Pathophysiology of Ischaemia & Infarction Flashcards
What is ischaemia?
a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism (hypoxia)
What is infarction?
obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue
What are the causes/types of hypoxia?
Low inspired O2 level or normal inspiration but low PaO2
Anaemia
Stagnant blood
Cytotoxic
Describe how hypoxia due to stagnant blood may arise
Abnormal delivery of blood
Can be local - due to occlusion of a vessel
Can be systemic - due to shock
Describe why cytotoxic hypoxia may arise
Normal delivery of oxygen to tissues
However, oxygen uptake/usage is ineffective at a cellular level
What factors affect oxygen supply?
Inspired O2
Lung function
Blood constituents
Blood flow
Integrity of vasculature
Tissue mechanisms
What factors affect tissue demand?
What type of tissue it is
What it’s doing:
- activity of tissue above baseline value
In terms if supply & demand
What is Ischaemic heart disease?
Mismatch between supply & demand of oxygen
Hypoxia of the heart muscles
What can cause a mismatch in supply & demand, for ischaemic heart disease?
Supply issues:
- coronary artery atheroma
- cardiac failure (flow)
- pulmonary function – other disease or pulmonary oedema (LVF)
- anaemia
- previous MI
Demand issues:
- heart has high intrinsic demand
- exertion/stress
- stenosis of aorta & all them ones
What are the clinical consequences of atheromas in the coronary arteries?
Normal atheroma = stable angina
Complicated atheroma = unstable angina
Fissured/ulcerated plaque = thrombosis = ischaemia or infarction (BAD)
What is the main risk associated with an atheroma in the aorta?
Aneurism
What are the clinical consequences of Ischaemic heart disease?
MI TIA Cerebral infarction Abdominal aortic aneurysm Peripheral vascular disease Cardiac failure
Coronary artery disease —-> MI —-> cardiac failure
Using physics n shit
What effect does an atheroma have on flow in an artery?
Resistance proportional to 1/r^4
So a very small decrease in lumen size due to a plaque causes a HUGE increase in resistance & therefore flow in an artery
What cells are most at risk of damage from ischaemia?
Cells with high metabolic rate
What are the general effects of ischaemia?
Dysfunction
Pain
Physical damage
“If a significant ischaemic event does not receive medical intervention or therapy, it will either _______ or progress to ________”
It will either resolve or progress to infarction
Define infarction
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
What are the main causes of infarction?
Thrombosis
Embolism
Strangulation - eg of gut
Trauma - cut/ruptured vessel
What determines the scale of damage done by ischaemia/infarction to an organ/tissue?
Time period
What organ/tissue it is
Patterns of blood supply
Previous disease
Why is the length of time that a tissue has been ischaemic/infarcted for an important determinant of damage?
Necrosis doesn’t happen instantly - cells/tissues can survive for some time without supply of blood
Blood supply lost –> Anaerobic M –> cell death –> Liberation of enzymes –> Breakdown of tissue
^the stage that the tissue is at determines the scale of damage
What are the 2 types of necrosis?
Coagulative necrosis:
- Heart, lungs etc
- Due to infarction/ischaemia
Colliquitive necrosis:
- Brain
- Associated with bacterial or fungal infections
Myocardial infarction happens when…
Coronary arteries are obstructed ∴ no blood flow to area of myocardium ∴ ischaemia ∴ dysfunction ∴ myocyte death
“Within seconds of the coronary arteries being blocked, ischaemia of areas of the myocardium begins and …..”
Anaerobic metabolism begins, depleting ATP levels
“Within 2 minutes of the onset of myocardial ischaemia, there is a loss of …”
There is a loss of Myocardial contractility - heart failure
“After a few minutes of myocardial ischaemia, there are permanent changes to the myocardium such as…”
Myofibrillar relaxation
Glycogen depletion
Cell & mitochondrial swelling
“After 20-30 mins of severe myocardial ischaemia, …”
The damage to the myocardium is irreversible, and monocyte necrosis has begun
Why can monocyte necrosis be detected in a blood test?
