Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.

Types of Cell Death

The two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.

• Necrosis:

Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of intracellular contents. Lysosomal enzymes digest cellular components, while released molecules like ATP and uric acid act as damage-associated molecular patterns. These signals are recognized by pattern recognition receptors on resident immune and vascular cells, triggering the release of inflammatory mediators and increasing vascular permeability. This promotes recruitment of neutrophils, followed by macrophages, which then clear necrotic debris through phagocytosis.

• Apoptosis

Apoptosis is a programmed, energy-dependent process that removes damaged or unnecessary cells without inflammation. It involves cell shrinkage, chromatin condensation, DNA fragmentation, and formation of apoptotic bodies. The membrane remains intact, and contents are enclosed and rapidly cleared by phagocytes, ensuring orderly removal.

Progression of Injury

Cell death follows reversible injury marked by ATP depletion, ion imbalance, swelling, and organelle dilation. Continued injury leads to irreversible damage, including mitochondrial dysfunction, calcium influx activating destructive enzymes, membrane breakdown, and lysosomal rupture. These events commit the cell to either necrosis or apoptosis.