Pathophysiology of Ischaemia and Infarction Flashcards
1
Q
Hypoxia
A
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue tissue/organ
2
Q
Classes of hypoxia
A
- Hypoxic
- Anaemic
- Stagnant
- Cytotoxic
3
Q
Hypoxic hypoxia
A
Low inspired O2 level Or
Normal inspired O2 but low PaO2
4
Q
Anaemic hypoxia
A
Normal inspired O2 but blood abnormal
5
Q
Stagnant hypoxia
A
Normal inspired O2 but abnormal delivery due to
- Local (occlusion of vessel)
- Systemic (shock)
6
Q
Cytotoxic hypoxia
A
Normal inspired O2 but abnormal at tissue level
7
Q
Factors affecting oxygen supply
A
- Inspired O2
- Pulmonary function
- Blood constituents
- Blood flow
- Integrity of vasculature
- Tissue mechanisms
8
Q
Factors affecting oxygen demand.
A
- Tissue itself: different tissues have different requirements
- Activity of tissue above baseline value
9
Q
What can cause supply issues in ischaemic heart disease?
A
- Coronary artery atheroma
- Cardiac failure
- Pulmonary function other disease
- Pulmonary oedema
- Anaemia
- Previous MI
10
Q
What can cause demand issues in ischaemic heart disease?
A
- Heart has high intrinsic demand
- Exertion/ stress
11
Q
Atheroma/ atherosclerosis
A
Localised accumulation of lipid and fibrous tissue in intima of arteries
12
Q
What does established atheroma in coronary artery lead to?
A
Stable angina
13
Q
What does complicated atheroma in coronary artery lead to?
A
Unstable angina
14
Q
What do ulcerated/ fissured plaques lead to?
A
Thrombosis causing ischaemia/infarction
15
Q
What does atheroma in the aorta lead to?
A
Aneurysm
16
Q
What are the consequences of atheroma?
A
- MI
- TIA
- Cerebral infarction-
- AAA
- PVD
- Cardiac failure
17
Q
How does atheroma lead to ischaemia and infarction??
A
- Change in vessel wall leads to thrombosis
- Thrombosis decreases the radius of the vessel
- Leads to decrease in flow causing decrease in oxygen transport
- Leads to ischaemia/infarction
18
Q
What are the functional effects of ischaemia?
A
- Blood/O2 supply fails to meet demand due to decreased supply and or increased demand
- Related to rate of onset
19
Q
How can the effects of ischaemia be categorised?
A
- Acute
- Chronic
- Acute-on-chronic
20
Q
What are the biochemical effects of ischaemia?
A
- In anaerobic metabolism pyruvate is converted to L-lactate
- There is a build up in cytotoxic lactate which leads to decreased oxygen
- The acidic environment leads to cell death
21
Q
What are the cellular effects of ischaemia?
A
Different tissues have variable O2 requirement and are variably susceptible to ischaemia
22
Q
What are the clinical effects of ischaemia?
A
- Dysfunction
- Pain
- Physical damage
23
Q
What are the outcomes of ischaemia?
A
- No clinical effect
- Resolution versus therapeutic intervention
- Infarction
24
Q
Infarction
A
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
25
What is the aetiology of infarction?
Cessation of blood flow
26
What may cause cessation of blood flow?
- Thrombosis
- Embolism
- Strangulation
- Trauma
27
What factors is the scale of damage of ischaemia/infarction dependent on?
- Time period
- Tissue/organ
- Pattern of blood supply
- Previous disease
28
How does anaerobic metabolism lead to the breakdown of tissue?
Anaerobic metabolism causes cell death. When cells die there is a liberation of enzymes which in turn bring about the breakdown of tissues
29
Coagulative necrosis
Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction. In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days.
30
Colliquitive necrosis
Liquefactive necrosis (or colliquative necrosis) is a type of necrosis which results in a transformation of the tissue into a liquid viscous mass
31
Where does coagulative necrosis occur?
- Heart
| - Lung
32
Where doe colliquitive necrosis occur?
Brain
33
How does myocyte death occur in infarction?
