Cell Death Mechanisms: Necrosis vs. Apoptosis

Necrosis is cell injury, while apoptosis is programmed cell death
Cells with necrosis swell and die externally, while apoptosis cells shrink externally and are cleaned up by phagocytosis
You need to be able to discuss cell death, mechanisms for injury, and cellular responses to stress and injury

Cells are constantly adapting to extracellular stresses
Cells actively maintain homeostasis
Cells encounter physiologic or pathologic stimuli.
Adaptation preserves cell viability and function
If the adaptive ability is exceeded, or an external stress is harmful, it causes cell injury
Cell injury can be reversed within limits.
Severe or persistent stress leads to irreversible injury and cell death.
Cell death is critical in normal cells and for disease development.

Cellular size increases, as does the size of the organ containing those cells
No new cells, but cells become bigger
Due to increased amounts of structural proteins and organelles
Happens when non-dividing cells are exposed to stress
Examples include myocardium and skeletal muscle cells. Increase in workload or hormonal stimulation can cause this.

Increase in number of cells; increases organ size
Only occurs in cells that can replicate (mitosis)
Can occur with hypertrophy in response to similar stimuli (physiologic or pathologic)
Physiological hyperplasia:
- Hormonal (e.g., breast development during puberty and pregnancy)
- Compensatory (e.g., liver regeneration after resection)
Pathologic hyperplasia:
- Excessive hormone or growth factor stimulation (e.g., HPV and warts)
Irreversible hyperplasia can lead to dysplasia and cancer

Reversible change where one cell type is replaced by another
Cells resistant to certain stressors replace other, more sensitive cells
Likely a result of "genetic reprogramming" of stem cells
Most common in short-lived, rapidly replaced epithelial cells (e.g., respiratory epithelium in cigarette smokers)
May result in reduced function or an increased chance of malignant transformation

Cell injury occurs when cells are severely stressed or exposed to damaging agents
Cells attempt to adapt, otherwise injury occurs
Injury may be reversible or irreversible
Pathways of cell death:
Necrosis
Apoptosis

Early or mild forms of injury
Functional and morphological changes are reversible if the stimulus is removed; Examples include swelling of the ER and mitochondria.

Specific examples include swelling of cells and the formation of surface blebs, such as in the kidney tubules

Major cell death pathway in many commonly encountered injuries
Always a pathological process
Cellular contents leak and cause inflammation
Includes:
- Degradative actions of enzymes
- Morphological alterations (nuclear shrinkage, fragmentation)
- Breakdown of plasma and organelle membranes
- Leakage and enzymatic digestion of cellular contents
Occurs in collections of cells in tissues or organs

Activated by a tightly controlled suicide program; involves cell's own enzymes degrading itself
Plasma membrane intact
No cellular contents leak out
No inflammatory response; cells recognized and removed by phagocytes
Involved in normal physiological processes and pathological situations
Cellular changes (cell shrinkage, chromatin condensation, membrane blebbing, nuclear fragmentation, formation of apoptotic bodies, phagocytosis)

Apoptosis is induced by both physiological and pathological conditions
- Physiological
  - Cells are eliminated when no longer needed or when cell populations in the tissue must be maintained
- Pathological
  - Elimination of cells genetically altered or injured beyond repair

Apoptosis follows a tightly regulated pathway, either intrinsic (mitochondrial) or extrinsic (receptor-ligand)

Cell death proceeds via apoptosis or necrosis based on stimuli. Both processes are tightly regulated at a molecular level via different pathways to maintain homeostasis. Apoptosis removes damaged cells while necrosis can lead to inflammation and further damage to surrounding tissues.