Cell Injury II Flashcards
What are the eight general causes of cell injury?
- Oxygen deprivation
- Chemical agents
- Infectious agents
- Immunologic reactions
- Genetic factors
- Nutritional imbalances
- Physical agents
- Aging
Carbon monoxide poisoning causes what type of general cell injury?
Oxygen deprivation by irreversibly binding to heme
Do different cells react differently to certain stresses?
Yeah
In cell injury, what is the temporal arrangement of the following: gross morphological changes, cell death, cellular function?
Cellular function is lost first, then cell death occurs, then gross morphological changes happen.
What are the four intracellular systems that are vulnerable to injury?
Cell membranes, aerobic respiration, protein synthesis, genetic integrity.
What are the two most important phenomena that correlate with the irreversibility of cell injury?
Mitochondrial dysfunction and membrane dysfunction. Note that the two are interrelated.
Does cell injury progress in steps, or in a continuous process?
In a continuous process
What is the difference between ischemia and hypoxia?
Ischemia is characterized by a deprivation of both oxygen and substrates (often occurs as a loss of blood supply). Hypoxia is systemic oxygen deprivation (example: going to high altitudes).
What are the three general changes that occur during reversible cell injury?
- Volume - cells swell
- Changes in energy metabolism
- Morphological changes
What causes cellular swelling that occurs during reversible cell injury?
Changes in membrane permeability and loss of function of ATP-driven ion pumps increase osmotic load in the cell from increased levels of Na+, Ca2+, and small molecules.
Name the changes in energy metabolism that occur during reversible cell injury.
ATP production drops due to decreased aerobic respiration. Anaerobic metabolism increases, lowering pH. Glycogen stores are used, protein synthesis decreases.
What morphological changes from reversible cell injury can be seen in a light microscope?
Cytoplasmic changes such as hydropic changes (vacuolar degeneration - ER buds that have pinched off into the cytoplasm; cell stains lighter, too). Nuclear changes like clumping of chromatin can be seen.
What morphological changes from reversible cell injury can be seen in an electron microscope? (4)
Dilation of the ER (from habitual drug abuse), decreased glycogen stores, swollen mitochondria with small densities, blebbing of the plasma membrane.
What causes the dysregulation of volume in cells that are irreversibly injured?
Caused by a permanent loss of selective permeability of the plasma membrane and leakage of large molecules out of the cell. Membrane phospholipids are lost due to enzymatic action and cytoskeletal abnormalities.
What four changes in energy metabolism occur after irreversible cell injury?
- OXPHOS decoupling
- Decreased PO4: O2 ratio
- Glycolysis increases, lactate increases, pH drops
- Mitochondrial dysfunction, including mt permeability transition pore leakage
An increase in eosinophilia and a decrease in basophilia in cells is indicative of what? What causes it?
Cell damage and swelling. Caused by denaturation of cytoplasmic proteins and a loss of RNA from the cell (RNA is basophilic), and increased osmotic load in the cytoplasm due to loss of selective permeability of the PM.
What is: 1. Pyknosis 2. Karyorrhexis 3. Karyolysis? What do these indicate?
Pyknosis is a shriveling of the nucleus and increased basophilia.
Karyorrhexis is nuclear fragmentation - looks like a chocolate chip cookie.
Karyolysis is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases.
They are indicative of necrosis.
What morphologic changes to the mitochondria can be seen on EM during irreversible injury?
- Dilation or rupture
2. Granules/amorphous densities
What role does calcium play in cell injury?
It is usually found in low cytoplasmic concentrations. When the cell is injured, altered membrane permeability allows for Ca2+ influx. Mitochondria will suck up the Ca2+ from cytoplasm, resulting in decreased ATP production.
What can increase rates of free radical formation? (4)
Radiant energy exposure, enzymatic reactions, transitional metals react with H2O2 to generate a hydroxyl radical via the Fenton reaction, Nitric oxide can produce free radicals.
Name two examples of physiologic free radical generation.
- Respiratory burst in neutrophils and macrophages.
2. Byproduct of aerobic respiration.
What are the three main ways in which reactive oxygen species cause cell injury?
- Lipid peroxidation of membranes.
- Cross-linking of proteins - results in protein degradation.
- DNA damage.
What do scavengers do to free radicals?
Capture them!
What are the five mechanisms by which cells deal with free radicals?
- Superoxide dismutases
- Glutathione peroxidases
- Catalase
- Antioxidants A, C, and E
- Metal binding proteins (transferrins, ferritin, lactoferrin, etc.)
