Pathophysiology of Ischaemia and Infarction Flashcards
What is ischaemia?
Lack of blood supply leading to inadequate O2 supply to meet the needs of the tissue/organ -> hypoxia
What is hypoxic hypoxia?
Low inspired O2 level
Normal inspired O2 but low PaO2
What is anaemic hypoxia?
Normal inspired O2 but blood abnormal
What is stagnant hypoxia?
Normal inspired O2 but abnormal delivery due to:
Local (occlusion)
Systemic (shock)
What is cytotoxic hypoxia?
Organelles cannot function properly even though they have adequate oxygen
What are 6 factors affecting oxygen supply?
Inspired O2 Pulmonary function Blood constituents Blood flow integrity of vasculature Tissue mechanisms
What are 2 factors that will increase oxygen demand?
Tissue itself may have different requirement
Activity of tissue above baseline
What can cause low inspired O2 leading to hypoxic hypoxia?
High altitude
Wh might blood flow be compromised leading to decreased O2 supply?
Heart failure
Why might the integrity of the vasculature be compromised, lead to decreased O2 supply?
Compression or occlusion
What can cause supply issues that would lead to ischaemic heart issues?
Coronary artery atheroma Cardiac failure (decreased flow) Pulmonary function - pul. oedema (due to LVF) Anaemia Previous MI
What are demand issues that can cause ischaemic heart disease?
Heart has high intrinsic demand
Exertion
Stress
What is an atheroma?
Localised accumulation of lipid and fibrous tissue in the intima of arteries
What can established atheroma in coronary arteries cause?
Stable angina
What can a complicated atheroma in coronary arteries cause?
Unstable angina
What can an atheroma in the aorta cause?
Aneurysm - from dilatation due to weakening of the vascular wall from inflammation
What can an ulcerated/fissured plaque cause?
Thrombosis leading to ischaemia or infarction
What are the clinical consequences of atheroma?
MI TIA Cerebral infarction AAA Peripheral vascular disease Cardiac failure (CAD -> MI -> cardiac failure)
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?
16 fold decrease
Shows large effect of radius of vessels on flow and why explains why plaques significantly reduce flow and cause ischaemia
Give an example of where ischaemia can be chronic?
Sufferers of peripheral vascular disease getting claudication when walking
Give an example of when ischaenia can be acute-on-chronic?
Claudication in peripheral vascular disease (chronic) but can turn into an acute event
How does ischaemia affect the biochemistry of cells?
Increases anaerobic metabolism, meaning less O2 is produced -> cell death
Which cells are more affected by ischaemia?
Cells with high metabolic rate
Which cells are less affected by ischaemia?
Cell with low metabolic rate
What are the three general clinical effects of ischaemia?
Dysfunction
Pain
Physical damage
What are the three potential outcomes of ischaemia?
No clinical effect
Resolution vs therapeutic intervention
Infarction
What is infarction?
Ischaemic necrosis with a tissue/organ in living body produced by occlusion of either the arterial supply or venous damage
What are the 4 possible causes of infarction?
Thrombosis
Embolism
Strangulation i.e. gut
Trauma - cut/ruptured vessel
What is the scale of damage caused by the ischaemia/infarction dependent on?
Time period
Tissue/organ
Pattern of blood supply
Previous disease
How does infarction cause necrosis?
More anaerobic metabolism therefore less O2 produced -> cell death -> release of enzymes -> breakdown of tissue
What is coagulative necrosis?
Cell death is caused by lack of blood flow, and the cells become dry, hard and white
I.e. heart, lung
What is colliquitive necrosis?
Transformation of the tissue into a liquid viscous mass
I.e. brain
Describe the sequence of events in necrosis
Coronary arterial obstruction -> decrease blood flow to region of myocardium -> ischaemia causing rapid myocardial dysfunction -> myocyte death
What occurs in the first seconds of myocardial ischaemia?
Anaerobic metabolism causing ATP depletion
How long is severe ischaemia and is it reversible?
20-30mins and causes irreversible damage
What occurs in the first 2mins of myocardial ischaemia?
Loss of myocardial contractility (leading to heart failure)
What ultrastructural changes occur in the first few minutes of myocardial ischaemia?
Myofibrillar relaxation
Glycogen depletion
Cell and mitochondrial swelling
What happens in the first 20-40mins of infarction?
Myocyte necrosis
What happens in the first hour after infarction?
Injury to the microvascular
Describe the appearance of infarcts in the 24hrs after infarction
No change visually
Up to 12hrs after - swollen mitochondria on electron microscopy
Describe the appearance of infarcts 24-48hrs after infarction
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
Describe the appearance of infarcts 72hrs after infarction
Macroscopically: pale - yellow/white and red periphery and no change to red infarct
Microscopically: chronic inflammation -> macrophages remove debris -> granulation tissue -> fibrosis
What is the end result appearance of infarcts?
Scar replaces area of tissue damage
Shape depends on territory of occluded vessel
Reperfusion injury
What is a repercussion injury?
Tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen
What is the process of repair after infarction?
- Cell death
- Acute inflammation
- Macrophage phagocytosis of dead cells
- Granulation tissue
- Collagen deposition (fibrosis)
- Scar formation
What is a transmural infarction?
Ischaemic necrosis affects the full thickness of the myocardium
What is a subendocardial infarction?
Ischaemic necrosis limited to a zone under the endocardium
What are acute infarcts classified by?
Whether there is elevation of the ST segment on the ECG
List some complications of myocardial infarctions
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
