Pathophysiology of Ischaemia & Infarction Flashcards by Michael Alcorn

What is ischaemia?

a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism (hypoxia)

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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

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What are the causes/types of hypoxia?

Low inspired O2 level or normal inspiration but low PaO2

Anaemia

Stagnant blood

Cytotoxic

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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

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Describe why cytotoxic hypoxia may arise

Normal delivery of oxygen to tissues

However, oxygen uptake/usage is ineffective at a cellular level

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What factors affect oxygen supply?

Inspired O2
Lung function

Blood constituents

Blood flow
Integrity of vasculature

Tissue mechanisms

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What factors affect tissue demand?

What type of tissue it is

What it’s doing:
- activity of tissue above baseline value

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In terms if supply & demand

What is Ischaemic heart disease?

Mismatch between supply & demand of oxygen

Hypoxia of the heart muscles

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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

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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)

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What is the main risk associated with an atheroma in the aorta?

Aneurism

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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

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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

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What cells are most at risk of damage from ischaemia?

Cells with high metabolic rate

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What are the general effects of ischaemia?

Dysfunction

Pain

Physical damage

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“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

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Define infarction

Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage

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What are the main causes of infarction?

Thrombosis

Embolism

Strangulation - eg of gut

Trauma - cut/ruptured vessel

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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

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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

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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)