pathology of ischaemia and infarction Flashcards
what is ischaemia?
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ: hypoxia
what is hypoxic?
Low inspired O2 level
(b) Normal inspired O2 but low PaO2
what is anaemic?
Normal inspired O2 but blood abnormal
what is stagnant?
Normal inspired O2 but abnormal delivery
Local e.g. occlusion of vessel
Systemic e.g. shock
what is cytoxic?
Normal inspired O2 but abnormal at tissue level
factors affecting oxygen supply?
Inspired O2
- Pulmonary function
- Blood constituents
- Blood flow
- Integrity of vasculature
- Tissue mechanisms
factors affecting oxygen demand?
Tissue itself - different tissues have different requirements
- Activity of tissue above baseline value
what are the supply issues for ischaemic heart disease?
coronary artery atheroma, cardiac failure (flow), pulmonary function – other disease or pulmonary oedema (LVF), anaemia, previous MI
what are the demand issues for ischaemic heart disease?
heart has high intrinsic demand, exertion/stress
what is atheroma/atherosclerosis?
Localised accumulation of lipid and fibrous tissue in intima of arteries
whats the correlation between atheroma and stable angina?
established atheroma in coronary artery
whats the correlation between atheroma and unstable angina?
Complicated atheroma in coronary artery
what would an atheroma in aorta be?
aneurysm
what would ulcerated/fissured plaques be?
thrombosis which could lead to ischaemia/infarction
what are the effects of ischaemia functionally ?
Blood/O2 supply fails to meet demand due to supply; demand; or both
Related to rate of onset
what are the effects of ischaemia biochemically?
Normal aerobic metabolism
glucose+36ADP+36Pi+36H++6O2 6CO2+36ATP+42H2O
Anaerobic metabolism
glucose+2Pi+2ADP 2lactate+2ATP+2H2O
L-lactatepyruvate
Pyruvate+NAD++CoAacetylCoA+CO2+NADH
decreased O2 anaerobic metabolism leads to cell death
what is infarction?
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
whats the aetiology of infraction?
cessation of blood flow For example: 1. Thrombosis 2. Embolism 3. Strangulation e.g. gut 4. Trauma - cut/ruptured vessel
what is the scale of infarction dependent on?
Time period
Tissue/organ
Pattern of blood supply
Previous disease
what happens with an infarction?
Anaerobic metabolism goes to cell death goes to liberation of enzymes goes to breakdown of tissue
Coagulative necrosis e.g. heart, lung
how long does anaerobic metabolism, onset of ATP depletion take
seconds
how long does loss of myocardial contractility leading to heart failure
over 2 minutes
how long does myocyte necrosis take?
20-40 minutes
how long does injury to the microvasculature take?
over 1 hour
what visual changes can you see in less than 24 hours?
No change on visual inspection
A few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy
what visual changes can you see in less than 24 - 48 hours?
Pale infarct: e.g. myocardium, spleen, kidney Solid tissues
Red infarct: e.g. in lung, liver Loose tissues, previously congested tissue; second/continuing blood supply, venous occlusion
Microscopically: acute inflammation initially at edge of infarct; loss of specialised cell features
what visual changes can you see in less than 72 hours ?
Macroscopically:
Pale infarct - yellow/white and red periphery
Red infarct - little change
Microscopically: chronic inflammation; macrophages remove debris; granulation tissue; fibrosis
whats the end result of infarcts?
Scar replaces area of tissue damage
Shape depends on territory of occluded vessel
Reperfusion Injury
what is the repartive process of MI
Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue Collagen deposition (fibrosis) Scar formation
what would you see in 4-12 hours in myocardial infarction?
Early coagulation necrosis, oedema, haemorrhage
what would you see in 12-24 hours in myocardial infarction?
Ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
what would you see in 1-3 days in myocardial infarction?
Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
what would you see in 3-7 days in myocardial infarction?
Disintegration of dead myofibres, dying neutrophils, early phagocytosis
what would you see in 7-10 days
in myocardial infarction?
Well developed phagocytosis, granulation tissue at margins
what would you see in 10-14 days
in myocardial infarction?
Well established granulation tissue with new blood vessels and collagen deposition
what would you see in 2-8 weeks in myocardial infarction?
Increased collagen deposition, decreased cellularity
what would you see in >2 months
in myocardial infarction?
Dense collagenous scar
what is Transmural infarction
: ischaemic necrosis affects full thickness of the myocardium
what is Subendocardial infarction
ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
what are acute infarcts classified as?
whether there is elevation of the ST segment on the ECG
what would a ‘If no ST segment elevation but a significantly elevated serum troponin level’ mean?
non-STEMI
what are the complications of myocardial infarction?
Immediate; early; late
Sudden death; arrhythmias; angina; cardiac failure; cardiac rupture - ventricular wall, septum, papillary muscle; reinfarction; pericarditis; pulmonary embolism secondary to DVT; papillary muscle dysfunction - necrosis/rupture mitral incompetence; mural thrombosis; ventricular aneurysm; Dressler’s syndrome
