L21 Ischaemia and Infarction Flashcards
What is ischaemia and what does it cause?
Inadequate local blood supply to a tissue, causing reduced transfer of metabolic substances in and out of tissues.
What is hypoxia?
Deficiency of oxygen which causes cell injury by reducing aerobic respiration
What is anoxia?
Complete lack of oxygen
What is infarction?
Necrosis of a tissue due to ischaemia
Why do ischaemic tissues due via necrosis and not apoptosis?
Lack of ATP due to ischaemic conditions
What is external occlusion?
Tumors or bed sores
What is internal occlusion?
Atherosclerosis, thrombosis, embolism
Which cells are more susceptible to ischaemia than others?
- Neurons are highly sensitive to O2, irreversibly damage within 3 mins
- Myocardium is sensitive to ischaemia, damage after 20 mins
- Skeletal muscle cells are slightly sensitive, can still do anoxic work
- Fibroblasts and macrophages (stromal cells) are insensitive to oxygen levels.
Which cell’s activity is enhanced under hypoxic conditions?
Neutrophils
Explain how O2-related gene expression changes promote neutrophil survival in low O2 conditions.
Anoxia promotes HIF transcription system activity, which leads to increased NFkB activity, leading to pro-survival of target RNAs. Increased protein production and maintenance leads to increased survival chances.
Normoxia leads to apoptosis, due to sufficient levels of ATP
What are the effects of ischaemia on cells?
- Ischaemia, not sufficinetly severe or of long duration to kill a cell may change the biology of a cell.
- Reduced ATP availability to the cell
- Activation of signalling cascades
What changes in the channel pumps are observed when a cell has low ATP? What does this lead to on an organelle level?
- Decreased functional Na+ pump activity (ATPase pump)
- Influx of Ca, H2O, efflux of K
- Leads to ER swelling, cellular swelling, loss of microvilli.
What type of glycolysis occurs under low ATP? What does this lead to?
- Anaerobic glycolysis - breakdown of glucose under anaerobic conditions
- Leads to lower glycogen levels and lower pH (due to H+ production)
- Leads to clumping of nuclear chromatin)W
What other effects are seen in the cells under low ATP conditions?
- Detachment of ribosomes
- Decreased protein synthesis
- Lipid deposition
What is the difference between necrosis and apoptosis?
- Apoptosis is regulated, ordered cell death, whereby the cell breaks off into smaller apoptotic fragments. The fragments are later phagocytosed.
- Necrosis is a passive, emergency, messy cell death –> autolysis (cell lysis and release of enzymes which digest the cell), messy due to leak of contents into suroundings. Cleaned up by macrophages
What are the potential effects of ischaemia at tissue level?
- Functional defects due to sub-optimal tissue perfusion –> less damage (i.e. myocardial dysrhythmia and renal insufficiency)
- Adaptation (i.e. fatty change), atrophy, and shut down –> more damage
- Apoptosis of isolated cells –> even more damage
- Infarction (necrosis) of most/alll cells in a tissue due to overwhelming ischaemic injury –> most damage
Which factors influence the outcome (of ischaemia) for tissues of vessel occlusion?
- Anatomy of blood supply to organs (end organs- single route, collateral circulation - alternative routes)
- Size of occluded vessel (larger area = larger area killed)
- Speed and Duration of onset
- Reperfusion –> further damage due to oxidative stress
- Metabolic demands of the tissue at the time
- Adequacy of circulatory system –> if px has anaemia, less O2 capacity to carry to tissues.
How does reperfusion cause damage (via ROS)?
- Attack double bonds of UFA (unsaturated fatty acids) –> lipid peroxidation
- oxidise amino acid side chains –> enzyme damage
- React with thymine to cause DNA damage
What is infarction?
Necrosis of a tissue due to ischemia
Autocatalytic reactions propagate….
…a chain of reactions
What does infarction result from?
Infarction results from thrombosis or embolism, spasm, torsion, or extrinsic compression of vessels
What is red infarct?
Haemoraggic –> when the major blood supply to the organ is compromised, but there are still other blood vessels bringing blood to the tissue. They do not bring in enough O2 so the cell still dies. However, there is still blood pumping in and out of the dead tissue.
i.e. in lungs
What is white infarct?
- Anaemic infarcts occur in single (end) arteries, with no haemorage (no blood coming out)
- Coagulative necrosis is the usual pattern after infarction in solid organs
What is ischaemic heart disease usually caused by?
- Atherosclerotic narrowing of coronary arteries that supply myocardium
