Necrosis and Apoptosis
Presentor: Dr. Bishal Paudel
1st Year Orthopaedics Resident

Objectives
• To define necrosis and apoptosis
• To explain morphology and mechanism
• To illustrate different types of necrosis
• To discuss briefly about the difference
between necrosis and apoptosis

Cell injury

Reversible vs Irreversible cell injury

Necrosis
• Series of changes that accompany cell death,
largely resulting from the degradative action
of enzymes on lethally injured cells
• characterized by swelling, denaturation and
coagulation of proteins, breakdown of cellular
organelles and cell rupture
• caused by extra-cellular enzymes, liberated
from inflammatory cells

NECROSIS: MORPHOLOGY
Light microscopy (H & E stains)
• Necrotic cells -eosinophilia, glassy
homogeneous appearance
• Cytoplasm- vacuolated
• Myelin figures- whorled phospholipid masses
• Calcified dead cells

• Nuclear changes :
- Karyolysis - gradual fading away of the
basophilic nuclear material, presumably due
to action of DNAses.
- Karyorrhexis - fragmentation of nucleus and
the debris is either phagocytosed by other
cells or just disappears.
- Pyknosis - condensation of nucleus into a deep
basophilic mass. This stage is often followed
by karyorrhexis.

Necrosis: nuclear changes
NORMAL
PYKNOSIS
KARYORHHEXIS
KARYOLYSIS

Types of Necrosis
1) Coagulative necrosis:
- denaturation of cytoplasmic proteins with preservation
of the framework of the coagulated cell
- lschemia/infracts in most tissues (except brain)

• Liquefaction necrosis
- autolysis and heterolysis prevail over protein
denaturation
- necrotic area is soft and filled with fluid with
obliteration of normal architecture
- localized bacterial infection (abscesses) and brain

Caseation necrosis-
- Cellular death with complete loss of architectural
pattern
- Necrotic area is dry, cheesy and friable
- Example: Tuberculosis

• Fat necrosis:
- Enzymatic: acute pancreatitis (saponification of peripancreatic
fat)
- Nonenzymatic: traumatic (eg injury to breast tissue}

• Fibrinoid necrosis:
- Immune vascular reactions (eg, PAN)
- Nonimmune vascular reactions (eg. Hypertensive emergency,
preeclampsia)

• Gangrenous necrosis:
- Distal extremity and GI tract, after chronic ischemia

Apoptosis
• named after the Greek designation for “falling
off”
• 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
• Dead cells are rapidly cleared before its
content are leaked out
• Hence does not elicit inflammatory reaction in
the host

Causes of apoptosis
Apoptosis in physiologic situation:
- programmed destruction of cells during embryogenesis, including
implantation, organogenesis, developmental involution, and
metamorphosis
- Involution of hormone-dependent tissues upon hormone withdrawal,
such as endometrial cell breakdown during the menstrual cycle
- Elimination of potentially harmful self-reactive lymphocytes, either
before or after they have completed their maturation
- Death of host cells that have served their useful purpose, such as
neutrophils in an acute inflammatory response

• Apoptosis in pathologic conditions:
- DNA damage. Radiation, cytotoxic anticancer drugs, and
hypoxia
- Accumulation of misfolded proteins- damage caused by free
radicals
- Cell death in certain infections, particularly viral infections, in
which loss of infected cells is largely due to apoptosis-
adenovirus or HIV infection

Morphologic and biochemical changes
in Apoptosis
• Morphology:
- Cell shrinkage : cell is smaller in size; the cytoplasm is
dense and the organelles are more tightly packed
- Chromatin condensation: chromatin aggregates
peripherally, under the nuclear membrane, into dense
masses of various shapes and sizes
- Formation of cytoplasmic blebs and apoptotic bodies
- Phagocytosis of apoptotic cells or cell bodies, usually
by macrophages

Mechanism of Apoptosis

Intrinsic(mitochondrial) pathway
• result of increased mitochondrial permeability and release of
pro-apoptotic molecules (death inducers) into the cytoplasm
Triggered by:
-Loss of survival signal
- DNA damage
-Accumulation of misfolded
proteins
Inhibited by:
- Survival signals- growth factors

Extrinsic death receptor pathway
Responsible for elimination
of self-reactive
lymphocytes and damage
by cytotoxic T lymphocytes

Disorders associated with
Dysregulated Apoptosis
• Defective apoptosis and increased cell survival
- Cancer
- Autoimmune disorders
• Increased apoptosis and excessive cell death
- Neurodegenerative diseases
- Ischemic injury
- Death of virus infected cells

Different between necrosis and apoptosis

Necrosis vs Apoptosis

References
• Robbins Basic Pathology 9th edition
• First Aid 2019

Thank you