Cellular Injury and Its Mechanisms
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Questions and Answers

Which of the following conditions directly impairs ATP formation by inactivating cytochrome oxidase?

  • Cyanide (correct)
  • Lactic acid
  • Oxalic acid
  • Ethylene glycol

Which of the following is a critical factor in determining whether cell injury is reversible or irreversible?

  • The cell type affected
  • The extent of membrane disturbances and mitochondrial dysfunction (correct)
  • The duration of exposure to the injurious stimulus
  • The presence of cellular swelling

What cellular change is characteristic of reversible cell injury when observed under a light microscope?

  • Nuclear karyolysis
  • Nuclear fragmentation (karyorrhexis)
  • Cellular swelling and fatty change (correct)
  • Shrinkage of the nucleus (pyknosis)

Which process is directly facilitated by glutathione in preventing cell injury from reactive oxygen species?

<p>Breakdown of hydroxyl radicals (B)</p> Signup and view all the answers

Why is Ischemia more damaging to cells compared to Hypoxia?

<p>Ischemia involves both a lack of oxygen and a reduced supply of nutrients, alongside the buildup of toxic metabolites. (A)</p> Signup and view all the answers

What is a critical early event in cell injury that leads to cellular swelling?

<p>Failure of the sodium-potassium (Na+/K+) pump (B)</p> Signup and view all the answers

Which of the following is a typical cause of cell injury?

<p>Infectious agents (C)</p> Signup and view all the answers

Which of the following events is characteristic of irreversible cell injury when viewed under an electron microscope?

<p>Rupture of lysosomes and lysis of the endoplasmic reticulum (C)</p> Signup and view all the answers

How does increased mitochondrial cytosolic calcium contribute to cell injury?

<p>It leads to lipid peroxidation and triggers apoptosis via cytochrome c release. (B)</p> Signup and view all the answers

What is the primary mechanism by which free radicals cause damage to cell membranes?

<p>Lipid peroxidation (A)</p> Signup and view all the answers

In reversible cell injury, what is primarily responsible for the generalized swelling of cells and their organelles?

<p>Disruption of the Na+/K+ pump and increased sodium influx (D)</p> Signup and view all the answers

How do vitamins A, C, and E protect against cell injury?

<p>By acting as antioxidants that neutralize free radicals (B)</p> Signup and view all the answers

Which cellular system is NOT identified as especially vulnerable to cellular injury?

<p>The Golgi apparatus (A)</p> Signup and view all the answers

How does the accumulation of lactic acid during hypoxia contribute to cellular damage?

<p>By decreasing the cellular pH, causing ribosome disaggregation from the endoplasmic reticulum (D)</p> Signup and view all the answers

Which of the following is an example of a direct effect of a toxin causing cell injury, without requiring metabolic conversion?

<p>Cyanide (C)</p> Signup and view all the answers

Which of the following is a morphological change associated with irreversible cell injury?

<p>Pyknosis (B)</p> Signup and view all the answers

Under which circumstances does cell injury occur?

<p>When cells cannot adapt to changes (B)</p> Signup and view all the answers

Cell swelling, an early morphological manifestation of most forms of cell injury, is a result of what alteration?

<p>Failure of ion pumps leading to influx of sodium ions (D)</p> Signup and view all the answers

Which statement accurately describes the generation process of free radicals in cells?

<p>Free radicals are generated during normal physiological processes. (D)</p> Signup and view all the answers

Which of the following is a condition or agent that can cause cellular hypoxia, leading to cell injury?

<p>Ischemia (C)</p> Signup and view all the answers

Which of the following processes is considered an adaptation to prevent the formation of reactive oxygen species (ROS) and mitigate cell damage?

<p>Increased levels of superoxide dismutase, catalase and use of Vitamins A, C and E. (A)</p> Signup and view all the answers

Which of the following best explains how free radicals lead to cell injury?

<p>By causing lipid peroxidation (D)</p> Signup and view all the answers

Which feature is most associated with irreversible cell damage under an electron microscope?

<p>Rupture of lysosomes (C)</p> Signup and view all the answers

Ethylene glycol itself is primarily not toxic. However, how does it cause damage to the cells?

<p>It metabolizes into a toxic compound. (B)</p> Signup and view all the answers

Which of the following best explains the appearance of lipid vacuoles in the cytoplasm in fatty change?

<p>Cells actively involved in lipid metabolism (C)</p> Signup and view all the answers

Which of the following processes leads to the development of fatty liver disease following cell injury?

<p>Lipid peroxidation damages cells. (A)</p> Signup and view all the answers

What triggers apoptosis following an increase in mitochondrial cytosolic calcium?

<p>It releases cytochrome c (B)</p> Signup and view all the answers

What effect do free radicals have on proteins during cell injury?

<p>Protein cross-linking (D)</p> Signup and view all the answers

Under light microscopy, what is the phenomenon of nuclear fading called?

<p>Karyolysis (C)</p> Signup and view all the answers

Flashcards

Cell Injury

Occurs when cells can't adapt to a new environment.

Hypoxia

Lack of oxygen, leads to decreased ATP.

Ischemia

Reduced blood flow, more damaging than hypoxia due to nutrient deprivation and metabolite build-up.

