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Apoptosis.
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Theme
Definition of cell injury. Causes of cell injury: hypoxia, immune reactions,
microorganisms, chemicals, aging, nutritional imbalances, physical agents,
genetic defects.
Mechanisms of cell injury: ischemic, free-radical mediated, chemical
mediated, age mediated.
Types of cell injury: reversible, irreversible. Reversible cell injury
(degeneration): definition, patterns (cellular swelling, fatty change),
morphology, outcomes.
Cell death: definition, morphology. Necrosis (irreversible cell injury):
definition, morphogenesis, gross and microscopic morphology.
Types of necrosis: Coagulative, Liquefactive, fat, caseous, fibrinoid, gangrene.
Functional significance and outcomes of necrosis.
Apoptosis – definition, pathogenesis, morphology.
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“Normal homeostasis; Adaptation”
Normal homeostasis - is maintenance of static or constant structure or
function of cells, permitting changes in structure and function within a
narrow range.
Adaptation - is a condition when cells encounter physiologic stresses or
pathologic stimuli, they achieve an altered but steady state while
preserving their health in the face of continued stress.
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Causes of cell injury.
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Mechanisms of cell injury.
1. Ischemic and hypoxic cell injury.
1) Reversible cell injury:
Tissue ischemia (loss of blood supply to tissues) → Tissue hypoxia →
Decreased oxidative phosphorilation in mitochondria → Decreased ATP
(energy) production.
Reversible cell injury may be correct if oxygen supply is restored.
2) Irreversible cell injury.
If ischemia and hypoxia persist beyond reversible injury → irreversible injury
occurs, characterized by the following:
a) injury to lysosomes,
b) injury to plasma membrane - central factor in pathogenesis,
c) injury to mitochondria
3) Cell death. mbbshelp.com
Following irreversible cell injury, cell death
occurs, characterized by:
a) extensive plasma membrane damage,
b) progressive degradation of cell organelles,
c) leakage of intracellular enzymes into extracellular space,
d) entry of extracellular macromolecules into the dead cell,
e) finally, dead cell is replaced by large masses, composed of
phospholipids in the form of “myelin figures”, which are either
phagocytosed by neutrophils and macrophages or degraded
into fatty acids.
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2. Free radical-mediated cell injury.
Free radical refers to a chemical species that has a single unpared electron in
outermost orbital. Free radicals are highly reactive and initiated autocatalytic
reactions whereby molecules (organic or inorganic) with which they react are
themselves converted into free radicals, thereby propagating the chain of
damage.
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Morphology of necrosis.
A. Microscopic morphology - consists of three stages:
1) Changes in nucleus:
a) Pyknosis - it refers to condensation and shrinkage of DNA into a solid mass of
increased basophilia (blue staining);
b) Karyorrhexis - it refers to fragmentation of pyknotic (condensed) nuclear mass;
c) Karyolysis - it refers to fading of basophilia of chromatin due to digestion of DNA
by DNAses activated by decrease pH. Nucleus disappears in 1 or 2 days.
2) Changes in cytoplasm:
a) Increased eosinophilia (pink staining) due to loss of RNA and denaturation of
cytoplasmic proteins;
b) Digestion of cytoplasmic organelles leading to vacuolated cytoplasm and appears
moth-eaten.
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B. Gross morphology
(Types of necrosis).
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1) Coagulative necrosis.
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Source: Internet
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2) Colliquative necrosis.
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3) Fat necrosis.
a) Enzymatic - most characteristically occurs in acute pancreatitis
(inflammation of pancreas) and pancreatic injures when pancreatic
enzymes are liberated from the ducts into surround tissue.
The gross appearance is one of opaque chalky white plaques and
nodules in the adipose tissue surrounding the pancreas;
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4) Caseous necrosis.
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5) Fibrinoid necrosis.
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6) Gangrene.
It is necrosis of tissues which contacting with air and bacteria.
a) Dry - most commonly occurs in the extremities as a result of ischemic
coagulative necrosis of tissues due to arterial obstruction. The necrotic area
appears black, dry, shriveled, and sharply demarcated from adjacent viable
tissue. Treatment consists of surgical removal of dead tissue;
b) Wet - results from severe bacterial infection superimposed on necrosis. It
occurs in the extremities as well as in internal organs such as the intestine
and lungs. The necrotic area becomes swollen and reddish-black with
extensive liquefaction of dead tissue. Wet gangrene is a spreading
necrotizing inflammation that is not clearly demarcated from adjacent
healthy tissue.
c) Gas - is a wound infection caused by Clostridium perfringens and other
clostridial species. It is characterized by extensive necrosis of tissue and
production of gas by the fermentative action of the bacteria. The gross
appearance is similar to that of wet gangrene, with additional presence of
gas in the tissues.
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C. Outcomes (local fate) of necrosis:
1) Organization - formation of scar due to growth of fibrous
tissue.
2) Calcification - deposition of calcium in dead tissue.
3) Ossification - formation of bone tissue, usually associated
with calcification.
4) Encapsulation - formation of fibrous capsule around of
necrotic tissue.
5) Cyst formation - formation of cavity surrounded with thin
capsule and filled with serous fluid.
6) Supportive (suppuration, purulence) inflammation -
formation of pus due to action of bacteria.
7) Ulceration of epithelial surfaces - defect of epithelium due to
shed of dead epithelial cells.
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3. Apoptosis - programmed cell death.
(“Dropping off’).
It is a pattern of cell death in which single or cluster of cells appear on
sections stained with H. & E. as round or oval masses of intensely
eosinophilic cytoplasm and dense nuclear chromatin fragments (apoptotic
bodies) which are taken up and degraded by phagocytotic cells.
Characteristic features:
1) Chromatin condensation and formation of membrane blebs.
2) Fragmentation of DNA into nucleosome - sized particles (apoptotic
bodies) due to activation of endonuclease caused by increase cyotsolic
Ca++.
3) Requires for RNA and protein synthesis.
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