The document discusses the differences between apoptosis and necrosis. Apoptosis is a highly regulated and programmed process where cells undergo controlled death without inflammatory consequences. It occurs through mitochondrial changes, DNA fragmentation, cellular shrinkage, and formation of membrane-bound apoptotic bodies that are phagocytosed. In contrast, necrosis is unregulated cell death caused by external factors that results in cell swelling and rupture, releasing intracellular contents and triggering inflammation. The document outlines the multi-step process of apoptosis and provides examples of where it is important, such as in development and elimination of damaged cells.

1. Which to choose?
Apoptosis or Necrosis

2. Apoptosis
• (Gr. apo, off + ptosis, a falling).
• highly regulated cellular activity
• occurs rapidly and produces small membrane-enclosed
apoptotic bodies,
• undergo phagocytosis by neighbouring cells or
macrophages.
• BUT cells undergoing necrosis as a result of
accidental injury.

3. Desire to have Apoptosis
• Apoptotic cells: do not rupture and
release none of their contents.
• release of cellular components causes a rapid
series of local reactions & cause inflammatory
response.
• In DNA Damaged Cells; such response is
undesirable.
• Apoptosis occurs rapidly and eliminate the cell
without repercussions.

4. A few examples
• Inside the thymus, T lymphocytes that may
react against self-antigens receive signals that
activate the apoptotosis.
• In the mature ovary, apoptosis happen in both
the monthly loss of luteal cells and removal of
excess occytes + follicles.
• Plays an important role in formation of the
central nervous system.
• Eliminating cells because of: lack of nutrients,
by damage by free radicals; radiation, or by the
action of tumor suppressor proteins
• Note: First discovered in embryos, where
apoptosis is an essential for morphogenesis.
Quicker than Mitosis; no traces.

5. How it happens?
• Most cells of the body can activate their
apoptotic program when major changes
occur in their DNA
• Ex: mutations accumulate in the DNA.
prevents the proliferation to form a
tumour.
• Malignant cells deactivate the genes
that control the apoptotic process, thus
avoiding death and allowing cancer
progression.

6. The Process
1. Loss of mitochondrial function
2. Fragmentation of DNA
3. Shrinkage of nuclear and cell volumes
4. Cell membrane changes
5. Formation and phagocytic removal of these
apoptotic bodies

7. 1- Loss of mitochondrial function
I. Mitochondrial membrane integrity is not
maintained,
II. End of normal activity
III. release of cytochrome c into the cytoplasm
IV. Activates proteolytic enzymes(caspases).
V. Initial caspases activate a cascade of other
caspases, resulting in protein degradation
throughout the cell.

8. Step 2&3
2- Fragmentation of DNA
I. Endonucleases are activated
II. They cleave DNA between nucleosomes into
small fragments.
3- Shrinkage of cell and volume:
Small dark-stained (pyknotic) nuclei
can sometimes be identified with
the light microscope

9. 4-Cell membrane changes
I. The integrity of the plasmalemma is
maintained,
II. cell undergoes dramatic shape changes,
such as "blebbing“
III. Phospholipids normally found only in the inner
layer move to the outer layer, serving as
signals to induce phagocytosis.

10. (A) in epithelium of a villus from the lining of the small intestine (a), in
a corpus luteum beginning to undergo involution (b), and epithelium of
a uterine endometrial gland at the onset of menstruation (c). X400.
H&E.

11. Necrosis
• Caused by microorganisms, viruses,
chemicals, and other harmful agents.
• Necrotic cells swell; their organelles
increase in volume; and finally they burst,
releasing their contents into the
extracellular space.
• Macrophages engulf the debris of necrotic
cells by phagocytosis and then secrete
molecules that activate other
immunodefensive cells to promote
inflammation.

12. Reference
Junqueira's Basic Histology 12th ed.