Pathophysiology of Ischaemia & Infarction Flashcards
What is ischaemia?
restriction in blood supply to tissues, causing a shortage of oxygen.
What is hypoxia?
a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level.
Describe the four ways that hypoxia can occur?
4
- Hypoxic = low inspired O2, or inspired O2 normal and PaO2 abnormal.
- Anaemic = normal inspired O2, abnormal blood e.g. low Hb
- Stagnation = normal inspired O2, abnormal delivery e.g. ischaemia, shock
- Cytoxic = normal inspired O2, abnormal at tissue level
What is infarction?
tissue death (necrosis) due to inadequate blood supply to the affected area
What are the factors affecting oxygen supply?
6
- inspired O2
- pulmonary function
- blood flow (e.g. atheroma)
- blood constituents (e.g. Hb level)
- integrity of vasculature
- tissue mechanisms
Which factors affect oxygen demand?
2
- tissue itself - different tissues have varying O2 requirements.
- activity of tissue e.g. during exercise
What is cytotoxic hypoxia?
organelles cannot function properly even though they have adequate oxygen e.g. cyanide poisoning
What are the supply issues that can cause ischaemic heart disease?
(5)
- coronary artery atheroma
- cardiac failure (flow)
- pulmonary function: pulmonary oedema (from LVF)
- anaemia
- previous MI
What are demand issues that can cause ischaemic heart disease?
(2)
heart has high intrinsic demand
exertion/stress
How can atherosclerosis cause stable angina?
3
- established atheroma
- sufficient O2 supply at rest
- demand > supply on exertion = angina
How can atherosclerosis cause unstable angina?
4
- complicated atheroma
- insufficient O2 supply at rest
- demand > supply at rest = angina
- worsening pain
What do ulcerated and fissure plaques in the coronary artery lead to?
(2)
- rupture/thrombosis
- ischaemia/infarction
What does atheroma in aorta cause?
How?
aneurysm
dilatation of the aorta due to weakening of the vascular wall from inflammation
What conditions can atheromatous plaques lead to?
6
- Coronary artery disease, MI
- TIA
- Cerebral infarction
- Abdominal aortic aneurysm
- Peripheral vascular disease
- Cardiac failure
Briefly how would you describe the relationship between flow and radius of vessel?
What clinical problem does this result in?
small decrease in radius = large decrease in flow
ischaemia
Give an example of where ischaemia can be chronic?
2
- peripheral vascular disease
- claudication on walking
Give an example of when ischaemia can be acute-on-chronic?
3
- peripheral vascular disease
- claudication on walking
- can become an acute incident e.g. CLI
How does ischaemia affect the biochemistry of cells?
5
- reduced aerobic respiration
- increases anaerobic respiration
- lactate builds up
- acid-base imbalance
- infarction/necrosis
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.
What are the three potential outcomes of ischaemia?
- no clinical effect
- resolution (normally need therapeutic intervention)
- infarction
What are the 4 possible causes of infarction?
- thrombosis
- embolism
- strangulation
- trauma-cut/ruptured vessel
What are the factors that determine the scale of damage from ischaemia or infarction?
(4)
- Time period
- Tissue/organ
- Pattern of blood supply
- Previous disease e.g. MI
What is coagulative necrosis?
Give an example of where this may occur?
necrosis in which the organ maintains its shape after necrosis
e.g. heart, lung
What is colliquitive necrosis?
Give an example of where this may occur?
necrosis in which the tissue loses its gross structure as there is loss of connective tissue
e.g. brain
Outline the sequence of events in necrosis.
hint: focus on the biochemical processes
(4)
- anaerobic respiration
- cell death
- liberation of enzymes
- tissue breakdown
Outline the sequence of events occurring during ischaemia within coronary arteries.
(4)
- coronary artery obstruction (atheroma)
- reduced blood flow/ischaemia
- myocardial dysfunction
- myocyte death
How long is severe ischaemia in the heart and is it reversible?
20-30mins
no - irreversible
What happens in the first few seconds of myocardial ischaemia?
(2)
- anaerobic metabolism
- ATP depletion
What happens within two minutes of myocardial ischaemia?
2
- loss of myocardial contractility - heart failure
What happens after the first two minutes of myocardial ischaemia?
(3)
Ultrastructural changes:
- myofibrillar relaxation
- glycogen depletion
- cell/mitochondrial swelling
At what time phase of myocardial ischaemia does myocyte necrosis take place?
How is this picked up in blood tests?
20-40 minutes
increased troponin levels
After how long of ischaemia is there injury to the microvasculature of the heart?
> 1 hour
How do infarcts appearances change following ischaemic necrosis?
(3)
- mitochondria swells (electron microscopy)
- pale/red colour change
In which tissue does an infarct appear red?
3
lung, liver, loose tissues
In which tissue does an infarct appear pale?
4
myocardium, spleen, kidney, solid tissues
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 in infarcts at 72 hours after event?
(colour/microscopy changes)
(5)
Pale infarct - yellow/white and red periphery
Red infarct - little change
Chronic inflammation:
- macrophages remove debris
- granulation tissue
- fibrosis
What is the end result of infarction?
2
- scar replaces area of tissue damage
- reperfusion injury
What is reperfusion injury?
3
- following ischaemic period:
- blood reperfuses scar tissue
- causes inflammation and further damage to the tissue (oxidative injury)
What are the reparative processes of myocardial infarction?
6
- Cell death
- Acute inflammation
- Macrophage phagocytosis of dead cells (chronic inflammation)
- Granulation tissue
- Collagen deposition (fibrosis)
- Scar formation
What is a transmural 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
________ thought to correlate with a subendocardial infarct.
NSTEMI
What are some of the complication of myocardial infarction?
C PEAR DROP
Cardiac arrhythmias/shock Pericarditis Emboli Aneurysm Rupture of free wall Dresslers syndrome Rupture of ventricle Papillary muscle rupture
SCD,
What does papillary muscle dysfunction lead to?
mitral regurgitation
