilson's disease and familial cholestatic disorders of childhood. A genetically determined disturbance in copper metabolism appears to be the most likely cause.
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PMID:Hepatic copper overload and features of Indian childhood cirrhosis in an American sibship. 708 87


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