Chapter 2 Cellular Responses to Stress, Injury, and Aging

PRE LECTURE QUIZ 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. F T

PRE LECTURE QUIZ 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. Apoptosis cardiac decrease Dose Dystrophic

Cellular Adaptation Allows the stressed tissue to survive or maintain function 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? 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 Accumulations Stressed cells may fill up with: Unused foods Lipids Glycogen Abnormal proteins Pigments Calcium salts

Injurious Agents Hypoxia Heat and cold Electricity Chemical agents Biologic agents Radiation Nutritional imbalances

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” Aerobic metabolism stops  less ATP is produced Na+/K+ ATPase cannot run fast enough 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? Directly damages DNA Diminishes ATP production Forms free radicals 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.

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?

Molecules with an unpaired electron in the outer electron shell 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

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 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

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 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: Signaling factor attached to “death domains” of cell surface receptors Mitochondrial damage inside the cell Protein p53 activated by DNA damage

Cell death and degradation Cells may undergo: Necrosis Cell death and degradation Cells may undergo: Liquefaction Coagulation Infarction Caseous necrosis Cell contents often released Inflammation often results

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 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)? Dry Wet Gas 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? 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