Cell Response to Injury: Ultra-structural Changes Flashcards
what causes cell injury?
Results from disruption of structure and function of sub-cellular components
what are the consequences of cell injury?
damage to cellular components
where is the damage seen?
- Mitochondria
- Plasma membrane
- Lysosomes
- Nucleus
what can damage the mitochondria?
Hypoxia, hypoglycaemia & toxins
how are mitochondria damaged?
- Development of vacuoles
* Cristae become damaged
what does a decrease in oxidative phosphorylation lead to?
Reduced levels of ATP
what is reduced ATP level known as?
low amplitude swelling
can low amplitude swelling be reversed?
yes
what are the effects of reduced ATP?
- Reduced activity of Na pump which leads to changes in Na+ and K+ concentration
- Net influx of H2O across plasma membrane which leads to swelling
- Failure of intracellular Ca2+ homeostasis
Why is Ca2+ concentration in cytosol low?
Ca2+ activates cytosolic enzymes
Which enzymes keep calcium levels in check?
ATP dependent enzymes
What does a reduction in cellular ATP lead to in terms of calcium levels?
It leads to increase intracellular calcium
what does intracellular calcium increase lead to?
Activation of:
• Phospholipases
• Endonucleases
• Proteases
how is plasma membrane damage caused?
The damaged mitochondria lead to reduced ATP which leads to reduced activity of the Na pump and a net influx of H2O into the cell, which causes cellular swelling and the formation of blebs
what does the disruption of membrane lead to?
the leakage of enzymes
what does leakage of enzymes lead to?
Activation of acid hydrolases:
• RNAases
• DNAases
• Proteases
Enzymatic digestion/irreversible damage
If acid hydrolases are activated which pathway of cell death will occur?
Necrosis
how is the endoplasmic reticulum damaged?
- Vacuolation and swelling seen early in injury
* Prolonged injury leads to detachment of ribosomes
what does ribosome detachment result in?
Decreased protein synthesis
how can the nucleus be damaged?
- Invagination of nuclear membrane
- Chromatin clumping
- Distinct nuclear changes
what are the features of necrosis?
- Loss of membrane integrity/enzymatic destruction
- Leakage of cellular constituents
- Inflammatory response
- Necrotic cell changes reflect key processes
Why do cells that have undergone necrosis stain pink with H&E?
- Demonstrate denatured and coagulation of protein
* Loss of cytoplasmic RNA
What are the features of cells that lose definition?
- Loss of organelles
- Enzyme digestion: phospholipases and proteases
- Replacement of dead cells: myelin figures and calcium deposition
what is Pkynosis?
nuclear shrinkage
what is Karyorrhexis?
nuclear fragmentation
what is Karyolysis?
nuclear disintegration
what are the distinct nuclear changes?
pkynosis, kerhyorrhexis, Karyolysis
what can be seen in a normal cell (stages of necrosis)?
distinct nucleus and nucleolus
cytoplasm:pale pink/purple due to cellular RNA in rough endoplasmic reticulum
what are the features of an early necrotic cell (stages of necrosis)?
cytoplasm shrinks and increase in eosinophilia (pink staining) - loss of ribosomes
nucleus shrinks and basophilic (purple) cessation DNA transcription
what happens to the cell as necrosis occurs?
after early necrotic cell features:-
the cell remains small and eosinophilic and the cell membrane breakdown results in irregular shape and karyorrhexis occurs
finally the cell is partly denatured mass protein and the cytoplasm is eosinophilic and the nucleus completely dissolves
what are the features of apoptosis?
- Programmed cell death – induced by a tightly regulated suicide programme
- Deletion of individual cells
- No inflammatory response
what do apoptotic cell changes involve?
- Cells shrink – dense cytoplasm, more tightly packed organelles
- Chromatin condensation – aggregation chromatin under nuclear membrane; fragmentation of nucleus
- Formation of blebs and apoptotic bodies – extensive surface blebbing leads to fragmentation
- Phagocytosis of apoptotic bodies by macrophages
