NECROSIS AND APOPTOSIS
(Foundation Block, pathology)
Lecturer name: Dr. Maha Arafah
Lecture Date: 25-9-2011
Cell injury L2
Objectives
Define necrosis and apoptosis
 List the different conditions associated
with apoptosis, its morphology and its
mechanism
 List the different types of necrosis,
examples of each and its features
 Know the difference between apoptosis
and necrosis

Reference book and the
relevant page numbers..

Robbins Basic Pathology 8th edition,

pages: 9-22.
Cell Death
Death of cells occurs in two ways:
1. Necrosis--changes produced by enzymatic digestion
ofcells after irreversible injury
2. Apoptosis--vital process that helps eliminate unwanted
cells--an internally programmed series of events
effected by dedicated gene products
Autolysis
Autolysis is the death of individual cells and tissues after the death of
the whole organism.
The cells are degraded by the post-mortem release of digestive
enzymes from the cytoplasmic lysosomes.
Cell Death
Apoptosis
• Vital process.
• Programmed cell death.
• Can occurs in physiological or pathological
conditions.
Apoptosis
Physiologic process to die
This process helps to eliminate unwanted cells by an internally
programmed series of events effected by dedicated gene products. It
serves several vital functions and is seen under various settings.
Remember: apoptosis require energy to die
Apoptosis


SEEN IN THE FOLLOWING CONDITIONS:
A. Physiologic
1.
During development for removal of excess
cells during embryogenesis
2.
To maintain cell population in tissues with high
turnover of cells, such as skin, bowels.
3.
To eliminate immune cells after cytokine
depletion, and autoreactive T-cells in
developing thymus.
4.
Hormone-dependent involution Endometrium, ovary, breasts etc.
Apoptosis
B. Pathologic
1.
2.
3.
4.
To remove damaged cells by virus
Atrophy (virtually never accompanied by
necrosis).
To eliminate cells after DNA damage
by radiation, cytotoxic agents etc.
Cell death in tumors.
Morphology of Apoptosis
1.
Shrinkage of cells
2.
Condensation of nuclear chromatin peripherally under
nuclear membrane
3.
Formation of apoptotic bodies by fragmentation of the
cells and nuclei. The fragments remain membranebound and contain cell organelles with or without
nuclear fragments.
4.
Phagocytosis of apoptotic bodies by adjacent healthy
cells or phagocytes.
5.
Unlike necrosis, apoptosis is not accompanied by
inflammatory reaction
Apoptosis: liver cells are dying individually from injury by
viral hepatitis.
Liver biopsy - viral hepatitis: acidophilic body
(councilman body)
(apoptosis, i.e., induced, or programmed, individual cell death).
Vacuolar change is reversible.
Skin, apoptotic Keratinocyte
MECHANISMS OF APOPTOSIS
1. Chromatin condensation is mediated by calcium-sensitive
endonuclease leading to internucleosomal DNA
fragmentation.
2. Alteration in cell volume (shrinkage) due to action of
transglutaminase.
3. Phagocytosis of apoptotic bodies is mediated by
receptors on the macrophages.
4. Apoptosis is dependent on gene activation and new
protein synthesis, e.g. bcl-2, c-myc oncogene and p53.
Apoptosis summary
Apoptosis regulating genes
Genes that regulate apoptosis:
Oncogene Bcl-2




Bcl-2 overexpression prevents apoptosis
Antagonized by cell death (ced) genes & others (bax,bad)
Localized to mitochondria, nuclear envelope and ER
Bcl-2 overexpression is found in follicular lymphoma.
Tumor suppressor gene p-53



Will cause cells with DNA damage (eg amplified myc) to go
apoptosis
Induce bax expression
Reversed by overexpression of bcl-2
Objectives




Define necrosis and apoptosis
List the different conditions associated with
apoptosis, its morphology and its mechanism
List the different types of necrosis, examples
of each and its features
Know the difference between apoptosis and
necrosis
Necrosis



Necrosis is defined as the morphological changes
that result from cell death within living tissues.
In necrosis, death of a large number of cells in one
area occurs.
These changes occur because of digestion and
denaturation of cellular proteins.
Morphology of necrosis:
1.
Cellular swelling or rupture
2.
Denaturation and coagulation of cytoplasmic
proteins
3.
Breakdown of cell organelles
4.
Breakdown of nuclear DNA
The results of cell death can include:




