2. HOMEOSTASIS
Def
Mechanism
Narrow range of function and structure by
Its genetic programs of metabolism
Differentiation and specialization by
Constraints of neighboring cells
The availability of metabolic substrates
3. ADAPTATIONS
A condition during which new but altered steady
states are achieved, preserving the viability of
the cell and modulating its function as it
responds to such stimuli.
The adaptive response may consist
Hyperplasia
Hypertrophy
Atrophy
4.
5. CELL INJURY
Dif: If the limits of adaptive response to a
stimulus are exceeded or in certain
instances when the cell is exposed to an
injurious agent or stress, a sequence of
events follows that is loosely termed cell
injury.
Types:
1. Reversible cell injury
2. Irreversible cell injury
6. GENERAL CONSIDERATIONS
Morphology becomes apparent late in cell injury,
changes in physiology early
Reaction of cell to injury depends on type of
injury, duration and severity
Reaction of cell to injury also depends on the
type, state & adaptability of the cell
9. FREE RADICALS
Free radicals are chemical species with a
single unpaired electron in an outer orbital
Free radicals are chemically unstable and
therefore readily react with other molecules,
resulting in chemical damage
Free radicals initiate autocatalytic reactions;
molecules that react with free radicals are in
turn converted to free radicals
11. INTRACELLULAR SOURCES OF FREE
RADICALS
Normal redox reactions generate free radicals
Nitric oxide (NO) can act as a free radical
Ionizing radiation (UV, X-rays) can hydrolyze
water into hydroxyl (OH) and hydrogen (H) free
radicals
Metabolism of exogenous chemicals such as CCl4
can generate free radicals
Fenton Reaction: Transition metals such as
copper and iron also accept or donate free
electrons during certain intracellular reactions
and thereby catalyze free-radical formation (Fe2+
+ H2O2 → Fe3+
+ OH•
+ O).
12. NEUTRALIZATION OF FREE RADICALS
Spontaneous decay
Superoxide dismutase(SOD)
2O2+ 2H →O2+ H2O2
Glutathione (GSH):
2OH+ 2GSH →2H2O + GSSG
Catalase:
2H2O2→O2+ H2O
5.Endogenous and exogenous antioxidants
(Vitamins E, A, C and β-carotene)
13. FREE RADICAL-INDUCED INJURY
If not adequately neutralized, free
radicals can damage cells by three basic
mechanisms:
1. Lipid Peroxidation of membranes: double
bonds in polyunsaturated membrane lipids are
vulnerable to attack by oxygen free radicals
2. DNA fragmentation: Free radicals react with
thymine in nuclear and mitochondrial DNA to
produce single strand breaks
3. Protein cross-linking: Free radicals promote
sulfhydryl-mediated protein cross-linking,
resulting in increased degradation or loss of
activity