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LECTURE NO 4 & 5
Irreversible cell injury (Apoptosis vs Necrosis)
Types of Necrosis
Irreversible cell injury
Microscopic morphological Changes
Once cell death occurs, degradation of the cell begins
o Increased eosinophilia
o Moth eaten cytoplasm
o Loss of cellular detail
Nuclear Changes
Pyknosis: Nuclear condensation
Karyorrhexis: Fragmentation of the nucleus
Karyolysis: lysis of the nucleus by endonuclease
Irreversible cell injury- Nuclear Changes
Irreversible Cell injury (Pathological Change that can not be reversed)
Apoptosis Vs Necrosis.
Apoptosis
Predefined cell suicide or programmed cell
death. Natural physiological Process. Involve
one cell at a time.
Cell shrinkage (Dense eosinophilic cytoplasm)
Pyknosis (Condensation) and Karyorrhexis
(fragmentation) of nuclear material
Formation of membrane blebs and apoptotic
bodies
Phagocytosis of apoptotic bodies by
Macrophages
Caspase dependent pathway
No Inflammation (no immune response)
Necrosis
Premature, unprogrammed cell death always
pathological. Involve many cells
Cell Swelling (Swelling of endoplasmic
reticulum and mitochondria) and membrane
blebs
Pyknosis (condensation), Karyorrhexis
(Fragmentation) and Karyolysis (lysis)of the
nucleus.
Breakdown of the plasma membrane, organelles
(enzymatic digestion), leakage of cellular
contents
Increased eosinophilia, Accumulation of Myelin
figures (whorled precipitated Phospholipids)
Start Inflammation (Strong immune response)
Necrobiosis: the natural death of cells or tissues
through aging
- Not the same as necrosis or pathological death
- Enterocytes forming crypts in the intestines
- Keratinocytes in the skin (skin cells slough off)
Cells are constantly dying & being replaced
Types or Morphological patterns of necrosis
Classical morphological patterns of necrosis
Coagulative Necrosis
Liquefactive Necrosis
Caseous Necrosis
Gangrenous Necrosis
Fat Necrosis
Coagulative necrosis
• Coagulative necrosis is a form of necrosis in which the component cells are
dead, but the basic tissue architecture is preserved for several days.
• The affected tissues take on a firm texture, denaturation of cell structural
proteins and enzymes without lyses of cell membrane (cellular structure is
preserved), enzymes are denatured and so block the proteolysis of the dead
cells; as a result, an eosinophilic, anucleate cell may persist for days or
weeks.
• E.g. infarcts that occur in hypoxic injury of any solid tissues, i.e. liver , heart,
kidney, except the brain.
Coagulative necrosis
Gross Morphology
 Tissue retains original form
 Firm, pale, dry consistency
(visibly distinct from both
caseous & liquefactive)
 Will eventually become friable
(easily crumbled)
 Often surrounded by a
reddened area or hyperemia
l
The nucleus shrivels and darkens
(pyknosis), then fragments (karyorrhexis),
then vanishes (karyolysis).
Eosinophilia with maintained cellular
architecture
Coagulative Necrosis
• Microscopic morphology
• Tissue organization remains
able to recognize
• Cell outline remains with loss
of cellular detail
• Nuclear changes: Pyknosis,
karyorrhexis, karyolysis
• Cytoplasmic coagulation &
hypereosinophilia
Coagulative necrosis—kidney infarction
This is the typical pattern with ischemia and infarction. Here, there is a wedge-
shaped pale area of coagulative necrosis in the renal cortex of the kidney.
Microscopically, the renal cortex has undergone anoxic injury at the left so that the
cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where
the cells are dying or have not quite died, and then normal renal parenchyma at the
far right.
The green star shows healthy
cells that are less pink and
have nuclei present. The blue
star is a Bowman's capsule.
The yellow star indicates the
necrotic portion. Notice that
the architectural structure of
the cell is still present, but no
nuclei can be seen. You
could almost draw a line
between damaged and non-
damaged cells.
Liquefactive necrosis
•Liquefactive necrosis (or colliquative necrosis) is a
type of necrosis that results in a transformation of
the tissue into a liquid viscous mass.
