Pathophysiology of Ischaemia and Infarction

Question 1

What is ischaemia?

Answer 1

Lack of blood supply leading to inadequate O2 supply to meet the needs of the tissue/organ -> hypoxia

Question 2

What is hypoxic hypoxia?

Answer 2

Low inspired O2 level

Normal inspired O2 but low PaO2

Question 3

What is anaemic hypoxia?

Answer 3

Normal inspired O2 but blood abnormal

Question 4

What is stagnant hypoxia?

Answer 4

Normal inspired O2 but abnormal delivery due to:
Local (occlusion)
Systemic (shock)

Question 5

What is cytotoxic hypoxia?

Answer 5

Organelles cannot function properly even though they have adequate oxygen

Question 6

What are 6 factors affecting oxygen supply?

Answer 6

Inspired O2 
Pulmonary function 
Blood constituents 
Blood flow 
integrity of vasculature 
Tissue mechanisms

Question 7

What are 2 factors that will increase oxygen demand?

Answer 7

Tissue itself may have different requirement

Activity of tissue above baseline

Question 8

What can cause low inspired O2 leading to hypoxic hypoxia?

Answer 8

High altitude

Question 9

Wh might blood flow be compromised leading to decreased O2 supply?

Answer 9

Heart failure

Question 10

Why might the integrity of the vasculature be compromised, lead to decreased O2 supply?

Answer 10

Compression or occlusion

Question 11

What can cause supply issues that would lead to ischaemic heart issues?

Answer 11

Coronary artery atheroma 
Cardiac failure (decreased flow)
Pulmonary function - pul. oedema (due to LVF)
Anaemia 
Previous MI

Question 12

What are demand issues that can cause ischaemic heart disease?

Answer 12

Heart has high intrinsic demand
Exertion
Stress

Question 13

What is an atheroma?

Answer 13

Localised accumulation of lipid and fibrous tissue in the intima of arteries

Question 14

What can established atheroma in coronary arteries cause?

Answer 14

Stable angina

Question 15

What can a complicated atheroma in coronary arteries cause?

Answer 15

Unstable angina

Question 16

What can an atheroma in the aorta cause?

Answer 16

Aneurysm - from dilatation due to weakening of the vascular wall from inflammation

Question 17

What can an ulcerated/fissured plaque cause?

Answer 17

Thrombosis leading to ischaemia or infarction

Question 18

What are the clinical consequences of atheroma?

Answer 18

MI
TIA
Cerebral infarction 
AAA
Peripheral vascular disease 
Cardiac failure (CAD -> MI -> cardiac failure)

Question 19

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?

Answer 19

16 fold decrease
Shows large effect of radius of vessels on flow and why explains why plaques significantly reduce flow and cause ischaemia

Question 20

Give an example of where ischaemia can be chronic?

Answer 20

Sufferers of peripheral vascular disease getting claudication when walking

Question 21

Give an example of when ischaenia can be acute-on-chronic?

Answer 21

Claudication in peripheral vascular disease (chronic) but can turn into an acute event

Question 22

How does ischaemia affect the biochemistry of cells?

Answer 22

Increases anaerobic metabolism, meaning less O2 is produced -> cell death

Question 23

Which cells are more affected by ischaemia?

Answer 23

Cells with high metabolic rate

Question 24

Which cells are less affected by ischaemia?

Answer 24

Cell with low metabolic rate

Question 25

What are the three general clinical effects of ischaemia?

Answer 25

Dysfunction Pain Physical damage

Question 26

What are the three potential outcomes of ischaemia?

Answer 26

No clinical effect Resolution vs therapeutic intervention Infarction

Question 27

What is infarction?

Answer 27

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

Question 28

What are the 4 possible causes of infarction?

Answer 28

Thrombosis Embolism Strangulation i.e. gut Trauma - cut/ruptured vessel

Question 29

What is the scale of damage caused by the ischaemia/infarction dependent on?

Answer 29

Time period Tissue/organ Pattern of blood supply Previous disease

Question 30

How does infarction cause necrosis?

Answer 30

More anaerobic metabolism therefore less O2 produced -> cell death -> release of enzymes -> breakdown of tissue

Question 31

What is coagulative necrosis?

Answer 31

Cell death is caused by lack of blood flow, and the cells become dry, hard and white I.e. heart, lung

Question 32

What is colliquitive necrosis?

Answer 32

Transformation of the tissue into a liquid viscous mass | I.e. brain

Question 33

Describe the sequence of events in necrosis

Answer 33

Coronary arterial obstruction -> decrease blood flow to region of myocardium -> ischaemia causing rapid myocardial dysfunction -> myocyte death

Question 34

What occurs in the first seconds of myocardial ischaemia?

Answer 34

Anaerobic metabolism causing ATP depletion

Question 35

How long is severe ischaemia and is it reversible?

Answer 35

20-30mins and causes irreversible damage

Question 36

What occurs in the first 2mins of myocardial ischaemia?

Answer 36

Loss of myocardial contractility (leading to heart failure)

Question 37

What ultrastructural changes occur in the first few minutes of myocardial ischaemia?

Answer 37

Myofibrillar relaxation Glycogen depletion Cell and mitochondrial swelling

Question 38

What happens in the first 20-40mins of infarction?

Answer 38

Myocyte necrosis

Question 39

What happens in the first hour after infarction?

Answer 39

Injury to the microvascular

Question 40

Describe the appearance of infarcts in the 24hrs after infarction

Answer 40

No change visually | Up to 12hrs after - swollen mitochondria on electron microscopy

Question 41

Describe the appearance of infarcts 24-48hrs after infarction

Answer 41

Pale infarct: myocardium, spleen kidney, solid tissues Red infarct: lung, liver - loose tissues, previously congested tissue Microscopically: acute inflammation initially at edge of infarct, loss of specialised cell features

Question 42

Describe the appearance of infarcts 72hrs after infarction

Answer 42

Macroscopically: pale - yellow/white and red periphery and no change to red infarct Microscopically: chronic inflammation -> macrophages remove debris -> granulation tissue -> fibrosis

Question 43

What is the end result appearance of infarcts?

Answer 43

Scar replaces area of tissue damage Shape depends on territory of occluded vessel Reperfusion injury

Question 44

What is a repercussion injury?

Answer 44

Tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen

Question 45

What is the process of repair after infarction?

Answer 45

1. Cell death 2. Acute inflammation 3. Macrophage phagocytosis of dead cells 4. Granulation tissue 5. Collagen deposition (fibrosis) 6. Scar formation

Question 46

What is a transmural infarction?

Answer 46

Ischaemic necrosis affects the full thickness of the myocardium

Question 47

What is a subendocardial infarction?

Answer 47

Ischaemic necrosis limited to a zone under the endocardium

Question 48

What are acute infarcts classified by?

Answer 48

Whether there is elevation of the ST segment on the ECG

Question 49

List some complications of myocardial infarctions

Answer 49

``` Sudden death Arrhythmias Angina Heart failure Rupture of wall, septum, papillary muscle due to weakening wall from necrosis Pulmonary embolism secondary to DVT Papillary muscle dysfunction/rupture causing mitral incompetence Mural thrombosis Ventricular aneurysms Dresslers syndrome ```