Lecture 3 Flashcards
What are the main causes of cell injury?
The main causes of cell injury are:
- Oxygen deficiency (Hypoxia, Oxidative phosphorylation)
- Physical agents (Heat, cold, radiation, toxins, trauma)
- Infectious agents (bacteria, viruses, parasites, prions)
- Nutritional deficiencies/imbalances (protein deficiency, vitamins/minerals)
- Genetic derangement (inherited, acquired)
- Workload imbalance (too much, too little)
- Chemicals, drugs, toxins
- Immune dysfunction
9. Aging
What are the causes of hypoxia?
The causes of hypoxia are:
- Ischemia (thrombus, trauma)
- Anemia (decreased RBC, Hb)
- Carbon Monoxide (decreased oxygen)
- Respiratory failure (asphyxia; decreased gas exchange)
- Cardiac failure (decreased cardiac output)
The consequences of hypoxia depends on ______ _________.
The consequences of hypoxia depends on cell type.
Which cell types are highly susceptible to hypoxia?
- Neurons
- Cardiac myocytes
- Renal tubules
- Endothelial cells
- Hepatocytes
- Pneumocytes
are all highly susceptible to hypoxia
Which cell types are least susceptible to hypoxia?
- Cartilage
- Bone
- Fat
- Skin
Are the least susceptible to hypoxia
What three signs reflect non-reversible damage, i.e. that a cell is absolutely going to die?
- Mitochondrial damage
- Cell membrane damage
- Pyknosis / karyolysis
Once a cell is displaying one of these signs, it’s toast.
What are the three forms of cell death?
The three forms of cell death are:
- necrosis
- apoptosis
- post-mortem autolysis
How does acute cell swelling occur?
Acute cell swelling occurs via:
Hypoxia, leading to decreased ATP
Which leads to
Membrane injury, resulting in a loss of environment control
What are some of the causes of the loss of selective permeability of a membrane?
The loss of selective permeability of a membrane can result from:
- Free Radicals, leading to lipid peroxidation
- Carbon tetrachloride
- Beta-radiation
- Toxins, venom
- Physical causes: cold/heat/pressure
- Immune attack: complement, NK (natural killer) cells
What two cellular pathways can occur as a result of lipid peroxidation?
Lipid peroxidation of a membrane can lead to:
- Fatty change/fatty liver
- Cell swelling/necrosis
In a normal cell, concentrations of Na is higher ___________ the cell, and concentrations of K is higher _________ the cell.
In a normal cell, concentrations of Na is higher outside the cell, and concentrations of K is higher inside the cell.
What are some ramifications of increased cytosolic calcium?
Increased cytosolic calcium can lead to:
Increased mitochocondrial permeability transition, leading to decreased ATP
Activation of cellular enzymes, like:
Phospholipase, leading to decreased phospholipids and membrane damage
Protease, leading to disruption of membrane and cytoskeletal proteins, and eventual membrane damage
Endonuclease, leading to nuclear damage
ATPase, leading to decreased ATP
Which enzymes, when activated by increased cytosolic calcium, lead to membrane damage?
Phospholipase, leading to decreased phospholipids and membrane damage
Protease, leading to disruption of membrane and cytoskeletal proteins, and eventual membrane damage
Which enyzme, when activated by increased cytosolic calcium, leads to nuclear damage?
Endonuclease leads to nuclear damage
Describe the route to fatty change, in a cell.
(Due to lipid peroxidation)
When you’ve had an autocatalytic spread of lipid peroxidation that’s going along the lipid bilayer, that’s going to damage the RER
If you’ve damaged the rough endoplasmic reticulum, then you have detachment of all the ribosomes and the units of ribosomes
You’ll have decreased protein synthesis, which ultimately will lead to the intake of fat globules that can not get processes due to the lack of apoproteins
Et voilà! That is the route to fatty change.
Describe to route to cell swelling/necrosis, in a cell.
(due to lipid peroxidation)
The route to cell swelling, just as an individual change:
Remember that the lipid bilayer is made of lipid, and so when a lipid membrane breaks down, that will generate all kinds of free radicals
So it’s a self-perpetuating process; a little bit of damage can go a long way.
When you have damage to the plasma membrane, then you’ll end up with increased permeability to sodium, water, and Ca. All of these contribute to cell swelling
When there’s a large amount of Ca entering the cell, then that’s further compromise to the cell
So then you have inactivation of mitochondria, multiple cell enzymes, and denaturation of proteins
Ultimately, you now have a dead cell
What compounds help to decrease the effects of ROS (reactive oxygen species)?
Why do we care about ROS?
Vitamins E, A, and beta carotenes are compounds that will scavenge free radicals and make our cells less susceptible to free radical damage.
ROS can cause membrane lipid peroxidation, DNA fragmentation, protein cross-linking and fragmentation
What’s going on here? What is 1, 2, 3?
This is an EM of a cell that’s swelling.
- Myelin figure. Can be an indication of prior cell damage; something that you look for in a cell, to see if the cell’s been undergoing some stress
It, in and of itself, is not a lethal feature, except in situations of some genetic diseases where they store excessive materials in lysosomes, and that disrupts the cell’s ability to perform whatever function that cell is supposed to do
- Jacked up, swollen mitochondria (note that non-parallel/aligned cisternae)
- Swollen smooth endoplasmic reticulum
