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

 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.

 The ischaemic episode can last from 15s up to 15 minutes, meaning that no (/minimal?) myocyte necrosis occurs.

 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.

 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

 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.

 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

 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**

TimeMacroscopic featuresMicroscopic features 0-30minsNone 30mins – 4hrNoneNone… border fibres wavy? 4hrs – 12 hrs (12 – 24 hrs) Dark mottlingHaemorrhage, oedema, early coagulative necrosis (wavy myofibrils, more space b/n cells, cells shrink and become more dense/ darker) daysMottling with yellow- tan infarct centre Neutrophil infiltration, coagulation necrosis (myofibrils lose nuclei) daysHyperemic border, central yellow-tan softening Macrophages performing phagocytosis at border. Dying neutrophils 10 – 14 daysRed-gray infarct bordersGranulation tissue (angiogenesis + collagen) 2 – 8 weeksGrey-white scar, progressive from border to the core of infarct ↑ collagen deposition, ↓ cellularity > 2 monthsScarring completeDense collagenous scar

 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.

 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.)

 Dilated cardiomyopathy  Genetic  Myocarditis (sometimes due to viruses)  Alcohol and other toxins  Childbirth (↑ volume?)  Ventricular remodelling  Response to injury or changes in loading  Adaptive

 Robbins and Cotran