Lecture 3, Acute Cell Swelling 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
What are the two ways that decreased ATP can result from increased cytosolic calcium?
Increased mitochocondrial permeability transition can occur, leading to decreased ATP
Activation of cellular enzymes like ATPase can occur, leading to decreased ATP
The significance of hypoxia depends on…?
The significance of hypoxia depends on:
- Organ/cell type
- Degree (mild, complete)
- Duration (1 minute? 1 hour?)
- Extent (Small vs. large, thankfully we have paired organs…)
What are some of the useful functions of apoptosis?
Useful functions of apoptosis:
Digit formation (embryologic development)
Cell infection (viral)
Neoplastic (DNA damage)
Immune system (cells that recognize self)
Normal involution (thymus,uterus)
Old/senescent cells
What’s one of the ramifications of losing ATP?
What’s one of the ramifications of losing ATP? We can’t regulate ions because it loses the functionality of the sodium potassium pump
What happens if sodium can freely come into the cell?
What happens if sodium can freely come into the cell? Water follows.
What happens when you bring in water? You get a lot of water where it’s not supposed to be, and cells can’t deal with that. They lyse, and then it’s game over.
What is the definition of hypoxia?
A lack of, or a suboptimal amount of oxygen
Why do we care about post-mortem autolysis?
When the body dies, not all cells die at the same time
Some cells may be living, even though the organism as a whole is no longer considered alive. Cells die in different lengths of time, depending on the cell.
It’s an important thing to know about (post-mortem autolysis) because it can really complicate findings if we’re doing a necropsy. Know that there’s a set of lesions out there, that when that animal was alive, it didn’t have those changes (they have appeared due to post-mortem artifact).
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 is some gross morphology of cell swelling?
Gross morphology of cell swelling:
It’s subtle
Swelling of organ/increased weight
Bulges on cut surface
Pallor
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
Necrosis vs apoptosis? Go.
Necrosis: A cell can potentially recover, in this situation. May be pale because it’s taken on water. Tend to see amorphous changes
When there’s necrosis in the living body, necrosis recruits inflammation (note the neutrophils). There’s a whole cascade of cell mediators that are released in the face of necrosis, often by the necrotic cells themselves, that recruits inflammatory cells, and so when there’s necrosis, there will be inflammation.
Maybe not immediately, but as soon as the neutrophils can get there and do what they do. Neutrophils show up in an area of necrosis to clean it up; they have all these proteases, they love nothing more than to spit out all these proteases on a bunch of junk. Then the macrophages show up, hoover it away, and you’ve got a nice clean up system
Apoptosis: The cell shrinks. Visibly smaller, becoming glassy. Portions of the cell that are still viable, like organelles, can be repackaged and can be phagocytosed by another cell.
Minimal to no inflammation in apoptosis. Residual bodies that are generated from an apoptotic cell can be phagocytized and perhaps used for other things
Think of apoptosis as a recycling process. It affects an individual cell, inflammation is absent, and there are no gross changes.
