Apoptosis occurs normally during development and aging and as a homeostatic mechanism to maintain cell populations in tissues. Apoptosis also occurs as a defense mechanism such as in immune reactions or when disease or noxious agents damage cells. Although there are a wide variety of stimuli and conditions, both physiological and pathological, that can trigger apoptosis, not all cells will necessarily die in response to the same stimulus. Irradiation or drugs used for cancer chemotherapy results in DNA damage in some cells, which can lead to apoptotic death through a p53-dependent pathway. Some hormones, may lead to apoptotic death in some cells although other cells are unaffected or even stimulated.
Some cells express Fas or TNF receptors that can lead to apoptosis via ligand binding and protein cross-linking. Other cells have a default death pathway that must be blocked by a survival factor such as a hormone or growth factor. There is also the issue of distinguishing apoptosis from necrosis, two processes that can occur independently, sequentially, as well as simultaneously (Zeiss, 2003). In some cases it’s the type of stimuli and/or the degree of stimuli that determines if cells die by apoptosis or necrosis. At low doses, a variety of injurious stimuli such as heat, radiation, hypoxia and cytotoxic anticancer drugs can induce apoptosis but these same stimuli can result in necrosis at higher doses. Finally, apoptosis is a coordinated and often energy-dependent process that involves the activation of a group of cysteine proteases called “caspases” and a complex cascade of events that link the initiating stimuli to the final demise of the cell Loss of control of apoptosis may result in disease. Excessive apoptosis is implicated in AIDS and Alzheimers disease and insufficient apoptosis may lead to cancer.
Morphology of Apoptosis
Light and electron microscopy have identified the various morphological changes that occur during apoptosis. During the early process of apoptosis, cell shrinkage and pyknosis are visible by light microscopy. With cell shrinkage, the cells are smaller in size, the cytoplasm is dense and the organelles are more tightly packed. Pyknosis is the result of chromatin condensation. On examination with hematoxylin and eosin stain, apoptosis involves single cells or small clusters of cells. The apoptotic cell appears as a round/oval mass. Plasma membrane blebbing occurs followed by karyorrhexis and separation of cell fragments into apoptotic bodies during a process called “budding.” Apoptotic bodies consist of cytoplasm with tightly packed organelles with or without a nuclear fragment. The organelle integrity is maintained and all of this is enclosed within an intact plasma membrane. These bodies are subsequently phagocytosed by macrophages, or neoplastic cells and degraded within phagolysosomes. Macrophages that engulf and digest...