Bit · Pathology
Apoptosis vs Necrosis
Two ways a cell can die. Apoptosis is planned, energy-dependent, and inflammation-free. Necrosis is unplanned, energy-failure-driven, and inflammatory.
Mechanism
Both end with cell death but the mechanism and consequences are opposite:
- Apoptosis — programmed cell death. The cell receives an internal (mitochondrial / intrinsic) or external (death receptor / extrinsic) signal, activates caspases in an orderly cascade, fragments its DNA at internucleosomal sites (ladder pattern), packages itself into apoptotic bodies, and is phagocytosed by macrophages. No inflammation because cell membrane stays intact until the body is consumed. Energy-dependent (requires ATP).
- Necrosis — unplanned cell death from lethal injury (ischemia, toxin, infection, mechanical). Membrane integrity is lost early, intracellular contents spill out (including DAMPs), and the surrounding tissue mounts an acute inflammatory response. Several morphologic patterns (coagulative, liquefactive, caseous, fat, fibrinoid — see that Bit).
Apoptosis pathways: intrinsic (mitochondrial) — cellular stress, DNA damage, growth-factor withdrawal → Bcl-2 family balance shifts → cytochrome c released → caspase-9 → executioner caspases. Extrinsic — Fas-FasL or TNFR signalling → caspase-8 → executioner caspases.
Differentiator Table
| Apoptosis | Necrosis | |
| Stimulus | Physiological or pathologic (DNA damage, growth-factor loss, signalling) | Always pathologic (ischemia, toxin, severe injury) |
| Energy requirement | Active — requires ATP | Passive — ATP failure |
| Cell size | Shrinkage | Swelling |
| Nucleus | Pyknosis → karyorrhexis → karyolysis; DNA cleaved at nucleosomes (ladder pattern) | Same final steps (pyknosis/karyorrhexis/karyolysis), but DNA degraded randomly (smear) |
| Plasma membrane | Intact — blebs that pinch off (apoptotic bodies) | Disrupted early — contents leak |
| Inflammation | Absent | Present (acute inflammation) |
| Clearance | Phagocytosed by macrophages (PS flips to outer leaflet, signals 'eat me') | Inflammatory recruitment, scarring |
| Distribution | Single cells | Often confluent fields of cells |
| Classic examples | Embryologic webbing loss, thymocyte selection, hormone-dependent involution, cytotoxic T-cell killing, viral infection clearance | MI, stroke, gangrene, pancreatitis, abscess |
The Pivot
One feature is usually decisive: is there inflammation?
- Single cells dying without surrounding inflammation, with intact membrane and PS flipped outward? → Apoptosis.
- Confluent dead tissue with acute inflammatory infiltrate and membrane rupture? → Necrosis.
On histology, the apoptotic cell looks like a tight, pink, shrunken corpuscle with condensed chromatin — often called a 'Councilman body' in the liver.
NBME-Style Stem
A 6-week embryo undergoes interdigital cell death during finger development. The dying cells show nuclear chromatin condensation, cell shrinkage, blebbing of the plasma membrane, and are engulfed by neighbouring macrophages. No inflammatory response is observed. Which mechanism is most directly responsible?
Concept Anchor
Apoptosis is a planned controlled demolition — the cell folds itself up, pockets the debris, and a macrophage hauls it away without a single neighbour noticing. Necrosis is an explosion — contents spill out, neighbours hear the alarm, and inflammation comes running.