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 Cell death (Irreversible cell injury)

There are two morphological types of cell death

1. Apoptosis
2. Necrosis

Apoptosis
o Programmed cell death or "cellular suicide"
o The plasma membrane of the apoptotic cell remains intact, but is
altered in order to become targets for phagocytes.
o Contents have not leaked out, and therefore no inflammatory reaction
in the host.

Which differ from Necrosis, which shows;

o loss of membrane integrity
o leakage of cellular contents
o Host reaction.

Types ofApoptosis
Physiologic endometrial cell breakdown during the menstrual cycle
Pathologic DNA Damage (exposure of cells to radiation or cytotoxic drugs)

Morphology:
° Cell shrinkage
0
Nuclear condensation & fragmentation
° Formation of apoptotic bodies
0
Apoptotic bodies engulf by macrophages

Necrosis
Necrosis is the type of cell death that is associated with loss of membrane
integrity and leakage of cellular contents causing inflammation
Causes of Cell Injury
1. Hypoxia insufficient supply of oxygen.
Causes of hypoxia:
• Ischemia decrease blood supply in a tissue .
• Inadequate oxygenation of blood: Cardiac & respiratory diseases

• Low oxygen-carrying capacity of the blood, e.g. anemia

•

2. Chemical agents: drugs and insecticides.

3. Infectious agents: viruses, bacteria, fungi and parasites.
4. Immunologic reactions; autoimmune diseases
5. Genetic: sickle cell anemia

6. Nutritional imbalances:
Protein & vitamins insufficiencies
diets rich in animal fat (will induce atherosclerosis)
7. Physical agents: trauma, extremes temperatures, radiation, electric shock.
8. Aging: impairment of replicative and repair abilities of individual cells.

MECHANISMS OF CELL INJURY (Pathogenesis)

Cell injury depend on injurious agent and the cells (exposed to the injury):
o Depletion of ATP
o Accumulation of Free Radicals
o Defects in Membrane Permeability
o Influx of Calcium
o Damage to DNA

Depletion of ATP
ATP is the energy fuel of cells, is produced within the mitochondria.
Causes of ATP depletion:
1. Reduced supply of oxygen and nutrients
2. Mitochondrial damage
3. toxins (e.g., cyanide)

Free Radicals: Reactive oxygen species (ROS)

Free radical is any molecule with a single unpaired electron in the outer orbital. It React
with chemicals, when the reaction happen inside the cell it will attack nucleic acids.
Defects in Membrane Permeability
Cell membrane dan1age:
Direct: extremes temperature, toxins, or viruses
Indirect: hypoxia

Influx of Calcium
Cytoplasmic free calcium concentrations are normally lower than of extra-cellular
calciwn. This maintained by ATP-dependent calcium pump

Cell membrane damage >> increased intracellular calcium level>> activates enzymes>>
damage cellular organelles

Damage to DNA
Cells have mechanisms that repair damage to DNA, but if this damage is too severe to be
corrected (e.g., after radiation injury), the cell initiates its suicide program and dies by
apoptosis.

Necrosis
Excess fluid enters the cell >> cellular swelling>> ruptures cell membrane>>
leakage of the cellular contents through the damaged plasma membrane>>
inflammation.

Morphologic features of necrosis

o Cytoplasmic changes
o increased cytoplasmic eosinophilia (deep pink)

o Nuclear changes
o Pyknosis (nuclear shrinkage+ increase basophilia of the nucleus)
o Karyorrhexis (fragmentation with nuclear dust)
o Karyolysis (nuclear loss)
 Patterns of Tissue Necrosis

• Coagulative necrosis
Results from sudden interruption of blood supply to the organ
0
Grossly: fmnness of the affected tissue due to proteins denaturation
0
Microscopically: necrotic cells show preserved outlines, eosinophilic
cytoplasm, loss of nuclei

• Liquefactive necrosis
Complete digestion of the dead cells, resulting in transformation of the affected tissue
into thick liquid mass. Liquefied necrotic tissue is enclosed within a cystic cavity.
Causes:
o Focal pyogenic bacterial infections. (abscess); contain pus.
o Ischemic destruction of the brain tissue

• Gangrenous necrosis (gangrene)

o Gangrene: is a term used in clinical for a limb that loss its blood supply and has
undergone coagulative necrosis involving multiple tissue layers (dry gangrene).
o When bacterial infection is superimposed, coagulative necrosis is modified by the
liquefactive action of the bacteria and the attracted leukocytes (wet gangrene).

• Caseous necrosis
Tissue architecture is completely lost and cellular outlines cannot be detected.
. in tuberculous infection.
"caseous" mean cheese-like.
I o Microscopically: the necrotic focus appears as pinkish, and granular in
appearance. Caseous necrosis is often bordered by a granulomatous inflammation.
I
o Grossly cheesy like material
I
• Fat necrosis
Fat necrosis can be caused by trauma to tissue with high fat content, such as the breast
or it can also be caused by acute hemorrhagic pancreatitis in which pancreatic enzymes
diffuse into the inflamed pancreatic tissue & digest it Fat necrosis in acute pancreatitis.

• Fibrinoid necrosis
'j Seen in immWle reactions involving blood vessels.
Deposits of inunW1e complexes, together with fibrin that has leaked out of vessels result
in a homogeneous bright pink appearance, e.g. polyarteritis nodos.

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