Cessation of function of a tissue or organ.
Release of cellular enzymes, these can sometimes
be detected in the blood and used as markers of
the extent or timing of damage to a particular
organ, e.g. cardiac enzyme after myocardial
infarction.
Initiation of the inflammatory response (vital
reaction).
Patterns of Necrosis:
In Tissues or Organs

1.
2.
3.
4.
5.
6.
As a result of cell death the tissues or organs
display one of these six macroscopic changes:
Coagulative necrosis
Liquifactive necrosis
Caseous necrosis
Fat necrosis
Gangrenous necrosis
Fibrinoid necrosis
Patterns of Necrosis In
Tissues or Organs
1.


Coagulative necrosis:
Denaturation of intracellular protein leads to the pale firm
nature of the tissues affected. The cells show the
microscopic features of cell death but the general
architecture of the tissue and cell ghosts remain discernible
for a short time.
The outline of the dead cells are maintained
and the tissue is somewhat firm.

Example: kidney and heart injury caused by ischaemia.
Coagulative necrosis
Kidney: ischemia and infarction
(loss of blood supply and resultant
tissue anoxia).
Removal of
the dead
tissue
leaves
behind a
scar
Coagulative necrosis: is due to loss of blood supply
Infarcts (vascular distribution) are wedge-shaped
with a base on the organ capsule.
Spleen
Necrosis of the liver induced by herpesvirus.
Herpesvirus invades liver cell nuclei producing nuclear ('ground
glass') mildly basophilic inclusions.
Coagulative Necrosis
Changes in the cytoplasm
and the nucleus
Karyorrhexis
Pyknosis
Karyolysis
Acute renal tubular necrosis (ischemia) :
increased eosinophilia and pyknosis in necrotic cells
Normal
Necrotic
Coagulative necrosis:

Remember: True coagulation necrosis involves
groups of cells, and is almost always
accompanied, by acute inflammation (infiltrate)
Patterns of Necrosis In
Tissues or Organs
2. Liquefactive necrosis:
 The dead cells undergo
disintegration and affected tissue is
liquefied.

This results from release of hydrolytic lysosomal
enzymes and leads to an accumulation of semifluid tissue.
Example:

cerebral infarction.
 Abscess
Cerebral infarction - this will liquefy eventualy
Liquefactive necrosis in brain leads to resolution with cystic spaces.
Liquefactive necrosis in the brain: in a patient suffered a "stroke"
Liquefactive necrosis of the brain: macrophages cleaning
up the necrotic cellular debris
Removal of the
dead tissue
leaves behind a
cavity
Necrotic myocardium
… a mess - so many
cells have died - the
tissue is not
recognizable. Nuclei
have become pyknotic
(shrunken and dark),
undergone karorrhexis
(fragmentation) and
karyolysis(dissolution)
Liquefactive necrosis: two lung abscesses
Removal
of the
dead
tissue
leaves
behind a
cavity or
scar
Localized liquefactive necrosis liver abscess
Removal of the
dead tissue
leaves behind a
scar
Patterns of Necrosis In
Tissues or Organs
3. Caseous necrosis:



A form of coagulative necrosis but appear
cheese-like.
The creamy white appearance of the dead tissue is probably
a result of the accumulation of partly digested waxy lipid cell
wall components of the TB organisms. The tissue architecture is
completely destroyed.
Example:
tuberculosis lesions
 fungal infections




Coccidioidomycosis
blastomycosis
histoplasmosis
Caseous necrosis in a hilar
pulmonary lymp node
infected with tuberculosis.
Caseous necrosis:
confluent cheesy tan granulomas in the lung in a patient
with tuberculosis
Caseous necrosis: confluent cheesy tan granulomas in the lung in a
patient with tuberculosis.
This is characteristic of a poorly understood subtype of immune injury,
seen in certain granulomatous
diseases (tuberculosis and certain
fungal infections (coccidioidomycosis,
blastomycosis and histoplasmosis)
The macrophage-derived protein
tumor-necrosis factor alpha
("cachectin") is the principal toxin
that causes cells to undergo
caseous necrosis
Pulmonary tuberculosis:tubercle contains amorphous finely
granular, caseous ('cheesy') material typical of caseous necrosis.
Removal
of the
dead
tissue
leaves
behind
a scar
Caseous necrosis is characterized by acellular pink areas of
necrosis, surrounded by a granulomatous inflammatory process.
N
Patterns of Necrosis In
Tissues or Organs
4. Fat necrosis:
This can result from direct trauma or enzyme released
from the diseased pancreas.
Example:


Necrosis of fat by pancreatic enzymes.

