Q2 LONG ANSWER 10M ★ High-yield

Describe the pathogenesis, morphological evolution, laboratory diagnosis and complications of myocardial infarction.

Pathology · 2nd Professional — Para-Clinical

Definition and Types

Myocardial infarction is ischaemic necrosis of the myocardium resulting from a critical reduction in coronary blood flow, almost always from acute thrombosis on a ruptured atherosclerotic plaque.

Type	Extent	Cause	ECG
Transmural	Full thickness of the ventricular wall	Complete occlusion by thrombus on a ruptured plaque	ST elevation (STEMI), later Q waves
Subendocardial	Inner one-third to one-half only	Partial occlusion, lysed thrombus, or global hypoperfusion (shock, severe anaemia)	ST depression, T inversion (NSTEMI)

The subendocardium is the last region to be perfused and the first to infarct, being furthest from the epicardial vessels and subject to the highest wall tension

Coronary Distribution

Artery	Frequency	Region infarcted
Left anterior descending	40–50%	Anterior wall of left ventricle, apex, anterior two-thirds of the interventricular septum
Right coronary	30–40%	Inferior and posterior wall of the left ventricle, posterior third of the septum, right ventricle; supplies the SA and AV nodes in most people — hence bradyarrhythmias with inferior infarcts
Left circumflex	15–20%	Lateral wall of the left ventricle

Evolution of the Infarct

Time	Gross appearance	Microscopy
0–30 minutes	None	Reversible injury only
Under 4 hours	None	None by light microscopy; wavy fibres at the border
4–12 hours	Dark mottling; TTC stain negative in the infarct	Early coagulative necrosis, oedema, haemorrhage
12–24 hours	Dark mottling	Coagulative necrosis, pyknosis, contraction band necrosis at the margins, early neutrophils
1–3 days	Yellow-tan infarct centre	Full coagulative necrosis with loss of nuclei and striations; dense neutrophil infiltrate
3–7 days	Hyperaemic border around a softened yellow-tan centre	Macrophages remove dead myocytes; the wall is at its weakest — the period of rupture
7–10 days	Depressed red-tan margins	Early granulation tissue at the margins
10–14 days	Red-grey and depressed	Well-established granulation tissue with new vessels and collagen
2–8 weeks	Grey-white scar forming	Increasing collagen, decreasing cellularity
Over 2 months	Dense grey-white scar	Dense fibrous scar; healing is complete

CLINICAL PEARL

Knowing when the wall is weakest tells you when it ruptures. Macrophages have digested the dead myocytes by days 3 to 7 but collagen has not yet been laid down, so the wall has the least tensile strength it will ever have. That is precisely when free wall rupture, papillary muscle rupture and septal rupture occur — the timing follows directly from the histology.

Cardiac Markers

Marker	Rises	Peaks	Returns to normal	Comment
Myoglobin	1–2 hours	6–8 hours	24 hours	The earliest but the least specific
Troponin I and T	3–4 hours	18–24 hours	7–10 days	The most sensitive and specific — the standard of diagnosis; the long window allows late presentation to be detected
CK-MB	3–12 hours	24 hours	48–72 hours	Because it falls quickly, it is the marker of choice for detecting RE-infarction
LDH	10 hours	2–3 days	6–8 days	Obsolete; non-specific

Troponin is raised by causes other than infarction — myocarditis, pulmonary embolism, sepsis, renal failure, cardiac failure; a raised troponin means myocardial injury, not necessarily infarction

Complications

Complication	Timing	Notes
Arrhythmia	Immediate — first hours	Ventricular fibrillation; the commonest cause of death, and usually before the patient reaches hospital
Left ventricular failure and cardiogenic shock	Hours to days	Shock when over 40% of the left ventricle is lost; mortality above 70%
Papillary muscle rupture	3–7 days	Acute severe mitral regurgitation with pulmonary oedema
Free wall rupture	3–7 days	Haemopericardium and tamponade; usually fatal
Interventricular septal rupture	3–7 days	New harsh pansystolic murmur with a left-to-right shunt
Mural thrombus	Days to weeks	Systemic embolism to brain, kidney, spleen, limbs
Fibrinous pericarditis	2–4 days	Over a transmural infarct; a friction rub
Dressler syndrome	Weeks to months	Autoimmune pericarditis with fever and a raised ESR
Ventricular aneurysm	Weeks to months	Bulging thinned scar; persistent ST elevation; mural thrombus and arrhythmia, but rarely ruptures because it is fibrous
Right ventricular infarction	With inferior infarcts	Hypotension with raised JVP and clear lungs; treated with fluids, and nitrates are dangerous

Angina and the Acute Coronary Syndromes

Syndrome	Mechanism	Features
Stable angina	Fixed stenosis above about 70%; demand exceeds a limited supply	Predictable chest pain on exertion, relieved by rest or nitrates; no myocyte necrosis, troponin normal
Prinzmetal (variant) angina	Coronary spasm	Occurs AT rest, often at night; ST elevation during the attack; responds to calcium channel blockers, and beta-blockers may worsen it
Unstable angina	Plaque disruption with non-occlusive thrombus	Pain at rest or of increasing frequency; troponin normal — the only thing separating it from NSTEMI
NSTEMI	Partial or transient occlusion	Troponin raised; ST depression or T inversion
STEMI	Complete occlusion by thrombus	Troponin raised; ST elevation; requires immediate reperfusion
Sudden cardiac death	Lethal arrhythmia on a background of coronary disease	Death within an hour of symptom onset

Unstable angina and NSTEMI differ only by the troponin — the mechanism and the initial management are the same, which is why they are grouped as non-ST-elevation acute coronary syndrome

Applied Aspects

"Time is muscle" — reperfusion by primary percutaneous coronary intervention or thrombolysis salvages myocardium in proportion to how early it is given
Reperfusion injury — restoring flow itself causes further damage through free radicals and calcium overload, seen histologically as contraction band necrosis and grossly as a haemorrhagic infarct
Silent infarction is common in diabetics and the elderly, because of autonomic neuropathy; a normal history does not exclude it
Sudden cardiac death is usually from ventricular fibrillation on a background of coronary disease, and the only effective treatment is prompt defibrillation
Secondary prevention — aspirin, a statin, a beta-blocker and an ACE inhibitor, with cardiac rehabilitation; each has independent mortality benefit
TTC (triphenyltetrazolium chloride) staining at autopsy demonstrates an infarct too early to be seen otherwise — viable myocardium stains brick-red, the infarct remains pale

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