Ischaemia and Infarction Flashcards
What is ischaemia?
The relative lack of blood supply to a tissue or organ, leading to hypoxia.
What are the different types of hypoxia?
Hypoxic - lower inspired O2 or PaO2.
Anaemic - abnormal blood O2.
Stagnant - abnormal delivery of O2.
Cytotoxic - abnormal O2 at tissue level.
What factors affect oxygen supply?
Inspired O2.
Pulmonary function.
Blood constituents and flow.
Vasculature integrity.
Tissue mechanisms.
What factors affect oxygen demand?
Tissue requirements.
Activity of tissue above baseline value.
How is ischaemic heart disease related to supply and demand issues?
Supply issues - coronary artery atheroma, cardiac failure (flow), pulmonary function, pulmonary oedema (LVF), anaemia, MI.
Demand issues - high intrinsic demand of the heart, exertion.
What can atherosclerosis cause?
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.
What are the clinical consequences of ischaemia?
TIA.
Cerebral infarction.
Abdominal aortic aneurysm.
Peripheral vascular disease.
Coronary artery disease (MI, cardiac failure).
How is atheroma linked to blood flow?
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.
What are the effects of ischaemia?
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.
What are the outcomes of ischaemia?
No clinical effect.
Resolution vs therapeutic intervention.
Infarction.
What is infarction?
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.
What are the two types of necrosis?
Coagulative - in the heart and lungs.
Colliquative - in the brain.
What are the reversible effects of myocardial ischaemia?
Seconds - anaerobic metabolism, ATP depletion.
<2mins - loss of contractility, heart failure.
>2mins - myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling.
What are the irreversible effects of myocardial ischaemia?
20-30mins - severe ischaemia.
30-40mins - sarcolemma membrane damage, leakage of intracellular macromolecules.
>1hr - microvasculature injury.
What is the appearance of an infarct within 24 hours?
No change on visual inspection.
Swollen mitochondria on electron microscopy (3-12hrs post insult).
What is the appearance of an infarct between 24 and 48 hours?
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.
What is the appearance of an infarct between 48 and 72 hours?
Pale infarct - yellow and white, with a red periphery.
Red infarct - little change.
Chronic inflammation; macrophages remove debris; granulation; fibrosis.
What does the end result of an infarct depend on?
The territory of the occluded vessel.
Scarring occurs; reperfusion injury can occur.
What are the processes occurring in an MI within 24 hours?
4-12hrs - early coagulation necrosis, oedema, haemorrhages.
12-24hrs - ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate.
What are the processes occurring in an MI within a week?
1-3 days - coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate.
3-7 days - disintegration of dead myofibres, dying neutrophils, early phagocytosis.
What are the processes occurring in an MI after a week?
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.
What are the similarities and differences between a transmural and subendocardial infarction?
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).
How are acute infarcts classified?
Elevation of the ST segment on an ECG.
No elevation, but significantly elevated serum troponin - NSTEMI (may correlate to a subendocardial infarct).
What do the effects of infarction depend on?
Site and size.
Death and dysfunction.
Previous disease or infarction.
What are the complications of MI?
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.
