1. Types Of Cell Death Flashcards
What are the 2 main types of cell death? What is the difference between the 2?
- Apoptosis
- cell death with shrinkage
- induced by a regulated intracellular programme involving activation of enzymes that degrade own nuclear DNA and proteins - Oncosis
- cell death with swelling
- induced in cells injured by hypoxia or some other agents
What is necrosis?
The morphological changes in a living organism that occur after a cell has been dead for some time (4-24hrs).
Is an appearance and not a process.
Name the 2 main types, and 2 special types of necrosis.
Main types:
- coagulative
- liquefactive (colliquitive)
Special types:
- fat necrosis
- caseous
What molecular changes cause necrosis?
- Cell membrane (plasma and organelle) damage.
- Lyosomal enzymes are released into cytoplasm and digest the cell… cell contents leaks out of cell… inflammation.
What happens to necrotic tissue?
- Eventually removed by enzymatic degradation and phagocytosis by WBCs.
- Any remaining tissue may calcify - dystrophic calcification.
What is the difference between coagulative and liquifactive necrosis? In which tissue type do each occur?
- Coagulative: proteins are denatured and coagulate.
Occurs after ischaemia of solid organs (e.g. Kidney) - Liquifactive: proteins are dissolved by cell’s own enzymes - autolysis.
Occurs after ischaemia in loose tissues (e.g. Brain) or in presence of many neutrophils (e.g. infection)
How can one differentiate between coagulative and liquefactive necrosis under the microscope?
- Coagulative: cellular architecture is somewhat preserved - ‘ghost outline’ of cells, some karyolysis, some neutrophil presence.
- Liquefactive: complete liquefaction of tissue, inflammation causes swelling of surrounding tissue.
What is caseous necrosis?
- Contains amorphous (structureless) debris but not uniform ghost outline as in coagulative.
- Associated with infection, especially tuberculosis.
What is fat necrosis?
Break down of lipids by lipase, producing fatty acids that react with calcium - form calcium soaps.
Associated with accumulation of macrophages.
When/where does fat necrosis occur?
- Trauma of panceas or acute pancreatitis.
- Can also occur in the breast.
Define the terms infarction and infarct.
Infarction = reduction in arterial blood flow (ischaemia) causing necrosis.
Infarct = area of necrotic tissue as a result of loss of arterial blood supply - ischaemic necrosis.
What is gangrene and when do the different types occur?
Gangrene = necrosis visible to the naked eye.
- Dry gangrene = necrosis modified by exposure to air (coagulative necrosis).
- Wet/gas gangrene = necrosis modified by infection with gas-producing anaerobic bacteria (liquefactive necrosis).
What are the most common causes of infarction (i.e. Types of ischaemia)? How else can tissue become infarcted?
- Thrombosis (formation of blood clot in blood vessel) and embolism (bit of thrombus breaks off and blocks small vessels).
- Can also occur due to external pressure on BV, e.g. In testicular torsion or sigmoid vulvulus.
When would an infarct appear white?
- As a result of embolism occluding an end artery in solid organs.
- Involves coagulative necrosis.
When would an infarct appear red?
- When blood vessels bleed into tissue as a result of a thrombus.
- Occurs in:
1. Loose tissue (liquidative necrosis)
2. Lungs - dual blood supply
3. Tissues with numerous anastamoses (e.g. Bowel)
4. Prior congestion
5. Raised venous pressure
6. Re-perfusion
What is the result of potassium leakage out of injured cells? When might this occur?
- Can cause heart arrest.
- Occurs in:
1. Massive area of MI
2. Severe burns
3. Too successful chemotherapy- tumourlysis syndrome
Which enzyme leaking out of injured cells is used to diagnose MI?
Troponin I
What is rhabdomyolysis and what is the consequence of this?
- Breakdown of skeletal muscle, e.g. As a result of crush injury, strenuous exercise, heat stroke…
- Causes release of myoglobin - blocks kidney glomeruli, may lead to kidney failure.
What is apoptosis, how is it induced?
- Cell death with shrinkage.
- Induced by a regulated intracellular program where a cell activates enzymes that degrade it’s own nuclear DNA.
When does apoptosis occur physiologically?
- Maintenance of steady state (cell turnover)
- Hormone-controlled involution (e.g. Ovaries in menopause as oestrogen no longer maintains size)
- Digit formation in embryogenesis
When does apoptosis occur pathologically?
- Cytotoxic T cell-killing of virus-infected or neoplastic cells.
- Damaged cells, esp damaged DNA.
- Graft vs host disease after bone marrow transplant (new leukocytes stimulate apoptosis of host cells, esp skin and bowel endothelium).
How is apoptosis initiated?
2 pathways: extrinsic and intrinsic.
- Most commonly triggered by irreparable DNA damage or withdrawal of growth factors/hormones.
- p53 protein is activated… outer mitochondrial membrane becomes leaky.
- Release of cytochrome C from MT - activates caspases.
- Cause cleavage of DNA and cytoskeleton proteins.
- Cell shrinks and breaks up into apoptotic bodies.
What happens to apoptotic bodies?
Express specific proteins on surface which allow recognition by phagocytes or neighbouring cells - are engulfed and degraded.
Describe the differences between oncosis/necrosis and apoptosis.
ONCOSIS/NECROSIS. APOPTOSIS
- Contiguous group of cells. 1. Single cells
- Cell swelling. 2. Cell shrinking
- Pyknosis, karyolysis or 3. Fragmentation into nucleosome
Karyorrhexis. size fragments, form clumps
beneath nuclear membrane - Disrupted, early lysis of PM. 4. Intact PM
- Enzymatic digestion and 5. Intact cellular content released
leakage of cellular contents. In apoptotic bodies - Inflammation. 6. No inflammation
- Invariably pathologic. 7. Often phsyiologic (elimination of
Unwanted cells), may be
pathologic after some forms of cell
Injury
What is the difference between pyknosis, karyorrhexis and karyolysis?
- Pyknosis = shrinking and darkening of nucleus.
- Karyorrhexis = nucleus fragmentation.
- Karyolysis = nucleus disappearance.
Describe the appearance of injured and dead (oncotic) cells under a light microscope.
Injured: pale and swollen due to water and sodium entering the cell.
Dead: pyknosis, karyorrhexis or karyolysis, and very pink cytoplasm (denatured proteins stained very strongly by eosin).
Describe the appearance of a reversibly-injured (hypoxic) cell under an electron microscope.
- Generalised swelling
- Membrane blebbing due to cytoskeleton breakdown
- Clumping of nuclear chromatin
- ER and MT swelling
- Autophagy by lysosomes
- Dispersion of ER ribosomes
Describe the appearance of an irreversibly-injured (hypoxic) cell under an electron microscope.
- Pyknosis, karyolysis or karyorrhexis
- Defects in cell membrane
- Myelin figures
- ER lysis
- Lysosomal rupture and autolysis
