Pathology of Ischaemia and Infarction Flashcards
What does the heart need to function?
Oxygen
Definition of ischaemia
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet the needs of the tissue/organ - hypoxia
Types of hypoxia
Hypoxic
Anaemia
Stagnant
Cytotoxic
What is hypoxic hypoxia?
Low inspired O2 level
or
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
- local e.g. occlusion of vessel
- systemic e.g. shock
What is cytotoxic hypoxia?
Normal inspired O2 but abnormal at tissue level
When does infarction occur?
When ischaemic necrosis within a tissue / organ in living body produced by occlusion of either the arterial supply or venous drainage
Definition of atheroma/atherosclerosis
Localised accumulation of lipid and fibrous tissue in intima of arteries
What does an established atheroma in coronary artery result in?
Stable angina
What does complicated atheroma in coronary artery result in?
Unstable angina
What does ulcerated / fissured plaques result in?
Thrombosis leading to ischaemia / infarction
What does atheroma in the aorta result in?
Aneurysm
What does stable angina result in?
Ischaemic pain in heart on exertion
What does unstable angina result in?
Ischaemia pain in heart on rest
A change in the vessel wall can lead to what?
Thrombosis
Effects of ischaemia
Blood/O2 supply fails to meet demand due to decreased supply
Anaerobic metabolism
- L lactate reversibly converted to pyruvate via LDH - which can be converted to acetyl CoA and CO2
Dysfunction, pain, physical damage
What type of cells are affected the most in ischaemia?
Specialised cells
Clinical consequences of ischaemia
MI TIA Stroke AAA Peripheral vascular disease Cardia failure
What is another name for stroke?
Cerebral infarction
Factors affecting O2 supply
Inspired O2 Pulmonary function Blood constituents eg. haemoglobin Blood flow Integrity of vasculature e.g. atheroma, embolis / tumour Tissue mechanisms
Factors affecting oxygen demand
Tissue - different ones have different O2 requirements
Activity of tissue above baseline value
Supply issues in ischaemic heart disease
Coronary artery atheroma Cardiac failure Pulmonary function, other disease or pulmonary oedema (LVF) Anaemia Previous MI
Demand issues in ischaemic heart disease
Heart has high intrinsic demand
Exertion/stress
Possible causes of infarction
Thrombosis
Embolism
Strangulation e.g. gut
Trauma - cut/ruptured vessel
Scale of damage of ischaemia/infarction depends on…..
Time period
Tissue / organ
Pattern of blood supply
Previous disease (decreased reserve)
What does anaerobic metabolism lead to?
Cell death which leads to liberation of enzymes which leads to breakdown of tissue
Types of necrosis
Coagulative e.g. heart, lung
Colliquitive e.g. brain
Which is the most common type of necrosis?
Coagulative
Pathology of myocardial ischaemia
- Anaerobic metabolism - onset of ATP depletion (seconds)
- Loss of myocardial contractility (leads to HF) - < 2 mins
- Ultrastructural changes (few mins) - possibly reversible
Severe ischaemia is in in 20 - 30 mins - this causes irreversible damage - Myocyte necrosis (20 - 40 mins)
- Injury to the microvasculature > 1 hour
Appearance of infarct less than 24 hours
No change on visual inspection
A few hours to 12 hours post insult (swollen mitochrondia)
Appearance of infarct 24 - 48 hours
Pale - myocardium, solid tissues, spleen etc
Red infarct - lung, liver etc
Microscopically - acute inflammation initially at edge of infarct, loss of specialised cell features
Appearance of infarct at 72 hours onwards
Pale infarct - yellow / white in periphery
Red infarct - little change
Microscopically
- chronic inflammation
- macrophages remove debris
- granulation tissue and new vessel formation
- fibrosis - new tissue is laid down
End results of infarct
Scar replaces area of tissue damage
Shape of the scar after an infarct depends on what?
Territory of occluded vessel
What is the scar called after an infarct?
Reperfusion injury
Definition of transmural infarction
Ischaemic necrosis affects full thickness of the myocardium
Definition of subendocardial infarction
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What are acute infarcts classified according to?
Whether there is elevation of the ST segment on the ECG
What does it mean if there is no ST segment elevation but significantly elevated troponin level?
N-STEMI
Complications of MI
Sudden death Arrythmias Angina Cardiac failure Cardiac rupture - ventricular wall Septum Papillary muscle Reinfarction Pericarditis PE 2ndry to DVT Papillary muscle dysfunction - necrosis / rupture - mitral incompetence Mural thrombosis Ventricular aneurysm Dresslers syndrome
What is dresslers syndrome?
Immune system response after damage to heart tissue or to the pericardium
MI reparative process
Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue Collagen deposition (fibrosis) Scar formation
MI 4 - 12 hours
Early coagulation necrosis
Oedema
Haemorrhage
MI 12 - 24 hours
Ongoing coagulation necrosis
Myocyte changes
Early neutrophilic infiltrate
MI 1 - 3 days
Coagulation necrosis
Loss of nuclei and striations
Brisk neutrophilic infiltrate
MI 3 - 7 days
Disintegration of dead myofibres
Dying neutrophils
Early phagocytosis
MI 7 - 10 days
Well developed phagocytosis
Granulation tissue at margins - red rim with pale infarct
MI 10 - 14 days
Well established granulation tissue with new blood vessels and collagen deposition
MI 2-8 weeks
Increased collagen deposition
Decreased cellularity
MI > 2 months
Dense collagenous scar
What does an ASD allow?
A paradoxical stroke - where an embolism from peripheral veins may bypass the pulmonary circulation
What murmur would be heard with an ASD?
Systolic Murmur
Radiating through to the back
Fixed S2 splitting
