病理学英文课件：Cell Injury(1)2013 for 8 years.ppt

* * * * * * * * * * * * * * * * * * * * * * Mitochondria are important targets for virtually all types of injurious stimuli, including hypoxia and toxins. Cell injury is frequently accompanied by morphologic changes in mitochondria. Mitochondria can be damaged by increases of cytosolic Ca2+, by oxidative stress, by breakdown of phospholipids through the phospholipase A2 and sphingomyelin pathways, and by lipid breakdown products derived there from, such as free fatty acids and ceramide. Mitochondrial damage often results in the formation of a high-conductance channel, the so-called mitochondrial permeability transition, in the inner mitochondrial membrane (Fig. 1–12). Although reversible in its early stages, this nonselective pore becomes permanent if the inciting stimuli persist, precluding maintenance of mitochondrial proton motive force, or potential. Because maintenance of membrane potential is critical for mitochondrial oxidative phosphorylation, it follows that irreversible mitochondrial permeability transition is a deathblow to the cell. Mitochondrial damage can also be associated with leakage of cytochrome c into the cytosol. Because cytochrome c is an integral component of the electron transport chain and can trigger apoptotic death pathways in the cytosol, this pathologic event is also likely to be a key determinant of cell death. * * * * Intracellular accumulations cause by four main pathways: Exceeding normal substance is produced or metabolic rate decreases. For example the fatty liver. Because of genetic defect normal or abnormal substance accumulates. For example, storage disorders (glycogen storage disease, Gaucher’s disease). Absence of critical enzyme which can breakdown certain substance (lysosomal storage disease). Exogenous substance deposits. For example, carbon pigment, silicon particles. * FIGURE 1–39 Mechanisms of protein folding and the role of chaperones. A, Chaperones, such as heat shock proteins (Hsp), protect unfolded or partially f