Ischaemia and Infarction

Question 1

What is ischaemia?

Answer 1

The relative lack of blood supply to a tissue or organ, leading to hypoxia.

Question 2

What are the different types of hypoxia?

Answer 2

Hypoxic - lower inspired O2 or PaO2.
Anaemic - abnormal blood O2.
Stagnant - abnormal delivery of O2.
Cytotoxic - abnormal O2 at tissue level.

Question 3

What factors affect oxygen supply?

Answer 3

Inspired O2.
Pulmonary function.
Blood constituents and flow.
Vasculature integrity.
Tissue mechanisms.

Question 4

What factors affect oxygen demand?

Answer 4

Tissue requirements.
Activity of tissue above baseline value.

Question 5

How is ischaemic heart disease related to supply and demand issues?

Answer 5

Supply issues - coronary artery atheroma, cardiac failure (flow), pulmonary function, pulmonary oedema (LVF), anaemia, MI.
Demand issues - high intrinsic demand of the heart, exertion.

Question 6

What can atherosclerosis cause?

Answer 6

Established atheroma in a coronary artery - stable angina.
Complicated atheroma in a coronary artery - unstable angina.
Ulcerated or fissured plaques - thrombosis (can causes ischaemia or infarction).
Atheroma in the aorta - aneurysm.

Question 7

What are the clinical consequences of ischaemia?

Answer 7

TIA.
Cerebral infarction.
Abdominal aortic aneurysm.
Peripheral vascular disease.
Coronary artery disease (MI, cardiac failure).

Question 8

How is atheroma linked to blood flow?

Answer 8

A thrombosis changes the vessel wall. Halving lumen radius causes a decrease in flow (and hence oxygen, leading to ischaemia and infarction) by 16-fold.

Question 9

What are the effects of ischaemia?

Answer 9

Functional - decreased supply; increased demand; or both. Related to the rate of onset.
General - acute, chronic, acute-on-chronic.
Biochemical - anaerobic metabolism, cell death.
Cellular - different tissue requirements.
Clinical - dysfunction, pain, physical damage.

Question 10

What are the outcomes of ischaemia?

Answer 10

No clinical effect.
Resolution vs therapeutic intervention.
Infarction.

Question 11

What is infarction?

Answer 11

Ischaemic necrosis within a tissue or organ, produced by occlusion of a blood vessel.
The scale of damage depends on time, the tissue, blood supply, and previous disease.

Question 12

What are the two types of necrosis?

Answer 12

Coagulative - in the heart and lungs.
Colliquative - in the brain.

Question 13

What are the reversible effects of myocardial ischaemia?

Answer 13

Seconds - anaerobic metabolism, ATP depletion.
<2mins - loss of contractility, heart failure.
>2mins - myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling.

Question 14

What are the irreversible effects of myocardial ischaemia?

Answer 14

20-30mins - severe ischaemia.
30-40mins - sarcolemma membrane damage, leakage of intracellular macromolecules.
>1hr - microvasculature injury.

Question 15

What is the appearance of an infarct within 24 hours?

Answer 15

No change on visual inspection.
Swollen mitochondria on electron microscopy (3-12hrs post insult).

Question 16

What is the appearance of an infarct between 24 and 48 hours?

Answer 16

Pale infarct (Ex. Myocardium, spleen, kidney) - in solid tissues.
Red infarct (Ex. Lung, liver) - in loose tissues and previously congested tissue.
Acute inflammation at the edge of infarct; loss of specialised features.

Question 17

What is the appearance of an infarct between 48 and 72 hours?

Answer 17

Pale infarct - yellow and white, with a red periphery.
Red infarct - little change.
Chronic inflammation; macrophages remove debris; granulation; fibrosis.

Question 18

What does the end result of an infarct depend on?

Answer 18

The territory of the occluded vessel.
Scarring occurs; reperfusion injury can occur.

Question 19

What are the processes occurring in an MI within 24 hours?

Answer 19

4-12hrs - early coagulation necrosis, oedema, haemorrhages.
12-24hrs - ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate.

Question 20

What are the processes occurring in an MI within a week?

Answer 20

1-3 days - coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate.
3-7 days - disintegration of dead myofibres, dying neutrophils, early phagocytosis.

Question 21

What are the processes occurring in an MI after a week?

Answer 21

7-10 days - well-developed phagocytosis, granulation tissue at margins.
10-14 days - well-established granulation tissue with new blood vessels and fibrosis.
2-8 weeks - increased fibrosis and decreased cellularity
>2 months - a dense collagenous scar.

Question 22

What are the similarities and differences between a transmural and subendocardial infarction?

Answer 22

Transmural infarction - ischaemic necrosis affects the full thickness of the myocardium.

Subendocardial infarction - ischaemic necrosis, mostly limited to a zone of the myocardium under the endocardial lining of the heart.

They have the same histological features (granulation tissue is followed by fibrosis).

Question 23

How are acute infarcts classified?

Answer 23

Elevation of the ST segment on an ECG.
No elevation, but significantly elevated serum troponin - NSTEMI (may correlate to a subendocardial infarct).

Question 24

What do the effects of infarction depend on?

Answer 24

Site and size.
Death and dysfunction.
Previous disease or infarction.

Question 25

What are the complications of MI?

Answer 25

Sudden death.
Arrhythmias.
Angina.
Cardiac failure.
Cardiac rupture (ventricular wall, septum, papillary muscle).
Reinfarction.
Pericarditis.
Pulmonary embolism.
Papillary muscle dysfunction (necrosis and rupture cause mitral incompetence).
Mitral incompetence.
Mural thrombosis.
Ventricular aneurysm.