Fundamentals: Pathology - Cellular injury and adaptation Flashcards
(51 cards)
When does cell injury occur?
If the limits of adaptive responses are exceeded or if cells are exposed to damaging insults, deprive of critical nutrients, or compromised by mutations that affect essential cellular function
What is the ultimate consequence of persistent or severe cell injury?
Cell death
What are the two principal patterns of cell death?
Necrosis
Apoptosis
What is the difference between necrosis and apoptosis?
Necrosis: severe cell swelling or rupture
Apoptosis: programmed cell death, cells removed with minimum of disruption
List 7 possible causes of cell injury
Oxygen deprivation (hypoxia)
Physical agents
Chemical agents and drugs
Infectious agents
Immunologic reactions
Genetic derangements
Nutritional imbalances
What is the difference between hypoxia and ischaemia?
Hypoxia: oxygen depravation
Ischaemia: loss of blood supply (one possible cause of hypoxia)
List three possible causes of hypoxia
Ischaemia
Inadequate blood oxygenation due to cardiorespiratory failure
Decreased oxygen-carrying capacity of the blood (e.g. anaemia, CO poisoning, blood loss)
Give 5 examples of physical agents that may cause cell injury
Mechanical trauma
Extremes of temperature
Sudden changes in atmospheric pressure
Radiation
Electric shock
Why does ischaemia cause tissue injury faster than hypoxia?
In contrast to hypoxia, during which glycolytic energy production can continue, ischaemia compromises the availability of metabolic substrates
Cellular response to injurious stimuli is dependent on what three factors?
Type, duration, and severity of injury
Consequences of cell injury are determined by what three factors?
Type, state and adaptability of injured cell
What four intracellular systems are particularly vulnerable to cell injury?
Maintenance of membrane integrity
Aerobic respiration
Protein synthesis
Preservation of the integrity of the genetic apparatus of the cell
Outline 7 general biochemical mechanisms of cell injury and necrosis
- ATP depletion: results in failure of energy-dependent functions
- Mitochondrial damage: results in ATP depletion, ROS formation (due to incomplete oxidative phosphorylation), and leakage of mitochondrial proteins which can trigger apoptosis
- Increased permeability of cellular membranes: including plasma membrane, lyosomal membranes, and mitochondrial membranes; caused by ROS, decreased phospholipid synthesis and increased breakdown, and cytoskeleton abnormalities (does not occur in apoptosis)
- Accumulation of damaged DNA and misfolded proteins: activates p53-dependent pathways to trigger apoptosis
- Accumulation of ROS: results in covalent modification of cellular proteins, lipids, and nucleic acids
- Calcium influx: activation of enzymes that damage cellular components (e.g. phospholipases, proteases, ATPases, endonucleases), and may also trigger apoptosis
- Unfolded protein response and ER stress: accumulation of misfolded proteins in the ER activates adaptive mechanisms that help the cell to survive, but if their repair capacity is exceeded they trigger apoptosis
Compare and contrast necrosis and apoptosis in terms of cell size
Necrosis: enlarged (swelling)
Apoptosis: reduced (shrinkage)
Compare and contrast necrosis and apoptosis in terms of their effect on the nucleus
Necrosis: pyknosis, karyorrhexis, karyolysis
Apoptosis: fragmentation into nucleosome-size fragments
Compare and contrast necrosis and apoptosis in terms of their effect on the plasma membrane
Necrosis: disrupted
Apoptosis: intact but with altered structure (especially orientation of lipids)
Compare and contrast necrosis and apoptosis in terms of their effect on cellular contents
Necrosis: enzymatic digestion (may leak out of cell)
Apoptosis: intact (may be released in apoptotic bodies)
Compare and contrast necrosis and apoptosis in terms of the presence of absence of adjacent inflammation
Necrosis: frequent
Apoptosis: no
Compare and contrast necrosis and apoptosis in terms of their physiologic/pathologic roles
Necrosis: usually pathologic (culmination of irreversible cell injury)
Apoptosis: often physiologic, means of eliminating unwanted cells (may be pathologic after some forms of cell injury, especially DNA damage)
Explain the phenomenon of reperfusion injury in ischaemia
Restoration of blood flow to ischaemic tissues can promote recovery of cells if they reversibly injured but can also paradoxically exacerbate cell injury and cause cell death
What are the two consistent early patterns of reversible cell injury?
- Cellular swelling
- Fatty change
What is the first manifestation of almost all forms of injury to cells? Why and how does this occur? What are the macroscopic and microscopic effects?
Cellular swelling is the first manifestation of almost all forms of injury to cells
Occurs whenever cells are incapable of maintaining ionic and fluid homeostasis
When it affects all cells in an organ, it causes some pallor, increased turgor and increase in weight of the organ
On microscopic examination, vacuolar degeneration (also known as hydropic change) is observed (small clear vacuoles seen within the cytoplasm)
What can be observed microscopically with fatty change as a result of tissue injury?
The appearance of small or large lipid vacuoles in the cytoplasm
Outline 5 ultrastructural changes of reversible cell injury visible by electron microscopy
- Plasma membrane alterations (e.g. blebbing, blunting, loss of microvilli)
- Mitochondrial changes, including swelling and the appearance of small amorphous densities
- Accumulation of “myelin figures” in the cytosol composed of phospholipids derived from damaged cellular membranes
- Dilation of the ER, with detachment of polysomes
- Nuclear alterations, with dissaggregation of granular and fibrillar elements (decreased cytoplasmic RNA results in increased eosinophilia)
