2.  “Falling off” / “Dropping off”
 Defined as pathway of cell death that is induced
by a tightly regulated suicide program in which
cells destined to die activate enzymes capable of
degrading the cells own nuclear DNA and nuclear
and cytoplasmic proteins

3. CAUSES OF APOPTOSIS:
 Physiologic conditions include:
1. During embryogenesis
2. Hormone-dependent involution
3. Cell deletion in intestinal crypt epithelium
4. Involution of thymus
5. Deletion of autoreactive T cells in thymus
6. Cell death by CTLs (viruses, tumor cells,
transplant rejection)

4.  Pathologic conditions include:
1. DNA damage e.g.
 Hypoxia
 Radiation
 Cytotoxic anticancer drugs
2 . Pathologic atrophy in parenchymal organs after
duct obstruction

5. Morphology:
 Light Microscopy (H & E):
◦ Seen in single cells or clusters of cells
◦ Cells appear as round or oval masses
◦ Cell shrinkage – intensely eosinophilic
cytoplasm

6. ◦ Nuclear C hromatin condenses
◦ Karyorrhexis
◦ Apoptotic bodies form
◦ Phagocytosis of apoptotic bodies
◦ No inflammatory response

8. Mechanisms of Apoptosis:
1. Signaling
 i.e. ‘death signals’ or ‘survival signals’
2. Control & Regulation
 By specific proteins (‘inhibits’ or ‘promotes’
apoptosis) &
 Activation of caspases
 2 pathways
i. Mitochondrial pathway
ii. Death receptor pathway

14. 3. Execution
 By specific executioner caspases
 Their functions include:
i. Protein cleavage (cytoskeletal & nuclear
proteins)
ii. DNA breakdown (by cytoplasmic DNase
activation)
4. Removal of apoptotic cells

15.  Dysregulated apoptosis (“too little” or “too
much”) will lead to either:
1. Disorders associated with defective apoptosis
and increased cell survival e.g.
i. Cancers
ii. Autoimmune disorders

16. 2. Disorders associated with increased apoptosis
and excessive cell death, e.g.
i. Neurodegenerative diseases
ii. Ischemic injury
iii. Death of virus-infected cells

18.  With age,Oxidative phosphorylation by
mitochondria is reduced, as is synthesis of nucleic
acids,proteins etc .
 Senescent cells have a decreased capacity for
uptake of nutrients and for repair of chromosomal
damage.
 There is a steady accumulation of the pigment
lipofuscin, which represents a product of lipid
peroxidation and evidence of oxidative damage .