L3: Irreversible cell Injury Flashcards
What is the definition of necrosis?
Local death of a group of cells or tissue within a living body.
What are the causes of necrosis?
Living:-
- Bacteria.
- Fungus.
- Virus.
Non-living:-
- Physical causes; Excess heat or cold and mechanical trauma.
- Chemical agents: Poisons and drugs, Pancreatic secretion, Toxins e.g. diphtheria toxins
- Ischemia: Cut of arterial blood supply, causing ischemic
necrosis as an infraction. - Hypersensitivity reactions: i.e. antigen-antibody reaction as necrosis of tuberculous lesion.
- Free radicals e.g. 02, H202 & OH
What is the pathogenesis of necrosis?
- Severe mitochondrial damage leads to marked reduction of ATP production with the metabolic shift to anaerobic glycolysis resulting in
decrease intracellular PH (acidosis). - Reduction of ATP results in loss of integrity of cellular membranes as disruption of lysosomal membranes and lysosomal enzymes set free.
- Increase intracellular Ca: ATP reduction leads to failure of Ca pump, Ca is normally maintained at extremely low levels by energy-dependent transport. Increased Ca leads to activation of the following enzymes:
Proteases: leading to the breakdown of cytoskeleton protein.
Phospholipases: leading to the destruction of membrane phospholipids.
Endonucleases: leading to the breakdown of DNA and chromatin fragmentation (pyknosis, karyorrhexis, and karyolysis).
What is the N/E of the necrotic area?
The necrotic area is: (SODYI):
a. Swollen.
b. Opaque.
c. Well defined.
d. Pale yellow.
e. Surrounded by a zone of redness (acute
inflammation) .
What is the M/E of the necrotic area?
Cell membrane
> disappear and become indistinct, but the cellular outline is recognized.
Cytoplasm
> Swollen and coagulated (denaturation of protein)
Deeply eosinophilic (increased eosinophilia is due to
loss of normal basophilia “imparted by RNA in the
cytoplasm”
Increased binding of eosin to denaturated intra-
cytoplasmic protein).
Nucleus
> Pyknosis: Nuclei become condensed and dense.
Karyorrhexis: Nuclei become fragmented.
Karyolysis: Nuclei are dissolved.
What are the clinical effects of necrosis?
Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis
Coagulation necrosis
Characteristic of infarction (areas of ischemic necrosis) in all of the solid organs except the brain.
Liquefactive necrosis
Characteristic of brain infarction.
Caseous necrosis
seen in tuberculous infection
Fat necrosis
> occurs in abdominal emergency known as acute
pancreatitis (enzymatic fat necrosis).
> Occurs after trauma to the breast (traumatic fat necrosis).
Fibrinoid necrosis
A special form of necrosis, visible by light microscopy, usually in autoimmune diseases e.g. polyarteritis nodosa (PAN)
What is the fate of necrosis?
Depends on the size of the necrotic area:
Small area of necrosis: Healing occurs by regeneration or by granulation tissue and fibrosis.
Large area of necrosis:
• Surrounded by a fibrous capsule.
• Unabsorbed contents dry and may show dystrophic calcification (Necrosis associated with a change in pH of the tissue favoring the deposition of calcium)
What is apoptosis?
> Programmed cell death, usually involving a single cell.
> Based on sequential activation of suicide pathway enzymes (Cell suicide).
What are the causes of apoptosis?
Physiological: as in endometrium during the menstrual cycle.
Pathological:
- Viral hepatitis: Councilman bodies
- Cell death by cytotoxic T-lymphocytes
- Radiation cell injury
What is the pathogenesis of apoptosis?
Extrinsic (Death receptor-initiated) pathway
© Active binding of death receptor (e.g. TNF receptor) by its ligand
© Cause activation of proteolytic enzymes that initiate apoptosis.
Intrinsic (Mitochondrial) pathway
© Withdrawal of growth factors (survival signals) increases the mitochondrial permeability.
© This leads to the release of molecules that activate proteolytic enzymes and initiate apoptosis.