• Infiltration of dead tissue by large numbers of
neutrophils leads to digestion (rather than
coagulation) of cell proteins. This leads to loss of
normal tissue architecture. Common in brain.
Liquefactive necrosis
Enzyme breakdown of tissues (tissue liquefies)
• Gross Morphology
• A fluid filled cavity in a tissue
• White to pale tan, brown, red,
green colored liquid
• Cream-like consistency
• Foul smelling than coagulative or
caseous necrosis
Liquefactive necrosis
Enzyme breakdown of tissues (tissue liquefies)
• Microscopic morphology
• Pink, proteinacious fluid or hole,
if the fluid has already poured
out
• Surrounded by
inflammatory cells
Liquefactive necrosis
A small abscess filled with many neutrophils an example of localized liquefactive necrosis.
Liquefactive Necrosis in brain showing dissolution of brain
tissue
Caseous necrosis
•Caseous necrosis is a type of cell death that causes tissues
to become “cheese-like” in appearance. The most
common cause is tuberculosis, where granulomas form in
your lungs.
It happen when immune system cannot successfully
remove the foreign body. Then it seals off the foreign
matter by making granuloma which is made of
fibroblasts and white blood.
Granulomas
• A granuloma is an organized and
compact immunological structure
rich with immune cells, such as
macrophages, monocytes, dendritic
cells, neutrophils, epithelioid cells,
foamy macrophages, and multi-
nucleated giant cells surrounded by
fibrosis.
• Granulomas seem to be a
defensive mechanism that triggers
the body to "wall off" foreign
invaders such as bacteria or fungi
to keep them from spreading.
Caseous necrosis
• Gross Morphology
• Dull but slightly greasy &
somewhat liquefactive
• Firm, no cohesive strength,
usually pale to white (cottage
cheese)
• Easily separated with a blunt
instrument (like a finger)
• Microscopic Morphology
• Loss of all tissue outline (no
discernible tissue)
• Amorphous, granular debris,
mass
• Infiltrated with macrophages
multinucleated giant cells
• Often surrounded by fibrous
connective tissue capsules
Caseous necrosis
Caseous necrosis
Caseous necrosis (Granuloma)
Gangrenous Necrosis
• A type of coagulative ischemic necrosis. It is usually applied to
the lower leg, which has lost its blood supply and has
undergone coagulative necrosis. Severe frostbite injuries can
lead to dry gangrene.
• Dry gangrene occurs when the blood supply to the tissue is cut
off. The necrosed area becomes dry, shrinks, and turns black.
• Wet gangrene occurs if bacteria invade the ischemic necrosed
tissue. This makes the area swell, liquefied, and smell bad.
• Gas gangrene when ischemic necrosis develops deep inside the
body and the bacteria responsible begin releasing gas. which is
commonly found with clostridia infection.
Dry Gangrenous necrosis
(Coagulative)
•Gross Morphology
•Tissue is shrunken,
wrinkled, leathery, often
firm
•Can be pale or darker
than normal
•Marginal hyperemia: red
line of inflammatory
demarcation between
infected & normal tissue
MoistGangrene
(Coagulative + Bacteria)
•Gross Morphology
•Swollen, soft, pulpy, dark
in color with putrefactive
smell
Fat necrosis
• Fat necrosis is the pattern of damage associated with the
destruction of adipose tissue by trauma, hypoxia, or lipase
digestion (e.g. pancreatitis).
• This can be seen in acute pancreatitis (acute inflammation of the
pancreas causing necrosis of pancreatic cells and lipase release).
• Grossly can be seen as chalky white deposits due to saponification.
Foci of fat necrosis with
saponification “Pancreatitis”
Fatty acids are released via hydrolysis react with Calcium to form
chalky white areas Saponification
Fat Necrosis Lipid-laden macrophages
are foamy macrophages
Fibrinoid Necrosis
This is a special form of necrosis
usually seen in immune reactions
involving the blood vessels. This
pattern of necrosis is prominent when
complexes of antigens and antibodies
are deposited in the walls of arteries.
Deposits of these immune complexes,
"together with fibrin that has leaked out
of vessels, resulted in a bright pink and
amorphous appearance in H&E stains,
called fibrinoid (fibrin-like)

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Difference between Apoptosis versus Necrosis and Types of Necrosis.pptx

  • 1. LECTURE NO 4 & 5 Irreversible cell injury (Apoptosis vs Necrosis) Types of Necrosis
  • 2. Irreversible cell injury Microscopic morphological Changes Once cell death occurs, degradation of the cell begins o Increased eosinophilia o Moth eaten cytoplasm o Loss of cellular detail Nuclear Changes Pyknosis: Nuclear condensation Karyorrhexis: Fragmentation of the nucleus Karyolysis: lysis of the nucleus by endonuclease
  • 3. Irreversible cell injury- Nuclear Changes
  • 4.
  • 5. Irreversible Cell injury (Pathological Change that can not be reversed) Apoptosis Vs Necrosis. Apoptosis Predefined cell suicide or programmed cell death. Natural physiological Process. Involve one cell at a time. Cell shrinkage (Dense eosinophilic cytoplasm) Pyknosis (Condensation) and Karyorrhexis (fragmentation) of nuclear material Formation of membrane blebs and apoptotic bodies Phagocytosis of apoptotic bodies by Macrophages Caspase dependent pathway No Inflammation (no immune response) Necrosis Premature, unprogrammed cell death always pathological. Involve many cells Cell Swelling (Swelling of endoplasmic reticulum and mitochondria) and membrane blebs Pyknosis (condensation), Karyorrhexis (Fragmentation) and Karyolysis (lysis)of the nucleus. Breakdown of the plasma membrane, organelles (enzymatic digestion), leakage of cellular contents Increased eosinophilia, Accumulation of Myelin figures (whorled precipitated Phospholipids) Start Inflammation (Strong immune response)
  • 6.
  • 7. Necrobiosis: the natural death of cells or tissues through aging - Not the same as necrosis or pathological death - Enterocytes forming crypts in the intestines - Keratinocytes in the skin (skin cells slough off) Cells are constantly dying & being replaced
  • 8. Types or Morphological patterns of necrosis Classical morphological patterns of necrosis Coagulative Necrosis Liquefactive Necrosis Caseous Necrosis Gangrenous Necrosis Fat Necrosis
  • 9. Coagulative necrosis • Coagulative necrosis is a form of necrosis in which the component cells are dead, but the basic tissue architecture is preserved for several days. • The affected tissues take on a firm texture, denaturation of cell structural proteins and enzymes without lyses of cell membrane (cellular structure is preserved), enzymes are denatured and so block the proteolysis of the dead cells; as a result, an eosinophilic, anucleate cell may persist for days or weeks. • E.g. infarcts that occur in hypoxic injury of any solid tissues, i.e. liver , heart, kidney, except the brain.
  • 10. Coagulative necrosis Gross Morphology  Tissue retains original form  Firm, pale, dry consistency (visibly distinct from both caseous & liquefactive)  Will eventually become friable (easily crumbled)  Often surrounded by a reddened area or hyperemia
  • 11. l The nucleus shrivels and darkens (pyknosis), then fragments (karyorrhexis), then vanishes (karyolysis). Eosinophilia with maintained cellular architecture
  • 12. Coagulative Necrosis • Microscopic morphology • Tissue organization remains able to recognize • Cell outline remains with loss of cellular detail • Nuclear changes: Pyknosis, karyorrhexis, karyolysis • Cytoplasmic coagulation & hypereosinophilia
  • 13. Coagulative necrosis—kidney infarction This is the typical pattern with ischemia and infarction. Here, there is a wedge- shaped pale area of coagulative necrosis in the renal cortex of the kidney. Microscopically, the renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died, and then normal renal parenchyma at the far right.
  • 14. The green star shows healthy cells that are less pink and have nuclei present. The blue star is a Bowman's capsule. The yellow star indicates the necrotic portion. Notice that the architectural structure of the cell is still present, but no nuclei can be seen. You could almost draw a line between damaged and non- damaged cells.
