Pathology of Ischaemia and Infarction Flashcards
What is Ischaemia
• Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet the needs of tissue/organ: hypoxia
Types of Hypoxia (4)
Hypoxic
Anaemic
Stagnant
Cytotoxic
Hypoxic (2)
a) Low inspired O2 level
b) Normal inspired O2 but low PaO2
Anaemic
a) Normal inspired O2 but blood abnormal (carrying capacity)
Stagnant (3)
Normal inspired air but abnormal delivery
a) Local e.g. occlusion of vessel
b) Systemic e.g. shock
Cytotoxic
a) Normal inspired O2 but abnormal at tissue level
Factors affecting oxygen supply (6)
- 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 causes supply issues (6)
Coronary atheroma Cardiac failure Pulmonary function Pulmonary oedema Anaemia Previous
What causes demand issues
High intrinsic demand
What is atheroma/atherosclerosis
Localised accumulation of lipid and fibrous tissue in the intima of arteries
Established atheroma in coronary artery =
Stable angina
Complicated atheroma in coronary artery
Unstable angina
Ulcerated/fissured plaques (2)
Thrombosis
Ischaemia/Infarction
Atheroma in the aorta
Aneurysm
Clinical consequences of Atheroma in the aorta (7)
- MI
- TIA (transient ischaemic attack)
- Cerebral Infarction
- Abdominal aneurysm
- Peripheral vascular disease
- Cardiac failure
- Coronary artery disease
Effects of Atheroma on Blood Flow (3)
Vessel Wall
Blood Flow
Resistance
Blood flow (Q) =
Pressure gradient/ Resistance
Poiseuille’s formula demonstrates
Relationship between radius and resistance
Function effects of ischaemia
Blood/O2 supply fails to meet demand due to decreased supply and increased demand
General effects of ischaemia
Acute
Chronic
Biochemical effects of ischaemia
Anaerobic metabolism
cell death
Cellular effects of ischaemia
Different tissues have different O2 requirements
High metabolic are more susceptible
Clinical effects of ischaemia (3)
a) Dysfunction
b) Pain
c) Physical damage- specialised cells
Outcomes of Ischaemia (3)
a) No clinical effect
b) Resolution versus therapeutic intervention
c) Infarction
What is Infarction
Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either
the arterial supply or venous drainage
Cessation of blood supply can be caused by (4)
- Thrombosis
- Embolism
- Strangulation e.g. gut
- Trauma- cut/ruptured vessel
What is the scale of damage of ischaemia/infarction dependent on (4)
- Time period
- Tissue/organ
- Pattern of blood supply
- Previous disease
How does infarction lead to the break down of tissues
Anaerobic metabolism leads to cell death with liberates the enzymes and causes the breakdown of tissues
What is coagulative necrosis and where does it occur
. heart and lung- semi-solid debris due to the presence of protein fibres
What is colliquative necrosis and where does it occur
brain- characterized by the digestion of dead cells to form a viscous liquid mass.
What does coronary arterial obstruction cause
Myocardial dysfunction and myocyte death
Events that follow myocardial ischaemia
- Anaerobic metabolism - seconds
- ATP depletion
- Loss of myocardial contractility- <2 minutes
- Heart failure
- Ultrastructural changes- a few minutes
- Myocyte necrosis- 20-40 minutes
- Injury to microvasculature >1 hour
Appearance of infarcts less than 24 hours (2)
No change on visual inspection
A few hours to 12 hours post insult, see swollen mitochondria on electron microscopy
Appearance of infarct 24-48 hours (3)
Pale infarcts e.g. myocardium, kidney, spleen- solid tissue
Red infarcts 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
Appearance of infarcts 72 hours (3)
Macroscopically: pale infarct- yellow/white and red periphery
Red infarct- little change
Microscopically: Chronic inflammation; macrophages remove debris granulation tissue fibrosis
End result of infarcts (3)
Scar replaces area of tissue damage
Shape depends on territory of occluded vessel
Reperfusion injury
Name Reparative Processes (6)
- Cell death
- Acute inflammation
- Macrophage phagocytosis of dead cells
- Granulation tissue
- Collagen deposition (fibrosis)
- Scar formation
MI 4-12 hours
Early coagulation necrosis, oedema, haemorrhage
MI 12-24 hours
ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
1-3 days MI
Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
3-7 days MI
Disintegration of dead myofibres, dying neutrophil, early phagocytosis
7-10 days MI
well developed phagocytosis, granulation tissue at margins
10-14 days MI
well established granulation tissue with new blood vessels and collagen deposition
2-8 weeks
Increased collagen deposition, decreased cellularity
> 2months
Dense collagenous scar
Transmural Infarctions
Ischemic necrosis affects full thickness of the myocardium
Subendocardial infarction
Ischemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What infarction correlates with NSTEMI
Subendocardial infarction
What are the histological features of transmural and subendocardial infarction like
They are the same
the repair time in subendocardial is slightly shortened
