Hepatocytes nuclei

In rats treated with disulfiram prior to oral dosing with 1,2-dibromoethane (Plotnik et al. 1979), there was decreased clearance of radiolabeled 1,2-dibromoethane from the body with increased concentration in tissues (liver, kidney, spleen, testis, and brain). In the liver of the disulfiram-1,2-dibromoethane group, there was preferential uptake of labeled 1,2-dibromoethane in hepatocyte nuclei, indicative of DNA binding. 

Microscopic investigation of the mice from group I revealed the presence of vessel congestion, small numerous intralobular and perivenular infiltrates, moderate focal protein-hydropic degeneration combined with polymorphism of hepatocyte nuclei and inconstant lymphoid infiltration of portal tracts. Marked activation of histiomacrophage elements — hepatic macrophages must be emphasized. Homotypic moderate inflammatory alterations remained in the liver on Days 3, 5, 7 and 10. The presence of inflammatory mononuclear infiltration in the walls of central veins, typical for a viral infection, reflects a massive lesion of the vascular... 

Fig. 13. Liver of A/PR/8/34(HlNl) infected, (a) Intralobular protein-hydropic and ballon degeneration of the liver, (b) Small intralobular infiltrates and marked reaction of hepatic macrophages, (c) Polimorphysm of hepatocytes nuclei, (d) Mononuclear infiltration in the wall of the central vein. Hematoxilin-eosin staining, magnification x 400.

Death cap mushroom. Responsible for > 90% of mushroom deaths in the UK. Contains the peptides, amanitine and phalloidine. Hepato-toxic a-amanitine is the major toxic component. Direct attack on hepatocyte nuclei. Vomiting 8-12 h post-ingestion cramping abdominal pain diarrhoea. 2-3 days latent period then jaundice, circulatory collapse, haemorrhage, death. Death rate 30% in best hands . 

FIGURE 19.4 PK/PD modeling results using the fifth-generation model. Symbols and differential equations for the model are defined in Eqs. (19.1)-(19.11). Adrenalectomized rats received 50mg/kg intravenous injection of MPL at Oh. (A) Plasma MPL concentration (B) simulated drug-receptor complex in hepatocyte nucleus (DR(N)) (C) GR mRNA level in hver (D) free GR density in liver (E) TAT mRNA level in liver and (F) TAT activity in liver versus time. Solid circles are the observed data and bars are the standard deviations. Lines are model predictions. (Adapted from Refs. 6 and 7.)... 

Like living organisms themselves, cells come in a remarkable variety of flavors. Brown has described what might be a human cell with elaborate internal structure. However, there is no such a thing as a typical cell. Afunctional liver cell, a hepatocyte, is quite distinct from a nerve cell, a neuron, that, in turn, is not much like a cell of the retina of the eye. Skin cells, pancreatic cells, kidney cells, cells of the testis and ovary, red blood cells, bone cells, and on and on, are all structurally, functionally, and metabolically distinct. Indeed, there are several types of cells in the skin, pancreas, kidney, testis, ovary, and bone. Then there are the cells of bacteria and other microorganisms that have no nucleus or other membrane-limited organelles very different. Diversity abounds. 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

Hexoldnase IV (glucokinase) is sequestered in the nucleus of the hepatocyte, but is released when the cytosolic glucose concentration rises. 

Figure 29-4. Stellate cell lipid droplets present in a biopsy obtained from the liver of a patient experiencing vitamin A toxicity. Image obtained from electron microscopy of a biopsied human liver showing the characteristic lipid droplets (LD) found in hepatic stellate cells (SC).These lipid droplets are highly enriched in vitamin A, and the size and number of lipid droplets is influenced by dietary vitamin A intake and nutritional status. In this image of a human stellate cell, the nucleus (N) is compressed by the surrounding lipid droplets, and very little cell cytoplasm within the stellate cell can be seen in this view.Adjoining the stellate cell are two hepatocytes (H).

Figure 16.7. Microscopic appearance of necrosis. (A) Coagulative necrosis in a virally infected avian liver. Hepatocytes in the lower half of the photo are in various stages of necrosis, with small, pyknotic or fragmented nuclei and increased cytoplasmic eosinophilia. (B) Necrotic cells in immune-mediated skin disease, canine. The central cell has a pyknotic nucleus and intensely eosinophilic cytoplasm, while the cells at lower left and upper left are injured and swollen. The smaller cells are neutrophils. See color insert.

A separate pool has been proposed for the nucleus however, that finding remains in dispute. Mitochondrial glutathione is a separate physiological pool of glutathione in agreement with the observation that the liver has two pools of GSH. One has a fast (2-hr) and the other a slow (30-hr) turnover. In freshly isolated rat hepatocytes, the mitochondrial pool of GSH (about 10% of the total cellular pool) has a half-life of 30 hr while the half-life of the cytoplasmic pool is 2 hr. It has been concluded that the mitochondrial pool represents the stable pool of GSH observed in whole animals. 

Fig. 2.8 Spatial relationship of sinusoid and hepatic cells hepatocytes (H) in the form of boundary lamella (BL), cell nucleus (CN), canahculus (BC), Disse s space (D), endothelial cells (E), sieve plate (SP), Kuplfer cell (K), Ito cell (I). The cellular interchange area is increased by microvilli (modified from D. Sasse, 1986)...

Hepatocytes were discovered by M.H. Dutrochet, who recognized cellules vesiculaires agglomerees in liver tissue in 1824. This first description was confirmed and expanded by F. Kiernan (1833), J. Henle (1836) and J. E. Pur-KiNJE (1837) they also discovered the liver cell nucleus. 

Liver cells comprise the cell nucleus (= karyoplasm) and the cell body (= cytoplasm). Hepatocytes and sinusoidal cells have various types of organelles in their eosinophilic cytoplasm such as endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, peroxisomes, ribosomes, centrioles and kinetosomes. Numerous and diverse metabolic processes take place with their help. Almost all cytoplasmic structures of liver cells are continuously renewed (up to twice daily). (20, 27, 30, 33, 35, 46-48, 50, 53, 58, 59, 69, 74) (s. figs. 2.9, 2.16-2.18) (s. tab. 2.1)... 

Fig. 2.17 Hyaloplasm of the hepatocyte glycogen granules (G), mitochondria (M), rough endoplasmic reticulmn with ribosomes (R) edge of the cell nucleus (CN) x 32,000 (s. fig. 2.9)...

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