Pathophysiology of ischaemia + infarction Flashcards
Define ischaemia
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ:
What are the factors affecting oxygen supply
- Inspired O2
- Pulmonary function
- Blood constituents
- Blood flow
- Integrity of vasculature
- Tissue mechanisms
What are the factor affecting oxygen demand
- Tissue itself - different tissues have different requirements
- Activity of tissue above baseline value
What are examples of conditions that causes ischaemia
Hypoxia - Low oxygen
Anaemia - abnormal delivery
Stagnant - abnormal delivery
Cytotoxic - abnormal tissue
What are the potential oxygen supply issues that can cause myocardial ischaemia
coronary artery atheroma, cardiac failure (flow), pulmonary function – other disease pulmonary oedema (LVF), anaemia, previous MI
What are the potentially oxygen demand issue that can cause myocardial ischaemia
heart has high intrinsic demand, exertion/stress
What is the clinical consequences of ischaemia due to atheroma
MI TIA - symptoms of a stroke that are resolved Cerebral infarction Abdominal aortic aneurysm Peripheral vascular disease Cardiac failure Stable/unstable angina
How does atheroma cause ischaemia
Atheroma causes vessels radius to decrease, decreasing the flow of blood, decreasing oxygen delivery resulting in decreased supply of oxygen to an organ - ischaemia
What is the biochemical effect of ischaemia
Decreased oxygen results in anaerobic respiration which promotes cell death
What cells are more susceptible to ischaemia
Cells with a high metabolic rate
What is the clinical effects of ischaemia
(a) Dysfunction - e.g. abnormal heart rhythms
(b) Pain
(c) Physical damage
Specialised cells
What is the there possible outcomes of ischaemia
No clinical effect
Resolution versus therapeutic intervention
Infarction
Define infarction
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
cessation of blood flow
What are examples of the aetiology of infarction
- Thrombosis
- Embolism
- Strangulation e.g. gut
- Trauma - cut/ruptured vessel
What does the scale of damage in infarction depend upon
Time period
Tissue/organ
Pattern of blood supply
Previous disease
What is the pathology of infarction
Anaerobic metabolism cell death liberation of enzymes breakdown of tissue
What is the two types of necrosis
Coagulative necrosis e.g. heart, lung
Colliquitive necrosis e.g. brain
How long does it take in myocardial ischaemia for anaerobic metabolism to occur/ ATP depletion
few seconds
How long does it take in myocardial ischaemia for loss of myocardial contractility i.e. heart failure
< 2 minutes
After a few minutes in a myocardial ischameia what ultrasound changes can be seen
myofibrillar relaxation,
glycogen depletion,
cell and mitochondrial swelling
At what timing and stage does the affect of myocardial infarction become irreversible and why is this
Severe ischaemia 20-30 mins
As myocyte necrosis is occurring
What occurs in myocyte necrosis
disruption of integrity of sarcolemmal membrane resulting in leakage of intracellular macromolecules
What happens after one hour into a myocardial infarction
Injury to the microvasculature
What is the appearance of infarcts 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 is the microscopic appearance if infarcts from 24-48 hours
acute inflammation initially at edge of infarct; loss of specialised cell features
What is classified as pale infarct
Solid tissues
myocardium, spleen, kidney
What is classified as red infarct
Loose tissue - previously congested
Lung, liver
72 hours onwards into MI what is the appearance of pale and rd infarcts
Pale infarct - yellow/white and red periphery
Red infarct - little change
72 hours onward into MI what can be seen microscopically
chronic inflammation;
macrophages remove debris;
granulation tissue;
fibrosis
What is Reperfusion injury
tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen
What is the reparative process of MI and what is the end result
Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue Collagen deposition (fibrosis) Scar formation As Scar replaces area of tissue damage
What is two different type of MI
Subendocardial infarction
transmural infarction
What is the affect of Subendocardial infarction
ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What is the affect of transmural infarction
ischaemic necrosis affects full thickness of the myocardium
What is the similarity and differences in reparative process in subendocardial and transmural
They have the same histological features but granulation tissue stage followed by fibrosis - in subendocardial infarct possibly slightly shortened compared to transmural infarct
How is acute infarcts classified in investigation with ECG
according to whether there is elevation of the ST segment on the ECG
What does it mean If no ST segment elevation but a significantly elevated serum troponin level:
non-STEMI
What kind of infarct is is non STEMI thought to correlate with
a subendocardial infarct
Why is it Difficult to carry out detailed studies to show link between ECG changes seen with an infarct and exact pathological features
because declining post mortem rates
people don’t stick around long enough for us to see the pathology
What is the complications of myocardial infarction
Sudden death;
arrhythmias - abnormal heart rhythm
angina;
cardiac failure;
cardiac rupture - ventricular wall, septum, papillary muscle;
reinfarction - repeat infarction
pericarditis;
pulmonary embolism secondary to DVT;
mural (bv/cavity) thrombosis;
ventricular aneurysm;
Dressler’s syndrome
