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Chapter 2
Cellular Responses to
Stress, Injury, and Aging
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
stresses
affect normal cell function
failure to
maintain
function
adaptive
changes
to
maintain
function
injury
maladaptive
changes
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
cell
death
Cellular Adaptation
• Allows the stressed
tissue to survive or
maintain function
– Atrophy
– Hypertrophy
– Hyperplasia
– Metaplasia
– Dysplasia
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
True
Rationale: 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.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
What Kinds of Cell and Tissue Adaptations
Occurred in this Case?
• A woman broke her left leg; 3 weeks later you
find:
– The left leg is smaller than the right leg
– The circumference of the right calf has
increased by 2 cm
– New calluses on the right foot
– A nodule of skin tissue has formed a fluidfilled cyst near her incision
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Intracellular Accumulations
• Stressed cells may fill up
with:
– Unused foods
º Lipids
º Glycogen
– Abnormal proteins
– Pigments
– Calcium salts
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Injurious Agents
• Hypoxia
• Heat and cold
• Electricity
• Chemical agents
• Biologic agents
• Radiation
• Nutritional imbalances
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Stresses Damage Cells By:
• Direct damage to
proteins,
membranes, DNA
• ATP depletion
• Free radical
formation
• Increased
intracellular calcium
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Hypoxia Causes ATP Depletion or “Power
Failure”
• 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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
How does hypoxia cause cell damage?
a. Directly damages DNA
b. Diminishes ATP production
c. Forms free radicals
d. Increases intracellular calcium
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
b. Diminishes ATP production
Rationale: 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.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Free Radicals
• Molecules with an unpaired electron in the outer
electron shell
• Extremely unstable and reactive
• Can react with normal cell components:
– Damaging them
– Turning them into more free radicals
• Normally removed from body by antioxidants
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
º Letting in more calcium
º “Calcium cascade”
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cell Death
• 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
• Necrotic cell death
– Unregulated death caused by injuries to cells
– Cells swell and rupture
– Inflammation results
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Apoptosis or Programmed Cell Death
• 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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Apoptosis Can Be Caused by:
• Signaling factor attached to “death domains”
of cell surface receptors
• Mitochondrial damage inside the cell
• Protein p53 activated by DNA damage
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Necrosis
• Cell death and degradation
• Cells may undergo:
– Liquefaction
– Coagulation
– Infarction
– Caseous necrosis
• Cell contents often released
• Inflammation often results
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Tell whether the following statement is true or false.
Necrotic tissue may be reversed using high concentrations
of oxygen.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
False
Rationale: Necrotic tissue is already dead, so it cannot be
restored to functional tissue.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Gangrene
• 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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
c. Gas
Rationale: The only type of gangrene that causes crepitus
is gas gangrene. The bubbles are the result of gas
produced by the Clostridium infection.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cell Changes With Aging—Why?
• Is it programmed into the cells?
– Telomeres become too short; cell can no longer
divide
• 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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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