Pathology

1. CELL INJURY

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

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

7. CAUSES
 Reduced oxygen -Ischemia, Infarction
 Physical agents
 Chemicals
 Toxins
 Biological agents -Viruses, Bacteria etc.
 Immune reaction -Hypersensitivity
 Nutritional deficiencies
 Genetic abnormality -Sickle, Hemophilia

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

10. FREE RADICAL GENERATION

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

14. ROLE OF CA+
IN CELL INJURY

19. MEMBRANE DAMAGE

23. DECREASED INTRACELLULAR ATP
DURING CELL INJURY.