1. Necrosis and Apoptosis: Dr Umar Hamid 1
NECROSIS
Dr. Umar Hamid
Lecturer, Program In charge (AHS) Ex-Consultant BSL-III Lab
Department of Allied Health Sciences District Headquarter Hospital
Superior University, Pakistan Sargodha

2. Necrosis
Cell Injury and Adaptation By: Dr Umar Hamid 2

3. “Irreversible death of cells or tissues within a living organism, typically as a result of injury, infection, or
inadequate blood supply”.
• It is a pathological process characterized by the breakdown of cellular components and the release of
cellular contents, which can lead to inflammation and further tissue damage.
• Type of cell death, that is associated with loss of membrane integrity and leakage of cellular contents
culminating in dissolution of cells, largely resulting from the degradative action of enzymes on
lethally injured cells.
• Leaked cellular contents often promote a local host reaction, called inflammation.
• Enzymes responsible for digestion of cell, may be derived from lysosomes of the dying cells
themselves and from lysosomes of leukocytes (that are recruited as a part of inflammatory reaction
to dead cells.
• Leakage of intracellular proteins through the damaged cell membrane and ultimately into the
circulation provides a means of detecting tissue-specific necrosis using blood or serum samples.
E.g.
- Cardiac muscle, contains a unique isoform of the enzyme creatine kinase and of the contractile
protein troponin.
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4. - Hepatic bile duct epithelium contains the enzyme alkaline phosphatase.
- Hepatocytes contain transaminases.
Irreversible injury and cell death in these tissues elevate the serum levels of these proteins, which
makes them clinically useful markers of tissue damage.
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5. Causes
Necrosis can occur due to various reasons, including:
• Ischemia: Insufficient blood supply to an area, leading to oxygen and nutrient deprivation.
• Trauma: Physical injury, such as severe impact or crushing, that disrupts the cells' integrity.
• Infection: Invasion of microorganisms, such as bacteria or viruses, that cause tissue damage and cell
death.
• Toxins: Exposure to harmful substances, like certain chemicals or drugs, that induce cellular damage
and necrotic changes.
• Immunological reactions: Inflammatory responses triggered by autoimmune conditions or
hypersensitivity reactions can lead to tissue necrosis.
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6. Types
Different types of necrosis can be classified based on their characteristics and underlying causes. Some
common types include:
1. Coagulative necrosis:
• This type involves the preservation of tissue architecture with a firm texture.
• It occurs primarily in ischemic conditions, such as heart attacks or kidney infarctions.
2. Liquefactive necrosis:
• This form is characterized by the transformation of tissue into a liquid or pus-like consistency. It is
commonly seen in bacterial or fungal infections, particularly in the brain.
3. Caseous necrosis:
• This type is typically observed in tuberculosis infections and presents as a cheesy or granular tissue
appearance.
4. Fat necrosis:
• It occurs when adipose (fat) tissue undergoes necrosis, often due to trauma or inflammation.
Pancreatitis-related fat necrosis is a notable example.
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7. 5. Gangrenous necrosis:
• This type typically affects limbs and results from a combination of ischemia, bacterial infection, and
tissue death. It can be dry gangrene (coagulative necrosis) or wet gangrene (liquefactive necrosis).
6. Fibrinoid necrosis:
• It is associated with immune-mediated diseases, particularly involving blood vessel walls, such as in
vasculitis.
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8. Examples
1. Myocardial infarction:
• A heart attack occurs when the blood flow to a section of the heart muscle is blocked, leading to
ischemic necrosis of the affected heart tissue.
2. Cerebral infarction:
• Stroke can result in necrotic brain tissue due to the interruption of blood supply to a particular brain
region.
3. Gangrenous appendicitis:
• An inflamed appendix can undergo necrosis, leading to gangrenous appendicitis, which often requires
surgical removal.
4. Pressure ulcers:
• Prolonged pressure on specific body areas, such as bedridden patients or wheelchair users, can cause
tissue necrosis, resulting in pressure ulcers or bedsores.
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9. 5. Frostbite:
• Exposure to extreme cold temperatures can lead to frostbite, which causes tissue damage and
necrosis due to freezing.
6. Severe burns:
• Extensive burns can cause necrosis of the affected skin and underlying tissues, requiring medical
intervention and skin grafting.
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10. Morphology
1. Cytoplasmic changes:
• Cells show increased eosinophilia (i.e. pink staining from eosin dye).
• Cells may have a more glassy appearance, homogenous appearance, mostly b/c of loss of glycogen
particles.
• Myelin figures; more prominent.
• Mouth eaten appearance; when enzymes have digested cytoplasmic organelles, the cytoplasm
becomes vacuolated and appears “mouth-eaten”.
• Irreversible damage to mitochondria manifested by severe vacuolization.
• Extensive damage to plasma membrane.
• Massive calcium influx acting as poison for mitochondria.
• Loss of enzymes and proteins due to increased membrane permeability.
• Lysosomal swelling and leakage of enzymes.
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11. • Electron microscopy shows:
- Discontinuities in plasma and organelle membrane.
- Marked dilation of mitochondria with the appearance of large amorphous densities.
- Intracytoplasmic myelin figures.
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12. 2. Nuclear changes: (all due to breakdown of DNA and chromatin)
• Pyknosis:
- Chromatin of dead cell clumps into coarse (rough) strands.
- Nucleus becomes shrunken, dense and deeply basophilic mass & increased basophilia.
- DNA condenses into a solid shrunken mass.
• Karyorrhexis:
- Pyknotic nucleus undergo fragmentation.
- In 1 to 2 days, nucleus in a dead cell may completely disappear.
- Electron microscopy shows nuclear dissolution.
• Karyolysis:
- Basophilia of chromatin may fade.
- Pyknotic nucleus may undergo lysis by enzyme DNAse.
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13. 3. Fate of necrotic cells:
• May persist for some time or
• May be digested by enzymes and disappear.
• May be replaced by myelin figures (which are either phagocytosed by other cells or further degraded
into fatty acids).
- These fatty acids bind calcium salts, which may result in the dead cells ultimately becoming calcified.
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