Introduction
This topic covers apoptosis, a programmed physiological cell death, its morphological and histological features, how it differs from necrosis, and its role.
Apoptosis
- Definition: programmed and coordinated physiological cell death in the living body.
- Causative agents: physiological and pathological processes.
Morphological features
- Shrunken cell.
- Chromatin condensation.
- Cytoplasmic blebs on the membrane and apoptotic bodies.
- Phagocytosis of apoptotic cells or bodies by macrophages.
- Death of single cells; no inflammatory reaction.
Histological features
- On H&E, apoptosis involves single cells or small clusters of cells.
- The apoptotic cell is a round or oval mass of eosinophilic cytoplasm with dense nuclear chromatin fragments.
- Because cell shrinkage and formation of apoptotic bodies are rapid and the fragments are quickly phagocytosed, degraded or extruded into the lumen, apoptosis may occur without being apparent in histological sections.
- Apoptosis does not elicit an inflammatory reaction.
Mechanism: intrinsic and extrinsic pathways
- Apoptosis can be initiated by the intrinsic pathway (senses cell stress, e.g. a virus) or the extrinsic pathway (signal received from other cells). Both activate caspases, enzymes that degrade proteins.
- Extrinsic pathway: a T cell targets a cell and produces Fas ligand; Fas ligand binds its receptor Fas on target cells, which binds proteins linking the receptor to procaspase-8 molecules. These aggregate and cleave one another, starting a proteolytic cascade that leads to apoptosis.
- Intrinsic (mitochondrial) pathway: when cells are stressed, damaged or abnormal, pro-apoptotic signals induce the mitochondria to release cytochrome c into the cytosol, where it binds and activates Apaf-1. Apaf-1 aggregates into an apoptosome that recruits procaspase-9 molecules, which activate and trigger a caspase cascade leading to apoptosis.
- As caspases break down the cell it shrinks and sends distress signals that attract macrophages, which degrade the shrunken cell, leaving no trace and preventing inflammation.