Vulnerable cellular systems

Damage to DNA, cell membranes, protein generation, and ATP production.

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Free Radical

Molecule with an unpaired electron in its outer orbit.

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Antioxidants

Catalase, superoxide dismutase, glutathione, and vitamins A, C, E.

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Reversible cell injury

Characterized by swelling and fatty change.

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Irreversible cell Injury

Characterized by membrane damage, DNA loss, or mitochondrial loss.

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Reversible injury (light)

Cellular swelling and fatty change within microscopy.

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Irreversible injury (light)

Nuclear breakdown: karyolysis, pyknosis, and karyorrhexis.

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Study Notes

  • Cell injury occurs when cells cannot adapt to their new environment.

Causes of Cell Injury

  • Hypoxia
  • Ischemia
  • Physical and chemical agents
  • Trauma
  • Infectious agents
  • Radiation
  • Toxins
  • Metabolic abnormalities, either acquired or genetic
  • Aging and nutritional imbalances
  • Immune dysfunction, including hypersensitivity reactions and autoimmune diseases

Hypoxia and Ischemia

  • Two common sources of cellular injury.
  • Ischemia is more damaging than hypoxia because it involves hypoxia, lack of other nutrients, and accumulation of toxic cellular metabolites.
  • Cell injury varies from cell to cell, based on the injury's type, duration, and severity, as well as the cell's type, adaptability, and makeup.

Systems Vulnerable to Cell Injury

  • DNA
  • Cell membranes
  • Protein generation
  • Adenosine triphosphate (ATP) production

Mechanisms of Cellular Injury

Hypoxia

  • Decreased oxygen leads to decreased ATP production.
  • ATP is required by the Na/K and Ca2 pumps.
  • When ATP levels decreases, these pumps fail and sodium (followed by water) enters the cell causing swelling.
  • Calcium entering the cell activates endonucleases, proteases, phospholipases, and DNAses, damaging the cell.
  • Cells switch to anaerobic respiration to produce ATP, accumulating lactic acid.
  • Lactic acid accumulation decreases cellular pH, causing ribosome disaggregation from the endoplasmic reticulum.

Oxygen-Derived Free Radicals

  • Generated by a stressing agent.
  • A free radical consists of a molecule with an unpaired electron in the outer orbit.
  • Free radicals are generated by normal physiologic reduction-oxidation reactions, UV light, x-rays, ionizing radiation, metals like H2O2 +Fe3+ Fe3+OH+OH,and exogenous chemicals
  • Effects of Free Radicals

Lipid Peroxidation

  • Damages cell membranes and increases apoprotein synthesis, resulting in fatty liver
  • Cell swelling results in influx of Ca+2 and inactivation of mitochondria, cell enzymes, and denaturation of proteins.

DNA Fragmentation

Protein Cross-Linking

  • Sulfhydryl groups cause increased degradation and decreased activity.

Methods to Prevent Formation of Reactive Oxygen Species

  • Catalase degrades hydrogen peroxide.
  • Superoxide dismutase: converts superoxide to hydrogen peroxide.
  • Glutathione: catalyzes breakdown of hydroxyl radicals.
  • Vitamins A, C, and E have an antioxidant effect.

Chemical Injury

  • Some chemicals are directly toxic to cells, while others require conversion to a toxic metabolite.
  • Ethylene glycol converts into toxic oxalic acid.
  • Cyanide directly inactivates cytochrome oxidase, impairing ATP formation.

Increased Mitochondrial Cytosolic Calcium

  • Leads to lipid peroxidation and formation of mitochondrial permeability transition, which is a nonselective pore that dissipates the proton gradient.
  • Causes release of cytochrome c, activating apoptosis.

Reversible Cell Injury

  • Characterized by functional and structural alterations in early or mild injury forms, correctable if the damaging stimulus is removed.
  • Generalized swelling occurs in the cell as well as its organelles.
  • Decreased ATP production causes sodium to enter the cell, then water follows causing the cell and organelles to swell.
  • Fatty change occurs in organs that are actively involved in lipid metabolism, such as the liver, and is manifested by lipid vacuoles in the cytoplasm.

Irreversible Cell Injury

  • Occurs with damage to plasma or lysosomal membranes.
  • Occurs with loss of DNA, or loss of mitochondria.
  • Damage cannot be reversed in irreversible cell injury.
  • Membrane disturbances and the inability to reverse mitochondrial dysfunction are the primary factors.

Morphologic Changes of Cellular Injury

Light Microscope Observations

  • Reversible injury: cellular swelling and fatty change.
  • Irreversible injury: nuclear karyolysis (basophilia loss), pyknosis (nucleus shrinkage), and karyorrhexis (nucleus fragmentation).

Electron Microscope Observations

  • Reversible injury: cellular blebs and small mitochondrial densities.
  • Irreversible injury: ruptured lysosomes, myelin figures (phospholipid precipitation), lysis of endoplasmic reticulum, large calcium-rich mitochondrial densities.

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Explore the causes and mechanisms of cellular injury, including hypoxia, ischemia, and various agents. Understand how cell injury affects vital systems like DNA, cell membranes, and ATP production. Learn about the specific pathways through which hypoxia leads to cellular damage and dysfunction.

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