Lecture 19 Flashcards
What is ischaemia?
Restraint of blood - inadequate blood supply to a tissue (the needs of the tissue are not met). Due to lack of blood supply there is also reduced transfer of metabolic substances (can’t have their metabolites removed - thus the acidity builds up in tissues).
What is hypoxia?
Lack of oxygen.
What is anoxia?
Complete lack of oxygen.
What is infarction?
The process of ischaemia goes so far that the tissue dies (dies via necrosis).
Why does the ischemic tissue die via necrosis in an infarction?
This is because there is not enough energy to die cleanly via apoptosis. The lack of energy comes form the lack of oxygen.
What are the possible causes of ischaemia?
- Eternal occlusion of vessels e.g. bed spores (lying with their leg pushing on something).
- Internal occlusion of vessels e.g. atherosclerosis.
- Spasm of vessel e.g. frost bite.
- Blockage of capillaries e.g. sickle cell disease (leads overall to less perfusion of vessels near individual cells and tissues).
- Shock - inadequate apparent blood volume (shock can be caused by haemorrhage (individual cells of body aren’t getting enough perfusion); yet shock can be caused by other etiologies i.e. septic shock (bacteria -immune response - massive dilation in the periphery - not enough blood volume).
- Increased demand (all make ourselves ischaemic from exercise). if you already have a compromised vessel, this will have enough flow through it to meet the needs at rest. if yous tart doing exercise it will lead to angina, as the increased demands cannot be met. Sometimes hypertrophy (bigger heart muscle) from heart failure, but if there is a coronary blockage, there is not enough blood flow to the heart (it’s newly increased tissue size).
- Venous obstruction.
Describe the susceptibility of different cells to ischaemia?
Fibroblasts, macrophages have a low susceptibility, skeletal muscles are relatively immune to ischaemia. The Renal proximal tubular epithelium and neurons are very sensitive to ischaemia. Neutrophils are off the scale with ischaemia, they survive better if they are ischaemic. A number of molecules are upregulated with gene transcription (hypoxia inducible factor - HIF - which activates NFkB which turns on pro-survival target RNAs).
Describe the effects of ischaemia on the cells?
Ischaemia will cause cell injury (not sufficiently severe or is only brief and blood flow is restored) - then the cell will not be killed however the biology will change as well. There will be reduced ATP availability - less oxygen coming into the tissue (oxygen phosphorylation cannot occur). Less blood flow - so less removal of lactic acid, hydrogen ions etc. Activation of signalling cascades.
Describe reduced ATP?
Increased anaerobic glycolysis, so there is decreased glycogen and decrease in pH (so there is clumping of nuclear chromatin). There is a decrease in activity of the sodium pump which will cause an influx of calcium and sodium and efflux of potassium.
What are the potential effects of ischaemia at tissue level?
Often stromal cells are more resistant to ischaemia. The overall appearance can range from no effect to infarction (necrosis of most/all cells in a tissue). Adaption can occur (microscopic appearance) when there has been medium type damage. Parenchymal cells are more susceptible to ischameia.
What are the other factors that influence the outcome for tissues of vessel occlusion?
The anatomy of the blood supply to the organ (end organs and organs with collateral circulation). Six of the occluded vessel, speed of onset, duration of occlusion, repercussion.
What are the two types of infarction?
Red and White. Haemorrhage (red)is when blood gets out. Anaemic (white) is common in solid tissues supplied by a single artery.
Describe cerebral ischaemic injury?
The heart not supplying enough organs in the blood will affect other organs in the body e.g. the brain.
Describe the timing of a typical infarction?
Sudden blockage of coronary artery (due to thrombosis); the calls downstream become ischaemic and die via necrosis. Within 24hrs neutrophils come in via the viable margins of the dead tissue. By 1-3 days macrophages and lymphocytes come in. Fibroblasts and endothelial cells are then recruited to form granulation tissue. 2 weeks after the macrophages pull in blood vessels to form this granulation tissue.
Describe the treatment of myocardial infarction?
Thrombolitic agents (e.g. streptokinase) have to be done very quickly; before the molecular events occur.
What are the potential complications of infarction?
- Mural thrombus - thrombus formed inside the chamber of the heart.
- Dysrhythmias - dead heart muscle can’t conduct.
- Heart failure - the heart can’t pump enough oxygen/blood to meet the body’s need.
- Repurfusion injury - there is sudden introduction of blood to a tissue that has been ischaemic (suddenly reintroduces oxygen).
Describe repurfusion injury?
Long periods of ischaemia followed by reintroduction of oxygen. The ischaemic cells have changed so that when oxygen comes in; there is rapid production of reactive oxygen species. Damage from ROS leads to an autolytic chain of damage.
