Fig. 2.13 Morphologicappearanceofapoptoticcells.Apoptoticcells(someindicatedbyarrows)incolonicepitheliumareshown.(Somepreparativeregimensforcolonoscopymayinduceapoptosisinepithelialcells,whichexplainsthepresenceofdeadcellsinthisbiopsy.)Notethefragmentednucleiwithcondensedchromatinandtheshrunkencellbodies,somewithpiecesfallingoff.(Courtesy of Dr. Sanjay Kakar, Department of Pathology, University of California San Francisco, San Francisco, California.) microbes cause the death of infected cells. Its role in other pathologic situations is unknown.
Autophagy (“self-eating”) refers to lysosomal digestion of the cell’s own components. It is a survival mechanism in times of nutrient deprivation, so that the starved cell can live by eating its own contents and recycling these contents to provide nutrients and energy. In this process, intracellular organelles and portions of cytosol are first sequestered within an ER-derived autophagic vacuole, whose formation is initiated by cytosolic proteins that sense nutrient deprivation (
Fig. 2.14 ). The vacuole fuses with lysosomes to form an autophagolysosome, in which lysosomal enzymes digest the cellular components. In some circumstances, autophagy may be associated with atrophy of tissues (discussed later) and may represent an adaptation that helps cells survive lean times. If, however, the starved cell can no longer cope by devouring its contents, autophagy may eventually lead to apoptotic cell death.
Extensive autophagy is seen in ischemic injury and some types of myopathies. Polymorphisms in a gene involved in autophagy have been associated with inflammatory bowel disease, but the mechanistic link between autophagy and intestinal inflammation is not known. The role of autophagy in cancer is discussed in Chapter 6. Thus, a once little-appreciated survival pathway in cells may prove to have wide-ranging roles in human disease.
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Fig. 2.14 Autophagy. Cellular stresses, such as nutrient deprivation, activate autophagy genes, which initiate the formation of membrane-bound vesicles in which cellular organelles are sequestered. These vesicles fuse with lysosomes, in which the organelles are digested, and the products are used to provide nutrients for the cell. The same process can trigger apoptosis by mechanisms that are not well defined.
Reversible cell injury: cell swelling, fatty change, plasma membrane blebbing and loss of microvilli, mitochondrial swelling, dilation of the ER, eosinophilia (resulting from decreased cytoplasmic RNA)
Necrosis: Accidental cell death manifested by increased cytoplasmic eosinophilia; nuclear shrinkage, fragmentation, and dissolution; breakdown of plasma membrane and organellarmembranes; abundant myelin figures; leakage and enzymaticdigestion of cellular contents
Morphologic types of tissue necrosis: under different conditions, necrosis in tissues may assume specific patterns: coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid.