Pathophysiology of ischaemia and infarction Flashcards
What is ischaemia ?
Reduced blood flow to organs/ tissues
What is hypoxia ?
Inadequate oxygen supply to meet the needs of tissue/ organs ?
What is hypoxic hypoxia ?
Low inspired O2 levels
Normal inspired o2 but low PaCO2
What is anaemic hypoxia ?
Normal inspired O2 but blood abnormal;
What is stagnant hypoxia ?
Normal inspired O2 but abnormal delivery
Local e.g. occlusion of artery
Systemic e.g. shock
What is cytotoxic hypoxia ?
Normal inspired O2 but abnormal at tissue level
What are the factors affecting O2 supply ?
Inspired O2 Pulmonary function Blood constituents Blood flow Integrity of vasculature Tissue mechanisms
What are the factors affecting O2 demand ?
Tissue itself- different tissues have different requirements
Activity of tissue above baseline value
What are the supply issues with iscahmic heart disease ?
Coronary artery atheroma
Cardiac failure (flow)
Pulmonary function- other disease or pulmonary oedema (LVF)
Anaemia, previous MI
What are the demand issues with ischaemic heart disease ?
Heart has high intrinsic demand
exertion/ stress
What is an atheroma/atherosclerosis ?
Localised accumulation of lipid and fibrous tissue in intima of arteries
What is the clinical correlation with established atheroma in coronary artery ?
Stable angina
What is the clinical consequence of complicated atheroma in coronary artery ?
Unstable angina
What is the clinical correlation of an ulcerated/fissured plaque ?
Leads to thrombosis, then leads to ischaemia and infarction
What are the clinical consequences of atheroma ?
MI TIA Cerebral infacrtion Abdominal aortic aneurysm Peripheral vascular diease Cardiac failure Coronary artery disease-> MI-> cardiac failure
What are the effects of atheroma on blood flow ?
Changes in vessel wall-> thrombosis
Poiseuille’s formula- R= 8ηl/πr2
Blood flow- Q = ∆P/R
What are the functional effects of ischaemia ?
Blood/ O2 supply fails to meet demand due to decreased supply; increased demand; or both
Related to rate of onset
What are the general effects of ischaemia ?
Acute
Chronic
Acute-on-chronic
What are the biochemical effects of ischaemia ?
- Normal aerobic metabolism
glucose+36ADP+36Pi+36H++6O2 ®6CO2+36ATP+42H2O- Anaerobic metabolism
glucose+2Pi+2ADP ®2lactate+2ATP+2H2O - L-lactate¬®pyruvate
- Pyruvate+ NAD++CoA®acetylCoA+CO2+NADH
- O2 ® anaerobic metabolism ® cell death
- Anaerobic metabolism
What are the cellular effects of ischaemia ?
Different tissues have variable O2 requirement and are variably susceptible to ischaemia
Cells with high metabolic rate
Cells with low metabolic rate
What are the clinical effects of ischaemia ?
Dysfunction
Pain
Physical damage- specialised cells
What is the outcome of the effects of ischaemia ?
No clinical effect
Resolution vs therapeutic intervention
Infacrtion
What is infarction ?
Ischamic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage
What are the possible aetiologies for infarction ?
Thrombosis
Embolism
Strangulation e.g. gut
Trauma - cut/ruptured vessel
What does the scale of damage of ischamia/infarction depend on ?
Time period
Tissue/organ
Pattern of blood supply
Previous disease
What is the mechanism of tissue breakdown caused by infarction ?
Anaerobic metabolism - cell death - liberation of enzymes
What are the two types of necrosis ?
Coagulative necrosis e.g. Heart, lung
Colliquative necrosis e.g. Brain
What can coronary arterial obstruction lead to ?
Reduced blood flow to region of myocardium, leads to ischaemia, rapid myocardial dysfunction, leads to myocyte death
What happens within seconds of myocardial ischaemia ?
Anaerobic metabolism, onset of ATP depletion
What happens in under two minutes of myocardial ischaemia ?
Loss of myocardial contractility (heart failure)
What happens within a few minutes of myocardial ischaemia ?
Ultrastructural changes (myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling) ?reversible
How long does it take for ischaemia to cause irreversible damage to the heart ?
20-30 minutes
Myocyte necrosis (disruption of integrity of sarcolemma membrane leading to the leakage of intracellular macromolecules: blood tests) - Troponin?
Injury to the microvasculature - over 1 hour
What do areas of infarction look like less than 24 hours after insult ?
No change on visual inspection
A few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy
What do areas of infarction look like within 24-48hrs ?
Pale infarct: e.g. myocardium, spleen, kidney, 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
What do areas of infarction look like within 72hrs and onwards ?
Macroscopically:
- Pale infarct - yellow/white and red periphery
Red infarct - little change
Microscopically: chronic inflammation; macrophages remove debris; granulation tissue; fibrosis
What is the appearance of end result infarcts ?
Scar replaces area of tissue damage
Shape depends on territory of occluded vessel
Reperfusion injury
What is the reparative process of myocardial infarction ?
Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue Collagen deposition (fibrosis) Scar formation
What happens between 4-12hrs of an MI ?
Early coagulation necrosis, oedema, haemorrhage
What happens between 12-24hrs of an MI ?
Ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate
What happens between 1-3 days of an MI ?
Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
What happens between 3-7 days of an MI ?
Disintegration of dead myofibrils, dying neutrophils, early phagocytosis
What happens between 7-10 days of an MI ?
Well developed phagocytosis, granulation tissue at margins
What happens between 10-14 days of an MI ?
Well established granulation tissue with new blood vessels and collagen deposition
What happens between 2-8 weeks of an MI ?
Increased collagen deposition, decreased cellularity
What happens over 2 months of an MI ?
Dense collagenous scar
What is a transmural infarction ?
Ischaemic necrosis affects full thickness of the myocardium
What is a subendocardial infarction ?
ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart
What are the histological feature of transmural and subendocardial infarcts ?
Histological features are the same (repair time - granulation tissue stage followed by fibrosis - in subendocardial infarct possibly slightly shortened compared to transmural infarct)
How are acute infarcts classified ?
According to whether there is elevation of the ST segment on the ECG
What are the features of a NSTEMI ?
No ST segment elevation but a significantly elevated serum troponin level
What does a NSTEMI correlate with ?
subendocardial infarct
What do the effects of infarction depend ?
Site
Size of infarct
Death and dysfunction (pain)
Contribution of previous disease and infarction
What are the complications of myocardial infarction ?
Immediate; early; late
Sudden death arrhythmias; angina; cardiac failure; cardiac rupture - ventricular wall, septum, papillary muscle; reinfarction; pericarditis; pulmonary embolism secondary to DVT; papillary muscle dysfunction - necrosis/rupture ® mitral incompetence; mural thrombosis; ventricular aneurysm; Dressler’s syndrome
