Necrosis hepatic cell

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

TCDD is the most toxic member of the 75 dioxins. It causes death in rats by hepatic cell necrosis. Death can follow a lethal dose by weeks. Acute and subacute exposure result in wasting, hepatic necrosis, thymic atrophy, hemorrhage, lymphoid depletion, chloracne. A by-product of the manufacture... 

Hepatic lesions in the case of yellow fever are more likely to correspond to those of hepatosis, (s. p. 404) There is also evidence of distinct acidophilic hepatocellular necrosis as well as microvesicular fatty degeneration of the hepatocytes. Hyaline, eosinophilic inclusions in the cytoplasm of degenerated hepatic cells (so-called Councilman bodies) are characteristic and were first identified by w.T. Councilman in 1890 in yellow fever (s. p. 396). Acidophilic inclusion bodies in the hepatocellular nuclei which are arranged concentrically around the nucleolus (so-called Torres corpuscles) correspond to the yellow fever virus (C.M. Torres, 1928). The liver does not present any significant signs of inflammation. The reticular fibre structure is maintained, so that the liver architecture is usually completely restored-provided the outcome of the disease is favourable, (s. fig. 23.4)... 

Hepatic Effects. A single case study reported areas of focal necrosis and cell degeneration in the liver of a worker exposed to an undetermined concentration of hydrazine in air once a week for 6 months (Sotaniemi et al. 1971). Studies of workers exposed to 1,1-dimethylhydrazine have reported changes indicative of a hepatic effect including elevated scrum alanine aminotransferase activity, fatty degeneration, and a positive cephalin flocculation test (Petersen et al. 1970 Shook and Cowart 1957). Although the levels of hydrazine and 1,1-dimethylhydrazine exposure were not determined, these studies indicate qualitatively that tlie liver is a target for both hydrazines. 

Often there is no good clinical test available to determine the exact type of hepatic lesion, short of liver biopsy. There are certain patterns of enzyme elevation that have been identified and can be helpful (Table 38-3). ° The specificity of any serum enzyme depends on the distribution of that enzyme in the body. Alkaline phosphatase is found in the bile duct epithelium, bone, and intestinal and kidney cells. 5-Nucleotidase is more specific for hepatic disease than alkaline phosphatase, because most of the body s store of 5 -nucleotidase is in the liver. Glutamate dehydrogenase is a good indicator of centrolobular necrosis because it is found primarily in centrolobular mitochondria. Most hepatic cells have extremely high concentrations of transaminases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are commonly measured. Because of their high concentrations and easy liberation from the hepato-cyte cytoplasm, AST and ALT are very sensitive indicators of necrotic lesions within the liver. After an acute hepatic lesion is established, it may take weeks for these concentrations to return to normal. ... 

The mechanisms of the toxic actions of zinc remain obscure, though in-vitro (but not in-vivo) experiments have shown an inhibitory effect on respiration of the liver, kidney, and gills (Tort et al. 1984). Zinc exerts cytotoxic effects on fibroblastic cell lines of fishes which is stronger than those of copper or nickel but weaker than that of cadmium (Babich et al. 1986). Metallothio-nein induction occurs obviously also in fish (Roch and McCarter 1986). At high zinc concentrations (25 mg L ), necrosis of the hepatic cells and a veil-like film formation on the gills has been observed, affecting the respiration and blood circulation (Wong et al. 1977). 

The first well-documented case (Klatskin and Kimberg 1969) was that of an anaesthetist who developed hepatitis seven times in 5 years. Each of these attacks followed his return to work and re-exposure to halothane. Jaundice was preceded by systemic manifestations which could all be explained by, or interpreted as, manifestations of an immunologically mediated reaction. These included pyrexia, myalgia and eosinophilia. Serial liver biopsies which were carried out showed hepatic cell necrosis, followed by the development of post-necrotic cirrhosis. It had to be established whether that patient was sensitive to halothane, because of the nature of his occupation. Thus, he was exposed to subanaesthetic doses of that agent. 

At autopsy, few findings are striking. The body is often emaciated, and the cause of death may have been uremia, cachexia, or respiratory paralysis. The most conspicuous and consistent findings are in the liver and nervous system. The liver is congested, with central lobular necrosis and occasionally fatty degeneration. An iron-free lipochrome pigment is found in the hepatic cells of some patients. Chemical analysis of the liver demonstrates chromogen, but no porphyrins are found in spleen or bone marrow. 

The patient may have two liver defects—fatty liver and multilobular cirrhosis. Fatty liver results from malnutrition multilobular cirrhosis results from the occlusion of the intrahepatic bile ducts, followed by atrophy and necrosis of the hepatic cells with regeneration and fibrosis. When cirrhosis is severe, hepatic insufficiency and portal hypertension (hypersplenism, esophageal varices, ascites) develop. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

HBV, hepatitis B HCV, hepatitis C IAP, inhibitor of apoptosis protein DBM, IAP binding motifs INCA, inhibitory CARD NASH, non-alcoholic steatohepatitis PCD, programmed cell death PCI, pan-caspase inhibitor OA, osteoarthritis RA, rheumatoid arthritis Smac, second mitochondria-derived activator of caspases TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. 

TNF was originally identified because of its cytotoxic activity against some tumor cell lines and its ability to induce hemorrhagic necrosis of solid tumors in various animal models. However, the clinical use of TNF as an anticancer drug has been so far limited by its severe cardiovascular side effects. Therefore, TNF treatment is limited to regional and local administration of high doses of TNF, often in combination with chemotherapy, as accomplished in isolated limb and isolated hepatic perfusion (ILP and IHP, respectively) [5]. In the case of ILP, typically metastases are treated, patients benefit from this procedure by salvage of limbs from a loss by amputation. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Hepatic Effects. Hepatic effects have been reported in humans exposed orally or by the dermal and inhalation routes to toxic doses of 1,2-dibromoethane (Letz et al. 1984 Olmstead 1960 Saraswat et al. 1986). These effects consist of hepatocellular and Kupffer cell necrosis. Results in humans are supported by animal studies in which the liver is also a target organ for toxic effects of 1,2-dibromoethane following exposure by a variety of routes (Botti et al. 1986 Brandt et al. 1987 Broda 1976 NTP 1982 Rowe et al. 1952). 1,2-Dibromoethane, as well as inducing necrosis, can also act as a hepatocellular mitogen in rats (Ledda-Columbano et al. 1987a). 

Toxicologists classify hepatic toxicants according to the type of injuries they produce. Some cause accumulation of excessive and potentially dangerous amounts of lipids (fats). Others can kill liver cells they cause cell necrosis. Cholestasis, which is decreased secretion of bile leading to jaundice (accumulation of gruesome looking pigments that impart a yellowish color to the skin and eyes) can be... 

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