Traumatic fat necrosis in breast
Adipocytes rupture and the released fat undergoes lipolysis catalyzed
by lipases. Macrophages ingest the oily material and a giant cell
inflammatory reaction may follow. Another consequence is the
combination of calcium with the released fatty acids.

Fat necrosis secondary to acute pancreatitis
Fat Necrosis
Specific to adipose tissue with triglycerides.
With enzymatic destruction(lipases) of cells, fatty acids are
precipitated as calcium soaps.
Grossly- chalky white deposits in the tissue.
Microscopically – amorphous, basohilic /purple deposits at
the periphery of necrotic adipocytes.
Patterns of Necrosis In
Tissues or Organs
5. Gangrenous necrosis:


This life-threatening condition occurs when
coagulative necrosis of tissue is associated with
superadded infection by putrefactive bacteria.
These are usually anaerobic gram-positive
Clostridia spp. Derived from the gut or soil which
thrive in conditions of low oxygen tension.
Patterns of Necrosis In
Tissues or Organs
5. Gangrenous necrosis:




Gangrenous tissue is foul smelling and black.
The bacteria produce toxins which destroy collagen and
enable the infection to spread rapidly. If fermentation
occurs, gas gangrene ensues.
Infection can become systemic (i.e. reach the bloodstream,
septicaemia).
The commonest clinical situation is gangrene of the lower
limb caused by poor blood supply and superimposed
bacterial infection. This is a life-threatening emergency
and the limb should be amputated.
Example: necrosis of distal limbs,
usually foot and toes in diabetes.
“Wet" gangrene “ of the lower
extremity in patient with
diabetes mellitus:
1.
liquefactive component from
superimposed infection on
2.
coagulative necrosis from
loss of blood supply.
Patterns of Necrosis In
Tissues or Organs

6. Fibrinoid necrosis:

typically seen in vasculitis and glomerular
autoimmune diseases
Fibrinoid necrosis:
• fibrin appear bright red amorphous
material
• affect blood vessels and the glomerulus ,
infiltrated with fibrin
Fibrinoid necrosis of an artery
Fibrinoid necrosis: afferent arteriole and part of the glomerulus
are infiltrated with fibrin, (bright red amorphous material)
Outcome of necrosis
Depending on circumstances:
1. necrotic tissue may be walled off by scar tissue,
2. totally converted to scar tissue,
3. get destroyed (producing a cavity or cyst),
4. get infected (producing an abscess or "wet gangrene"),
5. or calcify.
If the supporting tissue framework does not die, and the dead
cells are of a type capable of regeneration, you may have
complete healing.
Objectives




Define necrosis and apoptosis
List the different conditions associated with
apoptosis, its morphology and its mechanism
List the different types of necrosis, examples
of each and its features
Know the difference between apoptosis and
necrosis
Difference between apoptosis and necrosis
Stimuli
Coagulation Necrosis
Apoptosis
Hypoxia, Toxins
Physiologic and pathologic conditions
Histologic
appearance
Cell swelling, coagulation necrosis
disruption of organelles
Single cell, chromatin condensation,
apoptotic bodies
DNA
breakdown
Random and diffuse
internucleosomal
Mechanism
ATP depletion membrane injury
Gene activation, endonucleases,
proteases
Tissue reaction
Inflammation
No inflammation, phagocytosis of
apoptotic bodies
Energy
Not needed
Needed
TAKE HOME MESSAGES:



Apoptosis is a form of programmed cell death
which could be physiological or pathological.
Necrosis is a death of group of cells scondary to
injury. It is associated with inflammatory reaction,
(unlike apoptosis).
Necrosis has many types which include Coagulative,
liquefaction, gangrenous, caseous and fat necrosis.
Thank You 
Dr. Maha Arafah
25-9-2011

(Foundation Block,
pathology)