POM Lecture 1 Flashcards
What are the causes of cell stress and injury?
Physical Injury Chemical Injury Biological causes Immunologic Injury Genetic Derangements Nutritional Imbalance
Cell Suicide
Apoptosis
Cell Murder
Oncosis/Necrosis
Why is there depletion of ATP during cell injury?
Depletion of Oxygen
Damage to Enzymes
Damage to mitochondria
What are the responses due to an injurious stimulous
Depletion of ATP
Membrane Damage
Increase of Intracellular Calcium
Reactive Oxygen species
Low energy for sodium pumps means?
Influx intracellularly of sodium and water, cells and organelles swell
Low energy for Calcium pumps means?
influx of calcium into the cytosol, inappropriate activation of calcium dependent channels. damage to cellular components.
How can cell membrane damage occur?
Directly via free radicals,
or hypoxia (stress due to a lack of oxygen),
or due to a membrane targeting bacteria toxin
or following failure of plasma membrane Calcium pump
Influx of calcium activates what destructive calcium dependent enzymes?
ATPases
Phospholipases
Proteases
Endonucleases
Oxidative stress
the accumulation of free radicals
Reactive Oxygen species
free radicals generated during cell injury,
Eg) O2 H2 NO
Heat Shock Factors
Transcription factors that induce the transcription of Heat Shock Proteins.
Heat shock Proteins
Proteins that are molecular chaperones, assist repair of damaged proteins.
Stress Kinases
Are released following stress or injury, initiate signalling cascades that co-ordinate the cells response to damage
What is bad about ATP depletion and how does this occur?
There is less energy for ATP membrane pumps (ionic/osmotic homeostasis ruined). Less energy for protein synthesis and DNA/protein repair.
this occurs during cell injury due to a lack of O2, enzyme or mitochondrial damage
What is bad about Cell membrane damage
Causes loss of cell contents, osmotic balance and proteins (enzymes, coenzymes, RNA)
What happens when lysosomal membranes leak?
leak enzymes into cytoplasm, and start digesting cell ; ‘autolysis’
What happens when mitochondrial membrane damage occurs?
formation of nonselective high conductance channels in IMM, ‘mitochondrial permeability transition’, takes away transmembrane potential for oxidative phosphorylation.
How do you get higher cytosolic Ca concentration?
when reduced activity of the plasma membrane calcium pump allows influx of Ca into cytosol.
What are reactive oxygen species
Free radicals generated during cell injury. The accumulation of these is called oxidative stress, and these cause secondary damage.
How do free radicals cause damage?
By attacking the double bonds in unsaturated fatty acids in membranes, oxidising aminoacids
How do we defend against free radicals?
With antioxidants and some enzymes. When there are too many FR too be handled = oxidative stress
Hyperplasia?
increase in cell numbers due to an increase functional demand or stimulation. Can be from the division of the cells in question or locally residing stem cells
Hypertrophy?
increase in cell size due to an increase functional demand or stimulation.
Atrophy?
Decrease in cell size. Cells responding to reduced functional demand/nutrient supply
Metaplasia?
reversibly changing from one adult cell type to another. Response to continuous mild damage. Results from the reprogramming of stem cells, to differentiate down a new path
Features of Necrosis
- no energy requirement
- often with autolysis ‘protein soup’
- cytosolic contents also leak across damaged plasma membrane into extracellular space (induces inflammatory response)
- uncontrolled messy process
- featureless cytoplasm due to denaturation and protein digestion
- fragmentation and fading of chromatin in nuclei
- Pyknosis
- usually quickly removed by phagocytosis
Pyknosis
Chromatin shrinks into a dense mass at the margin of the nucleus, prior to karolysis
Features of Apoptosis
requires energy
- common after DNA damage, hypoxia, accumulation of damaged proteins
- also eliminates unwanted cells
- chromatin cleaves and condenses, membrane bound blebs break off cell and are phagocytosed
what cascade of enzymes mediates apoptosis
Caspases
How does apoptosis NOT initiate inflammation?
As pyknosis occurs, membrane bound ‘blebs’ containing contents break off and are phagocytosed by neighbouring cells, so cytosolic contents don’t leak out