Download 03-Necrosis and apoptosis 2008

NECROSIS AND APOPTOSIS
Objectives
 Define necrosis and apoptosis
 List the different types of necrosis, examples
of each and its features
 List the different conditions associated with
apoptosis, its morphology and its mechanism
 Know the difference between apoptosis and
necrosis
Objectives
 Define necrosis and apoptosis
 List the different types of necrosis, examples
of each and its features
 List the different conditions associated with
apoptosis, its morphology and its mechanism
 Know the difference between apoptosis and
necrosis
Cell Death
Death of cells occurs in two ways:
1. Necrosis--(irreversible injury) changes produced by
enzymatic digestion of dead cellular elements
2. Apoptosis--vital process that helps eliminate unwanted
cells--an internally programmed series of events
effected by dedicated gene products
Objectives
 Define necrosis and apoptosis
 List the different types of necrosis, examples
of each and its features
 List the different conditions associated with
apoptosis, its morphology and its mechanism
 Know the difference between apoptosis and
necrosis
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
Patterns of Necrosis In Tissues or Organs
As a result of cell death the tissues or organs display
one of these six macroscopic changes:
1.
2.
3.
4.
5.
6.
Coagulative necrosis
Liquifactive necrosis
Caseous necrosis
Fat necrosis
Gangrenous necrosis
Fibrinoid necrosis
Patterns of Necrosis In Tissues or Organs
1. Coagulative necrosis:
the outline of the dead cells are maintained
and the tissue is somewhat firm.
Example: myocardial infarction
1. Liquefactive necrosis:
the dead cells undergo disintegration and
affected tissue is liquefied.
Example: cerebral infarction.
Patterns of Necrosis In Tissues or Organs
3. Caseous necrosis:
a form of coagulative necrosis (cheese-like).
Example: tuberculosis lesions.
4. Fat necrosis:
enzymatic digestion of fat.
Example: necrosis of fat by pancreatic enzymes.
5. Gangrenous necrosis:
Necrosis (secondary to ischemia) usually with superimposed
infection.
Example: necrosis of distal limbs, usually foot and toes in diabetes.
6. Fibrinoid necrosis: typically seen in vasculitis
and glomerular autoimmune diseases
Coagulative Necrosis
Changes in the cytoplasm
and the nucleus
Karyorrhexis
Pyknosis
Karyolysis
Necrosis of the liver induced by herpesvirus.
Herpesvirus invades liver cell nuclei producing nuclear ('ground
glass') mildly basophilic inclusions.
Acute renal tubular necrosis (ischemia) :
increased eosinophilia and pyknosis in necrotic cells
Normal
Necrotic
Ischemic neuronal injury:acidophilic cytoplasm & nuclear pyknosis
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)
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
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.
Remember: True coagulation necrosis involves groups of cells, and is
almost always accompanied, by acute inflammation (infiltrate)
Liquefactive Necrosis
Rate of dissolution of the necrotic cells is faster than the rate of
repair. Usually results in an abscess secondary to bacterial infection.
Liquefactive necrosis : hydrolysis of dead tissues or cells (rapidly
destroyed by lysosomal enzymes from neutrophilic leukocytes (i.e.,
bacterial infections), or clostridia or snake poison.
Liquefactive necrosis that is caused by neurophilic
leukocytes is called pus.
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
Cerebral infarction - this will liquefy eventualy
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
Liquefactive necrosis in brain leads to resolution with cystic spaces.
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.
Fat necrosis secondary to acute pancreatitis
Caseous necrosis:
 A form of coagulative necrosis but
appear cheese-like
 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
Gangrenous necrosis
Necrosis (secondary to ischemia) usually
with superimposed infection.
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.
Fibrinoid necrosis:
• fibrin appear bright red amorphous
material
• affect blood vessels and the glomerulus ,
infiltrated with fibrin
Fibrinoid necrosis: afferent arteriole and part of the glomerulus
are infiltrated with fibrin, (bright red amorphous material)
Fibrinoid necrosis of artery
Objectives
 Define necrosis and apoptosis
 List the different types of necrosis, examples
of each and its features
 List the different conditions associated with
apoptosis, its morphology and its mechanism
 Know the difference between apoptosis and
necrosis
Cell Death
Apoptosis
• vital process that helps eliminate unwanted cells
• an internally programmed series of events effected
by dedicated gene products
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
SEEN IN THE FOLLOWING CONDITIONS:
B. Pathologic
1. To remove damaged cells by virus
2. To eliminate cells after DNA damage by radiation,
cytotoxic agents etc.
3. Cell death in tumors.
Morphology of Apoptosis
1.
Shrinkage of cells
2.
3.
4.
Condensation of nuclear chormatin peripherally under nuclear membrane
5.
Phagocytosis of apoptotic bodies by adjacent healthy cells or phagocytes.
6.
Unlike necrosis, apoptosis is not accompanied by inflammatory reaction
Formation of apoptotic bodies by fragmentation of the cells and nuclei.
The fragments remain membrane-bound and contain cell organelles with
or without nuclear fragments.
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. Cause of chromatin condensation is internucleosomal
DNA fragmentation mediated by calcium-sensitive
endonuclease.
2. Alteration in cell volume 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 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
Tumor suppresor gene p-53
 Will cause cells with DNA damage (eg amplified myc) to go
apoptosis
 Induce bax expression
 Reversed by overexpression of bcl-2
Apoptosis summary
Objectives
 Define necrosis and apoptosis
 List the different types of necrosis, examples
of each and its features
 List the different conditions associated with
apoptosis, its morphology and its mechanism
 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 Single cell, chromatin condensation,
disruption of organelles
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