Pathophysiology of Ischaemia and Infarction Flashcards
Define ischaemia.
Lack of blood supply to tissues —> oxygen/nutrient shortage
(Can be due to supply or demand)
Define hypoxia.
Inadequate oxygen supply to meet the needs of the tissue or organ.
How can anaemics become hypoxic?
They inspire normal amount of oxygen, but lack of haemoglobin leads to inadequate delivery to tissues.
What are the four types of hypoxia?
- hypoxic hypoxia - low oxygen levels inspired or low PaO2
- anaemic hypoxia - due to anaemia
- stagnant hypoxia - abnormal delivery can be local, e.g. occlusion of vessel or systemic, e.g shock
- cytotoxic hypoxia - normal inspired O2 but abnormal at tissue level
How can the tissue itself affect oxygen supply?
Different tissues will have different oxygen demands dependent on workload and amount of activity.
What is atherosclerosis (an atheroma)?
Localised accumulation of lipid and fibrous tissue in intima of arteries.
What condition will arise from an atheroma in a coronary artery?
Stable angina.
What condition will arise from a complicated atheroma in a coronary artery?
Unstable angina.
What will result from ulcerated/fissured atheromatous plaques?
Thrombosis which can lead to ischaemia or infarction.
What is a thrombus?
A blood clot inside a blood vessel, that may obstruct the blood flow inside the circulatory system.
What can result from an atheroma in the aorta?
Aortic aneurysm - an unusual swelling of the aorta, large aneurysms can be fatal, if it ruptures can lead to huge internal, fatal bleed.
What might atherosclerosis lead to?
MI, TIA (transient ischaemic attack), cerebral infarction, abdominal aortic aneurysm, peripheral vascular disease, cardiac failure.
How do atheromas affect blood flow?
The change in vessel wall structure can lead to thrombus formation.
Blood flow is massively controlled by radius of lumen (to power of 4), so even a small decrease in blood flow can lead to a massive decrease in flow and a huge drop in oxygen delivery –> ischaemia and infarction.
What are the three classifications of ischaemia and how do they differ?
Acute - will be able to see changes (sudden onset)
Chronic - might go unnoticed for a while but just progressively worsen
Acute-on-chronic - sudden worsening of an already chronic disease
What are the biochemical consequences of ischaemia?
Cells may have to resort to anaerobic metabolism leading to the production of L-lactate (this would normally be turned back into pyruvate on repaying the oxygen debt but as this doesn’t happen can lead to toxic build up) –> cell death.
What are the cellular consequences of ischaemia?
Different cells have varying needs for oxygen and will be variably susceptible to ischaemia.
What are the clinical effects of ischaemia?
Dysfunction
Pain, e.g. claudication (pain in calf muscles)
Physical damage, specialised cells are often damaged first and most.
What are the possible outcomes of ischaemia?
1 - no clinical effect.
2 - resolution (w or w/o therapeutic intervention).
3 - infarction.
Define infarction.
Ischaemic necrosis within a tissue or organ in living body produced by occlusion of either the arterial supply or venous drainage.
What is the aetiology of infarction?
Cessation of blood flow, for example due to thrombosis, embolism, strangulation (e.g. gut) or trauma (cut or ruptured vessel).
What is the scale of damage in ischaemia or infarction dependent on? (4)
Time period, tissue/organ, patterns of blood supply, previous disease.
Describe the pathophysiology of infarction.
Anaerobic metabolism leads to build up of toxic metabolites, leading to cell death and liberation of enzymes which break down the tissue.
Distinguish between coagulative and colliquitive necrosis.
Coagulative necrosis - dead material forms gel-like substance in which structural integrity of tissue is maintained, seen in infarction of heart and lung
Colliquitive necrosis - digestive of dead cells forms viscous liquid, seen in infarction of brain
Describe how blockages in vessels of the heart lead to myocyte death.
Coronary arterial obstructive leads to decreased blood flow to region of myocardium leading to ischaemia, rapid myocardial dysfunction and myocardial death.
Describe the changes that occur during myocardial ischaemia leading to infarction and at what time scales these occur.
Anaerobic metabolism onset of ATP depletion - seconds.
Loss of myocardial contractility (–> heart failure) - less than 2 min.
Ultrastructural changes (myofibrillar relaxation glycogen depletion, cell and mitochondrial swelling ?reversible) - few mins.
For how long does severe ischaemia need to go untreated before there is irreversible damage?
20-30 mins.
What is involved in myocyte necrosis and how long does it take to happen?
20-40 mins. Involves disruption of integrity of sarcolemmal membrane –> leakage of intracellular macromolecules (troponin can be picked up in blood tests).
After one hour, what does the infarction cause?
Damage to the microvasculature.
How do the appearances of infarcts change over time?
Less than 24 hrs -
no change on visual inspection
12 post insult, see swollen mitochondria on electron microscopy
24-48 hrs -
pale infarct - e.g. myocardium, spleen, kidney, solid tissues
red infarct - e.g. in lung and 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 hrs onwards -
pale infarct - yellow/white and red periphery
little change to red infarct
microscopically - chronic inflammation, macrophages remove debris, granulation tissue, fibrosis
What is the end appearance of an infarct?
Scar replaces area of tissue damage. Shape depends on territory of occluded vessel. Reperfusion injury.
What are the reparative processes in MI?
Cell death acute inflammation macrophage phagocytosis of dead cells granulation tissue collagen deposition (fibrosis) scar formation
What happens in hours 4-12 of an MI?
early coagulation necrosis, oedema, haemorrhage
What happens in hours 12-24 of an MI?
ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
What happens in days 1-3 of an MI?
Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
What happens in days 3-7 of an MI?
Disintegration of dead myofibres, dying neutrophils, early phagocytosis
What happens in days 7-10 of an MI?
Well developed phagocytosis, granulation tissues at margins.
What happens in days 10-14 of an MI?
Well established granulation tissue with new blood vessels and collagen deposition.
What happens in weeks 2-8 of an MI?
Increased collagen deposition, decreased cellularity.
What happens after two months of an MI?
Dense collagenous scar.
Define transmural infarction.
Ischaemic necrosis affects full thickness of myocardium.
Define subendocardial infarction.
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart.
What differs in the histological features of the transmural and subendocardial infarction.
Subendocardial infarct possibly slightly shortened repair time compared to transmural.
What is a non-STEMI?
No ST elevation in ECG, but elevated serum troponin level.
What are STEMIs thought to correlate with?
Subendocaridal infarcts.
What are the effects of the infarction dependent on?
site dependent, within body and organ.
size of infarct
death, dysfunction (pain)
contribution of previous disease or infarction
Complications of MI can be immediate, early or late, give examples of possible complications.
Sudden death, arrhythmias, angina, cardiac failure, cardiac rupture - ventricular wall, septum, papillary muscle, reinfarction, pericarditis, pulmonary embolism secondary to DVT, papillary muscle dysfunction - necrosis or rupture –> mitral incompetence, mural thrombosis, ventricular aneurysm, Dressler’s syndrome.
