Pathology - Cell Injury, Adaptation, and Death
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What are the 9 causes of cell injury discussed?
- 1. Oxygen deprivation (hypoxia)
- 2. Free Radicals
- 3. Chemical Agents
- 4. Physical Agents
- 5. Infectious Agents
- 6. Immune Reactions
- 7. Genetic Defects
- 8. Nutritional Deficiencies
- 9. Aging
What are the causes of hypoxia, or Oxygen deprivation?
- -Ischemia (loss of blood supply)
- -Decreased oxygenation (heart failure)
- -Decreasd oxygen carrying capacity (anemia, CO poisoning)
What is the most common cause of cell injury?
Hypoxia (oxygen deprivation)
What are 4 ways to damage a cell?
- 1. Interfere with energy production.
- 2. Wreck the membranes.
- 3. Destroy the contents.
- 4. Cause it to commit suicide.
What are the consequences of mitochondrial damage?
- -Results in the formation of channels in the mitochondrial membrane.
- -Reduced ATP generation.
- -Channels allow Cytochrome C to leak out which then activates apoptotic pathways.
- -Increase in Reactive Oxygen Species.
What are some results of ATP depletion?
- -Influx of Ca2+.
- -Increase anaerobic glycolosis, which decreases glycogen, increases lactic acid and decreases pH causing clumping of chromatin.
- -Ribosomes detach decreasing protein synthesis.
What causes the initial rise in intracellular Ca concentrations?
- -Influx of Ca2+.
- -Release of Ca from mitochondria and ER.
What causes a sustained rise in intracellular Ca2+?
- -Increased membrane permeability.
- -(Can't be dealt with)
Increased cytosolic calcium results in the enzyme activation of what?
- (leads to cell death, apoptosis)
What are examples of Reactive Oxygen Species (ROS)?
- -Hydrogen peroxide
- -Hydroxyl radical
- -NO can act like a free radical, or form highly reactive nitrites.
What are some things that may cause cellular injury by free radicals?
- -Cellular aging
- -Chemical, physical and radiation injury
What are some effects of cellular injury via free radicals?
- -Lipid peroxidation leading to membrane damage.
- -Protein modifications leading to breakdown and misfolding of proteins.
- -DNA damage leading to mutations.
What do low levels of ROS's cause?
What do intermediate levels of ROS's cause?
What do high levels of ROS's cause?
What neutralizes free radicals?
- -Essential Enzymes
- -Electron trapping molecules
What is Ischemia Reperfusion injury?
- Further cell death following reversal of ischemia.
- -Results in inflammatory cell infiltrate, and release of Reactive Oxygen Species (ROS).
What are some examples of things that can cause membrane damage via a direct injury?
- -Bacterial toxins
- -Viral proteins
- -CTL, NK cells
- -Physical, chemical agents
What are some secondary injuries to membrane damage?
- -ATP depletion.
- -Activation of degradative enzymes.
- -ROS generation.
- -Failure of electrolyte gradients.
What makes an injury considered reversible?
Decreased cell mass
increased cell mass (size)
Increased cell number
Change from one mature cell type to another.
T/F - Atrophy can be physiological or pathological.
What are some examples of physiological atrophy?
- -Notochord in developing embryo.
- -Thymus at puberty.
What are some causes of pathologic atrophy?
- -loss of endocrine stimulation (menopause)
- -Space flight
What is the main event that occurs during atrophy?
Increased protein degradation.
Are there new cells produced during hypertrophy?
No, hypertrophy is an increase in cell size.
What are some physiological examples of hypertrophy?
- -Uterine hypertrophy and hyperplasia in pregnancy in response to estrogen.
- -muscle hypertrophy in weight lifters.
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