Chapter002

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Chapter 2

Cellular Responses to Stress, Injury, and Aging

Chapter 2

Cellular Responses to Stress, Injury, and Aging


Cellular AdaptationCellular Adaptation

• Allows the stressed tissue to survive or maintain function

– Atrophy

– Hypertrophy

– Hyperplasia

– Metaplasia

– Dysplasia


QuestionQuestion

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.


AnswerAnswer

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?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 fluid-filled cyst near her incision


Intracellular AccumulationsIntracellular Accumulations

• Stressed cells may fill up with:

– Unused foods

º Lipids

º Glycogen

– Abnormal proteins

– Pigments

– Calcium salts


Injurious AgentsInjurious Agents

• Hypoxia

• Heat and cold

• Electricity

• Chemical agents

• Biologic agents

• Radiation

• Nutritional imbalances


Stresses Damage Cells By:Stresses Damage Cells By:

• Direct damage to proteins, membranes, DNA

• ATP depletion

• Free radical formation

• Increased intracellular calcium


Hypoxia Causes ATP Depletion or “Power Failure”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


QuestionQuestion

How does hypoxia cause cell damage?

a. Directly damages DNA

b. Diminishes ATP production

c. Forms free radicals

d. Increases intracellular calcium


AnswerAnswer

b. 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.


ScenarioScenario

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?


Free RadicalsFree 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


Calcium 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”


ScenarioScenario

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?


Cell DeathCell 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


Apoptosis or Programmed Cell DeathApoptosis 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


Apoptosis Can Be Caused By: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


NecrosisNecrosis• Cell death and degradation

• Cells may undergo:

– Liquefaction

– Coagulation

– Infarction

– Caseous necrosis

• Cell contents often released

• Inflammation often results


QuestionQuestion

Tell whether the following statement is true or false:

Necrotic tissue may be reversed using high concentrations of oxygen.


AnswerAnswer

False

Necrotic tissue is already dead, so it cannot be restored to functional tissue.


GangreneGangrene

• 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


QuestionQuestion

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


AnswerAnswer

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?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

Chapter002

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