 Apoptosis [Gr., falling off, as petals from flowers] was referred to in the past as programmed cell death. Today the term programmed cell death is applied more broadly to any kind of cell death mediated by an intracellular death program, irrespective of the trigger mechanism. Apoptosis represents a physiologic process. During apoptosis, cells that are no longer needed are eliminated from the organism. This process may occur during normal embryologic development or other normal physiologic processes, such as follicular atresia in the ovaries. Cells can initiate their own death through activation of an internally encoded suicide program. Apoptosis is characterized by controlled autodigestion, which maintains cell membrane integrity; thus, the cell “dies with dignity” without spilling its contents and damaging its neighbors.
FIGURE 3.17 • Schematic diagram showing the relationship between cell death and cell division. Under normal physiologic conditions (homeostasis), the rates of cell division and cell death are similar. If the rate of cell death is higher than that of cell division, then a net loss of cell number will occur. Such conditions are categorized as cell loss disorders. When the situation is reversed and the rate of cell division is higher than the rate of cell death, then the net gain in cell number will be prominent, leading to a variety of disorders of cell accumulation.
TABLE Overview of Characteristic Features Distinguishing Necrosis from Apoptosis 3.2 Features of Dying Cells Necrosis Apoptosis Cell swelling —Cell shrinkage —Damage to the plasma membrane —Plasma membrane blebbing —Aggregation of chromatin —Fragmentation of the nucleus —Oligonucleosomal DNA fragmentation —Random DNA degradation —Caspase cascade activation —
In addition, certain cells or their secretions found in the immune system are toxic to other cells (e.g., cytotoxic T lymphocytes, natural killer [NK] cells); they initiate processes that destroy designated cells (e.g., cancer-transformed or virus-infected cells). In contrast to necrosis and apoptosis, cytotoxic death does not involve one specifc mechanism. For example, cell death mediated by cytotoxic T lymphocytes combines some aspects of both necrosis and apoptosis. For an overview of the apoptosis and necrosis, see Table 3.2.
Necrosis begins with impairment of the cell’s ability to maintain homeostasis.
As a result of cell injury, damage to the cell membrane leads to an influx of water and extracellular ions. Intracellular organelles such as the mitochondria, rER, and nucleus undergo irreversible changes that are caused by cell swelling and cell membrane rupture (cell lysis). As a result of the ultimate breakdown of the plasma membrane, the cytoplasmic contents, including lysosomal enzymes, are released into the extracellular space. Therefore, necrotic cell death is often associated with extensive surrounding tissue damage and an intense infammatory response (Fig. 3.18).
Apoptosis is a mode of cell death that occurs under normal physiologic conditions.
In apoptosis, the cell is an active participant in its own demise (“cellular suicide”). This process is activated by a variety of extrinsic and intrinsic signals. Cells undergoing apoptosis show the following characteristic morphologic and biochemical features (see Fig. 3.18);  DNA fragmentation occurs in the nucleus and is an irre versible event that commits the cell to die. DNA fragmen tation is a result of Ca2-dependent and Mg2-dependent activation of nuclear endonucleases. These enzymes selec tively cleave DNA, generating small oligonucleosomal fragments. Nuclear chromatin then aggregates, and the nucleus may divide into several discrete fragments bounded by the nuclear envelope.