Ischaemia and Infarction Flashcards
Ischaemia is
inadequate local blood supply to a tissue.
-Causes hypoxia and reduced transfer of metabolic substances (eg glucose and catabolites)
Hypoxia is
deficiency of O2 which causes cell injury
ANoxia is
COmplete lack of O2
Infarction. Results from?
necrosis of a tissue due to ischaemia.
thrombosis/embolism, spasm, extrinsic compression of vessel
Possible causes of Ischaemia
Ext/int occlusion of vessels (bed sores or atherosclerosis)
Spasm of vessel capillary block (sickle cell anaemia) shock (low arterial BP) Increased Demand (inc tissue mass, workload) venous obstruction
Sensitivity of different cell types to Ischaemia from least to most
Fibroblasts & macrophages Skeletal muscle Myocardium Renal proximal tubular epithelium Neurons
Neutrophils sensitivity to ischaemia?
Right OFF the scale, and actually do better with ischaemia!!
Their resistance to apoptosis and necrosis is enhance by hypoxia!
A number of genes are turned on at the transcriptional level, which turn on many enzymes required for survival.
Main Transcription factor turned on by hypoxic neutrophils?
HIF which leads to survival.
Why is is the Neutrophils are enhanced in hypoxic environments?
The role of neutrophils is often required in hostile, damaged environments, therefore it makes sense that their survival is enhanced.
Effect of ischaemia on cells, If not severe or of long enough duration
still changes cell biology.
Reduced ATP availability (all energy mechanisms crippled).
More activation of signalling cascades> protect and repair
How does ischaemia cause lowered ATP?
Increased anaerobic glycolysis
low glycogen
lower pH
nuclear chromatin clumping
Decr Na+ pumps
influx of calcium, water and Na+
ER swelling, cell Swelling, loss of micro villi.
Protein breakdown
Do ischaemic cells usually die by apoptosis or necrosis?
Necrosis, due to the lowered ATP levels there’s not enough energy to allow the process of apoptosis to occur
Levels of ischaemic effect?
No effect Functional defects (due to sub-optimal tissue perfusion) Adaptation, atrophy and shut down Apoptosis Infarction/necrosis
A LARGE RANGE, functional parenchyma more at risk
Other factors that influence the outcome for tissues of vessel occlusion
Anatomy, size of occlusion, speed of onset, repurfusion, metabolic demands, adequency
Red (haemorrhagic) infarcts may occur in?
- tissue with dual blood supply (lung)
- Tissues where blood flow is re-established after arterial occlusion
(pumping blood into dead tissue)
