pathophysiology of ischaemia + infarction Flashcards
what is ischaemia?
relative lack of blood supply to organ/tissue leading to inadequate oxygen supply to meet needs of tissue/organ
what are the 4 ways that hypoxia can occur?
- low inspired oxygen level or normal inspired oxygen but low PaO22 anaemia-normal inspired oxygen but blood abnormal3. stagnation- normal inspired oxygen but abnormal delivery4. cytotoxic- normal oxygen inspired but abnormal at tissue level
what can cause low in inspired oxygen levels leading to hypoxia?
high altitude
what can lead to local stagnation of blood flow leading to hypoxia?
occlusion of vessel
what can causes systemic stagnation of blood flow leading to hypoxia?
shock
what is cytotoxic hypoxia?
organelles cannot function properly even though they have adequate oxygen
what are the factors that affect oxygen supply?
- Inspired O22. Pulmonary function3. Blood constituents4. Blood flow5. Integrity of vasculature6. Tissue mechanisms
when might blood flow be compromised, decreasing oxygen supply?
when there is heart failure
when might the integrity of vasculature be compromised, decreasing oxygen supply?
occlusion/compression of vessels
what are the 2 factors that affect the oxygen demand of a tissue?
the type of tissueactivity of the tissue above the baseline
what are the supply issues that can cause ischaemic heart disease?
coronary artery atheromacardiac failurepulmonary function- pulmonary oedema (from LVF)anaemiaprevious MI
what are demand issues that can cause ischaemic heart disease?
heart has high intrinsic demandexertion/stress
how can atherosclerosis cause stable angina?
when it is established and doesnt occlude the coronary artery so much as to cause inadequate oxygen supply at rest. however on exertion oxygen supply becomes inadequate
how can atherosclerosis cause unstable angina?
when the atheromatous plaque in the coronary artery is complicated and so causes inadequate delivery of oxygen at rest
what do ulcerated and fissure plaques in the coronary artery lead to?
thombosis then ischaemia or infarction
how does atheroma cause an aortic aneurysm?
dilatation of the aorta due to weakening of the vascular wall from inflammation
what conditions can atheromatous plaques lead to?
MITIACerebral infarctionabdominal aortic aneurysmperipheral vascular diseasecardiac failure (could be from MI)
a reduction in radius of an artery from 4 to 2 will cause a decrease of what in blood flow? and how does this explain how plaques cause ischaemia?
16 fold decrease. this highlights the large effect of radius of vessels on flow. this explains why plaques significantly reduce flow and cause ischaemia
give an example of where ischaemia can be chronic?
sufferers of peripheral vascular disease getting claudication when walking
give an example of when ischaenia can be acute-on-chronic ?
claudication in peripheral vascular disease (chronic) but can turn into and acute event
how does ischaemia affect the biochemistry of cells?
causes cells to metabolise more by anaerobic respiration. So lactate builds up on cells, causing acid-bace imbalance and leads to cell death
which cells are more affected by ischaemia?
those with high metabolic rate, eg. renal tubule, myocyte, neurons
which cells are less affected by ischaemia?
those with a slower metabolic rate
what are the three general clinical effects of ischaemia?
-dysfunction-pain-physical damage
what dysfunction can ischaemia cause in the heart?
if it is next to the SA node then there is the chance that it may lead to cardiac arrhythmia
how does ischaemia cause heart pain/
due to pH changes and bracycardia
what are the three potential outcomes of ischaemia?
-no clinical effect-resolution (normally need therapeutic intervention)-infarction
what is infarction?
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
what are the 4 possible causes of infarction?
- thrombosis2. embolism3. strangulation4. trauma-cut/ruptured vessel
if an infarction occurs for a short time, how is the long-term damage different from if it was for a long time?
it is less
what are the factors that determine the scale of damage from ischaemia or infarction?
-Time period-Tissue/organ -Pattern of blood supply -Previous disease
what is coagulative necrosis?
necrosis in which the organ maintains its shape after necrosis
what is colliquitive necrosis?
necrosis in which the tissue loses its gross structure as there is loss of connective tissue
describe the sequence of events in necrosis
- Anaerobic metabolism 2. cell death3. liberation of enzymes 4. breakdown of tissue
give examples of tissue that undergo coagulative necrosis?
heart, lung
give examples of a tissue that undergo colliquitive necrosis?
brain
how long is severe ischaemia and is it reversible?
20-30 minutesirreversible damage
what happens in the first seconds of myocardial ischaemia?
anaerobic matabolism causes ATP depletion
what happens in the first 2 minutes of myocardial ischaemia?
loss of myocardial contractility leading to heart failure
what happens after the first 2 minutes of myocardial ischaemia?
-ultrastructural changes:-myofibrillar relaxation-glycogen depletion-cell and mitochondial swelling
after how long of ischaemia is there injury to the microvasculature of the heart?
> 1 hour
after 24-48 hours what is the appearance of an infarct in dense tissues such as the myocardium, spleen, kidney solid tissues
pale
after 24-48 hours what is the appearance of an infarct in loose tissues such as the lung, liver and perviously congested tissues?
red
under the microscope what can be seen around the edge of infarcts at 24-48 hours?
inflammatory cells such as neutrophils
under the microscope what can be seen i infarcts at 72 hours after event?
chronic inflammation:-macrophages remove debris-granulation tissue-fibrosis
what is the end result of infarction?
scar replaces area of tissue damagereperfusion injury
what is reperfusion injury?
after a period of ischaemia blood reperfuses the tissue.this causes inflammation and further damage to the tissue as there inflammation and oxidative injury
what are the reparative processes of mysocardial infarction?
Cell deathAcute inflammationMacrophage phagocytosis of dead cellsGranulation tissueCollagen deposition (fibrosis)Scar formation
what is a transmural myocardial infarction?
ischaemic necrosis affects full thickness of the myocardium
what is a subendocardial infarction?
ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
what sort of MI is a non-STEMI most likely to be?
subendocardial infarct
what sort of myocardial infarction is likely to have occurred if there is no ST elevation and elevated serum troponin level?
non-STEMI
what are some of the complication of myocardial infarction?
sudden deatharrythmiasanginacardiac failurecardiac rupture-ventricular wall, septum, papillary musclereinfarctionpericarditispulmonary embolism secondary to DVT-papillary muscle dysfunction from necrosis or rupture causing mitral incompetencemural thrombosisventricular aneurysmdressler’s syndrome
what is dressler’s syndrome?
Dressler syndrome is a secondary form of pericarditis that occurs in the setting of injury to the heart or the pericardium
what does papillary muscle dysfunction lead to?
usually mitral (but can be tricuspid) incompetence
