Transcript Cell Injury and Cell Death

Overview
Normal
cell
+ Stress
- Stress
Adapted
Cell
Injury
Reversibly
injured cell
Irreversibly
Injured cell
Apoptosis
Dead cell
Necrosis
LO
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Define necrosis
Enlist types of necrosis
Identify morphological (gross and
microscopic) features of different
types of necrosis on image.
Enlist three stages in loss of nucleus
resulting in cell death
Define apoptosis
(1) Definition: Localized death of
cell or tissue occurring in the living
body.
(2) Cell death is recognized by:
① Ultrastructural changes
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Margination or progressive loss of
nuclear chromatin
Focal rupture
membrane
of
the
nuclear
Breakdown of the plasmalemma.
Development
of
flocculent
densities in mitochondria.
② Changes in the nucleus.
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Pyknosis:
condensation
chromatin
of
chromatin
shrinkage of the nucleus.
of
and
Karyorrhexis: fragmentation of the
nucleus.
Karyolysis: dissolution of the
nucleus.
Normal
Pyknosis
Karyorrhexis
（参照武忠弼 病理学规划教材第一版 人民卫生出版社1979，修改)
Karyolysis
③
Changes
staining
in
cytoplasm
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Opacification:
denaturation
of
proteins lead to aggregation with
resultant opacification of the
cytoplasm.
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Eosino0.philia: exposure of basic
amino groups results in increased
affinity for acidic dyes such as
④ Biochemical changes
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Release of K+ by dead cells.
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Release of enzymes into the blood.
e. g. increased plasma levels of
creatine
kinases,
lactic
dehydrogenase
and
aspartate
aminotransferase.
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Release of protein or protein
breakdown products into the blood.
Morphology of Necrotic Cells
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Increased Eosinophilia
- loss of RNA (basophilia)
- denatured cytoplasmic protein
Nuclear Changes
- Pyknosis
- Karyorrhexis
- Karyolysis
Myelin figure
– large, whorled phospholipid
mass (phospholipid precipitate)
HISTOLOGIC FEATURES OF
COAGULATIVE NECROSIS
Karyorrhexis
Normal cell
Reversible
cell injury
with
cytoplasmic &
organelle
swelling,
blebbing &
ribosome
detachment
Irreversible
cell injury
with rupture of
membrane &
organelles, &
nuclear
pyknosis
Karyolysis
Morphologic pattern of Necrotic
Cell mass
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Coagulative necrosis special types of
coagulative necrosis
Liquefactive necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
Types:
① Coagulative necrosis:
Gross features: The necrosis area is
swollen, firm and pale.
LM: cell detail is lost, but architecture
preserved. The dead cells retain their
outline but only indistinctly.
This type of necrosis is frequently
caused by lack of blood supply and is
exemplified well in infarcts of solid
organs, e. g. heart, spleen, kidney.
This is an example of coagulative necrosis. This is the typical pattern
with ischemia and infarction (loss of blood supply and resultant tissue
anoxia). Here, there is a wedge-shaped pale area of coagulative necrosis
(infarction) in the renal cortex of the kidney.
Coagulative necrosis of the left ventricular wall
（From ROBBINS BASIC PATHOLOGY，2003）
Ischemic necrosis of the myocardium
A, Normal myocardium.
B, Myocardium with coagulation necrosis
Special types of coagulative necrosis
B. Gangrene
Definition: necrosis of big tissue with
superadded putrefaction, black, fousmelling appearance.
Necrosis of big tissue
green
Or organ or limb
appearance
(black or green
haemoglobin)
putrefactive
black,
organisms infection
due
to
breakdown
of
Types of gangrene :
a. Dry gangrene:
Conditions: only occurs on the skin
surface
following
arterial
obstruction. It is particularly liable
to affect the limbs, especially the
toes.
Character: mummification
Dry gangrene
Types of gangrene :
b. Wet gangrene:
Conditions: Both arterial and
venous
obstruction;
wet
in
environment;
Character: wet swollen,
smelling, black or green.
foul-
Commonly in small intestine,
appendix, lung, and uterus, also in
Moist gangrene
Types of gangrene :
c.
Gas gangrene:
Conditions: deep contaminated wounds
in which there is considerable muscle
damaged by gas formation bacteria.
Character: swollen obviously,
gas
bubbles formation. The infection rapidly
spreads and there is associated severe
toxaemia.
Only occasionally in civilian practice but
② Liquefactive necrosis:
Soft and liquid grossly. Enzymes
digest the cell and convert it to a
formless proteinaceous mass.
Ultimately, discharge of the
contents forms a cystic space. i. e.
central nervous system after
ischemic injury; abscesses.
Morphologic Pattern of Necrosis
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Caseous necrosis
:gross appearance
:microscopic – granulomatous
inflammation
A tuberculous lung with a large area of caseous
necrosis
Tuberculous granuloma showing an area of central
necrosis, epithelioid cells, multiple Langhans-type
giant cells, and lymphocytes.
Special type:
Fat necrosis:
Grossly: Opaque and chalky
LM: outline of necrotic fat cells
filled with amorphous basophilic
material (calcium soaps).
i. e. Digestion of peritoneal fat by
pancreatic enzymes in pancreatic
inflammation.
Foci of fat necrosis with saponification in the
mesentery
 Fibrinoid necrosis:
Definition: This is not a true
degeneration
but
a
strongly
eosinophilic stain like fibrin.
 Location: interstitial collagen and
blood vessels (small artery and
arteriole)
 Nature: one kind of necrosis.
 e. g. in allergic reactive diseases:
active rheumatism, polyarteritis
nodose.
 in non-allergic reactive diseases:
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Fibrinoid change in blood vessel
( 4 )
Consequences
necrosis
of
① Acute or chronic inflammation
② Immunological reactions to
sub
cellular
components
released by dead tissue or selfantigens
altered
by
denaturation.
③ lysis and absorption
④
Isolation
and
discharge:
ulceration and cavity formation
⑤ organization
⑥ encapsulation, calcification.
Apoptosis
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Programmed cell death
Physiologic
pathologic