- Coronary arterial obstruction leads to decreased blood flow to region of the myocardium
- This results in ischaemia and rapid myocardial dysfunction
- Overall resulting in myocyte death
34
Timeline of infarction: seconds
Anaerobic metabolism sets in and onset of ATP depletion
35
Timeline of infarction: <2min
Loss of myocardial contractility leading heart failure
36
Timeline of infarction: a few minutes
Ultrasound changes can be seen:
- Myofibrillar relaxation
- Glycogen depletion
- Cell and mitochondrial swelling
37
Timeline of infarction: 20-40 minutes
- Myocyte necrosis
| - Disruption of the integrity of the sarcolemma membrane causes leakage of intracellular macromolecules: blood tests
38
Timeline of infarction: >1 hr
Injury to the microvasculature
39
When will severe ischaemia lead to irreversible damage?
20-30 minutes
40
What is the appearance of the infarct less than 24 hrs after occurrence?
- No change on visual inspection
| - A few hrs to 12 hrs post insult able to see swollen mitochondria on electron microscopy
41
What is the appearance of the infarct 24-48 hrs after occurrence?
- Pale infarct: myocardium, spleen, kidney, solid tissues
- Red infarct: loose tissues, previously congested tissue; second/continuing blood supply, venous occlusion
- Microscopically: acute inflammation initially at edge of infarct; loss of specialised cell features
42
What is the appearance of the infarct 72 hours onwards after occurrence?
- Pale infarct- yellow/white and red periphery
- Red infarct- little change
- Microscopically: chronic inflammation: macrophages remove debris; granulation tissue; fibrosis
43
What is the end result of infarcts?
- Scar replaces area of tissue damage
- Shape depends on territory of occluded vessel
- Reperfusion injury
44
What reparative processes occur after myocardial infarction?
- Cell death
- Acute inflammation
- Macrophage phagocytosis of dead cells
- Granulation tissue
- Collagen deposition (fibrosis)
- Scar formation
45
Histological timeline of MI:4-12hrs
- Early coagulation necrosis
- Oedema
- Haemorrhage
46
Histological timeline of MI: 12-24 hrs
- Ongoing coagulation necrosis
- Myocyte changes
- Early neutrophilic infiltrate
47
Histological timeline of MI: 1-3 days
- Coagulation necrosis
- Loss of nuclei and striations
- Brisk neutrophilic infiltrate
48
Histological timeline of MI: 3-7 days
- Disintegration of dead myofibres
- Dying neutrophils
- Early phagocytosis
49
Histological timeline of MI: 7-10 days
- Well developed phagocytosis
| - Granulation tissue at margins
50
Histological timeline of MI: 10-14 days
-Well established granulation tissue with new blood vessels and collagen deposition
51
Histological timeline of MI: 2-8 weeks
- Increased collagen deposition
| - Decreased cellularity
52
Histological timeline of MI:>2 months
Dense collagenous scar
53
Transmural infarction
Ischaemic necrosis affects full thickness of the myocardium
54
Subendothelial infarction
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
55
What are the histological features of transmural/subendocardial infarctions?
- Features are the same
- Granulation tissue stage
- Fibrosis
- Possibly shorter time in the subendoccardial infarct
56
How are acute infarcts classified?
According to whether there is elevation of the ST segment on the ECG
57
Non-STEMI
- No ST segment elevation but significantly elevated serum troponin level
- Thought to correlate with a subendocardial infarct
58
What are the effects of infarction dependent on?
- Site dependent
- Size of infarct
- Death, dysfunction
- Contribution of previous disease/ infarction
59
When can complications following MI arise?
- Immediate
- Early
- Late
60
What can complications of MI include?
- Sudden death
- Arrhythmias
- Angina
- Cardiac failure
- Cardiac rupture (ventricular wall, septum, papillary muscle)
- Reinfarction
- Pericarditis
- Pulmonary embolism secondary to DVT
- Papillary muscle dysefunction (necrosis/rupture) leading mitral incompetence
- Mural thrombosis
- Ventricular aneurysm
- Dressler's syndrome
