Pathophysiology of Ischaemia and Infarction Flashcards
What is ischaemia?
lack of blood supply to tissue or organ- hypoxia
What are the four types of hypoxia?
- hypoxic
(a)low inspired oxygen level
(b) normal inspired oxygen level but little pulmonary artery pressure of oxygen in the blood - anaemic hypoxia- inspired oxygen level normal but blood abnormal- not enough haemoglobin to transport oxygen to tissues
- Stagnant
normal inspired oxygen but abnormal delivery
(a) local e.g. occlusion of vessel
(b) systemic e.g shock - Cytotoxic
normal inspired oxygen but abnormal at tissue level (can’t deal with oxygen being delivered to them)
Factors affecting oxygen supply?
- inspired oxygen
- pulmonary function
- blood constituents
- blood flow
- integrity of vasculature
- tissue mechanisms
What are the factors affecting oxygen demand?
- tissue itself- different tissues have different requirements
- activity of tissue above baseline value
What might supply issues be due to in ischaemic heart disease?
coronary artery atheroma, cardiac failure (affects flow), pulmonary function due to other disease or pulmonary oedema (LVF), anaemia, previous ,MI
demand issues
heart has high intrinsic demand, exertion/ stress
What is atherosclerosis?
localised accumulation of lipid and fibrous tissue in intima of arteries
When is it stable angina?
established atheroma in coronary artery
When is it unstable angina?
complicated atheroma (established atheroma with additional features such as haemorrhage in plaque in coronary artery)
What leads to thrombosis that can lead to ischaemia/ infarction?
ulcerated / fissured plaues
What can lead to aneurysm?
atheroma in aorta- inflammatory response to the atheroma weakens the wall that causes dilatation of aorta
Clinical consequences?
MI
Transient Ischaemic Attack (similar to stroke but only lasts short time)
Cerebral Infarction
Abdominal Aortic Aneurysm
Peripheral Vascular disease
Cardiac disease
COMMON SCENARIO: coronary artery atheroma- thrombus that forms- stops blood and oxygen getting to the myocardium- myocardial infarction - cardiac failure
What is Poiseuille’s formula?
R=8nl/Pi x r x cubed
R= resistance of vessel
8/Pi= constant
n= viscosity
l=length of tube
r=radius of lumen
What are the effects of ischaemia?
Functional:
-Blood oxygen supply fails to meet demand due to decreased oxygen supply ;increase in demand or both
-related to rate of onset
General:
-acute (see effects)
-chronic (gradual onset)
-acute on chronic (sudden deterioration of already chronic disease)
Biochemical: reduction in oxygen supply and that leads to anaerobic metabolism - then toxicity of lactate and damage causes cell death and ischaemia and infarction.
Cellular effects:
different tissues have variable oxygen requirement and are variably susceptible to ischaemia.
-cells with high metabolic rate
-cells with low metabolic rate (fat, bone cells)
Clinical effects:
dysfunction-
abnormal heart rhythm
pain- angina
physical damage- specialised cells
Outcome of effects of ischaemia?
no clinical effect
resolution through therapeutic intervention
infarction
What is infarction?
is ischaemic necrosis within tissue or organ and produced by occlusion of either arterial supply or venous drainage
Aetiology of infarction possibilities?
- thrombosis
2.embolism - strangulation e.g. gut
- Trauma- cut/ ruptured vessel
What is the scale of damage caused by ischaemia and infarction dependent on?
- time period
- tissue/ organ
- pattern of blood supply
- previous disease
What do we call infarction in the brain?
colliquitive necrosis
Process of infarction?
Anaerobic metabolism leads to cell death leads to liberation of enzymes and this leads to further breakdown of tissue
What is infarction in most organs called?
coagulated necrosis
What happens if have coronary arterial obstruction?
coronary arterial obstruction decreases blood flow to region of myocardium - leading to ischaemia.
Get rapid myocardial dysfunction and myocyte death.
Timescale of myocardial ischaemia?
anaerobic metabolism, onset of ATP depletion: seconds
loss of myocardial contractility: within 2 minutes
ultrastructural changes (myofibrillar relaxation, glycogen depletion, cell swelling and mitochondrial swelling) within a few minutes REVERSIBLE
severe ischaemia (20-30 mins)- irreversible damage
myocyte necrosis (disruption of integrity of sarcolemmal membrane and intracellular macromolecules can leak out: blood tests): 20-40 mins
Injury to microvasculature - more than an hour
How does appearance of infarcts change?
less than 24 hours:
no change on visual inspection
-a few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy
24-48 hours:
-pale infarct: e.g. myocardium, spleen, kidney and 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
72 hours onwards:
macroscopically:
pale infarct- yellow/ white and red periphery
red infarct- little change
microscopically:
chronic inflammation; macrophages remove debris; granulation tissue (new vessel formation); fibrosis
What is the end result of infarcts?
scar replaces area of tissue damage
shape depends on territory of occluded vessel
Why is restoring blood flow to area of infarction bad?
sometimes induces an inflammatory response so that restoring blood supply actually causes more tissue damage in that area due to oxygen free radicals and inflammatory response causing further damage to the tissue.
What are the reparative processes in myocardial infarction?
Cell death
acute inflammation
macrophage phagocytosis of dead cells
granulation tissue
collagen deposition (fibrosis)
scar formation
Myocardial infarction time line?
4-12 hours - early coagulation necrosis ,oedema and haemorrhage
12-24 hours- ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
1-3 days- coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
3-7 days: disintegration of dead myofibres, dying neutrophils and early phagocytosis by macrophages
7-10 days: well developed phagocytosis by macrophages and new vessel formation at the margins
10-14 days- well established tissue with new blood vessels and collagen deposition
2-8 weeks- increased collagen deposition, decreased cellularity
> 2 months- dense collagenous scar
What are the different types of myocardial infarcts?
transmural infarction: ischaemic necrosis affects full thickness of the myocardium
subendocardial infarction: ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
Difference between transmural and subendocardial infarction?
histological features are the same
in subendocardial infarction- shortened repair time for granulation tissue stage and fibrosis
What is a non ST segment elevation but significantly elevated serum troponin level?
non-STEMI
What is troponin?
macromolecule release when heart damage
What is a non STEMI thought to correlate with?
subendocardial infarct
Complications of myocardial infarction?
immediate; early ;late
sudden death
arrythmias
angina
cardiac failure
cardiac rupture -of ventricular wall, septum, papillary muscle
reinfarction
pericarditis
pulmonary embolism secondary to DVT
papillary muscle dysfunction- necrosis and rupture leading to mitral incompetence
mural thrombus forming where MI been
ventricular aneurysm
Dresslers syndrome (further inflammatory issues related to MI)
