Necrosis bridging

Cholestasis occurred in a woman with alpha-1 antitrypsin deficiency (phenotype PiZZ) who had taken prochlorperazine 5-10 mg qds for 27 months (3). She developed jaundice and ascites. Liver biopsy confirmed diffuse advanced chronic cholestasis, moderate portal and periportal inflammation, and bridging necrosis. Her liver function tests normalized within days of withdrawal of prochlorperazine. 

In persistent confluent and bridging necrosis, the development of correspondingly located fibrotic septa can be observed. Portoportal septa connect neighbouring portal tracts, such as in progressive piecemeal necrosis and in... 

The transformation of the lobular architecture is initiated and maintained by at least two histomorphological processes (i.) piecemeal necrosis and (2.) bridging necrosis, which provides string-like links between the central veins and the portal fields. Portocentral shunts, which are of significance for the fate of cirrhosis, make use of these bridges as routes for their development. During the course of time, these channels, which acquire solid basal membranes like capillaries, carry the portal blood directly to the venous flow-off. As a result, blood is withdrawn from the respective acini these areas become more susceptible to disruption and damage and are forced to restructure anew, (see chapter 35)... 

Stage ni The septal stage displays periportal and bridging necrosis as well as an increasing loss of bile ducts with a simultaneous decline in portal inflammatory infiltrations. Dense concentric fibrosis develops around... 

Chronic autoimmune hepatitis If untreated, AIH (especially type 2) develops almost inevitably into cirrhosis the condition is further aggravated by the presence of multilobular necrosis and bridging necrosis. In bridging necrosis, development of cirrhosis is more rapid between the portal fields and the central vein than between the portal fields themselves, (s. p. 683) (s. fig. 33.4)... 

Bartoli E, Massarelli G, Solinas A, Faedda R, Chiandussi L. Acute hepatitis with bridging necrosis due to hydralazine intake. Report of a case. Arch Intern Med 1979 139(6) 698-9. 

A 62-year-old man had taken a tea made from T. capi-tatum for 4 months when he developed anorexia, nausea, and malaise (25). He also noted dark urine and jaundice. He was admitted to hospital with acute icteric hepatitis. A liver biopsy showed bridging necrosis, inflammatory infiltration, and bile emboli. After withdrawal of the herbal tea he made a full recovery within 3 months. 

Six cases of acute hepatitis occurred in four patients during the first 10 weeks of treatment, and in two after 15 weeks of therapy (3). They were represented by jaundice (n = 5), itching (n = 2), weakness (n = 3), and anorexia, nausea, and vomiting (n = 2). Increases in liver enzymes varied from 1.5 to over 30 times the upper limit of the reference range. Liver biopsy showed centrilobular or panlobular bridging necrosis in the four women and intra-hepatic cholestasis in the two men. Complete recovery of normal liver function tests ensued at follow-up after interruption of nimesulide therapy. 

Severe destruction of liver cells with bridging necrosis was observed in all five patients. None of the individual chemicals in the mixture had known toxicology that matched the clinical characteristics that were observed. The authors of the study suggest that the various chemicals detected in the analysis underwent an interaction among themselves, which synergistically raised their toxicity compared with the original material. I33... 

Severe destruction of liver cells with bridging necrosis was observed in all five patients. 

Caspase and calpain function in cell death bridging the gap between apoptosis and necrosis, Ann. Clin. Biochem. 42, 415 31, 2005 Ho, P.K. and Hawkins, C J., Mammalian initiator apoptotic caspases, FEES J. 272, 5436-5453,2005 Fardeel, B. and Orrenius, S., Apoptosis a basic biological phenomenon with wide-ranging implications in human disease, J. Intern. Med. 258, 479-517, 2005 Cathelin, S R6be, C Haddaoui, L. et al Identification of proteins cleaved downstream of caspase activation in monocytes undergoing macrophage differentiation, J. Biol. Chem. 281, 17779-17788, 2006. 

Acute tubular necrosis can occur in the course of a hepatobiliary disease. In an aetiopathogenetical context, hypoxia, hypotension, nephrotoxins and so far undefined biochemical substances are deemed responsible. The outcome is a disruption in the reabsorption of sodium and water the urine is less concentrated (isosthenuria). There is a greater excretion of sodium (> 30 mEq/1) and of beta-2 microglobulin in the urine. Acute, yet in principle reversible renal failure can develop. Therapy thus consists of bridging the phase of insufficiency temporarily by dialysis. 

Confluent liver cell necrosis, possibly developing into bridging necroses (32) or multilobular (< 3% of cases) or even massive necroses in B, B/D and C hepatitis, as well as in E hepatitis during pregnancy collapse of the lattice fibre network. Formation of passive septa, cholestasis, accumulation of ceroid and siderin in macrophages and stellate cells. 

The incidence of symptomatic hepatic injury associated with ketoconazole is estimated to be about one in 10 000 treated cases (SEDA-18, 284). Biochemically, the pattern was hepatocellular in 54%, cholestatic in 16%, and mixed cholestatic-hepatocellular in 30%. Histology (14 cases) showed a predominantly hepatocellular pattern in 57%, with extensive centrilobular necrosis and mild to moderate bridging (14,15). Lethal cases of toxic hepatitis and a case necessitating transplantation have been reported (14,16,17). 

As embryogenesis involves extensive cellular proliferation, any interference with this process is potentially teratogenic. Interference with spindle formation, inhibition or arrest of DNA synthesis or the incorrect separation of chromatids all fall into this category. Inhibition of DNA synthesis, such as that caused by cytosine arabinoside, slows or arrests mitosis, which cannot progress beyond the S-phase. Thus those areas of the embryo which show extensive cellular proliferation are the most susceptible to both necrosis and subsequent malformation from cytotoxic compounds such as cytosine arabinoside. Inhibition of spindle formation such as that caused by vincristine or colchicine stops separation of chromosomes at anaphase (see page 240). Proper separation of chromatids may not occur because of stickiness or bridging between the chromatids. Clearly interference with mitosis, and hence cell proliferation, is an important cause of teratogenic effects. 

When hardened. Biodentine shows good biocompatibihty with the oral tissues and, in particular, exerts minimal influence on cells of the adjacent pulp. Some loss of cell viability has been reported, but this has been attributed to apoptosis and necrosis, rather than the toxicity of the material [71]. In one study of the performance of Biodentine, it was found that the material caused complete dentinal bridge formation in molars while creating no inflammatory response on the cells of the pulp [72]. Both of these features suggest that this material has promise for application in pulp capping. Its ability to promote regeneration of the hard tissue is particularly noteworthy, and will be considered in more detail in Chapter 9. 

The histopathologic grading is based upon the Broder s Classification System (I-IV) (Lucia and Miller 1992) grade I - cells well differentiated with keratinization, prominent intercellular bridges, and keratin pearls grade II to III - greater nuclear atypia, increased mitotic activity, and decreased keratin pearls grade IV - marked nuclear pleomorphism, nuclear mitoses, necrosis, lymphatic and perineural invasion, no keratin pearls, and deeply invasive. 

---