4. NECROSIS
DEFINITION
• Necrosis refers to a series of changes that accompany
cell death, resulting from degradative action of enzymes
on lethally injured cells.
• Irreversible cell injury
• Causes of Necrosis
– Ischemia
– Physical agents
– Chemical agents
– Immunological injury
– Microbial infection
5. NECROSIS
• Characteristics of Necrosis
– Denaturation of cellular proteins
– Leakage of cellular contents through damaged membranes,
– Local inflammation, and
– Enzymatic digestion of lethally injured cells
6. PATHOPHYSIOLOGY
Normal cells
Severe damage
to cell membrane
Entry of lysosomes
to cytoplasm
Digestion
of the cell
Leakage of
cellular contents
to extracellular
space
Host
inflammatory
response
Severe and
progressive
injury
7. PATHOPHYSIOLOGY
Specific substances released
from injured cells:k/a
Damage associated molecular
patterns (DAMP)
- ATP (from damaged
mitochondria)
- Uric acid ( DNA breakdown
product)
- Other molecules confined to
healthy cells
*Indicators of severe cell injury
Leaked DAMP recognized by receptors in macrophages
Trigger phagocytosis of debris and production of
cytokines -->induces inflammation
Accumulation of inflammatory cells
Production of Proteolytic enzymes
Leads to clearance of necrotic cells (due to
combination of phagocytosis and enzymatic digestion
9. CLINICAL APPLICATION
Clinical Application of Leakage of intracellular proteins
• Basis of blood tests that detect tissue specific cellular
injury
• Examples
– Injury of cardiac muscles cells : Increased cardiac specific
protein (troponin)
– Bile duct epithelium injury - Specific isoform of alkaline
phosphatase
– Hepatocyte injury - Transaminases
10. MORPHOLOGY
• Cytoplasmic Changes
– Increased eosinophilia in H&E stain --> Due to loss of
cytoplasmic RNA and accumulation of denatured cytoplasmic
proteins --> binds to eosin
– Glassy homogenous appearance (more compared to normal
cells) --> due to loss of glycogen
– Vacuolated, moth eaten appearing cytoplasm --> due to
enzymatic digestion of the organelles
12. MORPHOLOGY
– Precipitation of Myelin Figures --> Whorled phospholipid
precipitates which replaces the dead cells
– Myelin figures are phagocytosed by macrophages or further
degraded to fatty acids
– Calcification of these fatty acids residues --> Deposition of
calcium rich precipitates
13. MORPHOLOGY
Electron microscopic finding
– Discontinuities in the plasma membrane and organelle
membranes
– Marked dilation of mitochondria
– Deposition of large amorphous densities in the mitochondria
– Intracytoplasmic myelin figures
– Amorphous debris in the cytoplasm
– Fluffy material representing denatured protein
14. MORPHOLOGY
• Nuclear Changes
– Appears in one of three patterns (Due to break down of DNA)
– Karyolysis : Fading of the basophilic chromatin due to loss of
DNA as a result of enzymatic degradation by endonucleases
– Pyknosis : Characterized by nuclear shrinkage and increased
basophilia. Also seen in apoptosis. Chromatin is condensed to
a dense shrunken basophilic mass
– Karyorrhexis : Pyknotic nucleas undergoes fragmentation
– Necrotic cells disappear within one to two days
15. • Characteristics of Irreversible injury
– Inability to reverse mitochondrial dysfunction (lack of oxidative
phosphorylation and ATP generation)
– Profound disturbances in in membrane function
16. TYPES OF NECROSIS
• Necrosis of tissues have some distinct pattern which
gives the clue to the underlying cause
• TYPES
– Coagulative necrosis
– Liquifactive necrosis
– Gangrenous necrosis
– Caseous necrosis
– Fat necrosis
– Fibrinoid necrosis
17. COAGULATIVE NECROSIS
• Definition :Form of necrosis in which the architecture of
the dead tissue is preserved for the span of at least few
days
• Morphology
– Tissue affected has firm texture
--> Injury denatures both structural proteins and enzymes
--> Blocks proteolysis of dead cells
--> Results in intensely eosinophilic cells with indistinct/reddish
nuclei which persists for days to week
-->Finally, necrotic cells are broken down by lysosomal
enzymes derived from infiltrating leucocytes
18. COAGULATIVE NECROSIS
-->Infiltrating leucocytes remove necrotic debris by process of
phagocytosis
– Cause:
Ischemia caused by obstruction of blood vessel leads to
necrosis of tissue supplied by the vessel
– Seen in all the solid organs except Brain
– Localized area of coagulative necrosis is called an infarct
• Eg. Necrosis of heart, kidney spleen
20. LIQUIFACTIVE NECROSIS
• Definition : Necrosis characterized by digestion of the
dead cells resulting in the transformation of tissue into
viscous fluid
• Seen in focal bacterial and occasionally fungal infection
• Bacterial/ fungal infection --> stimulates accumulation of
leucocytes--> release of enzymes --> Liquifactive necrosis
21. LIQUIFACTIVE NECROSIS
• Necrotic material is creamy
yellow d/t presence of
leucocytes --> called PUS
• Example: Hypoxic death of
cells of Central Nervous
System forming brain
abscess
22. GANGRENOUS NECROSIS
• Not a specific pattern of cell death but term is used in
clinical practice
• Usually applied to limb, esp. lower limb that has lost its
blood supply and has gone necrosis (coagulative
necrosis) involving multiple tissue planes.
• Bacterial infection is superimposed leading to liquifactive
necrosis because of degradative action of bacterial and
leucocytic enzymes
• Also known as WET GANGRENE
24. CASEOUS NECROSIS
• Type of coagulative necrosis
• Caseous : Cheese-like; derived from friable white
appearance of necrosis; Tissue architecture is preserved
• Seen in foci of Tuberculosis
• Microscopic Features:
Appears as structureless collection of fragmented or lysed
cells and amorphous granular debris enclosed in a cuff of
inflammatory cells --> Granuloma
26. FAT NECROSIS
• Definition :
Refers to focal areas of fat destruction, typically resulting
from release of activated pancreatic lipases into the
substance of pancreas and peritoneal cavity
• Occurs in pancreatitis--> pancreatic enzymes leak out of
damaged acinar cells --> liquifies the membranes of fat
cells in the peritoneum --> releases triglyceride esters
split by pancreatic lipases
• Generates fatty acids that combines with calcium to
produce chalky white areas
27. FAT NECROSIS
• Histology
– Necrotic areas show
shadowy outlines of necrotic
fat cells
– Basophliic calcium deposits
– Inflammatory reaction
29. FIBRINOID NECROSIS
• Definition:
Special form of vascular damage usually seen in immune
reactions involving blood vessels.
• Antigen antibody complexes are deposited in the arterial
wall --> leaking of plasma proteins out of the vessels
• Results in pink amorphous appearance in H&E stain
• Example: immunologically mediated vasculitis syndromes