CHAPTER 2
CELLULAR RESPONSES TO
STRESS, INJURY, AND AGING
PRE LECTURE QUIZ
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Cells are able to adapt to changes in work demands or
threats to survival by changing their size, number,
type, and DNA composition.
Apoptotic cell death and necrotic cell death are both
pathologic forms of cell death that are unregulated
and invariably injurious to the organism.
Prolonged exposure to cold increases blood viscosity
and induces vasoconstriction.
Gas gangrene is a special type of gangrene that
results from infection of devitalized tissues by one of
several species of Clostridium bacteria.
All mechanisms of cell injury (e.g., hypoxia,
mechanical forces, extremes of temperature, electrical
injuries) lead to irreversible cellular damage with cell
destruction or death.
PRE LECTURE QUIZ
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Apoptosis
cardiac
decrease
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Dose
Dystrophic
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Atrophy is the ______________ in the size of a
tissue organ resulting from a decrease in the
cell size of the individual cells or in the number
of cells.
_________________ calcification involves the
abnormal deposition of calcium salts, together
with smaller amounts of iron, magnesium, and
other minerals, in dead or dying tissue.
_________________ is the term used for
programmed cell death or cell suicide.
The injurious effects of ionizing radiation vary
with the __________________.
Electrical forces can affect the body through
extensive tissue injury and disruption of neural
and __________________ impulses.
CELLULAR ADAPTATION
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Allows the stressed
tissue to survive or
maintain function
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Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
QUESTION
Tell whether the following statement is true or
false:
If a cell does not make adaptive changes as a
result of stress, it will die.
ANSWER
True
Adaptive changes, like the ones illustrated on
slide 3, allow the cell to survive and maintain
some degree of function. If the cell makes no
changes or makes maladaptive changes as a
result of stress, the cell will not survive.
WHAT KINDS OF CELL AND TISSUE
ADAPTATIONS OCCURRED IN THIS CASE?
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A woman broke her left leg; 3 weeks later you find:
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The left leg is smaller than the right leg
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The circumference of the right calf has increased by
2 cm
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New calluses on the right foot
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A nodule of skin tissue has formed a fluid-filled cyst
near her incision
INTRACELLULAR ACCUMULATIONS
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Stressed cells may fill
up with:
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Unused foods
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Lipids
Glycogen
Abnormal proteins
Pigments
Calcium salts
INJURIOUS AGENTS
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Hypoxia
Heat and cold
Electricity
Chemical agents
Biologic agents
Radiation
Nutritional imbalances
STRESSES DAMAGE CELLS BY:
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Direct damage to proteins,
membranes, DNA
ATP depletion
Free radical formation
Increased intracellular
calcium
HYPOXIA CAUSES ATP DEPLETION OR “POWER
FAILURE”
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Aerobic metabolism stops  less ATP is produced
 Na+/K+ ATPase cannot run fast enough
º Cell swells up with water
Anaerobic metabolism used  lactic acid produced
 Acid damages cell membranes, intracellular
structures, and DNA
QUESTION
How does hypoxia cause cell damage?
a. Directly damages DNA
b. Diminishes ATP production
c. Forms free radicals
d. Increases intracellular calcium
ANSWER
Diminishes ATP production
Oxygen is a key ingredient for the majority of ATP
production. With less oxygen, less ATP is
produced, and the cell cannot function at the
same level. If hypoxia is severe or prolonged,
the cell will die.
b.
SCENARIO
Two Boys Suffered Hypoxia
One was at a normal body temperature.
 The other one was very cold.
Questions:
 Which one will have a lower intracellular pH?
 Which one will have more cell swelling?
 Why?
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FREE RADICALS
Molecules with an unpaired electron in
the outer electron shell
 Extremely unstable and reactive
 Can react with normal cell components:
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 Damaging
them
 Turning them into more free radicals
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Normally removed from body by
antioxidants
CALCIUM
 Cell usually maintains low intracellular
calcium
 When calcium is released into the cell, it:
 Acts
as a “second messenger” inside the cell
 Turns on intracellular enzymes, some of
which can damage the cell
 Can open more calcium “gates” in the cell
membrane
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Letting in more calcium
“Calcium cascade”
SCENARIO
Mr. X Had a Stroke …
 Blood flow to part of his brain was cut off
 His wife can understand why they gave him an anticoagulant,
but she does not comprehend why he was also put on:
 Oxygen
 A calcium channel blocker
Question:
 What is the explanation?
RESULT OF CELL INJURY
CELL DEATH
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Programmed cell death: apoptosis or “cell
suicide”
 Removes
cells that are being replaced or
have “worn out”
 Removes unwanted tissue
 Normal process in the body
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Necrotic cell death
 Unregulated
death caused by injuries to cells
 Cells swell and rupture
 Inflammation results
APOPTOSIS OR PROGRAMMED CELL DEATH
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Damaged or worn-out cells
commit “suicide”
 Turn on their own
enzymes inside the cell,
especially caspases
 Digest their own cell
proteins and DNA
 Are then destroyed by
white blood cells
APOPTOSIS CAN BE CAUSED BY:
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Signaling factor attached to “death domains” of cell
surface receptors
Mitochondrial damage inside the cell
Protein p53 activated by DNA damage
NECROSIS
Cell death and
degradation
 Cells may undergo:
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 Liquefaction
 Coagulation
 Infarction
 Caseous
necrosis
Cell contents often
released
 Inflammation often
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QUESTION
Tell whether the following statement is true or
false:
Necrotic tissue may be reversed using high
concentrations of oxygen.
ANSWER
False
Necrotic tissue is already dead, so it cannot be
restored to functional tissue.
GANGRENE
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A large area of necrotic tissue
Dry gangrene: lack of arterial blood
supply but venous flow can carry fluid
out of tissue
 Tissue tends to coagulate
Wet gangrene: lack of venous flow lets
fluid accumulate in tissue
 Tissue tends to liquefy and
infection is likely
Gas gangrene: Clostridium infection
produces toxins and H2S bubbles
QUESTION
Which type of gangrene results in crepitus
(bubbles that can be felt under the skin)?
a. Dry
b. Wet
c. Gas
d. All of the above
ANSWER
c. Gas
The only type of gangrene that causes crepitus is
gas gangrene. The bubbles are the result of
gas produced by the Clostridium infection.
CELL CHANGES WITH AGING—WHY?
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Is it programmed into the cells?
 Telomeres
become too short; cell can no longer
divide
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Is it the result of accumulated damage?
 Older
cells have more DNA damage
 Older cells have more free radicals
 Cells can lose the ability to repair their
telomeres