Apoptosis is a tightly regulated intracellular program of cell death that results in the degradation of a cell's own nuclear DNA and cytoplasmic proteins. Key features of apoptosis include cell shrinkage, chromatin condensation, formation of cytoplasmic blebs and apoptotic bodies, and phagocytosis of apoptotic cells. Apoptosis occurs through both physiological and pathological pathways and involves an initiation phase that activates caspase proteins and an execution phase of protein cleavage, DNA breakdown, and phagocytic recognition.

1. APOPTOSIS
• It is a pathway of cell death that is induced by a tightly regulated intracellular
program in which cells destined to die activate enzymes that degrade cells own
nuclear DNA and cytoplasmic proteins.
• Apoptosis is programmed cell death, a normal physiological or pathological
response to specific internal suicidal signals.

2. Morphology
• Cell shrinkage
• Chromatin condensation
• Formation of cytoplasmic blebs and apoptotic bodies
• Phagocytosis of apoptotic cells or cell bodies, usually by macrophages

3. APOPTOSIS
• Physiological or Pathological
• Genetically controlled (Programmed cell
death, ordered disassembly of cells from
within)
NECROSIS
• Always pathological
• Caused by over whelming noxious
stimuli

4. APOPTOSIS
• MORPHOLOGY
• Death of single cell
• Plasma membrane integrity maintained
• Chromatin condensation
• Cell shrinkage
• Lysosomes and other cytoplasmic
organelles are intact
NECROSIS
• MORPHOLOGY
• Death of contiguous cells
• Plasma membrane disruption
• Nuclear swelling and lyses
• Cell swelling
• Lysosomal breakdown

5. • Fragmentation of nucleus and
cytoplasm
• Phagocytosis of apoptotic bodies by
adjacent cells and macrophages
• No inflammatory response
• Cell lysis and disintegration
• Phagocytosis by macrophages
• Inflammatory response present
APOPTOSIS
MORPHOLOGY
NECROSIS
MORPHOLOGY

6. • Apoptosis is responsible for numerous physiologic and pathologic
processes like:
PHYSIOLOGICAL:
• Programmed destruction of cells during embryogenesis
• Hormone dependent involution of the tissues
• Cell deletion in proliferating cell population in lymphoid organ
• Cellular death after completing its function.

7. PATHOLOGICAL:
• Cellular injury produced by a variety of injurious stimuli like radiation, cytotoxic
anticancer drugs, hypoxia.
• Cellular injury and death in certain viral diseases(HIV and adenovirus)
• Cell death in induced by cytoxic T cells in tumors
• Pathological atrophy in parenchymal organs after duct obstruction

9. PROTEIN CLEAVAGE -- caspases (HALLMARK)
ACTIVATE ENDONUCLEASES
NUCLEAR DNA BREAKDOWN
PHAGOCYTIC RECOGNITION
Biochemical features of apoptosis

10. DISTINCTIVE BIOCHEMICAL FEATURES OF APOPTOSIS
• Protein cleavage by cysteine proteases called caspases
• Protein crosslinking by transglutaminase which converts cytoplasmic proteins into
a linked meshwork
• Intranucleosomal cleavage of dna into characteristic ladder pattern of
oligonucleosomal multiples of about 200 base pairs
• Plasma membrane alterations ,such as flipping of the phosphatidylserine from
the inner to the outer surface

11. MECHANISM/CELLULAR EVENTS
2 Phases:
1) Initiation phase
• Intrinsic (mitochondrial) caspase 9 activation
• Extrinsic (death receptor) caspase 8 and 10 activation
1) Execution phase
• caspase 3, 6, 7 activation

13. Signaling

15. EXECUTION PHASE
• Protein cleavage
• DNA breakdown
• Protein cross-linking
• Phagocytic recognition

16. •CLINICAL SIGNIFICANCE
• Tumours – apoptotic index as a measure of proliferation
• Apoptosis in tumours increases following irradiation & immune
responses.
• Measurement of apoptosis in-vivo/ in-vitro following treatment
may predict effectiveness of therapy.

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