pathophysiology of myocardial ischaemia and acute coronary syndromes (acs)
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Pathophysiology of myocardial ischaemia and Acute Coronary Syndromes (ACS). Rick Allen. Acute coronary syndromes include: Unstable angina Acute myocardial infarction Sudden cardiac death Basics of pathophysiology Stable atherosclerotic plaque unstable atherothrombotic lesion - PowerPoint PPT PresentationTRANSCRIPT
PATHOPHYSIOLOGY OF MYOCARDIAL ISCHAEMIA AND ACUTE CORONARY
SYNDROMES (ACS)Rick Allen
Acute coronary syndromes include: Unstable angina Acute myocardial infarction Sudden cardiac death
Basics of pathophysiology Stable atherosclerotic plaque unstable
atherothrombotic lesion Rupture, superficial erosion deep haemorrhage,
ulceration, fissuring. Change results in the formation of a thrombis
which causes partial or complete occlusion of the vessel
Angina Stable
↑ myocardial O2 demand > ability of stenosed coronary art. to deliver.
Due to ↑ physical activity, emotional excitement or ↑ workload.
Prinzmetal Caused by vasospasm. May be no/minor
athersclerotic presence Unstable
plaque rupture partially occlusive thrombosis + vasoconstriction severe but transient ↓ in coronary blood flow.
Thromboemboli can micro infarcts. Occurs with low exercise or at rest.
Angina The ischaemic episode can last from 15s
up to 15 minutes, meaning that no (/minimal?) myocyte necrosis occurs.
Myocardial Infarction Acute plaque change
platelet adherence to exposed collagen/necrotic plaque contents, combine to form microthrombi
platelets release mediators causing vasospasm
TF release act. Coagulation cascade, ↑ thrombus
occludes lumen.
Myocardial Infarction Other causes
Vasospasm : platelet loitering or cocaine use Emboli: from LA due to AF, left sided mural
thrombosis, infective endocarditis vegitation, right sided source via patent foramen ovale
Low systemic BP: e.g. shock, ↓ perfusion Vasculitis, vascular dissection Haematological issues like sickle cell causing
occlusion
Myocardial Infarction Reversible:
Aerobic metabolism stops no ATP production and accumulation of toxic metabolites (lactic acid)
Loss of contractility in 60 secs. This can cause death prior to the production of an infarct.
Irreversible: Leaky cell membrane intracellular
components leak into cardiac interstitium microvasculature and lymph.
>1hr, damage to microvasculature Permanent myocardium damage 2 - 4hrs.
Progression of Infarct Begins as subendocardial (dependent on
cause) and then moves as a wavefront transmurally
The inner 1/3 is the least perfused region and is therefore the most susceptible. Regionally isolated if thrombus is lysed early Circumferential in prolonged, severe ↓
systemic BP (shock + non-critical stenosis) Transmural infarct gives ST elevation,
subendcardial does not
Factors Determining Morphology
Location, severity, rate of development of coronary obstructions
Size of vascular bed perfused by occluded artery
Duration of occlusion Metabolic/O2 needs of myocardium at risk. Collateral vessels Presence, site, severity of vascular spasm HR, rhythm, blood oxygenation.
**Necrosis is complete in 6hrs, longer if collaterals are present**
Time Macroscopic features
Microscopic features
0-30mins None None30mins – 4hr None None… border fibres wavy?
4hrs – 12 hrs
(12 – 24 hrs)
Dark mottling Haemorrhage, oedema, early coagulative necrosis (wavy myofibrils, more space b/n cells, cells shrink and become more dense/ darker)
1 - 3 days Mottling with yellow-tan infarct centre
Neutrophil infiltration, coagulation necrosis (myofibrils lose nuclei)
3 - 7 days Hyperemic border, central yellow-tan softening
Macrophages performing phagocytosis at border. Dying neutrophils
10 – 14 days Red-gray infarct borders
Granulation tissue (angiogenesis + collagen)
2 – 8 weeks Grey-white scar, progressive from border to the core of infarct
↑ collagen deposition, ↓ cellularity
> 2 months Scarring complete Dense collagenous scar
Sudden Cardiac Death atherosclerotic lesion disrupted plaque
regional myocardial ischaemia fatal ventricular arrythmia
Can be the first clinical presentation of IHD AMI is the most common trigger for fatal
arrhythmias (e.g. VF, asystole)
Injury can affect the conduction system and create electrochemical cardiac instability.
Fatal arrhythmias are usually caused by electrical instability distant from the conduction system – arrythmogenic foci are often located adjacent to scars of old MI’s.
Non-atherosclerotic causes include
Pulmonary HTN Congenital abnormalities Aortic valve stenosis Mitral valve prolapsed Myocarditis Dilated or hypertrophic cardiomyopathy Cardiac hypertrophy Genetic (channel or proteins which assist
the channels functioning are faulty, often leading to long QT intervals.)
Dilation of Ventricles Dilated cardiomyopathy
Genetic Myocarditis (sometimes due to viruses) Alcohol and other toxins Childbirth (↑ volume?)
Ventricular remodelling Response to injury or changes in loading Adaptive
References Robbins and Cotran