  • 15. Liquefactive necrosis •Liquefactive necrosis (or colliquative necrosis) is a type of necrosis that results in a transformation of the tissue into a liquid viscous mass. • Infiltration of dead tissue by large numbers of neutrophils leads to digestion (rather than coagulation) of cell proteins. This leads to loss of normal tissue architecture. Common in brain.
  • 16. Liquefactive necrosis Enzyme breakdown of tissues (tissue liquefies) • Gross Morphology • A fluid filled cavity in a tissue • White to pale tan, brown, red, green colored liquid • Cream-like consistency • Foul smelling than coagulative or caseous necrosis
  • 17. Liquefactive necrosis Enzyme breakdown of tissues (tissue liquefies) • Microscopic morphology • Pink, proteinacious fluid or hole, if the fluid has already poured out • Surrounded by inflammatory cells
  • 18. Liquefactive necrosis A small abscess filled with many neutrophils an example of localized liquefactive necrosis.
  • 19. Liquefactive Necrosis in brain showing dissolution of brain tissue
  • 20. Caseous necrosis •Caseous necrosis is a type of cell death that causes tissues to become “cheese-like” in appearance. The most common cause is tuberculosis, where granulomas form in your lungs. It happen when immune system cannot successfully remove the foreign body. Then it seals off the foreign matter by making granuloma which is made of fibroblasts and white blood.
  • 21. Granulomas • A granuloma is an organized and compact immunological structure rich with immune cells, such as macrophages, monocytes, dendritic cells, neutrophils, epithelioid cells, foamy macrophages, and multi- nucleated giant cells surrounded by fibrosis. • Granulomas seem to be a defensive mechanism that triggers the body to "wall off" foreign invaders such as bacteria or fungi to keep them from spreading.
  • 22. Caseous necrosis • Gross Morphology • Dull but slightly greasy & somewhat liquefactive • Firm, no cohesive strength, usually pale to white (cottage cheese) • Easily separated with a blunt instrument (like a finger) • Microscopic Morphology • Loss of all tissue outline (no discernible tissue) • Amorphous, granular debris, mass • Infiltrated with macrophages multinucleated giant cells • Often surrounded by fibrous connective tissue capsules
  • 26. Gangrenous Necrosis • A type of coagulative ischemic necrosis. It is usually applied to the lower leg, which has lost its blood supply and has undergone coagulative necrosis. Severe frostbite injuries can lead to dry gangrene. • Dry gangrene occurs when the blood supply to the tissue is cut off. The necrosed area becomes dry, shrinks, and turns black. • Wet gangrene occurs if bacteria invade the ischemic necrosed tissue. This makes the area swell, liquefied, and smell bad. • Gas gangrene when ischemic necrosis develops deep inside the body and the bacteria responsible begin releasing gas. which is commonly found with clostridia infection.
  • 27. Dry Gangrenous necrosis (Coagulative) •Gross Morphology •Tissue is shrunken, wrinkled, leathery, often firm •Can be pale or darker than normal •Marginal hyperemia: red line of inflammatory demarcation between infected & normal tissue
  • 28. MoistGangrene (Coagulative + Bacteria) •Gross Morphology •Swollen, soft, pulpy, dark in color with putrefactive smell
  • 29. Fat necrosis • Fat necrosis is the pattern of damage associated with the destruction of adipose tissue by trauma, hypoxia, or lipase digestion (e.g. pancreatitis). • This can be seen in acute pancreatitis (acute inflammation of the pancreas causing necrosis of pancreatic cells and lipase release). • Grossly can be seen as chalky white deposits due to saponification.
  • 30. Foci of fat necrosis with saponification “Pancreatitis” Fatty acids are released via hydrolysis react with Calcium to form chalky white areas Saponification
  • 31. Fat Necrosis Lipid-laden macrophages are foamy macrophages
  • 32. Fibrinoid Necrosis This is a special form of necrosis usually seen in immune reactions involving the blood vessels. This pattern of necrosis is prominent when complexes of antigens and antibodies are deposited in the walls of arteries. Deposits of these immune complexes, "together with fibrin that has leaked out of vessels, resulted in a bright pink and amorphous appearance in H&E stains, called fibrinoid (fibrin-like)