Cell Injury Concepts Flashcards
Includes themes of cell injury and free radicals
What is hypoxia due to?
Ischemia or decreased O2 carrying capacity of blood
What are some physical agents of cell injury?
Trauma, temperature, radiation, shock
Name some chemical agents and drugs that may cause cellular injury
- Biological agents
- Poisons/pollutants
- Industrial hazards
- Social and therapeutic drugs
List the themes of cellular injury
- Hypoxia
- Physical agents
- Chemical agents and drugs
- Infectious agents
- Immunological reactions
- Genetic defects
- Nutritional imbalances
Lack of oxygen (or oxygen excess) causes decreased synthesis of…
ATP
Increases in intracellular calcium and loss of calcium homeostasis lead to activation of…
calcium-dependent enzymes
With an increase in calcium in the cell, enzymes turn on causing…
cell death
Depletion of ATP causes…
loss of membrane function and intracellular processes, thus cell death
Defects in membrane permeability have what effect on the cell?
Holes in membranes, the cell’s or its organelles’, kill the cell
If a cell has decreased pH and ATP, and has swollen, is this reversible or irreversible?
Reversible
If ribosomes have detached from the rough endoplasmic reticulum, is this reversible or irreversible?
Reversible
What is the point of no return/irreversibility?
Mitochondrial vacuolization
What happens after mitochondrial vacuolization?
- Lysosome rupture
- Ca+ release into cytoplasm
What does cellular swelling mean for the cell’s activity?
Loss of activity of Na+/K+ ATPase pump activity meaning ion influx
What does steatosis mean for the cell’s activity?
Altered metabolism/transport of triglycerides
Is steatosis reversible or irreversible?
Reversible, but may become irreversible
Is cellular swelling reversible or irreversible?
Reversible, but may become irreversible
What is pyknosis?
Small, shrunken, and dark nuclei
What is karryorrhexis?
Fragmented nuclei
What is karyolysis?
Faded nuclei
In hypoxic/ischemic injury, is compromised aerobic respiration and increased rate of anaerobic glycolysis reversible?
Yes, these are before the point of no return
Is lysosomal membrane rupture/activation of Ca+ dependent enzymes reversible?
No, after the point of no return
What are free radicals?
Unstable atoms that can injure the cell
Free radicals serve what purpose normally?
A final common pathway in a variety of cell processes
Chemical and radiation injury, cellular aging, oxygen toxicity, and microbial killing by phagocytes can all be caused by…
free radicals
Free radicals consist of…
chemical species
What are three traits of chemical species of free radicals?
- Highly reactive
- Autocatalytic
- Unstable
Free radical induced damage involves:
- Lipid peroxidation of cell membranes
- Oxidative modification of cellular proteins
- Damage to cellular DNA
What enzymes are used to turn O2 into O2- (superoxide anion)?
NADPH oxidase and xanthine oxidase
O2- (superoxide anion) makes more…
free radicals
What enzyme and coenzyme is used to turn O2- into H2O2?
Superoxide dismutase and H2O
Name H2O2
Hydrogen peroxide
What enzyme is used to turn H2O2 into H2O + O2?
Catalase
What would happen without free radicals?
Most immunological processes would cease
What are the attributes of hydrogen peroxide (H2O2)?
Forms free radicals via Fe2+- catalyzed Fenton reaction
Diffuses widely within the cell
What is the Fenton reaction?
Fe2+ + H2O2 –> Fe3+ + OH- + .OH (free radical)
What is the Haber-Weiss reaction?
O2- + H+ + H2O2 –> O2 + H2o + .OH (free radical)
Where is superoxide anion (O2-) generated?
Generated by leaks in the electron transport chain and some cytosolic reactions
Superoxide anion (O2-) with xanthine oxidase produces…
other ROS
Does superoxide anion (O2-) diffuse from its origin?
Does not readily diffuse far from its origin
Where is hydroxyl radical (.OH) generated?
Generated from H2O2 by Fe+-catalyzed Fenton reaction
Which intracellular radical is most responsible for attack on macromolecules?
Hydroxyl radical (.OH)
What are the attributes of peroxynitrite (ONOO.)?
Formed from the reaction of nitric oxide (NO) with O2-; damages macromolecules
What are lipid peroxide radicals (RCOO.)?
Organic radicals produced during lipid peroxidation
What are the attributes of hypochlorous acid (HOCl)?
Produced by macrophages and neutrophils during respiratory burst that accompanies phagocytosis
Dissociates to yield hypochlorite radical (OCL-)
What is Fe2+?
Ferrous iron
Activated oxygen will lead to…
membrane damage thus cell injury
