Pathophysiology of Ischaemia and Infarction Flashcards
Define ischaemia
Lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ
What do we also have if we have ischaemia?
Hypoxia
What are the four types of hypoxia?
- Hypoxic
- Anaemic
- Stagnant
- Cytotoxic
When may you get hypoxic hypoxia?
- Low inspired O2 level
or
-Normal inspired O2 but low PaO2
When may you get anaemic hypoxia?
Normal inspired O2 but blood abnormal
When may you get stagnant hypoxia?
Normal inspired oxygen but abnormal delivery
When may you get cytotoxic hypoxia?
Normal inspired O2 but tissue cannot use the oxygen being delivered to it
How can oxygen delivery be abnormal?
Local delivery due to occlusion of vessel
Systemic due to shock
List some factors which can affect oxygen supply
- Inspired O2
- Pulmonary function
- Blood constituents
- Blood flow
- Integrity of vasculature
- Tissue mechanisms
What are some factors which affect oxygen DEMAND?
- Tissue itself - different tissues have different requirements
- Activity of tissue above baseline value
For ischaemic heart disease, what may cause issues with oxygen supply?
Coronary artery atheroma
Cardiac failure (flow)
Pulmonary function
Pulmonary oedema (LVF)
Anaemia
Previous MI
What is the key issue with oxygen demand?
Heart already has high intrinsic demand but will be higher under exertion/stress
RECAP- what is an atheroma?
Localised accumulation of lipid and fibrous tissue in intima of arteries
What can a established atheroma in a coronary artery lead to?
Stable angina
What can an complicated atheroma in a coronary artery lead to?
Unstable angina
What ca ulcerated/fissured plaques lead to?
Thrombosis which can in turn lead to ischaemia/infarction
What can an atheroma in the aorta lead to?
Aneurysm
What are some of the clinical consequences of ischaemia?
MI
TIA (transient ischemic attack)
Cerebral infarction
Abdominal aortic aneurysm
Peripheral vascular disease
Cardiac failure
Describe the common pathway of heart related conditions.
Coronary artery disease -> thrombosis -> MI -> Cardiac failure
What are the functional affects of ischaemia?
-Blood/O2 supply fails to meet demand due to decreased supply, increased demand, or both
What are the functional affects of ischaemia related to?
Rate of onset
What are the biochemical affects of ischemia?
Anaerobic metabolism due to lack of oxygen-
Less ATP produced
Lactate produced
Little ATP produced needed to removed the lactate
When there is less/no oxygen supply to a cell, what can happen?
Anaerobic metabolism leading to cell death
Discuss how cells with different metabolic rates get affected by ischaemia.
Cells w high metabolic rate get affected at a faster rate
Give some examples of cells with high metabolic rates which can lead to fast affects of ischaemia.
Muscle cells
Liver cells
Renal tubular epithelial cells
Give examples of cells with a low metabolic rate and will not be affected by ischaemia as quickly.
Fat cells
Bone cells
Connective tissue
What are some of the clinical effect you might see with someone with ischaemia?
Dysfunction
Pain
Physical damage- specialised cells
Describe how there can be dysfunction in a patient with ischaemia?
In the heart, the effects of ischaemia may cause an arrhythmia
What are some of the outcomes for a patient with ischaemia?
No clinical effect
Resolution- either w therapeutic intervention or not
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 is the cause of infarction?
Cessation of blood flow
What could cause cessation of blood flow, and therefore, infarction?
- Thrombosis
- Embolism
- Strangulation e.g. gut
- Trauma - cut/ruptured vessel
The scale of damage caused by ischemia/infarction is dependant on many factors.
List some of them.
Time period
Tissue/organ
Pattern of blood supply
Previous disease
What type of necrosis occurs in most tissues like the heart and lungs?
Coagulative necrosis
What type of necrosis occurs in the brain?
Colliquitive necrosis
How how coronary artery obstruction lead to myocyte death?
Decreased blood flow to region of myocardium ->
Ischaemia, rapid myocardial dysfunction ->
Myocyte death
In myocardial ischaemia, how long does it take for the depletion of ATP due to anaerobic metabolism?
Seconds
In myocardial ischaemia, how long does it take for the loss of myocardial contractibility?
< 2 mins
How long do you have to have severe ischemia for it to cause irreversible damage?
20-30 mins
How long does it take in myocardial ischaemia for there to be myocyte necrosis?
20-40 mins
How long does it take in myocardial ischaemia for there to be injury to the microvascular?
> 1 hour
Describe what the appearance of infarcts will look like in less than 24hrs.
No change on visual inspection
A few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy
Describe what the appearance of infarcts will look like in 48hrs.
Pale infarct in solid tissues, like spleen, kidney, heart.
Red infarct in loose tissues, like lungs and liver.
Microscopically: acute inflammation initially at edge of infarct; loss of specialised cell features
Describe what the appearance of infarcts will look like in 72hrs.
Macroscopically:
Pale infarct - yellow/white and red periphery
Red infarct - little change
Microscopically: chronic inflammation; macrophages remove debris; granulation tissue; fibrosis
What is the end result of infarcts?
Scars replaces area of tissue damage
What is reperfusion injury?
Damage that occurs after blood supply is restored to a tissue or organ after a period of ischemia.
What happens in reperfusion injury?
Absence of oxygen and nutrients in restored bloodstream causes inflammation and oxidative damage
Describe the reparative process which occurs in MI.
- Cell death
- Acute inflammation
- Macrophage phagocytosis of dead cells
- Granulation tissue forming
- Collagen deposition (fibrosis)
- Scar formation
What happens in 4-12hrs of MI?
Early coagulation necrosis, oedema, haemorrhage
What happens in 12-24hrs of MI?
Ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
What happens in 1-3 days of MI?
Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
What happens in 3-7 day of MI?
Disintegration of dead myofibres, dying neutrophils, early phagocytosis
What happens in 7-10 days of MI?
Well developed phagocytosis, granulation tissue at margins
What happens in 10-14 days of MI?
Well established granulation tissue with new blood vessels and collagen deposition
What happens in 2-8 weeks of MI?
Increased collagen deposition, decreased cellularity
What happens in >2 months of MI?
Dense collagenous scar
Therefore, how long does it take from development of MI to a scar?
At least two months
Where does transmural infraction affect?
Ischaemic necrosis affects full thickness of the myocardium
Where does subendocardial infarction affect?
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What are acute infarctions classified by?
Whether there is elevation of the ST segment on the ECG
What is it called if there is no elevation of the ST segment on ECG but a significantly elevated serum troponin level?
Non-STEMI
There are lots of complications with MI but list a few
Sudden death
Arrhythmias
Angina
Cardiac failure
Cardiac rupture - ventricular wall, septum, papillary muscle
What type of infarct is a non-STEMI thought to correlate with?
Subendocardial infarction