Disruption of the integrity of sarcolemmal membrane causes leakage of intracellular macromolecules into the blood
How long does it take, after the onset of myocardial ischaemia, before the body’s microvasculature to be injured?
> 1 hour
How long does it take before infarction becomes visible?
Visual changes of infarcted tissue after 24-48 hours
Microscopic changes occur in under 12 hours, for example, swollen mitochondria, which can be viewed under an electron microscope
How does infarction initially change the physical appearance of a tissue?
It depends on the tissue:
Pale infarcts - myocardium, spleen, kidney, solid tissues
Red infarcts - lung, liver, loose tissue, previously congested tissue & tissue that has venous occlusion
When looking under a microscope, what features would indicate infarction?
Swollen mitochondria & cells
Acute inflammation, initially at edge of infarct
Loss of specialised cell features
Describe the physical appearance of infarcted tissue after 72 hours
Pale infarct (heart, spleen, kidney etc): - yellow/white with red periphery
Red infarct (lung, liver etc) - little change
What is the end fate of an infarcted area?
Scar replaces the area of tissue damage
Reperfusion injury
What is reperfusion injury?
Damage to infarcted tissue when blood flow is restored
“Restoration of circulation results in inflammation and oxidative damage”
Summarise the repair process for infarcted tissue
Necrosis (cell death) of infarcted area
Acute inflammatory response recruits neutrophils (& macrophages i think)
Phagocytosis all the debris/dead cells
Granulation tissue formed & collagen secreted
Scar formed
Describe the state of myocardial tissue, 4-12 hours after infarction
Early coagulative necrosis
Oedema
Haemorrhage
(No macroscopic change to appearance)
What begins to happen in infarcted myocardium, 12-24 hours after infarction begins?
Ongoing coagulative necrosis
Mitochondria have swollen up, and myocytes have begun to change
Inflammatory response begins:
- Early neutrophilic infiltrate
What happens to the myocardial tissue, 1-3 days after infarction begins?
By this time, coagulative necrosis has caused significant changes to the myocyte’s cell architecture:
- Loss of nuclei and striations
There is also a large amount neutrophilic infiltrate
What happens 3-7 days after infarction of myocardial tissue begins?
By the end of the first week, myocytes have properly begun to break down:
- Disintegration of dead myofibrils
- Neutrophils are dying
Phagocytosis of all the dead stuff has begun^
What happens 7-10 days after infarction of myocardial tissue begins?
Lots of ongoing phagocytosis of all the dead stuff & debris
This is also when granulation tissue starts being produced, so this would start appearing at the edges of the infarcted area
What happens towards the end of the 2nd week of infarction of myocardial tissue?
(10-14 days)
Well established area of granulation tissue has formed with newly formed:
- Blood vessels
- Collagen
After 2 weeks of infarction, well established granulation tissue has formed.
Over the next few weeks, what happens to this granulation tissue?
Collagen is continually deposited into the granulation tissue
Loss of cellularity
^is basically turning into a scar
How long does it take before infarcted myocardium becomes all scarred n stuff?
> 2 months
Dense collagenous scar
What is a transmural infarction?
a myocardial infarction that involves the full thickness of the myocardium
Thus ischaemic necrosis involves the whole thickness of the myocardium
What is a sub-endocardial infarction?
ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What are the different types of MI’s
STEMI
NSTEMI
What is the difference between STEMI & NSTEMI?
Whether or not the ST segment on an ECG is elevated
If ST elevated = STEMI
If ST is not elevated but serum troponin levels are elevated, then NSTEMI
What type of MI is related to subendocardial infarction?
NSTEMI related to Subendocardial infarction
What are examples of complications of Myocardial infarctions?
(absolute fuck ton)
Sudden death Arrhythmias Angina Cardiac failure Cardiac rupture - ventricular wall, septum, papillary muscle Reinfarction Pericarditis Pulmonary embolism secondary to DVT Papillary muscle dysfunction - necrosis/rupture Mitral incompetence Mural thrombosis Ventricular aneurysm Dressler's syndrome
How long after the onset of infarction should you wait before taking bloods?
20-40 minutes
Macromolecules such as cTn are only released into the blood after myocyte necrosis (sarcolemmal membrane disruption)
